Full text data of POMGNT2
POMGNT2
(AGO61, C3orf39, EOGTL, GTDC2)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Protein O-linked-mannose beta-1,4-N-acetylglucosaminyltransferase 2; POMGnT2; 2.4.1.- (Extracellular O-linked N-acetylglucosamine transferase-like; Glycosyltransferase-like domain-containing protein 2)
Protein O-linked-mannose beta-1,4-N-acetylglucosaminyltransferase 2; POMGnT2; 2.4.1.- (Extracellular O-linked N-acetylglucosamine transferase-like; Glycosyltransferase-like domain-containing protein 2)
UniProt
Q8NAT1
ID PMGT2_HUMAN Reviewed; 580 AA.
AC Q8NAT1; B3KWC3; Q96SY3;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-2002, sequence version 1.
DT 22-JAN-2014, entry version 87.
DE RecName: Full=Protein O-linked-mannose beta-1,4-N-acetylglucosaminyltransferase 2;
DE Short=POMGnT2;
DE EC=2.4.1.-;
DE AltName: Full=Extracellular O-linked N-acetylglucosamine transferase-like;
DE AltName: Full=Glycosyltransferase-like domain-containing protein 2;
GN Name=POMGNT2; Synonyms=AGO61, C3orf39, EOGTL, GTDC2;
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 [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=23929950; DOI=10.1126/science.1239951;
RA Yoshida-Moriguchi T., Willer T., Anderson M.E., Venzke D., Whyte T.,
RA Muntoni F., Lee H., Nelson S.F., Yu L., Campbell K.P.;
RT "SGK196 is a glycosylation-specific O-mannose kinase required for
RT dystroglycan function.";
RL Science 341:896-899(2013).
RN [6]
RP VARIANT MDDGA8 HIS-158, AND TISSUE SPECIFICITY.
RX PubMed=22958903; DOI=10.1016/j.ajhg.2012.07.009;
RA Manzini M.C., Tambunan D.E., Hill R.S., Yu T.W., Maynard T.M.,
RA Heinzen E.L., Shianna K.V., Stevens C.R., Partlow J.N., Barry B.J.,
RA Rodriguez J., Gupta V.A., Al-Qudah A.K., Eyaid W.M., Friedman J.M.,
RA Salih M.A., Clark R., Moroni I., Mora M., Beggs A.H., Gabriel S.B.,
RA Walsh C.A.;
RT "Exome sequencing and functional validation in zebrafish identify
RT GTDC2 mutations as a cause of Walker-Warburg syndrome.";
RL Am. J. Hum. Genet. 91:541-547(2012).
CC -!- FUNCTION: O-linked mannose beta-1,4-N-
CC acetylglucosaminyltransferase that tranfers UDP-N-acetyl-D-
CC glucosamine to the 4-position of the mannose to generate N-acetyl-
CC D-glucosamine-beta-1,4-O-D-mannosylprotein. Involved in the
CC biosynthesis of the phosphorylated O-mannosyl trisaccharide (N-
CC acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-
CC 6-)mannose), a carbohydrate structure present in alpha-
CC dystroglycan (DAG1), which is required for binding laminin G-like
CC domain-containing extracellular proteins with high affinity.
CC -!- CATALYTIC ACTIVITY: UDP-N-acetyl-alpha-D-glucosamine + O-alpha-D-
CC mannosylprotein = UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-O-
CC alpha-D-mannosylprotein.
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC type II membrane protein.
CC -!- TISSUE SPECIFICITY: Highly expressed in the brain, muscle, heart,
CC and kidney in both fetus and adult. In the brain, highest
CC expression in the cortex and cerebellum. Highly expressed in the
CC pancreas.
CC -!- DISEASE: Muscular dystrophy-dystroglycanopathy congenital with
CC brain and eye anomalies A8 (MDDGA8) [MIM:614830]: An autosomal
CC recessive disorder characterized by congenital muscular dystrophy
CC associated with cobblestone lissencephaly and other brain
CC anomalies, eye malformations, profound mental retardation, and
CC death usually in the first years of life. Included diseases are
CC the more severe Walker-Warburg syndrome and the slightly less
CC severe muscle-eye-brain disease. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 61 family.
CC -!- SIMILARITY: Contains 1 fibronectin type-III domain.
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DR EMBL; AK027472; BAB55137.1; -; mRNA.
DR EMBL; AK092147; BAC03816.1; -; mRNA.
DR EMBL; AK124737; BAG54085.1; -; mRNA.
DR EMBL; AC092042; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW64690.1; -; Genomic_DNA.
DR EMBL; BC060861; AAH60861.1; -; mRNA.
DR RefSeq; NP_116195.2; NM_032806.5.
DR RefSeq; XP_005265572.1; XM_005265515.1.
DR UniGene; Hs.745002; -.
DR ProteinModelPortal; Q8NAT1; -.
DR CAZy; GT61; Glycosyltransferase Family 61.
DR PhosphoSite; Q8NAT1; -.
DR DMDM; 74729999; -.
DR PaxDb; Q8NAT1; -.
