Full text data of TRAPPC2
TRAPPC2
(SEDL)
[Confidence: low (only semi-automatic identification from reviews)]
Trafficking protein particle complex subunit 2 (Sedlin)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Trafficking protein particle complex subunit 2 (Sedlin)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P0DI81
ID TPC2A_HUMAN Reviewed; 140 AA.
AC P0DI81; A6NEG0; O14582; Q9HD16;
DT 21-SEP-2011, integrated into UniProtKB/Swiss-Prot.
read moreDT 21-SEP-2011, sequence version 1.
DT 22-JAN-2014, entry version 23.
DE RecName: Full=Trafficking protein particle complex subunit 2;
DE AltName: Full=Sedlin;
GN Name=TRAPPC2; Synonyms=SEDL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, AND INVOLVEMENT
RP IN SEDT.
RX PubMed=10431248; DOI=10.1038/11976;
RA Gedeon A.K., Colley A., Jamieson R., Thompson E.M., Rogers J.,
RA Sillence D., Tiller G.E., Mulley J.C., Gecz J.;
RT "Identification of the gene (SEDL) causing X-linked spondyloepiphyseal
RT dysplasia tarda.";
RL Nat. Genet. 22:400-404(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 1-130 (ISOFORM 3).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Ovary, and Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP GENOMIC ORGANIZATION, ALTERNATIVE SPLICING, AND SUBCELLULAR LOCATION.
RX PubMed=11031107; DOI=10.1006/geno.2000.6326;
RA Gecz J., Hillman M.A., Gedeon A.K., Cox T.C., Baker E., Mulley J.C.;
RT "Gene structure and expression study of the SEDL gene for
RT spondyloepiphyseal dysplasia tarda.";
RL Genomics 69:242-251(2000).
RN [6]
RP IDENTIFICATION IN TRAPP COMPLEX.
RX PubMed=11805826; DOI=10.1038/415141a;
RA Gavin A.-C., Boesche M., Krause R., Grandi P., Marzioch M., Bauer A.,
RA Schultz J., Rick J.M., Michon A.-M., Cruciat C.-M., Remor M.,
RA Hoefert C., Schelder M., Brajenovic M., Ruffner H., Merino A.,
RA Klein K., Hudak M., Dickson D., Rudi T., Gnau V., Bauch A.,
RA Bastuck S., Huhse B., Leutwein C., Heurtier M.-A., Copley R.R.,
RA Edelmann A., Querfurth E., Rybin V., Drewes G., Raida M.,
RA Bouwmeester T., Bork P., Seraphin B., Kuster B., Neubauer G.,
RA Superti-Furga G.;
RT "Functional organization of the yeast proteome by systematic analysis
RT of protein complexes.";
RL Nature 415:141-147(2002).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP IDENTIFICATION IN TRAPP COMPLEX.
RX PubMed=21525244; DOI=10.1091/mbc.E10-11-0873;
RA Scrivens P.J., Noueihed B., Shahrzad N., Hul S., Brunet S., Sacher M.;
RT "C4orf41 and TTC-15 are mammalian TRAPP components with a role at an
RT early stage in ER-to-Golgi trafficking.";
RL Mol. Biol. Cell 22:2083-2093(2011).
RN [9]
RP CHARACTERIZATION OF VARIANT SEDL TYR-47.
RX PubMed=14597397; DOI=10.1016/S0378-1119(03)00819-9;
RA Gecz J., Shaw M.A., Bellon J.R., de Barros Lopes M.;
RT "Human wild-type SEDL protein functionally complements yeast Trs20p
RT but some naturally occurring SEDL mutants do not.";
RL Gene 320:137-144(2003).
RN [10]
RP IDENTIFICATION IN TRAPP COMPLEX, AND INTERACTION WITH TRAPPC2L.
RX PubMed=19416478; DOI=10.1111/j.1600-0854.2009.00906.x;
RA Scrivens P.J., Shahrzad N., Moores A., Morin A., Brunet S., Sacher M.;
RT "TRAPPC2L is a novel, highly conserved TRAPP-interacting protein.";
RL Traffic 10:724-736(2009).
RN [11]
RP SELF-ASSOCIATION, INTERACTION WITH ENO1; PITX1 AND SF1, SUBCELLULAR
RP LOCATION, AND CHARACTERIZATION OF VARIANTS SEDL TYR-47; LEU-73; SER-83
RP AND ASP-130.
RX PubMed=20498720; DOI=10.1371/journal.pone.0010646;
RA Jeyabalan J., Nesbit M.A., Galvanovskis J., Callaghan R., Rorsman P.,
RA Thakker R.V.;
RT "SEDLIN forms homodimers: characterisation of SEDLIN mutations and
RT their interactions with transcription factors MBP1, PITX1 and SF1.";
RL PLoS ONE 5:E10646-E10646(2010).
RN [12]
RP VARIANTS SEDT TYR-47; LEU-73 AND ASP-130.
RX PubMed=11349230; DOI=10.1086/320592;
RA Gedeon A.K., Tiller G.E., Le Merrer M., Heuertz S., Tranebjaerg L.,
RA Chitayat D., Robertson S., Glass I.A., Savarirayan R., Cole W.G.,
RA Rimoin D.L., Kousseff B.G., Ohashi H., Zabel B., Munnich A., Gecz J.,
RA Mulley J.C.;
RT "The molecular basis of X-linked spondyloepiphyseal dysplasia tarda.";
RL Am. J. Hum. Genet. 68:1386-1397(2001).
RN [13]
RP VARIANT SEDT SER-83.
RX PubMed=11424925; DOI=10.1136/jmg.38.6.409;
RA Grunebaum E., Arpaia E., MacKenzie J.J., Fitzpatrick J., Ray P.N.,
RA Roifman C.M.;
RT "A missense mutation in the SEDL gene results in delayed onset of X
RT linked spondyloepiphyseal dysplasia in a large pedigree.";
RL J. Med. Genet. 38:409-411(2001).
CC -!- FUNCTION: Prevents transcriptional repression and induction of
CC cell death by ENO1 (By similarity). May play a role in vesicular
CC transport from endoplasmic reticulum to Golgi.
CC -!- SUBUNIT: Can homodimerize. Component of the multisubunit TRAPP
CC (transport protein particle) complex, which includes TRAPPC2,
CC TRAPPC2L, TRAPPC3, TRAPPC3L, TRAPPC4, TRAPPC5, TRAPPC8, TRAPPC9,
CC TRAPPC10, TRAPPC11 and TRAPPC12. Interacts with ENO1, PITX1 and
CC SF1.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region. Endoplasmic
CC reticulum. Golgi apparatus. Nucleus. Note=Localized in perinuclear
CC granular structures.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist;
CC Name=1; Synonyms=Major;
CC IsoId=P0DI81-1, O14582-1;
CC Sequence=Displayed;
CC Name=2;
CC IsoId=P0DI81-2, O14582-2;
CC Sequence=VSP_041681, VSP_006040, VSP_041682;
CC Name=3;
CC IsoId=P0DI81-3; Sequence=VSP_041681;
CC -!- TISSUE SPECIFICITY: Expressed in brain, heart, kidney, liver,
CC lung, pancreas, placenta, skeletal muscle, fetal cartilage,
CC fibroblasts, placenta and lymphocytes.
CC -!- DISEASE: Spondyloepiphyseal dysplasia tarda (SEDT) [MIM:313400]:
CC X-linked recessive disorder of endochondral bone formation.
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- MISCELLANEOUS: A paralogous gene encoding an identical protein
CC appears to have arisen by retrotransposition of a cDNA from this
CC locus and to have acquired a promoter and non-coding 5' UTR from
CC the ZNF547 gene.
CC -!- SIMILARITY: Belongs to the TRAPP small subunits family. Sedlin
CC subfamily.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/TRAPPC2";
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DR EMBL; AF157065; AAD49845.1; -; Genomic_DNA.
DR EMBL; AF157062; AAD49845.1; JOINED; Genomic_DNA.
DR EMBL; AF157063; AAD49845.1; JOINED; Genomic_DNA.
DR EMBL; AF157064; AAD49845.1; JOINED; Genomic_DNA.
DR EMBL; AC003037; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK310542; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; DA542477; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; DB101396; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC016915; AAH16915.1; -; mRNA.
DR EMBL; BC052618; AAH52618.1; -; mRNA.
DR RefSeq; NP_001011658.1; NM_001011658.3.
DR RefSeq; NP_001122307.2; NM_001128835.2.
DR RefSeq; NP_055378.1; NM_014563.5.
DR UniGene; Hs.592238; -.
DR UniGene; Hs.622292; -.
DR ProteinModelPortal; P0DI81; -.
DR SMR; P0DI81; 1-140.
DR IntAct; P0DI81; 9.
DR MINT; MINT-155352; -.
DR PRIDE; P0DI81; -.
DR DNASU; 6399; -.
DR Ensembl; ENST00000358231; ENSP00000350966; ENSG00000196459.
DR Ensembl; ENST00000359680; ENSP00000352708; ENSG00000196459.
DR Ensembl; ENST00000380579; ENSP00000369953; ENSG00000196459.
DR Ensembl; ENST00000458511; ENSP00000392495; ENSG00000196459.
DR GeneID; 6399; -.
DR KEGG; hsa:6399; -.
DR UCSC; uc022btf.1; human.
DR CTD; 6399; -.
DR GeneCards; GC0XM013640; -.
DR HGNC; HGNC:23068; TRAPPC2.
DR HPA; CAB004665; -.
DR MIM; 300202; gene.
DR MIM; 313400; phenotype.
DR neXtProt; NX_P0DI81; -.
DR OMA; GHNDNPI; -.
DR OrthoDB; EOG7JQBQ9; -.
DR ChiTaRS; TRAPPC2; human.
DR GeneWiki; TRAPPC2; -.
DR GenomeRNAi; 6399; -.
DR NextBio; 24860; -.
DR PRO; PR:P0DI81; -.
DR ArrayExpress; P0DI81; -.
DR Bgee; P0DI81; -.
DR CleanEx; HS_TRAPPC2; -.
DR Genevestigator; O14582; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
DR GO; GO:0006888; P:ER to Golgi vesicle-mediated transport; NAS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IDA:UniProtKB.
DR GO; GO:0001501; P:skeletal system development; IMP:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR InterPro; IPR011012; Longin-like_dom.
DR InterPro; IPR006722; Sedlin.
DR PANTHER; PTHR12403; PTHR12403; 1.
DR Pfam; PF04628; Sedlin_N; 1.
DR SUPFAM; SSF64356; SSF64356; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Cytoplasm; Disease mutation;
KW Endoplasmic reticulum; ER-Golgi transport; Golgi apparatus; Nucleus;
KW Reference proteome; Transcription; Transport.
FT CHAIN 1 140 Trafficking protein particle complex
FT subunit 2.
FT /FTId=PRO_0000211566.
FT VAR_SEQ 1 1 M -> MSSWKQDRSGLRSTELNVLEYQPLCAVRSHILKTM
FT (in isoform 2 and isoform 3).
FT /FTId=VSP_041681.
FT VAR_SEQ 80 80 H -> HILTFLVKVTN (in isoform 2).
FT /FTId=VSP_006040.
FT VAR_SEQ 81 140 Missing (in isoform 2).
FT /FTId=VSP_041682.
FT VARIANT 47 47 D -> Y (in SEDT; probable loss of
FT function).
FT /FTId=VAR_012358.
FT VARIANT 73 73 S -> L (in SEDT; loss of interaction with
FT ENO1, PITX1 and SF1).
