RBCC

Full text data of DDOST

DDOST (KIAA0115, OST48) [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Dolichyl-diphosphooligosaccharide--protein glycosyltransferase 48 kDa subunit; DDOST 48 kDa subunit; Oligosaccharyl transferase 48 kDa subunit; 2.4.99.18; Flags: Precursor

UniProt P39656
ID OST48_HUMAN Reviewed; 456 AA.
AC P39656; B2RDQ4; O43244; Q5VWA5; Q8NI93; Q9BUI2;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 16-JUN-2009, sequence version 4.
DT 22-JAN-2014, entry version 137.
DE RecName: Full=Dolichyl-diphosphooligosaccharide--protein glycosyltransferase 48 kDa subunit;
DE Short=DDOST 48 kDa subunit;
DE Short=Oligosaccharyl transferase 48 kDa subunit;
DE EC=2.4.99.18;
DE Flags: Precursor;
GN Name=DDOST; Synonyms=KIAA0115, OST48; ORFNames=OK/SW-cl.45;
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], AND VARIANT GLY-8.
RX PubMed=9367678; DOI=10.1006/geno.1997.4966;
RA Yamagata T., Tsuru T., Momoi M.Y., Suwa K., Nozaki Y., Mukasa T.,
RA Ohashi H., Fukushima Y., Momoi T.;
RT "Genome organization of human 48-kDa oligosaccharyltransferase
RT (DDOST).";
RL Genomics 45:535-540(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-8.
RC TISSUE=Bone marrow;
RX PubMed=7788527; DOI=10.1093/dnares/2.1.37;
RA Nagase T., Miyajima N., Tanaka A., Sazuka T., Seki N., Sato S.,
RA Tabata S., Ishikawa K., Kawarabayasi Y., Kotani H., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. III.
RT The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by
RT analysis of cDNA clones from human cell line KG-1.";
RL DNA Res. 2:37-43(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-8.
RC TISSUE=Synovium;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLY-8.
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-8.
RC TISSUE=Brain;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 9-456.
RC TISSUE=Colon adenocarcinoma;
RA Shichijo S., Itoh K.;
RT "Identification of immuno-peptidmics that are recognized by tumor-
RT reactive CTL generated from TIL of colon cancer patients.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [8]
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 [9]
RP VARIANT CDG1R ASP-217.
RX PubMed=22305527; DOI=10.1016/j.ajhg.2011.12.024;
RA Jones M.A., Ng B.G., Bhide S., Chin E., Rhodenizer D., He P.,
RA Losfeld M.E., He M., Raymond K., Berry G., Freeze H.H., Hegde M.R.;
RT "DDOST mutations identified by whole-exome sequencing are implicated
RT in congenital disorders of glycosylation.";
RL Am. J. Hum. Genet. 90:363-368(2012).
CC -!- FUNCTION: Essential subunit of the N-oligosaccharyl transferase
CC (OST) complex which catalyzes the transfer of a high mannose
CC oligosaccharide from a lipid-linked oligosaccharide donor to an
CC asparagine residue within an Asn-X-Ser/Thr consensus motif in
CC nascent polypeptide chains.
CC -!- CATALYTIC ACTIVITY: Dolichyl diphosphooligosaccharide + [protein]-
CC L-asparagine = dolichyl diphosphate + a glycoprotein with the
CC oligosaccharide chain attached by N-beta-D-glycosyl linkage to a
CC protein L-asparagine.
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC -!- SUBUNIT: Component of the oligosaccharyltransferase (OST) complex.
CC OST seems to exist in different forms which contain at least RPN1,
CC RPN2, OST48, DAD1, OSTC, KRTCAP2 and either STT3A or STT3B. OST
CC can form stable complexes with the Sec61 complex or with both the
CC Sec61 and TRAP complexes even after release from the ribosome (By
CC similarity).
CC -!- INTERACTION:
CC Q86WV6:TMEM173; NbExp=2; IntAct=EBI-358866, EBI-2800345;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC type I membrane protein.
CC -!- DISEASE: Congenital disorder of glycosylation 1R (CDG1R)
CC [MIM:614507]: A multisystem disorder caused by a defect in
CC glycoprotein biosynthesis and characterized by under-glycosylated
CC serum glycoproteins. Congenital disorders of glycosylation result