DR PRIDE; Q8NAT1; -.
DR DNASU; 84892; -.
DR Ensembl; ENST00000344697; ENSP00000344125; ENSG00000144647.
DR Ensembl; ENST00000441964; ENSP00000408992; ENSG00000144647.
DR GeneID; 84892; -.
DR KEGG; hsa:84892; -.
DR UCSC; uc003cmq.2; human.
DR CTD; 84892; -.
DR GeneCards; GC03M043121; -.
DR HGNC; HGNC:25902; POMGNT2.
DR HPA; HPA034870; -.
DR MIM; 614828; gene.
DR MIM; 614830; phenotype.
DR neXtProt; NX_Q8NAT1; -.
DR Orphanet; 899; Walker-Warburg syndrome.
DR PharmGKB; PA142672374; -.
DR eggNOG; NOG317275; -.
DR HOGENOM; HOG000006878; -.
DR HOVERGEN; HBG054852; -.
DR InParanoid; Q8NAT1; -.
DR OMA; YAVNPDH; -.
DR OrthoDB; EOG72G16T; -.
DR PhylomeDB; Q8NAT1; -.
DR UniPathway; UPA00378; -.
DR ChiTaRS; C3orf39; human.
DR GenomeRNAi; 84892; -.
DR NextBio; 75226; -.
DR PRO; PR:Q8NAT1; -.
DR Bgee; Q8NAT1; -.
DR CleanEx; HS_C3orf39; -.
DR Genevestigator; Q8NAT1; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0008375; F:acetylglucosaminyltransferase activity; IDA:UniProtKB.
DR GO; GO:0006493; P:protein O-linked glycosylation; IDA:UniProtKB.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR003961; Fibronectin_type3.
DR InterPro; IPR007657; Glycosyltransferase_AER61.
DR InterPro; IPR013783; Ig-like_fold.
DR Pfam; PF04577; DUF563; 1.
DR SUPFAM; SSF49265; SSF49265; 1.
DR PROSITE; PS50853; FN3; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Congenital muscular dystrophy; Disease mutation;
KW Dystroglycanopathy; Endoplasmic reticulum; Glycoprotein;
KW Glycosyltransferase; Lissencephaly; Membrane; Reference proteome;
KW Signal-anchor; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1 580 Protein O-linked-mannose beta-1,4-N-
FT acetylglucosaminyltransferase 2.
FT /FTId=PRO_0000249014.
FT TOPO_DOM 1 4 Cytoplasmic (Potential).
FT TRANSMEM 5 25 Helical; Signal-anchor for type II
FT membrane protein; (Potential).
FT TOPO_DOM 26 580 Lumenal (Potential).
FT DOMAIN 488 580 Fibronectin type-III.
FT CARBOHYD 99 99 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 276 276 N-linked (GlcNAc...) (Potential).
FT VARIANT 158 158 R -> H (in MDDGA8).
FT /FTId=VAR_068967.
SQ SEQUENCE 580 AA; 66615 MW; 57D7FD168373FD9D CRC64;
MHLSAVFNAL LVSVLAAVLW KHVRLREHAA TLEEELALSR QATEPAPALR IDYPKALQIL
MEGGTHMVCT GRTHTDRICR FKWLCYSNEA EEFIFFHGNT SVMLPNLGSR RFQPALLDLS
TVEDHNTQYF NFVELPAAAL RFMPKPVFVP DVALIANRFN PDNLMHVFHD DLLPLFYTLR
QFPGLAHEAR LFFMEGWGEG AHFDLYKLLS PKQPLLRAQL KTLGRLLCFS HAFVGLSKIT
TWYQYGFVQP QGPKANILVS GNEIRQFARF MTEKLNVSHT GVPLGEEYIL VFSRTQNRLI
LNEAELLLAL AQEFQMKTVT VSLEDHTFAD VVRLVSNASM LVSMHGAQLV TTLFLPRGAT
VVELFPYAVN PDHYTPYKTL AMLPGMDLQY VAWRNMMPEN TVTHPERPWD QGGITHLDRA
EQARILQSRE VPRHLCCRNP EWLFRIYQDT KVDIPSLIQT IRRVVKGRPG PRKQKWTVGL
YPGKVREARC QASVHGASEA RLTVSWQIPW NLKYLKVREV KYEVWLQEQG ENTYVPYILA
LQNHTFTENI KPFTTYLVWV RCIFNKILLG PFADVLVCNT
//
ID PMGT2_HUMAN Reviewed; 580 AA.
AC Q8NAT1; B3KWC3; Q96SY3;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-2002, sequence version 1.
DT 22-JAN-2014, entry version 87.
DE RecName: Full=Protein O-linked-mannose beta-1,4-N-acetylglucosaminyltransferase 2;
DE Short=POMGnT2;
DE EC=2.4.1.-;
DE AltName: Full=Extracellular O-linked N-acetylglucosamine transferase-like;
DE AltName: Full=Glycosyltransferase-like domain-containing protein 2;
GN Name=POMGNT2; Synonyms=AGO61, C3orf39, EOGTL, GTDC2;
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 [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=23929950; DOI=10.1126/science.1239951;
RA Yoshida-Moriguchi T., Willer T., Anderson M.E., Venzke D., Whyte T.,
RA Muntoni F., Lee H., Nelson S.F., Yu L., Campbell K.P.;
RT "SGK196 is a glycosylation-specific O-mannose kinase required for
RT dystroglycan function.";
RL Science 341:896-899(2013).