FT /FTId=VAR_012359.
FT VARIANT 83 83 F -> S (in SEDT; mild form; loss of
FT interaction with ENO1, PITX1 and SF1).
FT /FTId=VAR_012361.
FT VARIANT 130 130 V -> D (in SEDT; loss of interaction with
FT ENO1, PITX1 and SF1).
FT /FTId=VAR_012360.
SQ SEQUENCE 140 AA; 16445 MW; B099943C6F88952C CRC64;
MSGSFYFVIV GHHDNPVFEM EFLPAGKAES KDDHRHLNQF IAHAALDLVD ENMWLSNNMY
LKTVDKFNEW FVSAFVTAGH MRFIMLHDIR QEDGIKNFFT DVYDLYIKFS MNPFYEPNSP
IRSSAFDRKV QFLGKKHLLS
//
ID TPC2A_HUMAN Reviewed; 140 AA.
AC P0DI81; A6NEG0; O14582; Q9HD16;
DT 21-SEP-2011, integrated into UniProtKB/Swiss-Prot.
read moreDT 21-SEP-2011, sequence version 1.
DT 22-JAN-2014, entry version 23.
DE RecName: Full=Trafficking protein particle complex subunit 2;
DE AltName: Full=Sedlin;
GN Name=TRAPPC2; Synonyms=SEDL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, AND INVOLVEMENT
RP IN SEDT.
RX PubMed=10431248; DOI=10.1038/11976;
RA Gedeon A.K., Colley A., Jamieson R., Thompson E.M., Rogers J.,
RA Sillence D., Tiller G.E., Mulley J.C., Gecz J.;
RT "Identification of the gene (SEDL) causing X-linked spondyloepiphyseal
RT dysplasia tarda.";
RL Nat. Genet. 22:400-404(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 1-130 (ISOFORM 3).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Ovary, and Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP GENOMIC ORGANIZATION, ALTERNATIVE SPLICING, AND SUBCELLULAR LOCATION.
RX PubMed=11031107; DOI=10.1006/geno.2000.6326;
RA Gecz J., Hillman M.A., Gedeon A.K., Cox T.C., Baker E., Mulley J.C.;
RT "Gene structure and expression study of the SEDL gene for
RT spondyloepiphyseal dysplasia tarda.";
RL Genomics 69:242-251(2000).
RN [6]
RP IDENTIFICATION IN TRAPP COMPLEX.
RX PubMed=11805826; DOI=10.1038/415141a;
RA Gavin A.-C., Boesche M., Krause R., Grandi P., Marzioch M., Bauer A.,
RA Schultz J., Rick J.M., Michon A.-M., Cruciat C.-M., Remor M.,
RA Hoefert C., Schelder M., Brajenovic M., Ruffner H., Merino A.,
RA Klein K., Hudak M., Dickson D., Rudi T., Gnau V., Bauch A.,
RA Bastuck S., Huhse B., Leutwein C., Heurtier M.-A., Copley R.R.,
RA Edelmann A., Querfurth E., Rybin V., Drewes G., Raida M.,
RA Bouwmeester T., Bork P., Seraphin B., Kuster B., Neubauer G.,
RA Superti-Furga G.;
RT "Functional organization of the yeast proteome by systematic analysis
RT of protein complexes.";
RL Nature 415:141-147(2002).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP IDENTIFICATION IN TRAPP COMPLEX.
RX PubMed=21525244; DOI=10.1091/mbc.E10-11-0873;
RA Scrivens P.J., Noueihed B., Shahrzad N., Hul S., Brunet S., Sacher M.;
RT "C4orf41 and TTC-15 are mammalian TRAPP components with a role at an
RT early stage in ER-to-Golgi trafficking.";
RL Mol. Biol. Cell 22:2083-2093(2011).
RN [9]
RP CHARACTERIZATION OF VARIANT SEDL TYR-47.
RX PubMed=14597397; DOI=10.1016/S0378-1119(03)00819-9;
RA Gecz J., Shaw M.A., Bellon J.R., de Barros Lopes M.;
RT "Human wild-type SEDL protein functionally complements yeast Trs20p
RT but some naturally occurring SEDL mutants do not.";
RL Gene 320:137-144(2003).
RN [10]
RP IDENTIFICATION IN TRAPP COMPLEX, AND INTERACTION WITH TRAPPC2L.
RX PubMed=19416478; DOI=10.1111/j.1600-0854.2009.00906.x;
RA Scrivens P.J., Shahrzad N., Moores A., Morin A., Brunet S., Sacher M.;
RT "TRAPPC2L is a novel, highly conserved TRAPP-interacting protein.";
RL Traffic 10:724-736(2009).
RN [11]
RP SELF-ASSOCIATION, INTERACTION WITH ENO1; PITX1 AND SF1, SUBCELLULAR
RP LOCATION, AND CHARACTERIZATION OF VARIANTS SEDL TYR-47; LEU-73; SER-83
RP AND ASP-130.
RX PubMed=20498720; DOI=10.1371/journal.pone.0010646;
RA Jeyabalan J., Nesbit M.A., Galvanovskis J., Callaghan R., Rorsman P.,
RA Thakker R.V.;
RT "SEDLIN forms homodimers: characterisation of SEDLIN mutations and
RT their interactions with transcription factors MBP1, PITX1 and SF1.";
RL PLoS ONE 5:E10646-E10646(2010).
RN [12]
RP VARIANTS SEDT TYR-47; LEU-73 AND ASP-130.
RX PubMed=11349230; DOI=10.1086/320592;
RA Gedeon A.K., Tiller G.E., Le Merrer M., Heuertz S., Tranebjaerg L.,
RA Chitayat D., Robertson S., Glass I.A., Savarirayan R., Cole W.G.,
RA Rimoin D.L., Kousseff B.G., Ohashi H., Zabel B., Munnich A., Gecz J.,
RA Mulley J.C.;
RT "The molecular basis of X-linked spondyloepiphyseal dysplasia tarda.";
RL Am. J. Hum. Genet. 68:1386-1397(2001).
RN [13]
RP VARIANT SEDT SER-83.
RX PubMed=11424925; DOI=10.1136/jmg.38.6.409;
RA Grunebaum E., Arpaia E., MacKenzie J.J., Fitzpatrick J., Ray P.N.,
RA Roifman C.M.;
RT "A missense mutation in the SEDL gene results in delayed onset of X
RT linked spondyloepiphyseal dysplasia in a large pedigree.";
RL J. Med. Genet. 38:409-411(2001).
CC -!- FUNCTION: Prevents transcriptional repression and induction of
CC cell death by ENO1 (By similarity). May play a role in vesicular
CC transport from endoplasmic reticulum to Golgi.
CC -!- SUBUNIT: Can homodimerize. Component of the multisubunit TRAPP
CC (transport protein particle) complex, which includes TRAPPC2,
CC TRAPPC2L, TRAPPC3, TRAPPC3L, TRAPPC4, TRAPPC5, TRAPPC8, TRAPPC9,
CC TRAPPC10, TRAPPC11 and TRAPPC12. Interacts with ENO1, PITX1 and
CC SF1.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region. Endoplasmic
CC reticulum. Golgi apparatus. Nucleus. Note=Localized in perinuclear
CC granular structures.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist;
CC Name=1; Synonyms=Major;
CC IsoId=P0DI81-1, O14582-1;
CC Sequence=Displayed;
CC Name=2;
CC IsoId=P0DI81-2, O14582-2;
CC Sequence=VSP_041681, VSP_006040, VSP_041682;
CC Name=3;
CC IsoId=P0DI81-3; Sequence=VSP_041681;
CC -!- TISSUE SPECIFICITY: Expressed in brain, heart, kidney, liver,
CC lung, pancreas, placenta, skeletal muscle, fetal cartilage,
CC fibroblasts, placenta and lymphocytes.
CC -!- DISEASE: Spondyloepiphyseal dysplasia tarda (SEDT) [MIM:313400]:
CC X-linked recessive disorder of endochondral bone formation.
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
CC -!- MISCELLANEOUS: A paralogous gene encoding an identical protein
CC appears to have arisen by retrotransposition of a cDNA from this
CC locus and to have acquired a promoter and non-coding 5' UTR from
CC the ZNF547 gene.
CC -!- SIMILARITY: Belongs to the TRAPP small subunits family. Sedlin
CC subfamily.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/TRAPPC2";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF157065; AAD49845.1; -; Genomic_DNA.
DR EMBL; AF157062; AAD49845.1; JOINED; Genomic_DNA.
DR EMBL; AF157063; AAD49845.1; JOINED; Genomic_DNA.
DR EMBL; AF157064; AAD49845.1; JOINED; Genomic_DNA.
DR EMBL; AC003037; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK310542; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; DA542477; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; DB101396; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC016915; AAH16915.1; -; mRNA.
DR EMBL; BC052618; AAH52618.1; -; mRNA.
DR RefSeq; NP_001011658.1; NM_001011658.3.
DR RefSeq; NP_001122307.2; NM_001128835.2.
DR RefSeq; NP_055378.1; NM_014563.5.
DR UniGene; Hs.592238; -.
DR UniGene; Hs.622292; -.
DR ProteinModelPortal; P0DI81; -.
DR SMR; P0DI81; 1-140.
DR IntAct; P0DI81; 9.
DR MINT; MINT-155352; -.
DR PRIDE; P0DI81; -.
DR DNASU; 6399; -.
DR Ensembl; ENST00000358231; ENSP00000350966; ENSG00000196459.
DR Ensembl; ENST00000359680; ENSP00000352708; ENSG00000196459.
DR Ensembl; ENST00000380579; ENSP00000369953; ENSG00000196459.
DR Ensembl; ENST00000458511; ENSP00000392495; ENSG00000196459.
DR GeneID; 6399; -.
DR KEGG; hsa:6399; -.
DR UCSC; uc022btf.1; human.
DR CTD; 6399; -.
DR GeneCards; GC0XM013640; -.
DR HGNC; HGNC:23068; TRAPPC2.
DR HPA; CAB004665; -.
DR MIM; 300202; gene.
DR MIM; 313400; phenotype.
DR neXtProt; NX_P0DI81; -.
DR OMA; GHNDNPI; -.
DR OrthoDB; EOG7JQBQ9; -.
DR ChiTaRS; TRAPPC2; human.
DR GeneWiki; TRAPPC2; -.
DR GenomeRNAi; 6399; -.
DR NextBio; 24860; -.
DR PRO; PR:P0DI81; -.
DR ArrayExpress; P0DI81; -.
DR Bgee; P0DI81; -.
DR CleanEx; HS_TRAPPC2; -.
DR Genevestigator; O14582; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
DR GO; GO:0006888; P:ER to Golgi vesicle-mediated transport; NAS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IDA:UniProtKB.
DR GO; GO:0001501; P:skeletal system development; IMP:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR InterPro; IPR011012; Longin-like_dom.
DR InterPro; IPR006722; Sedlin.
DR PANTHER; PTHR12403; PTHR12403; 1.
DR Pfam; PF04628; Sedlin_N; 1.
DR SUPFAM; SSF64356; SSF64356; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Cytoplasm; Disease mutation;
KW Endoplasmic reticulum; ER-Golgi transport; Golgi apparatus; Nucleus;
KW Reference proteome; Transcription; Transport.
FT CHAIN 1 140 Trafficking protein particle complex
FT subunit 2.
FT /FTId=PRO_0000211566.
FT VAR_SEQ 1 1 M -> MSSWKQDRSGLRSTELNVLEYQPLCAVRSHILKTM
FT (in isoform 2 and isoform 3).