RN [6]
RP VARIANT MDDGA8 HIS-158, AND TISSUE SPECIFICITY.
RX PubMed=22958903; DOI=10.1016/j.ajhg.2012.07.009;
RA Manzini M.C., Tambunan D.E., Hill R.S., Yu T.W., Maynard T.M.,
RA Heinzen E.L., Shianna K.V., Stevens C.R., Partlow J.N., Barry B.J.,
RA Rodriguez J., Gupta V.A., Al-Qudah A.K., Eyaid W.M., Friedman J.M.,
RA Salih M.A., Clark R., Moroni I., Mora M., Beggs A.H., Gabriel S.B.,
RA Walsh C.A.;
RT "Exome sequencing and functional validation in zebrafish identify
RT GTDC2 mutations as a cause of Walker-Warburg syndrome.";
RL Am. J. Hum. Genet. 91:541-547(2012).
CC -!- FUNCTION: O-linked mannose beta-1,4-N-
CC acetylglucosaminyltransferase that tranfers UDP-N-acetyl-D-
CC glucosamine to the 4-position of the mannose to generate N-acetyl-
CC D-glucosamine-beta-1,4-O-D-mannosylprotein. Involved in the
CC biosynthesis of the phosphorylated O-mannosyl trisaccharide (N-
CC acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-
CC 6-)mannose), a carbohydrate structure present in alpha-
CC dystroglycan (DAG1), which is required for binding laminin G-like
CC domain-containing extracellular proteins with high affinity.
CC -!- CATALYTIC ACTIVITY: UDP-N-acetyl-alpha-D-glucosamine + O-alpha-D-
CC mannosylprotein = UDP + N-acetyl-beta-D-glucosaminyl-(1->4)-O-
CC alpha-D-mannosylprotein.
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC type II membrane protein.
CC -!- TISSUE SPECIFICITY: Highly expressed in the brain, muscle, heart,
CC and kidney in both fetus and adult. In the brain, highest
CC expression in the cortex and cerebellum. Highly expressed in the
CC pancreas.
CC -!- DISEASE: Muscular dystrophy-dystroglycanopathy congenital with
CC brain and eye anomalies A8 (MDDGA8) [MIM:614830]: An autosomal
CC recessive disorder characterized by congenital muscular dystrophy
CC associated with cobblestone lissencephaly and other brain
CC anomalies, eye malformations, profound mental retardation, and
CC death usually in the first years of life. Included diseases are
CC the more severe Walker-Warburg syndrome and the slightly less
CC severe muscle-eye-brain disease. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 61 family.
CC -!- SIMILARITY: Contains 1 fibronectin type-III domain.
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; AK027472; BAB55137.1; -; mRNA.
DR EMBL; AK092147; BAC03816.1; -; mRNA.
DR EMBL; AK124737; BAG54085.1; -; mRNA.
DR EMBL; AC092042; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW64690.1; -; Genomic_DNA.
DR EMBL; BC060861; AAH60861.1; -; mRNA.
DR RefSeq; NP_116195.2; NM_032806.5.
DR RefSeq; XP_005265572.1; XM_005265515.1.
DR UniGene; Hs.745002; -.
DR ProteinModelPortal; Q8NAT1; -.
DR CAZy; GT61; Glycosyltransferase Family 61.
DR PhosphoSite; Q8NAT1; -.
DR DMDM; 74729999; -.
DR PaxDb; Q8NAT1; -.
DR PRIDE; Q8NAT1; -.
DR DNASU; 84892; -.
DR Ensembl; ENST00000344697; ENSP00000344125; ENSG00000144647.
DR Ensembl; ENST00000441964; ENSP00000408992; ENSG00000144647.
DR GeneID; 84892; -.
DR KEGG; hsa:84892; -.
DR UCSC; uc003cmq.2; human.
DR CTD; 84892; -.
DR GeneCards; GC03M043121; -.
DR HGNC; HGNC:25902; POMGNT2.
DR HPA; HPA034870; -.
DR MIM; 614828; gene.
DR MIM; 614830; phenotype.
DR neXtProt; NX_Q8NAT1; -.
DR Orphanet; 899; Walker-Warburg syndrome.
DR PharmGKB; PA142672374; -.
DR eggNOG; NOG317275; -.
DR HOGENOM; HOG000006878; -.
DR HOVERGEN; HBG054852; -.
DR InParanoid; Q8NAT1; -.
DR OMA; YAVNPDH; -.
DR OrthoDB; EOG72G16T; -.
DR PhylomeDB; Q8NAT1; -.
DR UniPathway; UPA00378; -.
DR ChiTaRS; C3orf39; human.
DR GenomeRNAi; 84892; -.
DR NextBio; 75226; -.
DR PRO; PR:Q8NAT1; -.
DR Bgee; Q8NAT1; -.
DR CleanEx; HS_C3orf39; -.
DR Genevestigator; Q8NAT1; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0008375; F:acetylglucosaminyltransferase activity; IDA:UniProtKB.
DR GO; GO:0006493; P:protein O-linked glycosylation; IDA:UniProtKB.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR003961; Fibronectin_type3.
DR InterPro; IPR007657; Glycosyltransferase_AER61.
DR InterPro; IPR013783; Ig-like_fold.
DR Pfam; PF04577; DUF563; 1.
DR SUPFAM; SSF49265; SSF49265; 1.
DR PROSITE; PS50853; FN3; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Congenital muscular dystrophy; Disease mutation;
KW Dystroglycanopathy; Endoplasmic reticulum; Glycoprotein;
KW Glycosyltransferase; Lissencephaly; Membrane; Reference proteome;
KW Signal-anchor; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1 580 Protein O-linked-mannose beta-1,4-N-
FT acetylglucosaminyltransferase 2.
FT /FTId=PRO_0000249014.
FT TOPO_DOM 1 4 Cytoplasmic (Potential).
FT TRANSMEM 5 25 Helical; Signal-anchor for type II
FT membrane protein; (Potential).
FT TOPO_DOM 26 580 Lumenal (Potential).
FT DOMAIN 488 580 Fibronectin type-III.
FT CARBOHYD 99 99 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 276 276 N-linked (GlcNAc...) (Potential).
FT VARIANT 158 158 R -> H (in MDDGA8).
FT /FTId=VAR_068967.
SQ SEQUENCE 580 AA; 66615 MW; 57D7FD168373FD9D CRC64;
MHLSAVFNAL LVSVLAAVLW KHVRLREHAA TLEEELALSR QATEPAPALR IDYPKALQIL
MEGGTHMVCT GRTHTDRICR FKWLCYSNEA EEFIFFHGNT SVMLPNLGSR RFQPALLDLS
TVEDHNTQYF NFVELPAAAL RFMPKPVFVP DVALIANRFN PDNLMHVFHD DLLPLFYTLR
QFPGLAHEAR LFFMEGWGEG AHFDLYKLLS PKQPLLRAQL KTLGRLLCFS HAFVGLSKIT
TWYQYGFVQP QGPKANILVS GNEIRQFARF MTEKLNVSHT GVPLGEEYIL VFSRTQNRLI
LNEAELLLAL AQEFQMKTVT VSLEDHTFAD VVRLVSNASM LVSMHGAQLV TTLFLPRGAT
VVELFPYAVN PDHYTPYKTL AMLPGMDLQY VAWRNMMPEN TVTHPERPWD QGGITHLDRA
EQARILQSRE VPRHLCCRNP EWLFRIYQDT KVDIPSLIQT IRRVVKGRPG PRKQKWTVGL
YPGKVREARC QASVHGASEA RLTVSWQIPW NLKYLKVREV KYEVWLQEQG ENTYVPYILA
LQNHTFTENI KPFTTYLVWV RCIFNKILLG PFADVLVCNT
//
MIM
614828
*RECORD*
*FIELD* NO
614828
*FIELD* TI
*614828 GLYCOSYLTRANSFERASE-LIKE DOMAIN-CONTAINING PROTEIN 2; GTDC2
;;CHROMOSOME 3 OPEN READING FRAME 39; C3ORF39;;
read moreAGO61
*FIELD* TX
CLONING
Using whole-exome sequencing to identify genes mutated in Walker-Warburg
syndrome (see 236670), Manzini et al. (2012) identified GTDC2. The
deduced 580-amino acid protein has an N-terminal signal peptide, a
central putative glycosyltransferase domain, and a C-terminal
fibronectin (135600) type III domain. Quantitative PCR detected variable
GTDC2 expression in all adult and fetal tissues examined, with highest
expression in pancreas, followed by adult and fetal brain, testis,
skeletal muscle, heart, kidney, ovary, and prostate. Within specific
brain regions, highest expression was detected in cerebellum and cortex.
In situ hybridization showed high expression during brain and eye
development in mouse. Expression in embryonic mouse cortex peaked during
the last week of gestation in both neuronal progenitors in the
ventricular zone and migrating and differentiating neurons. Expression
declined around birth. A similar expression pattern was detected in
developing zebrafish.
GENE FUNCTION
Yoshida-Moriguchi et al. (2013) found that GTDC2 is a protein O-linked
mannose beta-1,4-N-acetylglucosaminyltransferase whose product could be
extended by beta-1,3-N-acetylgalactosaminyltransferase-2 (B3GALNT2;
610194) to form the O-mannosyl trisaccharide. Furthermore,
Yoshida-Moriguchi et al. (2013) identified SGK196 (615247) as an
atypical kinase that phosphorylates the 6-position of O-mannose,
specifically after the mannose has been modified by both GTDC2 and
B3GALNT2. Yoshida-Moriguchi et al. (2013) concluded that these findings
suggested how mutations in GTDC2, B3GALNT2, and SGK196 disrupt
dystroglycan receptor function and lead to congenital muscular
dystrophy.