FT /FTId=VSP_041681.
FT VAR_SEQ 80 80 H -> HILTFLVKVTN (in isoform 2).
FT /FTId=VSP_006040.
FT VAR_SEQ 81 140 Missing (in isoform 2).
FT /FTId=VSP_041682.
FT VARIANT 47 47 D -> Y (in SEDT; probable loss of
FT function).
FT /FTId=VAR_012358.
FT VARIANT 73 73 S -> L (in SEDT; loss of interaction with
FT ENO1, PITX1 and SF1).
FT /FTId=VAR_012359.
FT VARIANT 83 83 F -> S (in SEDT; mild form; loss of
FT interaction with ENO1, PITX1 and SF1).
FT /FTId=VAR_012361.
FT VARIANT 130 130 V -> D (in SEDT; loss of interaction with
FT ENO1, PITX1 and SF1).
FT /FTId=VAR_012360.
SQ SEQUENCE 140 AA; 16445 MW; B099943C6F88952C CRC64;
MSGSFYFVIV GHHDNPVFEM EFLPAGKAES KDDHRHLNQF IAHAALDLVD ENMWLSNNMY
LKTVDKFNEW FVSAFVTAGH MRFIMLHDIR QEDGIKNFFT DVYDLYIKFS MNPFYEPNSP
IRSSAFDRKV QFLGKKHLLS
//
MIM
300202
*RECORD*
*FIELD* NO
300202
*FIELD* TI
*300202 TRACKING PROTEIN PARTICLE COMPLEX, SUBUNIT 2; TRAPPC2
;;SEDLIN; SEDL
*FIELD* TX
read more
DESCRIPTION
TRAPPC2 is a component of the TRAPP multisubunit tethering complex
involved in intracellular vesicle trafficking (Scrivens et al., 2011).
CLONING
The spondyloepiphyseal dysplasia tarda (SEDT; 313400) locus had been
mapped by linkage to Xp22 in the approximately 2-Mb interval between
DXS16 and DXS987. Gedeon et al. (1999) confirmed and refined this
localization to an interval of less than 170 kb by critical
recombination events at DXS16 and AFMa124wc1 in 2 families. By genomic
sequence analysis, they identified a novel gene, which they designated
SEDL, within this region. The SEDL gene encodes a 140-amino acid
protein, sedlin, with a putative role in endoplasmic reticulum
(ER)-to-Golgi vesicular transport. Northern blot hybridization and
RT-PCR analysis indicated that SEDL is widely expressed in tissues,
including fibroblasts, lymphoblasts, and fetal cartilage. Two
transcripts were detected by Northern blot analysis, one at
approximately 2.8 kb encoding the X-linked SEDL and the other at
approximately 0.75 kb encoding the truncated transcript of the
chromosome 19 pseudogene. The latter is a processed pseudogene with an
additional exon 5-prime to the rest of the pseudogene and separated by
its sole intron. Gedeon et al. (1999) identified SEDL homologs in yeast,
Drosophila, Caenorhabditis elegans, mouse, and rat. The yeast homolog
was characterized as a member of a large multiprotein complex called
TRAPP (transport protein particle), which has a role in the targeting
and fusion of the ER-to-Golgi transport vesicles with their acceptor
compartment.
By Northern blot analysis, Mumm et al. (2001) detected additional minor
SEDL transcripts of 5.0 and 1.6 kb, the smallest of which may reflect a
pseudogene.
Gecz et al. (2000) performed transient transfection studies with tagged
recombinant mammalian SEDL proteins in COS-7 cells. The tagged SEDL
proteins localized to the perinuclear structures that partly overlapped
with the intermediate ER-Golgi compartment. Two human SEDL mutations
introduced into SEDL FLAG and GFP constructs led to the misplacement of
the SEDL protein primarily to the cell nucleus and partially to the
cytoplasm.
GENE STRUCTURE
Gecz et al. (2000) identified the genomic structure of the SEDL gene.
The SEDL gene contains 6 exons and spans a genomic region of
approximately 20 kb in Xp22. It has 4 Alu sequences in its 3-prime
untranslated region (UTR) and an alternatively spliced MER20 sequence in
its 5-prime UTR. Complex alternative splicing was detected for exon 4.
Mumm et al. (2001) confirmed the structure of the SEDL gene and
identified a potential splice variant lacking exon 2.
MAPPING
Gedeon et al. (1999) determined that the SEDL gene maps to chromosome
Xp22. Gecz et al. (2000) identified 7 SEDL pseudogenes in the human
genome.
GENE FUNCTION
Scrivens et al. (2011) used tandem affinity purification-tagged TRAPPC2
and TRAPPC2L (610970) to identify purified TRAPP complexes from HEK293
cells. Knockdown of individual components of the TRAPP complexes caused
Golgi fragmentation and arrested anterograde trafficking, suggesting
that the TRAPP complex functions in an early trafficking step between
the endoplasmic reticulum and Golgi. Gel filtration analysis suggested
that TRAPP complexes can join to form larger oligomers.
Venditti et al. (2012) found that TANGO1 (613455) recruits sedlin, a
TRAPP component that is defective in spondyloepiphyseal dysplasia tarda,
and that sedlin is required for the ER export of procollagen, prefibrils
of which are too large to fit into typical COPII vesicles. Sedlin bound
and promoted efficient cycling of SAR1 (603379), a guanosine
triphosphate that can constrict membranes, and thus allowed nascent
carriers to grow and incorporate procollagen prefibrils. This joint
action of TANGO1 and sedlin sustained the ER export of procollagen, and
its derangement may explain the defective chondrogenesis underlying
SEDT.
MOLECULAR GENETICS
Gedeon et al. (1999) identified 3 dinucleotide deletions in the SEDL
gene in affected members of 3 Australian families with SEDT. All 3
mutations caused frameshifts that resulted in protein truncation,
arousing speculation that less severe missense mutations of SEDL may
have different phenotypic effects, such as precocious osteoarthritis
only.
Gedeon et al. (2001) reviewed the spectrum of mutations found in 30 of
36 unrelated cases of X-linked SEDT ascertained from different ethnic
populations. It brought the total number of different disease-associated
mutations to 21 and showed that they were distributed throughout the
SEDL gene. Four recurrent mutations accounted for 13 of the 30 (43%).
Haplotype analyses and the diverse ethnic origins of the patients
supported recurrent mutations. Two patients with large deletions of SEDL
exons were found, 1 with childhood onset of painful complications, the
other relatively free of additional symptoms. Since no clear
genotype/phenotype correlation could be established, they concluded that
the complete unaltered SEDL gene product is essential for normal bone
growth.
Tiller et al. (2001) determined that the SEDL gene escapes X
inactivation. They reported that the closest flanking genes identified
at Xp22.2 also escape X inactivation. Clustering supported a model in
which reasonable mechanisms may control the expression of genes that
escape X inactivation. Most mutations in SEDL patients are predicted to
truncate severely the protein product or eliminate it entirely. The
observation that SEDL escapes X inactivation suggests that
haploinsufficiency at the locus is inadequate to produce any phenotypic
changes in female SEDL carriers. Although Whyte et al. (1999) observed
subtle radiographic changes in older SEDL carriers, no signs or symptoms
of premature osteoarthritis were noted in the women of the family
reported by Tiller et al. (2001) or those reported by Gedeon et al.
(1999).
Christie et al. (2001) characterized the SEDL mutations in 4 unrelated
spondyloepiphyseal dysplasia tarda kindreds of European origin. They
identified 2 nonsense and 2 intragenic deletional frameshift mutations.
The nonsense mutations occurred in exons 4 and 6. Both of the intragenic
deletions, which were approximately 750 and 1300 to 1445 bp in size,
involved intron 5 and part of exon 6 and resulted in frameshifts that
led to premature termination signals.
Grunebaum et al. (2001) identified a missense mutation (300202.0007) in
a 4-generation family with late-onset SED. Grunebaum et al. (2001)
suggested that the mild phenotype in this family might be caused by a
missense rather than a nonsense mutation.
The possibility that some mutations in the SEDL gene may result in a
mild phenotype like that of early primary osteoarthritis prompted
Fiedler et al. (2002) to collect a cohort of 37 male patients (age 50.6
+/- 7.6 years) with either early end-stage primary osteoarthritis of the
hip (26 patients) or knee (11 patients). Cases with risk factors for
secondary osteoarthritis, such as congenital hip dysplasia, rheumatoid
arthritis, joint trauma, obesity, or diabetes mellitus, were excluded.
Seven patients were stated to be the shortest in the family, while from
8 patients the father (with 158 cm), and from 4 the brother was the
shortest member. Six fathers of the patients and 1 brother needed joint
replacement because of end-stage osteoarthritis. Fiedler et al. (2002)
detected no mutations in the coding sequence of SEDL and found no
polymorphism indicating a highly conserved gene. Their findings
supported previous results of high homology between different species
(Gedeon et al., 2001; Gecz et al., 2000). The results indicated that
mutations in the coding sequence of SEDL are not a common cause of early
primary osteoarthritis in men.
ANIMAL MODEL
Jang et al. (2002) reported the 2.4-angstrom resolution structure of
mouse SEDL, which revealed an unexpected similarity to the structures of
the N-terminal regulatory domain of 2 SNAREs, Ykt6p (606209) and SEC22B
(604029), despite no sequence homology to these proteins. The similarity
and the presence of an unusually large number of solvent-exposed apolar
residues of SEDL suggested that it serves regulatory and/or adaptor
functions through multiple protein-protein interactions. Jang et al.
(2002) noted that of the 4 known missense mutations responsible for
SEDT, 3 map to the protein interior, where the mutations would disrupt
the structure, and the fourth maps on a surface at which the mutation
might abrogate functional interactions with a partner protein.
*FIELD* AV
.0001
SPONDYLOEPIPHYSEAL DYSPLASIA TARDA
SEDL, 2-BP DEL, 53TT
In a family with X-linked spondyloepiphyseal dysplasia tarda (313400),
Gedeon et al. (1999) observed a dinucleotide deletion of TT at positions
53 and 54 in exon 3 of the SEDL gene, in a string of 5 thymines.
.0002
SPONDYLOEPIPHYSEAL DYSPLASIA TARDA
SEDL, 2-BP DEL, 191TG
In a family with X-linked spondyloepiphyseal dysplasia tarda (313400),
Gedeon et al. (1999) reported a dinucleotide deletion of TG at positions
191 to 192 in exon 4 of the SEDL gene. Gedeon et al. (2001) found that
this was a recurrent mutation. The results of haplotype analyses and the
diverse ethnic origins of patients supported recurrence of the mutation.
.0003
SPONDYLOEPIPHYSEAL DYSPLASIA TARDA
SEDL, 2-BP DEL, 157AT
In a family with X-linked spondyloepiphyseal dysplasia tarda (313400),
Gedeon et al. (1999) identified a deletion of AT at positions 157 and
158 in exon 3 of the SEDL gene.
.0004
SPONDYLOEPIPHYSEAL DYSPLASIA TARDA
SEDL, 5-BP DEL, NT267
Whyte et al. (1999) described the clinical and radiographic evaluation
of a 6-generation kindred from Arkansas with X-linked recessive
spondyloepiphyseal dysplasia tarda (313400). Mumm et al. (2000)
investigated this family by mutation analysis. In an affected man and
obligate carrier woman, they found a 5-bp deletion (AAGAC) in exon 5 of
the sedlin gene. The defect causes a frameshift, resulting in 8 missense
amino acids and premature termination. The 5-bp deletion was then
demonstrated to segregate with SEDT in the 4 living generations,
including 8 affected males and 9 obligate carrier females. Furthermore,
the deletion was identified in 4 females who potentially were
heterozygous carriers for SEDT.