GENE STRUCTURE
Manzini et al. (2012) determined that GTDC2 is a single-exon gene.
MAPPING
By genomic sequence analysis, Manzini et al. (2012) mapped the GTDC2
gene to chromosome 3p22.1.
MOLECULAR GENETICS
In affected members of 3 unrelated consanguineous families with
congenital muscular dystrophy-dystroglycanopathy with brain and eye
anomalies type A8 (MDDGA8; 614830), Manzini et al. (2012) identified 3
different homozygous mutations in the GTDC2 gene
(614828.0001-614828.0003). The first 2 mutations were identified by
homozygosity mapping combined with whole-exome sequencing and confirmed
by Sanger sequencing. All patients had classic features of
Walker-Warburg syndrome, including cobblestone lissencephaly, enlarged
ventricles, cerebellar hypoplasia, and eye abnormalities, resulting in
early death.
ANIMAL MODEL
Manzini et al. (2012) found that knockdown of Gtdc2 expression in
zebrafish replicated many features of Walker-Warburg syndrome, including
hydrocephalus, ocular defects, and muscular dystrophy. Gtdc2 knockdown
severely decreased survival, but those embryos that survived were
shorter than controls and often had a bent tail, impaired motility,
smaller eyes in which the retina failed to fuse ventrally, and a domed
appearance of the top of the head. Other features included
hydrocephalus, a reduction in brain volume, disorganization of the
retinal epithelium, and impaired muscle development with a loss of both
dystrophin and glycosylated dystroglycan from the myosepta.
*FIELD* AV
.0001
MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE
ANOMALIES), TYPE A, 8
GTDC2, ARG445TER
In a Jordanian boy, born of consanguineous parents, with congenital
muscular dystrophy-dystroglycanopathy with brain and eye anomalies type
A8 (MDDGA8; 614830), Manzini et al. (2012) identified a homozygous
1333C-T transition in the GTDC2 gene, resulting in an arg445-to-ter
(R445X) substitution and premature protein truncation. The mutation,
which was identified by homozygosity mapping combined with whole-exome
sequencing and confirmed by Sanger sequencing, was not found in several
large databases or in 384 ethnically matched controls. Each unaffected
parent was heterozygous for the mutation. The patient had classic
features of Walker-Warburg syndrome, including cobblestone
lissencephaly, enlarged ventricles, cerebellar hypoplasia, and eye
abnormalities, and died at age 2 months.
.0002
MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE
ANOMALIES), TYPE A, 8
GTDC2, ARG158HIS
In a girl, born of Saudi Arabian parents, with MDDGA8 (614830), Manzini
et al. (2012) identified a homozygous 473G-A transition in the GTDC2
gene, resulting in an arg158-to-his (R158H) substitution at a highly
conserved residue adjacent to the start of the glycosyltransferase
domain. The mutation, which was identified by homozygosity mapping
combined with whole-exome sequencing and confirmed by Sanger sequencing,
was not found in several large databases or in 384 ethnically matched
controls. Each unaffected parent was heterozygous for the mutation. The
patient had classic features of Walker-Warburg syndrome, including
cobblestone lissencephaly, enlarged ventricles, cerebellar hypoplasia,
and eye abnormalities, and died at age 1 month.
.0003
MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE
ANOMALIES), TYPE A, 8
GTDC2, TRP197TER
In 2 sib fetuses, of consanguineous Indian parents, with MDDGA8
(614830), Manzini et al. (2012) identified a homozygous 590G-A
transition in the GTDC2 gene, resulting in a trp197-to-ter (W197X)
substitution and premature protein truncation in the glycosyltransferase
domain. Each unaffected parent was heterozygous for the mutation. The
pregnancies were terminated at gestation week 23 and 20 because of a
diagnosis of severe ventricular enlargement. Autopsy showed classic
features of Walker-Warburg syndrome, including cobblestone lissencephaly
and cerebellar hypoplasia.
*FIELD* RF
1. Manzini, M. C.; Tambunan, D. E.; Hill, R. S.; Yu, T. W.; Maynard,
T. M.; Heinzen, E. L.; Shianna, K. V.; Stevens, C. R.; Partlow, J.
N.; Barry, B. J.; Rodriguez, J.; Gupta, V. A.; and 10 others: Exome
sequencing and functional validation in zebrafish identify GTDC2 mutations
as a cause of Walker-Warburg syndrome. Am. J. Hum. Genet. 91: 541-547,
2012.
2. Yoshida-Moriguchi, T.; Willer, T.; Anderson, M. E.; Venzke, D.;
Whyte, T.; Muntoni, F.; Lee, H.; Nelson, S. F.; Yu, L.; Campbell,
K. P.: SGK196 is a glycosylation-specific O-mannose kinase required
for dystroglycan function. Science 341: 896-899, 2013.
*FIELD* CN
Ada Hamosh - updated: 01/06/2014
Cassandra L. Kniffin - updated: 9/24/2012
*FIELD* CD
Patricia A. Hartz: 9/21/2012
*FIELD* ED
alopez: 01/06/2014
carol: 9/25/2012
ckniffin: 9/24/2012
mgross: 9/21/2012
*RECORD*
*FIELD* NO
614828
*FIELD* TI
*614828 GLYCOSYLTRANSFERASE-LIKE DOMAIN-CONTAINING PROTEIN 2; GTDC2
;;CHROMOSOME 3 OPEN READING FRAME 39; C3ORF39;;
read moreAGO61
*FIELD* TX
CLONING
Using whole-exome sequencing to identify genes mutated in Walker-Warburg
syndrome (see 236670), Manzini et al. (2012) identified GTDC2. The
deduced 580-amino acid protein has an N-terminal signal peptide, a
central putative glycosyltransferase domain, and a C-terminal
fibronectin (135600) type III domain. Quantitative PCR detected variable
GTDC2 expression in all adult and fetal tissues examined, with highest
expression in pancreas, followed by adult and fetal brain, testis,
skeletal muscle, heart, kidney, ovary, and prostate. Within specific
brain regions, highest expression was detected in cerebellum and cortex.
In situ hybridization showed high expression during brain and eye
development in mouse. Expression in embryonic mouse cortex peaked during
the last week of gestation in both neuronal progenitors in the
ventricular zone and migrating and differentiating neurons. Expression
declined around birth. A similar expression pattern was detected in
developing zebrafish.
GENE FUNCTION
Yoshida-Moriguchi et al. (2013) found that GTDC2 is a protein O-linked
mannose beta-1,4-N-acetylglucosaminyltransferase whose product could be
extended by beta-1,3-N-acetylgalactosaminyltransferase-2 (B3GALNT2;
610194) to form the O-mannosyl trisaccharide. Furthermore,
Yoshida-Moriguchi et al. (2013) identified SGK196 (615247) as an
atypical kinase that phosphorylates the 6-position of O-mannose,
specifically after the mannose has been modified by both GTDC2 and
B3GALNT2. Yoshida-Moriguchi et al. (2013) concluded that these findings
suggested how mutations in GTDC2, B3GALNT2, and SGK196 disrupt
dystroglycan receptor function and lead to congenital muscular
dystrophy.
GENE STRUCTURE
Manzini et al. (2012) determined that GTDC2 is a single-exon gene.
MAPPING
By genomic sequence analysis, Manzini et al. (2012) mapped the GTDC2
gene to chromosome 3p22.1.
MOLECULAR GENETICS
In affected members of 3 unrelated consanguineous families with
congenital muscular dystrophy-dystroglycanopathy with brain and eye
anomalies type A8 (MDDGA8; 614830), Manzini et al. (2012) identified 3
different homozygous mutations in the GTDC2 gene
(614828.0001-614828.0003). The first 2 mutations were identified by
homozygosity mapping combined with whole-exome sequencing and confirmed
by Sanger sequencing. All patients had classic features of
Walker-Warburg syndrome, including cobblestone lissencephaly, enlarged
ventricles, cerebellar hypoplasia, and eye abnormalities, resulting in
early death.
ANIMAL MODEL
Manzini et al. (2012) found that knockdown of Gtdc2 expression in
zebrafish replicated many features of Walker-Warburg syndrome, including
hydrocephalus, ocular defects, and muscular dystrophy. Gtdc2 knockdown
severely decreased survival, but those embryos that survived were
shorter than controls and often had a bent tail, impaired motility,
smaller eyes in which the retina failed to fuse ventrally, and a domed
appearance of the top of the head. Other features included
hydrocephalus, a reduction in brain volume, disorganization of the
retinal epithelium, and impaired muscle development with a loss of both
dystrophin and glycosylated dystroglycan from the myosepta.
*FIELD* AV
.0001
MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE
ANOMALIES), TYPE A, 8
GTDC2, ARG445TER
In a Jordanian boy, born of consanguineous parents, with congenital
muscular dystrophy-dystroglycanopathy with brain and eye anomalies type
A8 (MDDGA8; 614830), Manzini et al. (2012) identified a homozygous
1333C-T transition in the GTDC2 gene, resulting in an arg445-to-ter
(R445X) substitution and premature protein truncation. The mutation,
which was identified by homozygosity mapping combined with whole-exome
sequencing and confirmed by Sanger sequencing, was not found in several
large databases or in 384 ethnically matched controls. Each unaffected
parent was heterozygous for the mutation. The patient had classic
features of Walker-Warburg syndrome, including cobblestone
lissencephaly, enlarged ventricles, cerebellar hypoplasia, and eye
abnormalities, and died at age 2 months.
.0002
MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE
ANOMALIES), TYPE A, 8
GTDC2, ARG158HIS
In a girl, born of Saudi Arabian parents, with MDDGA8 (614830), Manzini
et al. (2012) identified a homozygous 473G-A transition in the GTDC2
gene, resulting in an arg158-to-his (R158H) substitution at a highly
conserved residue adjacent to the start of the glycosyltransferase
domain. The mutation, which was identified by homozygosity mapping
combined with whole-exome sequencing and confirmed by Sanger sequencing,
was not found in several large databases or in 384 ethnically matched
controls. Each unaffected parent was heterozygous for the mutation. The
patient had classic features of Walker-Warburg syndrome, including
cobblestone lissencephaly, enlarged ventricles, cerebellar hypoplasia,
and eye abnormalities, and died at age 1 month.