.0005
SPONDYLOEPIPHYSEAL DYSPLASIA TARDA
SEDL, 5-BP DEL, NT271
Gedeon et al. (2001) stated that the deletion of nucleotides 271-275 was
recurrent. The results of haplotype analyses and the diverse ethnic
origins of patients with spondyloepiphyseal dysplasia tarda (313400)
supported recurrent mutations.
.0006
SPONDYLOEPIPHYSEAL DYSPLASIA TARDA
SEDL, IVS3DS, G-A, +5
Tiller et al. (2001) characterized an exon-skipping mutation in 2
unrelated families with spondyloepiphyseal dysplasia tarda (313400):
IVS3+5G-A at the intron 3 splice donor site. Using RT-PCR, they
demonstrated that the mutation resulted in elimination of the first 31
codons of the open reading frame. RT-PCR experiments using mouse/human
cell hybrids revealed that the SEDL gene escapes X inactivation.
Homologs of the SEDL gene include a transcribed retropseudogene on
chromosome 19, as well as expressed genes in mouse, rat, Drosophila, C.
elegans, and S. cerevisiae. The yeast homolog, p20, has a putative role
in vesicular transport from ER to Golgi complex. The data suggested that
SEDL mutations may perturb an intracellular pathway that is important
for cartilage homeostasis.
.0007
SPONDYLOEPIPHYSEAL DYSPLASIA TARDA
SEDL, PHE83SER
Grunebaum et al. (2001) identified a 4-generation family with late-onset
spondyloepiphyseal dysplasia (313400) caused by a T-to-C substitution at
nucleotide 248 in exon 5 of the SEDL gene, resulting in the substitution
of a phenylalanine by serine residue at amino acid 83 (p83). The
phenotype in this family was mild, and Grunebaum et al. (2001)
speculated that this might be due to the presence of a missense rather
than a nonsense mutation in this family.
.0008
SPONDYLOEPIPHYSEAL DYSPLASIA TARDA
SEDL, GLN131TER
In a 14-year-old Japanese boy with late-onset spondyloepiphyseal
dysplasia (313400), Takahashi et al. (2002) identified homozygosity for
a 391C-T transition in the SEDL gene, resulting in a gln131 (CAG)-to-ter
(TAG) (Q131X) substitution. The mother was heterozygous for the
mutation. There were 5 affected males in 3 generations connected through
carrier females.
.0009
SPONDYLOEPIPHYSEAL DYSPLASIA TARDA
SEDL, SER110TER
In a 16-year-old Taiwanese boy with late-onset spondyloepiphyseal
dysplasia (313400), the single affected individual in his family, Shi et
al. (2002) identified a 329C-A transversion in exon 6 of the SEDL gene,
resulting in a TCA (ser) to TAA (ter) change at codon 329 (S329X). The
authors stated that 'according to the family history,' 4 male children
and an uncle on the maternal side had the clinical features of SEDT.
Clinical details were not provided.
.0010
SPONDYLOEPIPHYSEAL DYSPLASIA TARDA
SEDL, IVS4, T-C, +4
In an Italian family with 2 brothers affected with SEDT (313400) of
different degrees of severity and with pubertal delay as an associated
finding, Shaw et al. (2003) found a mutation in the rare, noncanonical
5-prime splice site of intron 4 of the SEDL gene: IVS4+4T-C. RT-PCR
analysis showed that this mutation caused alternative splicing of exon 5
and, as a consequence, inclusion of exon 4b sequence. This gave rise to
an altered, truncated SEDL protein.
.0011
SPONDYLOEPIPHYSEAL DYSPLASIA TARDA
SEDL, 1-BP DEL, 613A
In an Ashkenazi Jewish family with spondyloepiphyseal dysplasia tarda
(313400), Bar-Yosef et al. (2004) identified a deletion of nucleotide A
at position 613 (613delA) in exon 6 of the SEDL gene, resulting in
truncation at codon 139 of the 140-codon-long protein. The authors noted
that the mutation also predicts a val130-to-phe substitution that would
likely interfere with proper folding of the protein. Bar-Yosef et al.
(2004) stated that this was the first report of an SEDL mutation in a
Jewish family.
*FIELD* RF
1. Bar-Yosef, U.; Ohana, E.; Hershkovitz, E.; Perlmuter, S.; Ofir,
R.; Birk, O. S.: X-linked spondyloepiphyseal dysplasia tarda: a novel
SEDL mutation in a Jewish Ashkenazi family and clinical intervention
considerations. Am. J. Med. Genet. 125A: 45-48, 2004.
2. Christie, P. T.; Curley, A.; Nesbit, M. A.; Chapman, C.; Genet,
S.; Harper, P. S.; Keeling, S. L.; Wilkie, A. O. M.; Winter, R. M.;
Thakker, R. V.: Mutational analysis in X-linked spondyloepiphyseal
dysplasia tarda. J. Clin. Endocr. Metab. 86: 3233-3236, 2001.
3. Fiedler, J.; Bittner, M.; Puhl, W.; Brenner, R. E.: Mutations
in the X-linked spondyloepiphyseal dysplasia tarda (SEDL) coding sequence
are not a common cause of early primary osteoarthritis in men. (Letter) Clin.
Genet. 62: 94-95, 2002.
4. Gecz, J.; Hillman, M. A.; Gedeon, A. K.; Cox, T. C.; Baker, E.;
Mulley, J. C.: Gene structure and expression study of the SEDL gene
for spondyloepiphyseal dysplasia tarda. Genomics 69: 242-251, 2000.
5. Gedeon, A. K.; Colley, A.; Jamieson, R.; Thompson, E. M.; Rogers,
J.; Sillence, D.; Tiller, G. E.; Mulley, J. C.; Gecz, J.: Identification
of the gene (SEDL) causing X-linked spondyloepiphyseal dysplasia tarda. Nature
Genet. 22: 400-404, 1999.
6. Gedeon, A. K.; Tiller, G. E.; Le Merrer, M.; Heuertz, S.; Tranebjaerg,
L.; Chitayat, D.; Robertson, S.; Glass, I. A.; Savarirayan, R.; Cole,
W. G.; Rimoin, D. L.; Kousseff, B. G.; Ohashi, H.; Zabel, B.; Munnich,
A.; Gecz, J.; Mulley, J. C.: The molecular basis of X-linked spondyloepiphyseal
dysplasia tarda. Am. J. Hum. Genet. 68: 1386-1397, 2001.
7. Grunebaum, E.; Arpaia, E.; MacKenzie, J. J.; Fitzpatrick, J.; Ray,
P. N.; Roifman, C. M.: A missense mutation in the SEDL gene results
in delayed onset of X linked spondyloepiphyseal dysplasia in a large
pedigree. (Letter) J. Med. Genet. 38: 409-411, 2001.
8. Jang, S. B.; Kim, Y.-G.; Cho, Y.-S.; Suh, P.-G.; Kim, K.-H.; Oh,
B.-H.: Crystal structure of SEDL and its implications for a genetic
disease spondyloepiphyseal dysplasia tarda. J. Biol. Chem. 277:
49863-49869, 2002.
9. Mumm, S.; Christie, P. T.; Finnegan, P.; Jones, J.; Dixon, P. H.;
Pannett, A. A. J.; Harding, B.; Gottesman, G. S.; Thakker, R. V.;
Whyte, M. P.: A five-base pair deletion in the sedlin gene causes
spondyloepiphyseal dysplasia tarda in a six-generation Arkansas kindred. J.
Clin. Endocr. Metab. 85: 3343-3347, 2000.
10. Mumm, S.; Zhang, X.; Vacca, M.; D'Esposito, M.; Whyte, M. P.:
The sedlin gene for spondyloepiphyseal dysplasia tarda escapes X-inactivation
and contains a non-canonical splice site. Gene 273: 285-293, 2001.
11. Scrivens, P. J.; Noueihed, B.; Shahrzad, N.; Hul, S.; Brunet,
S.; Sacher, M.: C4orf41 and TTC-15 are mammalian TRAPP components
with a role at an early stage in ER-to-Golgi trafficking. Molec.
Biol. Cell 22: 2083-2093, 2011.
12. Shaw, M. A.; Brunetti-Pierri, N.; Kadasi, L.; Kovacova, V.; Van
Maldergem, L.; De Brasi, D.; Salerno, M.; Gecz, J.: Identification
of three novel SEDL mutations, including mutation in the rare, non-canonical
splice site of exon 4. Clin. Genet. 64: 235-242, 2003.
13. Shi, Y.-R.; Lee, C.-C.; Hsu, Y.-A.; Wang, C.-H.; Tsai, F.-J.:
A novel nonsense mutation of the sedlin gene in a family with spondyloepiphyseal
dysplasia tarda. Hum. Hered. 54: 54-56, 2002.
14. Takahashi, T.; Takahashi, I.; Tsuchida, S.; Oyama, K.; Komatsu,
M.; Saito, H.; Takada, G.: An SEDL gene mutation in a Japanese kindred
of X-linked spondyloepiphyseal dysplasia tarda. (Letter) Clin. Genet. 61:
319-320, 2002. Note: Erratum: Clin. Genet. 64: 375 only, 2003.
15. Tiller, G. E.; Hannig, V. L.; Dozier, D.; Carrel, L.; Trevarthen,
K. C.; Wilcox, W. R.; Mundlos, S.; Haines, J. L.; Gedeon, A. K.; Gecz,
J.: A recurrent RNA-splicing mutation in the SEDL gene causes X-linked
spondyloepiphyseal dysplasia tarda. Am. J. Hum. Genet. 68: 1398-1407,
2001.
16. Venditti, R.; Scanu, T.; Santoro, M.; Di Tullio, G.; Spaar, A.;
Gaibisso, R.; Beznoussenko, G. V.; Mironov, A. A.; Mironov, A., Jr.;
Zelante, L.; Piemontese, M. R.; Notarangelo, A.; Malhotra, V.; Vertel,
B. M.; Wilson, C.; De Matteis, M. A.: Sedlin controls the ER export
of procollagen by regulating the Sar1 cycle. Science 337: 1668-1672,
2012.
17. Whyte, M. P.; Gottesman, G. S.; Eddy, M. C.; McAlister, W. H.
: X-linked recessive spondyloepiphyseal dysplasia tarda: clinical
and radiographic evolution in a 6-generation kindred and review of
the literature. Medicine 78: 9-25, 1999.