.0003
MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE
ANOMALIES), TYPE A, 8
GTDC2, TRP197TER
In 2 sib fetuses, of consanguineous Indian parents, with MDDGA8
(614830), Manzini et al. (2012) identified a homozygous 590G-A
transition in the GTDC2 gene, resulting in a trp197-to-ter (W197X)
substitution and premature protein truncation in the glycosyltransferase
domain. Each unaffected parent was heterozygous for the mutation. The
pregnancies were terminated at gestation week 23 and 20 because of a
diagnosis of severe ventricular enlargement. Autopsy showed classic
features of Walker-Warburg syndrome, including cobblestone lissencephaly
and cerebellar hypoplasia.
*FIELD* RF
1. Manzini, M. C.; Tambunan, D. E.; Hill, R. S.; Yu, T. W.; Maynard,
T. M.; Heinzen, E. L.; Shianna, K. V.; Stevens, C. R.; Partlow, J.
N.; Barry, B. J.; Rodriguez, J.; Gupta, V. A.; and 10 others: Exome
sequencing and functional validation in zebrafish identify GTDC2 mutations
as a cause of Walker-Warburg syndrome. Am. J. Hum. Genet. 91: 541-547,
2012.
2. Yoshida-Moriguchi, T.; Willer, T.; Anderson, M. E.; Venzke, D.;
Whyte, T.; Muntoni, F.; Lee, H.; Nelson, S. F.; Yu, L.; Campbell,
K. P.: SGK196 is a glycosylation-specific O-mannose kinase required
for dystroglycan function. Science 341: 896-899, 2013.
*FIELD* CN
Ada Hamosh - updated: 01/06/2014
Cassandra L. Kniffin - updated: 9/24/2012
*FIELD* CD
Patricia A. Hartz: 9/21/2012
*FIELD* ED
alopez: 01/06/2014
carol: 9/25/2012
ckniffin: 9/24/2012
mgross: 9/21/2012
MIM
614830
*RECORD*
*FIELD* NO
614830
*FIELD* TI
#614830 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE
ANOMALIES), TYPE A, 8; MDDGA8
read more;;WALKER-WARBURG SYNDROME OR MUSCLE-EYE-BRAIN DISEASE, GTDC2-RELATED
*FIELD* TX
A number sign (#) is used with this entry because this form of
congenital muscular dystrophy-dystroglycanopathy with brain and eye
anomalies (type A8; MDDGA8) is caused by homozygous mutation in the
GTDC2 gene (614828) on chromosome 3p22.
DESCRIPTION
Congenital muscular dystrophy-dystroglycanopathy with brain and eye
anomalies (type A) is an autosomal recessive disorder with
characteristic brain and eye malformations, profound mental retardation,
congenital muscular dystrophy, and death usually in the first years of
life. The phenotype includes the alternative clinical designation
Walker-Warburg syndrome (WWS). The disorder represents the most severe
end of a phenotypic spectrum of similar disorders resulting from
defective glycosylation of alpha-dystroglycan (DAG1; 128239),
collectively known as 'dystroglycanopathies' (summary by Manzini et al.,
2012).
For a general phenotypic description and a discussion of genetic
heterogeneity of muscular dystrophy-dystroglycanopathy type A, see
MDDGA1 (236670).
CLINICAL FEATURES
Manzini et al. (2012) reported 3 unrelated families with classic
features of Walker-Warburg syndrome, including cobblestone
lissencephaly, enlarged ventricles, cerebellar hypoplasia, eye
abnormalities, and hypotonia. The patients in 2 families died within the
first months of life. In the third family, 2 affected pregnancies were
terminated at 23 and 20 weeks' gestational age due to severe ventricular
enlargement.
INHERITANCE
The transmission pattern in the families with Walker-Warburg syndrome
reported by Manzini et al. (2012) was consistent with autosomal
recessive inheritance.
MOLECULAR GENETICS
In affected members of 3 unrelated consanguineous families with
Walker-Warburg syndrome, Manzini et al. (2012) identified 3 different
homozygous mutations in the GTDC2 gene (614828.0001-614828.0003). The
first 2 mutations were identified by homozygosity mapping combined with
whole-exome sequencing and confirmed by Sanger sequencing.
*FIELD* RF
1. Manzini, M. C.; Tambunan, D. E.; Hill, R. S.; Yu, T. W.; Maynard,
T. M.; Heinzen, E. L.; Shianna, K. V.; Stevens, C. R.; Partlow, J.
N.; Barry, B. J.; Rodriguez, J.; Gupta, V. A.; and 10 others: Exome
sequencing and functional validation in zebrafish identify GTDC2 mutations
as a cause of Walker-Warburg syndrome. Am. J. Hum. Genet. 91: 541-547,
2012.
*FIELD* CS
INHERITANCE:
Autosomal recessive
HEAD AND NECK:
[Eyes];
Retinal dysplasia;
Microphthalmia;
Macrophthalmia
MUSCLE, SOFT TISSUE:
Hypotonia
NEUROLOGIC:
[Central nervous system];
Lack of psychomotor development;
Hydrocephalus;
Enlarged ventricles;
Cobblestone lissencephaly;
Cerebellar hypoplasia
MISCELLANEOUS:
Onset prenatally or at birth;
Severe phenotype;
Most patients die within the first year of life
MOLECULAR BASIS:
Caused by mutation in the glycosyltransferase-like domain-containing
protein 2 gene (GTDC2, 614828.0001)
*FIELD* CD
Cassandra L. Kniffin: 9/24/2012
*FIELD* ED
joanna: 09/27/2012
ckniffin: 9/24/2012
*FIELD* CD
Cassandra L. Kniffin: 9/24/2012
*FIELD* ED
alopez: 06/10/2013
carol: 10/5/2012
terry: 10/5/2012
terry: 9/26/2012
carol: 9/25/2012
ckniffin: 9/24/2012
*RECORD*
*FIELD* NO
614830
*FIELD* TI
#614830 MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE
ANOMALIES), TYPE A, 8; MDDGA8
read more;;WALKER-WARBURG SYNDROME OR MUSCLE-EYE-BRAIN DISEASE, GTDC2-RELATED
*FIELD* TX
A number sign (#) is used with this entry because this form of
congenital muscular dystrophy-dystroglycanopathy with brain and eye
anomalies (type A8; MDDGA8) is caused by homozygous mutation in the
GTDC2 gene (614828) on chromosome 3p22.
DESCRIPTION
Congenital muscular dystrophy-dystroglycanopathy with brain and eye
anomalies (type A) is an autosomal recessive disorder with
characteristic brain and eye malformations, profound mental retardation,
congenital muscular dystrophy, and death usually in the first years of
life. The phenotype includes the alternative clinical designation
Walker-Warburg syndrome (WWS). The disorder represents the most severe
end of a phenotypic spectrum of similar disorders resulting from
defective glycosylation of alpha-dystroglycan (DAG1; 128239),
collectively known as 'dystroglycanopathies' (summary by Manzini et al.,
2012).
For a general phenotypic description and a discussion of genetic
heterogeneity of muscular dystrophy-dystroglycanopathy type A, see
MDDGA1 (236670).
CLINICAL FEATURES
Manzini et al. (2012) reported 3 unrelated families with classic
features of Walker-Warburg syndrome, including cobblestone
lissencephaly, enlarged ventricles, cerebellar hypoplasia, eye
abnormalities, and hypotonia. The patients in 2 families died within the
first months of life. In the third family, 2 affected pregnancies were
terminated at 23 and 20 weeks' gestational age due to severe ventricular
enlargement.
INHERITANCE
The transmission pattern in the families with Walker-Warburg syndrome
reported by Manzini et al. (2012) was consistent with autosomal
recessive inheritance.
MOLECULAR GENETICS
In affected members of 3 unrelated consanguineous families with
Walker-Warburg syndrome, Manzini et al. (2012) identified 3 different
homozygous mutations in the GTDC2 gene (614828.0001-614828.0003). The
first 2 mutations were identified by homozygosity mapping combined with
whole-exome sequencing and confirmed by Sanger sequencing.
*FIELD* RF
1. Manzini, M. C.; Tambunan, D. E.; Hill, R. S.; Yu, T. W.; Maynard,
T. M.; Heinzen, E. L.; Shianna, K. V.; Stevens, C. R.; Partlow, J.
N.; Barry, B. J.; Rodriguez, J.; Gupta, V. A.; and 10 others: Exome
sequencing and functional validation in zebrafish identify GTDC2 mutations
as a cause of Walker-Warburg syndrome. Am. J. Hum. Genet. 91: 541-547,
2012.
*FIELD* CS
INHERITANCE:
Autosomal recessive
HEAD AND NECK:
[Eyes];
Retinal dysplasia;
Microphthalmia;
Macrophthalmia
MUSCLE, SOFT TISSUE:
Hypotonia
NEUROLOGIC:
[Central nervous system];
Lack of psychomotor development;
Hydrocephalus;
Enlarged ventricles;
Cobblestone lissencephaly;
Cerebellar hypoplasia
MISCELLANEOUS:
Onset prenatally or at birth;
Severe phenotype;
Most patients die within the first year of life
MOLECULAR BASIS:
Caused by mutation in the glycosyltransferase-like domain-containing
protein 2 gene (GTDC2, 614828.0001)
*FIELD* CD
Cassandra L. Kniffin: 9/24/2012
*FIELD* ED
joanna: 09/27/2012
ckniffin: 9/24/2012
*FIELD* CD
Cassandra L. Kniffin: 9/24/2012
*FIELD* ED
alopez: 06/10/2013
carol: 10/5/2012
terry: 10/5/2012
terry: 9/26/2012
carol: 9/25/2012
ckniffin: 9/24/2012