*FIELD* CN
Ada Hamosh - updated: 10/24/2012
Patricia A. Hartz - updated: 7/22/2011
Marla J. F. O'Neill - updated: 5/18/2004
Victor A. McKusick - updated: 10/16/2003
Victor A. McKusick - updated: 3/5/2003
Victor A. McKusick - updated: 2/24/2003
Victor A. McKusick - updated: 8/21/2002
Victor A. McKusick - updated: 8/12/2002
Michael J. Wright - updated: 7/26/2002
Paul J. Converse - updated: 4/11/2002
John A. Phillips, III - updated: 3/5/2002
Victor A. McKusick - updated: 6/20/2001
John A. Phillips, III - updated: 3/21/2001
Ada Hamosh - updated: 1/3/2001
*FIELD* CD
Ada Hamosh: 8/4/1999
*FIELD* ED
alopez: 10/25/2012
terry: 10/24/2012
carol: 5/30/2012
wwang: 8/5/2011
terry: 7/22/2011
mgross: 4/20/2007
carol: 3/22/2007
carol: 5/26/2004
mgross: 5/19/2004
carol: 5/19/2004
terry: 5/18/2004
cwells: 10/21/2003
terry: 10/16/2003
tkritzer: 3/18/2003
tkritzer: 3/11/2003
terry: 3/5/2003
carol: 3/3/2003
tkritzer: 2/25/2003
terry: 2/24/2003
tkritzer: 8/27/2002
tkritzer: 8/26/2002
terry: 8/21/2002
tkritzer: 8/15/2002
tkritzer: 8/14/2002
terry: 8/12/2002
tkritzer: 8/2/2002
tkritzer: 8/1/2002
terry: 7/26/2002
mgross: 4/11/2002
alopez: 3/5/2002
cwells: 7/3/2001
terry: 6/20/2001
alopez: 3/21/2001
carol: 1/7/2001
terry: 1/3/2001
alopez: 8/5/1999
alopez: 8/4/1999
*RECORD*
*FIELD* NO
300202
*FIELD* TI
*300202 TRACKING PROTEIN PARTICLE COMPLEX, SUBUNIT 2; TRAPPC2
;;SEDLIN; SEDL
*FIELD* TX
read more
DESCRIPTION
TRAPPC2 is a component of the TRAPP multisubunit tethering complex
involved in intracellular vesicle trafficking (Scrivens et al., 2011).
CLONING
The spondyloepiphyseal dysplasia tarda (SEDT; 313400) locus had been
mapped by linkage to Xp22 in the approximately 2-Mb interval between
DXS16 and DXS987. Gedeon et al. (1999) confirmed and refined this
localization to an interval of less than 170 kb by critical
recombination events at DXS16 and AFMa124wc1 in 2 families. By genomic
sequence analysis, they identified a novel gene, which they designated
SEDL, within this region. The SEDL gene encodes a 140-amino acid
protein, sedlin, with a putative role in endoplasmic reticulum
(ER)-to-Golgi vesicular transport. Northern blot hybridization and
RT-PCR analysis indicated that SEDL is widely expressed in tissues,
including fibroblasts, lymphoblasts, and fetal cartilage. Two
transcripts were detected by Northern blot analysis, one at
approximately 2.8 kb encoding the X-linked SEDL and the other at
approximately 0.75 kb encoding the truncated transcript of the
chromosome 19 pseudogene. The latter is a processed pseudogene with an
additional exon 5-prime to the rest of the pseudogene and separated by
its sole intron. Gedeon et al. (1999) identified SEDL homologs in yeast,
Drosophila, Caenorhabditis elegans, mouse, and rat. The yeast homolog
was characterized as a member of a large multiprotein complex called
TRAPP (transport protein particle), which has a role in the targeting
and fusion of the ER-to-Golgi transport vesicles with their acceptor
compartment.
By Northern blot analysis, Mumm et al. (2001) detected additional minor
SEDL transcripts of 5.0 and 1.6 kb, the smallest of which may reflect a
pseudogene.
Gecz et al. (2000) performed transient transfection studies with tagged
recombinant mammalian SEDL proteins in COS-7 cells. The tagged SEDL
proteins localized to the perinuclear structures that partly overlapped
with the intermediate ER-Golgi compartment. Two human SEDL mutations
introduced into SEDL FLAG and GFP constructs led to the misplacement of
the SEDL protein primarily to the cell nucleus and partially to the
cytoplasm.
GENE STRUCTURE
Gecz et al. (2000) identified the genomic structure of the SEDL gene.
The SEDL gene contains 6 exons and spans a genomic region of
approximately 20 kb in Xp22. It has 4 Alu sequences in its 3-prime
untranslated region (UTR) and an alternatively spliced MER20 sequence in
its 5-prime UTR. Complex alternative splicing was detected for exon 4.
Mumm et al. (2001) confirmed the structure of the SEDL gene and
identified a potential splice variant lacking exon 2.
MAPPING
Gedeon et al. (1999) determined that the SEDL gene maps to chromosome
Xp22. Gecz et al. (2000) identified 7 SEDL pseudogenes in the human
genome.
GENE FUNCTION
Scrivens et al. (2011) used tandem affinity purification-tagged TRAPPC2
and TRAPPC2L (610970) to identify purified TRAPP complexes from HEK293
cells. Knockdown of individual components of the TRAPP complexes caused
Golgi fragmentation and arrested anterograde trafficking, suggesting
that the TRAPP complex functions in an early trafficking step between
the endoplasmic reticulum and Golgi. Gel filtration analysis suggested
that TRAPP complexes can join to form larger oligomers.
Venditti et al. (2012) found that TANGO1 (613455) recruits sedlin, a
TRAPP component that is defective in spondyloepiphyseal dysplasia tarda,
and that sedlin is required for the ER export of procollagen, prefibrils
of which are too large to fit into typical COPII vesicles. Sedlin bound
and promoted efficient cycling of SAR1 (603379), a guanosine
triphosphate that can constrict membranes, and thus allowed nascent
carriers to grow and incorporate procollagen prefibrils. This joint
action of TANGO1 and sedlin sustained the ER export of procollagen, and
its derangement may explain the defective chondrogenesis underlying
SEDT.
MOLECULAR GENETICS
Gedeon et al. (1999) identified 3 dinucleotide deletions in the SEDL
gene in affected members of 3 Australian families with SEDT. All 3
mutations caused frameshifts that resulted in protein truncation,
arousing speculation that less severe missense mutations of SEDL may
have different phenotypic effects, such as precocious osteoarthritis
only.
Gedeon et al. (2001) reviewed the spectrum of mutations found in 30 of
36 unrelated cases of X-linked SEDT ascertained from different ethnic
populations. It brought the total number of different disease-associated
mutations to 21 and showed that they were distributed throughout the
SEDL gene. Four recurrent mutations accounted for 13 of the 30 (43%).
Haplotype analyses and the diverse ethnic origins of the patients
supported recurrent mutations. Two patients with large deletions of SEDL
exons were found, 1 with childhood onset of painful complications, the
other relatively free of additional symptoms. Since no clear
genotype/phenotype correlation could be established, they concluded that
the complete unaltered SEDL gene product is essential for normal bone
growth.
Tiller et al. (2001) determined that the SEDL gene escapes X
inactivation. They reported that the closest flanking genes identified
at Xp22.2 also escape X inactivation. Clustering supported a model in
which reasonable mechanisms may control the expression of genes that
escape X inactivation. Most mutations in SEDL patients are predicted to
truncate severely the protein product or eliminate it entirely. The
observation that SEDL escapes X inactivation suggests that
haploinsufficiency at the locus is inadequate to produce any phenotypic
changes in female SEDL carriers. Although Whyte et al. (1999) observed
subtle radiographic changes in older SEDL carriers, no signs or symptoms
of premature osteoarthritis were noted in the women of the family
reported by Tiller et al. (2001) or those reported by Gedeon et al.
(1999).
Christie et al. (2001) characterized the SEDL mutations in 4 unrelated
spondyloepiphyseal dysplasia tarda kindreds of European origin. They
identified 2 nonsense and 2 intragenic deletional frameshift mutations.
The nonsense mutations occurred in exons 4 and 6. Both of the intragenic
deletions, which were approximately 750 and 1300 to 1445 bp in size,
involved intron 5 and part of exon 6 and resulted in frameshifts that
led to premature termination signals.
Grunebaum et al. (2001) identified a missense mutation (300202.0007) in
a 4-generation family with late-onset SED. Grunebaum et al. (2001)
suggested that the mild phenotype in this family might be caused by a
missense rather than a nonsense mutation.
The possibility that some mutations in the SEDL gene may result in a
mild phenotype like that of early primary osteoarthritis prompted
Fiedler et al. (2002) to collect a cohort of 37 male patients (age 50.6
+/- 7.6 years) with either early end-stage primary osteoarthritis of the
hip (26 patients) or knee (11 patients). Cases with risk factors for
secondary osteoarthritis, such as congenital hip dysplasia, rheumatoid
arthritis, joint trauma, obesity, or diabetes mellitus, were excluded.
Seven patients were stated to be the shortest in the family, while from
8 patients the father (with 158 cm), and from 4 the brother was the
shortest member. Six fathers of the patients and 1 brother needed joint
replacement because of end-stage osteoarthritis. Fiedler et al. (2002)
detected no mutations in the coding sequence of SEDL and found no
polymorphism indicating a highly conserved gene. Their findings
supported previous results of high homology between different species
(Gedeon et al., 2001; Gecz et al., 2000). The results indicated that
mutations in the coding sequence of SEDL are not a common cause of early
primary osteoarthritis in men.
ANIMAL MODEL
Jang et al. (2002) reported the 2.4-angstrom resolution structure of
mouse SEDL, which revealed an unexpected similarity to the structures of
the N-terminal regulatory domain of 2 SNAREs, Ykt6p (606209) and SEC22B
(604029), despite no sequence homology to these proteins. The similarity
and the presence of an unusually large number of solvent-exposed apolar
residues of SEDL suggested that it serves regulatory and/or adaptor
functions through multiple protein-protein interactions. Jang et al.
(2002) noted that of the 4 known missense mutations responsible for
SEDT, 3 map to the protein interior, where the mutations would disrupt
the structure, and the fourth maps on a surface at which the mutation
might abrogate functional interactions with a partner protein.
*FIELD* AV
.0001
SPONDYLOEPIPHYSEAL DYSPLASIA TARDA
SEDL, 2-BP DEL, 53TT
In a family with X-linked spondyloepiphyseal dysplasia tarda (313400),
Gedeon et al. (1999) observed a dinucleotide deletion of TT at positions
53 and 54 in exon 3 of the SEDL gene, in a string of 5 thymines.
.0002
SPONDYLOEPIPHYSEAL DYSPLASIA TARDA
SEDL, 2-BP DEL, 191TG
In a family with X-linked spondyloepiphyseal dysplasia tarda (313400),
Gedeon et al. (1999) reported a dinucleotide deletion of TG at positions
191 to 192 in exon 4 of the SEDL gene. Gedeon et al. (2001) found that
this was a recurrent mutation. The results of haplotype analyses and the
diverse ethnic origins of patients supported recurrence of the mutation.
.0003
SPONDYLOEPIPHYSEAL DYSPLASIA TARDA
SEDL, 2-BP DEL, 157AT
In a family with X-linked spondyloepiphyseal dysplasia tarda (313400),
Gedeon et al. (1999) identified a deletion of AT at positions 157 and
158 in exon 3 of the SEDL gene.
.0004
SPONDYLOEPIPHYSEAL DYSPLASIA TARDA
SEDL, 5-BP DEL, NT267
Whyte et al. (1999) described the clinical and radiographic evaluation
of a 6-generation kindred from Arkansas with X-linked recessive
spondyloepiphyseal dysplasia tarda (313400). Mumm et al. (2000)
investigated this family by mutation analysis. In an affected man and
obligate carrier woman, they found a 5-bp deletion (AAGAC) in exon 5 of
the sedlin gene. The defect causes a frameshift, resulting in 8 missense
amino acids and premature termination. The 5-bp deletion was then
demonstrated to segregate with SEDT in the 4 living generations,
including 8 affected males and 9 obligate carrier females. Furthermore,
the deletion was identified in 4 females who potentially were
heterozygous carriers for SEDT.
.0005
SPONDYLOEPIPHYSEAL DYSPLASIA TARDA
SEDL, 5-BP DEL, NT271
Gedeon et al. (2001) stated that the deletion of nucleotides 271-275 was
recurrent. The results of haplotype analyses and the diverse ethnic
origins of patients with spondyloepiphyseal dysplasia tarda (313400)
supported recurrent mutations.
.0006
SPONDYLOEPIPHYSEAL DYSPLASIA TARDA
SEDL, IVS3DS, G-A, +5
Tiller et al. (2001) characterized an exon-skipping mutation in 2
unrelated families with spondyloepiphyseal dysplasia tarda (313400):
IVS3+5G-A at the intron 3 splice donor site. Using RT-PCR, they
demonstrated that the mutation resulted in elimination of the first 31
codons of the open reading frame. RT-PCR experiments using mouse/human
cell hybrids revealed that the SEDL gene escapes X inactivation.
Homologs of the SEDL gene include a transcribed retropseudogene on
chromosome 19, as well as expressed genes in mouse, rat, Drosophila, C.
elegans, and S. cerevisiae. The yeast homolog, p20, has a putative role
in vesicular transport from ER to Golgi complex. The data suggested that
SEDL mutations may perturb an intracellular pathway that is important
for cartilage homeostasis.
.0007
SPONDYLOEPIPHYSEAL DYSPLASIA TARDA
SEDL, PHE83SER
Grunebaum et al. (2001) identified a 4-generation family with late-onset
spondyloepiphyseal dysplasia (313400) caused by a T-to-C substitution at
nucleotide 248 in exon 5 of the SEDL gene, resulting in the substitution
of a phenylalanine by serine residue at amino acid 83 (p83). The
phenotype in this family was mild, and Grunebaum et al. (2001)
speculated that this might be due to the presence of a missense rather
than a nonsense mutation in this family.
.0008
SPONDYLOEPIPHYSEAL DYSPLASIA TARDA
SEDL, GLN131TER
In a 14-year-old Japanese boy with late-onset spondyloepiphyseal
dysplasia (313400), Takahashi et al. (2002) identified homozygosity for
a 391C-T transition in the SEDL gene, resulting in a gln131 (CAG)-to-ter
(TAG) (Q131X) substitution. The mother was heterozygous for the
mutation. There were 5 affected males in 3 generations connected through
carrier females.
.0009
SPONDYLOEPIPHYSEAL DYSPLASIA TARDA
SEDL, SER110TER
In a 16-year-old Taiwanese boy with late-onset spondyloepiphyseal
dysplasia (313400), the single affected individual in his family, Shi et
al. (2002) identified a 329C-A transversion in exon 6 of the SEDL gene,
resulting in a TCA (ser) to TAA (ter) change at codon 329 (S329X). The
authors stated that 'according to the family history,' 4 male children
and an uncle on the maternal side had the clinical features of SEDT.
Clinical details were not provided.
.0010
SPONDYLOEPIPHYSEAL DYSPLASIA TARDA
SEDL, IVS4, T-C, +4
In an Italian family with 2 brothers affected with SEDT (313400) of
different degrees of severity and with pubertal delay as an associated
finding, Shaw et al. (2003) found a mutation in the rare, noncanonical
5-prime splice site of intron 4 of the SEDL gene: IVS4+4T-C. RT-PCR
analysis showed that this mutation caused alternative splicing of exon 5
and, as a consequence, inclusion of exon 4b sequence. This gave rise to
an altered, truncated SEDL protein.
.0011
SPONDYLOEPIPHYSEAL DYSPLASIA TARDA
SEDL, 1-BP DEL, 613A
In an Ashkenazi Jewish family with spondyloepiphyseal dysplasia tarda
(313400), Bar-Yosef et al. (2004) identified a deletion of nucleotide A
at position 613 (613delA) in exon 6 of the SEDL gene, resulting in
truncation at codon 139 of the 140-codon-long protein. The authors noted
that the mutation also predicts a val130-to-phe substitution that would
likely interfere with proper folding of the protein. Bar-Yosef et al.
(2004) stated that this was the first report of an SEDL mutation in a
Jewish family.
*FIELD* RF
1. Bar-Yosef, U.; Ohana, E.; Hershkovitz, E.; Perlmuter, S.; Ofir,
R.; Birk, O. S.: X-linked spondyloepiphyseal dysplasia tarda: a novel
SEDL mutation in a Jewish Ashkenazi family and clinical intervention
considerations. Am. J. Med. Genet. 125A: 45-48, 2004.
2. Christie, P. T.; Curley, A.; Nesbit, M. A.; Chapman, C.; Genet,
S.; Harper, P. S.; Keeling, S. L.; Wilkie, A. O. M.; Winter, R. M.;
Thakker, R. V.: Mutational analysis in X-linked spondyloepiphyseal
dysplasia tarda. J. Clin. Endocr. Metab. 86: 3233-3236, 2001.
3. Fiedler, J.; Bittner, M.; Puhl, W.; Brenner, R. E.: Mutations
in the X-linked spondyloepiphyseal dysplasia tarda (SEDL) coding sequence
are not a common cause of early primary osteoarthritis in men. (Letter) Clin.
Genet. 62: 94-95, 2002.
4. Gecz, J.; Hillman, M. A.; Gedeon, A. K.; Cox, T. C.; Baker, E.;
Mulley, J. C.: Gene structure and expression study of the SEDL gene
for spondyloepiphyseal dysplasia tarda. Genomics 69: 242-251, 2000.
5. Gedeon, A. K.; Colley, A.; Jamieson, R.; Thompson, E. M.; Rogers,
J.; Sillence, D.; Tiller, G. E.; Mulley, J. C.; Gecz, J.: Identification
of the gene (SEDL) causing X-linked spondyloepiphyseal dysplasia tarda. Nature
Genet. 22: 400-404, 1999.
6. Gedeon, A. K.; Tiller, G. E.; Le Merrer, M.; Heuertz, S.; Tranebjaerg,
L.; Chitayat, D.; Robertson, S.; Glass, I. A.; Savarirayan, R.; Cole,
W. G.; Rimoin, D. L.; Kousseff, B. G.; Ohashi, H.; Zabel, B.; Munnich,
A.; Gecz, J.; Mulley, J. C.: The molecular basis of X-linked spondyloepiphyseal
dysplasia tarda. Am. J. Hum. Genet. 68: 1386-1397, 2001.
7. Grunebaum, E.; Arpaia, E.; MacKenzie, J. J.; Fitzpatrick, J.; Ray,
P. N.; Roifman, C. M.: A missense mutation in the SEDL gene results
in delayed onset of X linked spondyloepiphyseal dysplasia in a large
pedigree. (Letter) J. Med. Genet. 38: 409-411, 2001.
8. Jang, S. B.; Kim, Y.-G.; Cho, Y.-S.; Suh, P.-G.; Kim, K.-H.; Oh,
B.-H.: Crystal structure of SEDL and its implications for a genetic
disease spondyloepiphyseal dysplasia tarda. J. Biol. Chem. 277:
49863-49869, 2002.
9. Mumm, S.; Christie, P. T.; Finnegan, P.; Jones, J.; Dixon, P. H.;
Pannett, A. A. J.; Harding, B.; Gottesman, G. S.; Thakker, R. V.;
Whyte, M. P.: A five-base pair deletion in the sedlin gene causes
spondyloepiphyseal dysplasia tarda in a six-generation Arkansas kindred. J.
Clin. Endocr. Metab. 85: 3343-3347, 2000.
10. Mumm, S.; Zhang, X.; Vacca, M.; D'Esposito, M.; Whyte, M. P.:
The sedlin gene for spondyloepiphyseal dysplasia tarda escapes X-inactivation
and contains a non-canonical splice site. Gene 273: 285-293, 2001.
11. Scrivens, P. J.; Noueihed, B.; Shahrzad, N.; Hul, S.; Brunet,
S.; Sacher, M.: C4orf41 and TTC-15 are mammalian TRAPP components
with a role at an early stage in ER-to-Golgi trafficking. Molec.
Biol. Cell 22: 2083-2093, 2011.
12. Shaw, M. A.; Brunetti-Pierri, N.; Kadasi, L.; Kovacova, V.; Van
Maldergem, L.; De Brasi, D.; Salerno, M.; Gecz, J.: Identification
of three novel SEDL mutations, including mutation in the rare, non-canonical
splice site of exon 4. Clin. Genet. 64: 235-242, 2003.
13. Shi, Y.-R.; Lee, C.-C.; Hsu, Y.-A.; Wang, C.-H.; Tsai, F.-J.:
A novel nonsense mutation of the sedlin gene in a family with spondyloepiphyseal
dysplasia tarda. Hum. Hered. 54: 54-56, 2002.
14. Takahashi, T.; Takahashi, I.; Tsuchida, S.; Oyama, K.; Komatsu,
M.; Saito, H.; Takada, G.: An SEDL gene mutation in a Japanese kindred
of X-linked spondyloepiphyseal dysplasia tarda. (Letter) Clin. Genet. 61:
319-320, 2002. Note: Erratum: Clin. Genet. 64: 375 only, 2003.
15. Tiller, G. E.; Hannig, V. L.; Dozier, D.; Carrel, L.; Trevarthen,
K. C.; Wilcox, W. R.; Mundlos, S.; Haines, J. L.; Gedeon, A. K.; Gecz,
J.: A recurrent RNA-splicing mutation in the SEDL gene causes X-linked
spondyloepiphyseal dysplasia tarda. Am. J. Hum. Genet. 68: 1398-1407,
2001.
16. Venditti, R.; Scanu, T.; Santoro, M.; Di Tullio, G.; Spaar, A.;
Gaibisso, R.; Beznoussenko, G. V.; Mironov, A. A.; Mironov, A., Jr.;
Zelante, L.; Piemontese, M. R.; Notarangelo, A.; Malhotra, V.; Vertel,
B. M.; Wilson, C.; De Matteis, M. A.: Sedlin controls the ER export
of procollagen by regulating the Sar1 cycle. Science 337: 1668-1672,
2012.
17. Whyte, M. P.; Gottesman, G. S.; Eddy, M. C.; McAlister, W. H.
: X-linked recessive spondyloepiphyseal dysplasia tarda: clinical
and radiographic evolution in a 6-generation kindred and review of
the literature. Medicine 78: 9-25, 1999.
*FIELD* CN
Ada Hamosh - updated: 10/24/2012
Patricia A. Hartz - updated: 7/22/2011
Marla J. F. O'Neill - updated: 5/18/2004
Victor A. McKusick - updated: 10/16/2003
Victor A. McKusick - updated: 3/5/2003
Victor A. McKusick - updated: 2/24/2003
Victor A. McKusick - updated: 8/21/2002
Victor A. McKusick - updated: 8/12/2002
Michael J. Wright - updated: 7/26/2002
Paul J. Converse - updated: 4/11/2002
John A. Phillips, III - updated: 3/5/2002
Victor A. McKusick - updated: 6/20/2001
John A. Phillips, III - updated: 3/21/2001
Ada Hamosh - updated: 1/3/2001
*FIELD* CD
Ada Hamosh: 8/4/1999
*FIELD* ED
alopez: 10/25/2012
terry: 10/24/2012
carol: 5/30/2012
wwang: 8/5/2011
terry: 7/22/2011
mgross: 4/20/2007
carol: 3/22/2007
carol: 5/26/2004
mgross: 5/19/2004
carol: 5/19/2004
terry: 5/18/2004
cwells: 10/21/2003
terry: 10/16/2003
tkritzer: 3/18/2003
tkritzer: 3/11/2003
terry: 3/5/2003
carol: 3/3/2003
tkritzer: 2/25/2003
terry: 2/24/2003
tkritzer: 8/27/2002
tkritzer: 8/26/2002
terry: 8/21/2002
tkritzer: 8/15/2002
tkritzer: 8/14/2002
terry: 8/12/2002
tkritzer: 8/2/2002
tkritzer: 8/1/2002
terry: 7/26/2002
mgross: 4/11/2002
alopez: 3/5/2002
cwells: 7/3/2001
terry: 6/20/2001
alopez: 3/21/2001
carol: 1/7/2001
terry: 1/3/2001
alopez: 8/5/1999
alopez: 8/4/1999
MIM
313400
*RECORD*
*FIELD* NO
313400
*FIELD* TI
#313400 SPONDYLOEPIPHYSEAL DYSPLASIA TARDA, X-LINKED; SEDT
;;SED TARDA, X-LINKED;;
read moreSPONDYLOEPIPHYSEAL DYSPLASIA, LATE
*FIELD* TX
A number sign (#) is used with this entry because spondyloepiphyseal
dysplasia tarda can be caused by mutations in the SEDL (TRAPPC2) gene
(300202).
CLINICAL FEATURES
Bannerman et al. (1971) cited early reports of this disorder (e.g.,
Nilsonne, 1927; Barber, 1960) and reviewed the clinical features in a
large American family of English origin originally described by Jacobsen
(1939). They described the major features of the disorder as short
stature first evident in childhood between 5 and 14 years; shortness due
to impaired growth of the spine; radiologically, characteristic
flattening of vertebrae with central humping; dysplastic changes of
femoral heads and neck; and minor changes in other bones. Bony changes
lead to secondary osteoarthritis, which becomes troublesome in the
forties and may be disabling in the sixties. Bannerman (1981) reviewed
this material and concluded that heterozygotes show no abnormality such
as short stature. Several females had arthritic complaints; e.g., M.Z.,
the daughter and mother of affected males, had considerable 'arthritis'
from age 33 years and by age 51 had almost no movement in either hip
and, by x-ray, bony fusion of the left hip.
The radiographic features of this disorder are so distinctive that the
diagnosis seems unequivocal in the sexually normal, 29-year-old woman
(with normal XX karyotype including banding) reported by Monteiro de
Pina Neto et al. (1982). No other persons in the family were affected.
The authors suggested that she was heterozygous and that chance
lyonization of most X chromosomes with the normal allele had occurred.
Heuertz et al. (1993) suggested that this disorder was first described
by Maroteaux et al. (1957) in a study of 3 large kindreds with 11
affected persons. The disorder is characterized by short stature which
becomes evident between 10 and 14 years of age and leads to an average
adult height of 1.45 m. Radiologic diagnosis cannot be established
before 4 to 6 years of age. Bone changes of the femoral head lead to
secondary osteoarthritis during adulthood and some patients require
total arthroplasty of the hip before the age of 40 years.
Whyte et al. (1999) described the clinical and radiographic evaluation
of a second large American kindred with X-linked recessive SEDT, the
first such family being the classic family reported by Jacobsen (1939).
POPULATION GENETICS
Wynne-Davies and Gormley (1985) estimated the prevalence to be 1 per
100,000 in a Scottish population.
MAPPING
Cosegregation of SEDT and deutan colorblindness (303800) suggested to
Kousseff et al. (1986) that the SEDT locus is in the Xq28 band.
Szpiro-Tapia et al. (1988) excluded linkage with markers in region Xq28.
They found linkage to DXS41 (maximum lod = 3.07 at theta = 0.08),
located in Xp22.1, and DXS92 (maximum lod = 2.95 at theta = 0.05). DXS92
had been thought to be located at Xq26-q27; hybridization to cells
containing X chromosome fragments, however, excluded location on Xq and
on the proximal part of Xp. Szpiro-Tapia et al. (1988) concluded that
DXS92 is located on Xp between Xp11.21 and Xpter. Reference was made to
another family with linkage mapping to the same region of Xp. It is of
interest that Bannerman et al. (1971), studying the original family
reported by Jacobsen (1939) in Buffalo, found a suggestion of linkage to
Xg blood group, which would be consistent with the findings of the
recent study.
Heuertz et al. (1993) extended the studies of Szpiro-Tapia et al. (1988)
by analyzing 15 families with 13 markers from the Xp22 region.
Multipoint linkage analysis indicated that the SEDT mutation is located
between DXS16 and DXS92.
Bernard et al. (1996) presented linkage data using microsatellite
markers on 2 Canadian X-linked SED families, one of Norwegian descent
and the other from Great Britain. Support of the previous localization
was obtained. One family showed a maximal lod score of 3.0 at theta =
0.0 with marker DXS1043 and the other family had a maximal lod score of
1.2 at theta = 0.0 with markers DXS1224 and DXS418.
Gedeon et al. (1999) confirmed and refined the localization of SEDT to
an interval of less than 170 kb by critical recombination events at
DXS16 and AFMa124wc1 in 2 families.
PATHOGENESIS
Venditti et al. (2012) found that TANGO1 (613455) recruits sedlin
(300202), a TRAPP component that is defective in spondyloepiphyseal
dysplasia tarda, and that sedlin is required for the endoplasmic
reticulum (ER) export of procollagen, prefibrils of which are too large
to fit into typical COPII vesicles. Sedlin bound and promoted efficient
cycling of SAR1 (603379), a guanosine triphosphate that can constrict
membranes, and thus allowed nascent carriers to grow and incorporate
procollagen prefibrils. This joint action of TANGO1 and Sedlin sustained
the ER export of procollagen, and its derangement may explain the
defective chondrogenesis underlying SEDT.
MOLECULAR GENETICS
Gedeon et al. (1999) detected 3 dinucleotide deletions in the SEDL gene
(300202.0001-300202.0003) in 3 Australian families, resulting in
frameshifts premature stop codons.
In an Ashkenazi Jewish family with SEDT, Bar-Yosef et al. (2004)
identified a single nucleotide deletion at position 613 in the SEDL gene
(300202.0011). The authors stated that this was the first report of an
SEDL mutation in a Jewish family.
*FIELD* SA
Bannerman (1969); Barber (1960); Branford et al. (1982); Hobaek
(1961); Iceton and Horne (1986); Lamy and Maroteaux (1960); Langer
(1964)
*FIELD* RF
1. Bannerman, R. M.: X-linked spondyloepiphyseal dysplasia tarda
(SDT). Birth Defects Orig. Art. Ser. V(4): 48-51, 1969.
2. Bannerman, R. M.: Personal Communication. Buffalo, N. Y. 10/13/1981.
3. Bannerman, R. M.; Ingall, G. B.; Mohn, J. F.: X-linked spondyloepiphyseal
dysplasia tarda: clinical and linkage data. J. Med. Genet. 8: 291-301,
1971.
4. Bar-Yosef, U.; Ohana, E.; Hershkovitz, E.; Perlmuter, S.; Ofir,
R.; Birk, O. S.: X-linked spondyloepiphyseal dysplasia tarda: a novel
SEDL mutation in a Jewish Ashkenazi family and clinical intervention
considerations. Am. J. Med. Genet. 125A: 45-48, 2004.
5. Barber, H. S.: An unusual form of familial osteodystrophy. Lancet 275:
1220-1221, 1960. Note: Originally Volume I.
6. Barber, H. S.: An unusual form of familial osteodystrophy. Lancet 276:
154-155, 1960. Note: Originally Volume II.
7. Bernard, L. E.; Chitayat, D.; Weksberg, R.; Van Allen, M. I.; Langlois,
S.: Linkage analysis of two Canadian families segregating for X linked
spondyloepiphyseal dysplasia. J. Med. Genet. 33: 432-434, 1996.
8. Branford, W. A.; Beveridge, G. W.; Wynne-Davies, R.: Two first
cousins with spondyloepiphyseal dysplasia tarda (X linked recessive
form), one also with poikiloderma atrophicans vasculare progressing
to lymphocytic lymphoma. J. Med. Genet. 19: 210-213, 1982.
9. Gedeon, A. K.; Colley, A.; Jamieson, R.; Thompson, E. M.; Rogers,
J.; Sillence, D.; Tiller, G. E.; Mulley, J. C.; Gecz, J.: Identification
of the gene (SEDL) causing X-linked spondyloepiphyseal dysplasia tarda. Nature
Genet. 22: 400-404, 1999.
10. Heuertz, S.; Nelen, M.; Wilkie, A. O. M.; Le Merrer, M.; Delrieu,
O.; Larget-Piet, L.; Tranebjaerg, L.; Bick, D.; Hamel, B.; Van Oost,
B. A.; Maroteaux, P.; Hors-Cayla, M.-C.: The gene for spondyloepiphyseal
dysplasia (SEDL) maps to Xp22 between DXS16 and DXS92. Genomics 18:
100-104, 1993.
11. Hobaek, A.: Problems of Hereditary Chondrodysplasia. Oslo:
Oslo Univ. Press (pub.) 1961.
12. Iceton, J. A.; Horne, G.: Spondylo-epiphyseal dysplasia tarda:
the X-linked variety in three brothers. J. Bone Joint Surg. Br. 68:
616-619, 1986.
13. Jacobsen, A. W.: Hereditary osteochondro-dystrophia deformans:
a family with twenty members affected in five generations. JAMA 113:
121-124, 1939.
14. Kousseff, B. G.; Hummel, M.; Phillips, J., III; Murphy, P.: Spondyloepiphyseal
dysplasia tarda and deutan color blindness in a family. (Abstract) 7th
Int. Cong. Hum. Genet., Berlin 258 only, 1986.
15. Lamy, M.; Maroteaux, P.: Les chondrodystrophies genotypiques.
Paris: L'Expansion (pub.) 1960. P. 67ff.
16. Langer, L. O., Jr.: Spondyloepiphyseal dysplasia tarda: hereditary
chondrodysplasia with characteristic vertebral configuration in the
adult. Radiology 82: 833-839, 1964.
17. Maroteaux, P.; Lamy, M.; Bernard, J.: La dysplasie spondylo-epiphysaire
tardive. Presse Med. 65: 1205-1208, 1957.
18. Monteiro de Pina Neto, J.; Bonfim, M. D.; Ferrari, I.: Classic
X-linked spondyloepiphyseal dysplasia tarda in a woman with normal
karyotype.In: Papadatos, C. J.; Bartsocas, C. S.: Skeletal Dysplasias.
New York: Alan R. Liss (pub.) 1982. Pp. 127-132.
19. Nilsonne, H.: Eigentuemliche Wirbelkorper-veraenderungen mit
familiaerem Auftreten. Acta Chir. Scand. 62: 550-554, 1927.
20. Szpiro-Tapia, S.; Sefiani, A.; Guilloud-Bataille, M.; Heuertz,
S.; LeMarec, B.; Frezal, J.; Maroteaux, P.; Hors-Cayla, M. C.: Spondyloepiphyseal
dysplasia tarda: linkage with genetic markers from the distal short
arm of the X chromosome. Hum. Genet. 81: 61-63, 1988.
21. Venditti, R.; Scanu, T.; Santoro, M.; Di Tullio, G.; Spaar, A.;
Gaibisso, R.; Beznoussenko, G. V.; Mironov, A. A.; Mironov, A., Jr.;
Zelante, L.; Piemontese, M. R.; Notarangelo, A.; Malhotra, V.; Vertel,
B. M.; Wilson, C.; De Matteis, M. A.: Sedlin controls the ER export
of procollagen by regulating the Sar1 cycle. Science 337: 1668-1672,
2012.
22. Whyte, M. P.; Gottesman, G. S.; Eddy, M. C.; McAlister, W. H.
: X-linked recessive spondyloepiphyseal dysplasia tarda: clinical
and radiographic evolution in a 6-generation kindred and review of
the literature. Medicine 78: 9-25, 1999.
23. Wynne-Davies, R.; Gormley, J.: The prevalence of skeletal dysplasias:
an estimate of their minimum frequency and the number of patients
requiring orthopaedic care. J. Bone Joint Surg. Br. 67: 133-137,
1985.
*FIELD* CS
INHERITANCE:
X-linked recessive
GROWTH:
[Height];
Short stature;
Short trunk;
Final adult height 131-156 cm
HEAD AND NECK:
[Eyes];
Corneal opacities;
[Neck];
Short neck
CHEST:
[External features];
Broad chest
SKELETAL:
Osteoarthritis (back, hip, knee);
Limited joint motion;
[Spine];
Platyspondyly;
Hump-shaped mound of bone in central and posterior portions of vertebral
endplate;
Kyphosis;
Mild scoliosis;
Lumbar hyperlordosis;
Narrow disc spaces;
[Pelvis];
Small iliac wings;
Coxa vara;
[Limbs];
Small capital femoral epiphyses;
Short femoral neck;
Mild epiphyseal irregularities
MISCELLANEOUS:
Age of onset 5-10 years;
Arthralgias;
Carrier females have arthralgias in middle age
MOLECULAR BASIS:
Caused by mutation in the sedlin gene (SEDL, 300202.0001)
*FIELD* CN
Kelly A. Przylepa - revised: 9/9/2002
*FIELD* CD
John F. Jackson: 6/15/1995
*FIELD* ED
joanna: 10/23/2013
joanna: 10/26/2010
joanna: 9/9/2002
*FIELD* CN
Ada Hamosh - updated: 10/24/2012
Marla J. F. O'Neill - updated: 5/18/2004
Ada Hamosh - updated: 8/2/1999
Victor A. McKusick - updated: 4/26/1999
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
alopez: 10/25/2012
terry: 10/24/2012
terry: 1/13/2011
carol: 9/14/2010
terry: 5/11/2010
carol: 9/24/2009
terry: 6/3/2009
terry: 3/31/2009
carol: 5/19/2004
terry: 5/18/2004
alopez: 3/2/2000
carol: 2/26/2000
alopez: 8/4/1999
terry: 8/2/1999
alopez: 5/10/1999
terry: 4/26/1999
mark: 7/9/1996
terry: 6/28/1996
davew: 7/18/1994
terry: 6/14/1994
warfield: 4/20/1994
pfoster: 3/30/1994
mimadm: 2/28/1994
carol: 11/24/1993
*RECORD*
*FIELD* NO
313400
*FIELD* TI
#313400 SPONDYLOEPIPHYSEAL DYSPLASIA TARDA, X-LINKED; SEDT
;;SED TARDA, X-LINKED;;
read moreSPONDYLOEPIPHYSEAL DYSPLASIA, LATE
*FIELD* TX
A number sign (#) is used with this entry because spondyloepiphyseal
dysplasia tarda can be caused by mutations in the SEDL (TRAPPC2) gene
(300202).
CLINICAL FEATURES
Bannerman et al. (1971) cited early reports of this disorder (e.g.,
Nilsonne, 1927; Barber, 1960) and reviewed the clinical features in a
large American family of English origin originally described by Jacobsen
(1939). They described the major features of the disorder as short
stature first evident in childhood between 5 and 14 years; shortness due
to impaired growth of the spine; radiologically, characteristic
flattening of vertebrae with central humping; dysplastic changes of
femoral heads and neck; and minor changes in other bones. Bony changes
lead to secondary osteoarthritis, which becomes troublesome in the
forties and may be disabling in the sixties. Bannerman (1981) reviewed
this material and concluded that heterozygotes show no abnormality such
as short stature. Several females had arthritic complaints; e.g., M.Z.,
the daughter and mother of affected males, had considerable 'arthritis'
from age 33 years and by age 51 had almost no movement in either hip
and, by x-ray, bony fusion of the left hip.
The radiographic features of this disorder are so distinctive that the
diagnosis seems unequivocal in the sexually normal, 29-year-old woman
(with normal XX karyotype including banding) reported by Monteiro de
Pina Neto et al. (1982). No other persons in the family were affected.
The authors suggested that she was heterozygous and that chance
lyonization of most X chromosomes with the normal allele had occurred.
Heuertz et al. (1993) suggested that this disorder was first described
by Maroteaux et al. (1957) in a study of 3 large kindreds with 11
affected persons. The disorder is characterized by short stature which
becomes evident between 10 and 14 years of age and leads to an average
adult height of 1.45 m. Radiologic diagnosis cannot be established
before 4 to 6 years of age. Bone changes of the femoral head lead to
secondary osteoarthritis during adulthood and some patients require
total arthroplasty of the hip before the age of 40 years.
Whyte et al. (1999) described the clinical and radiographic evaluation
of a second large American kindred with X-linked recessive SEDT, the
first such family being the classic family reported by Jacobsen (1939).
POPULATION GENETICS
Wynne-Davies and Gormley (1985) estimated the prevalence to be 1 per
100,000 in a Scottish population.
MAPPING
Cosegregation of SEDT and deutan colorblindness (303800) suggested to
Kousseff et al. (1986) that the SEDT locus is in the Xq28 band.
Szpiro-Tapia et al. (1988) excluded linkage with markers in region Xq28.
They found linkage to DXS41 (maximum lod = 3.07 at theta = 0.08),
located in Xp22.1, and DXS92 (maximum lod = 2.95 at theta = 0.05). DXS92
had been thought to be located at Xq26-q27; hybridization to cells
containing X chromosome fragments, however, excluded location on Xq and
on the proximal part of Xp. Szpiro-Tapia et al. (1988) concluded that
DXS92 is located on Xp between Xp11.21 and Xpter. Reference was made to
another family with linkage mapping to the same region of Xp. It is of
interest that Bannerman et al. (1971), studying the original family
reported by Jacobsen (1939) in Buffalo, found a suggestion of linkage to
Xg blood group, which would be consistent with the findings of the
recent study.
Heuertz et al. (1993) extended the studies of Szpiro-Tapia et al. (1988)
by analyzing 15 families with 13 markers from the Xp22 region.
Multipoint linkage analysis indicated that the SEDT mutation is located
between DXS16 and DXS92.
Bernard et al. (1996) presented linkage data using microsatellite
markers on 2 Canadian X-linked SED families, one of Norwegian descent
and the other from Great Britain. Support of the previous localization
was obtained. One family showed a maximal lod score of 3.0 at theta =
0.0 with marker DXS1043 and the other family had a maximal lod score of
1.2 at theta = 0.0 with markers DXS1224 and DXS418.
Gedeon et al. (1999) confirmed and refined the localization of SEDT to
an interval of less than 170 kb by critical recombination events at
DXS16 and AFMa124wc1 in 2 families.
PATHOGENESIS
Venditti et al. (2012) found that TANGO1 (613455) recruits sedlin
(300202), a TRAPP component that is defective in spondyloepiphyseal
dysplasia tarda, and that sedlin is required for the endoplasmic
reticulum (ER) export of procollagen, prefibrils of which are too large
to fit into typical COPII vesicles. Sedlin bound and promoted efficient
cycling of SAR1 (603379), a guanosine triphosphate that can constrict
membranes, and thus allowed nascent carriers to grow and incorporate
procollagen prefibrils. This joint action of TANGO1 and Sedlin sustained
the ER export of procollagen, and its derangement may explain the
defective chondrogenesis underlying SEDT.
MOLECULAR GENETICS
Gedeon et al. (1999) detected 3 dinucleotide deletions in the SEDL gene
(300202.0001-300202.0003) in 3 Australian families, resulting in
frameshifts premature stop codons.
In an Ashkenazi Jewish family with SEDT, Bar-Yosef et al. (2004)
identified a single nucleotide deletion at position 613 in the SEDL gene
(300202.0011). The authors stated that this was the first report of an
SEDL mutation in a Jewish family.
*FIELD* SA
Bannerman (1969); Barber (1960); Branford et al. (1982); Hobaek
(1961); Iceton and Horne (1986); Lamy and Maroteaux (1960); Langer
(1964)
*FIELD* RF
1. Bannerman, R. M.: X-linked spondyloepiphyseal dysplasia tarda
(SDT). Birth Defects Orig. Art. Ser. V(4): 48-51, 1969.
2. Bannerman, R. M.: Personal Communication. Buffalo, N. Y. 10/13/1981.
3. Bannerman, R. M.; Ingall, G. B.; Mohn, J. F.: X-linked spondyloepiphyseal
dysplasia tarda: clinical and linkage data. J. Med. Genet. 8: 291-301,
1971.
4. Bar-Yosef, U.; Ohana, E.; Hershkovitz, E.; Perlmuter, S.; Ofir,
R.; Birk, O. S.: X-linked spondyloepiphyseal dysplasia tarda: a novel
SEDL mutation in a Jewish Ashkenazi family and clinical intervention
considerations. Am. J. Med. Genet. 125A: 45-48, 2004.
5. Barber, H. S.: An unusual form of familial osteodystrophy. Lancet 275:
1220-1221, 1960. Note: Originally Volume I.
6. Barber, H. S.: An unusual form of familial osteodystrophy. Lancet 276:
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1985.
*FIELD* CS
INHERITANCE:
X-linked recessive
GROWTH:
[Height];
Short stature;
Short trunk;
Final adult height 131-156 cm
HEAD AND NECK:
[Eyes];
Corneal opacities;
[Neck];
Short neck
CHEST:
[External features];
Broad chest
SKELETAL:
Osteoarthritis (back, hip, knee);
Limited joint motion;
[Spine];
Platyspondyly;
Hump-shaped mound of bone in central and posterior portions of vertebral
endplate;
Kyphosis;
Mild scoliosis;
Lumbar hyperlordosis;
Narrow disc spaces;
[Pelvis];
Small iliac wings;
Coxa vara;
[Limbs];
Small capital femoral epiphyses;
Short femoral neck;
Mild epiphyseal irregularities
MISCELLANEOUS:
Age of onset 5-10 years;
Arthralgias;
Carrier females have arthralgias in middle age
MOLECULAR BASIS:
Caused by mutation in the sedlin gene (SEDL, 300202.0001)
*FIELD* CN
Kelly A. Przylepa - revised: 9/9/2002
*FIELD* CD
John F. Jackson: 6/15/1995
*FIELD* ED
joanna: 10/23/2013
joanna: 10/26/2010
joanna: 9/9/2002
*FIELD* CN
Ada Hamosh - updated: 10/24/2012
Marla J. F. O'Neill - updated: 5/18/2004
Ada Hamosh - updated: 8/2/1999
Victor A. McKusick - updated: 4/26/1999
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
alopez: 10/25/2012
terry: 10/24/2012
terry: 1/13/2011
carol: 9/14/2010
terry: 5/11/2010
carol: 9/24/2009
terry: 6/3/2009
terry: 3/31/2009
carol: 5/19/2004
terry: 5/18/2004
alopez: 3/2/2000
carol: 2/26/2000
alopez: 8/4/1999
terry: 8/2/1999
alopez: 5/10/1999
terry: 4/26/1999
mark: 7/9/1996
terry: 6/28/1996
davew: 7/18/1994
terry: 6/14/1994
warfield: 4/20/1994
pfoster: 3/30/1994
mimadm: 2/28/1994
carol: 11/24/1993