CC in a wide variety of clinical features, such as defects in the
CC nervous system development, psychomotor retardation, dysmorphic
CC features, hypotonia, coagulation disorders, and immunodeficiency.
CC The broad spectrum of features reflects the critical role of N-
CC glycoproteins during embryonic development, differentiation, and
CC maintenance of cell functions. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the DDOST 48 kDa subunit family.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-18 is the initiator.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB93478.1; Type=Erroneous initiation;
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DR EMBL; D89060; BAA23670.1; -; Genomic_DNA.
DR EMBL; D29643; BAA06126.1; -; mRNA.
DR EMBL; AK315633; BAG38001.1; -; mRNA.
DR EMBL; AL391357; CAH73476.1; -; Genomic_DNA.
DR EMBL; CH471134; EAW94938.1; -; Genomic_DNA.
DR EMBL; BC002594; AAH02594.1; -; mRNA.
DR EMBL; AB062391; BAB93478.1; ALT_INIT; mRNA.
DR PIR; S66254; A44654.
DR RefSeq; NP_005207.2; NM_005216.4.
DR UniGene; Hs.523145; -.
DR ProteinModelPortal; P39656; -.
DR IntAct; P39656; 19.
DR MINT; MINT-1144346; -.
DR STRING; 9606.ENSP00000364188; -.
DR BindingDB; P39656; -.
DR ChEMBL; CHEMBL4239; -.
DR PhosphoSite; P39656; -.
DR DMDM; 239938926; -.
DR PaxDb; P39656; -.
DR PRIDE; P39656; -.
DR DNASU; 1650; -.
DR Ensembl; ENST00000375048; ENSP00000364188; ENSG00000244038.
DR Ensembl; ENST00000602624; ENSP00000473655; ENSG00000244038.
DR GeneID; 1650; -.
DR KEGG; hsa:1650; -.
DR UCSC; uc001bdo.1; human.
DR CTD; 1650; -.
DR GeneCards; GC01M020978; -.
DR HGNC; HGNC:2728; DDOST.
DR HPA; CAB009746; -.
DR MIM; 602202; gene.
DR MIM; 614507; phenotype.
DR neXtProt; NX_P39656; -.
DR Orphanet; 300536; DDOST-CDG syndrome.
DR PharmGKB; PA27195; -.
DR eggNOG; NOG263094; -.
DR HOGENOM; HOG000173744; -.
DR HOVERGEN; HBG053378; -.
DR InParanoid; P39656; -.
DR KO; K12670; -.
DR OMA; LEHTQYE; -.
DR OrthoDB; EOG7K6PV7; -.
DR PhylomeDB; P39656; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_6900; Immune System.
DR Reactome; REACT_71; Gene Expression.
DR UniPathway; UPA00378; -.
DR ChiTaRS; DDOST; human.
DR GeneWiki; DDOST; -.
DR GenomeRNAi; 1650; -.
DR NextBio; 6796; -.
DR PRO; PR:P39656; -.
DR ArrayExpress; P39656; -.
DR Bgee; P39656; -.
DR CleanEx; HS_DDOST; -.
DR Genevestigator; P39656; -.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0008250; C:oligosaccharyltransferase complex; ISS:UniProtKB.
DR GO; GO:0004579; F:dolichyl-diphosphooligosaccharide-protein glycotransferase activity; IEA:InterPro.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
DR GO; GO:0018279; P:protein N-linked glycosylation via asparagine; IC:HGNC.
DR GO; GO:0034097; P:response to cytokine stimulus; IDA:UniProtKB.
DR GO; GO:0006614; P:SRP-dependent cotranslational protein targeting to membrane; TAS:Reactome.
DR GO; GO:0042110; P:T cell activation; IDA:UniProtKB.
DR GO; GO:0006412; P:translation; TAS:Reactome.
DR InterPro; IPR005013; WBP1.
DR PANTHER; PTHR10830; PTHR10830; 1.
DR Pfam; PF03345; DDOST_48kD; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Congenital disorder of glycosylation;
KW Disease mutation; Endoplasmic reticulum; Glycosyltransferase;
KW Membrane; Polymorphism; Reference proteome; Signal; Transferase;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1 42 By similarity.
FT CHAIN 43 456 Dolichyl-diphosphooligosaccharide--
FT protein glycosyltransferase 48 kDa
FT subunit.
FT /FTId=PRO_0000021957.
FT TOPO_DOM 43 427 Lumenal (Potential).
FT TRANSMEM 428 447 Helical; (Potential).
FT TOPO_DOM 448 456 Cytoplasmic (Potential).
FT VARIANT 8 8 R -> G (in dbSNP:rs537816).
FT /FTId=VAR_047911.
FT VARIANT 217 217 G -> D (in CDG1R).
FT /FTId=VAR_067544.
FT CONFLICT 343 343 G -> A (in Ref. 1; BAA23670).
FT CONFLICT 434 434 S -> P (in Ref. 1; BAA23670 and 2;
FT BAA06126).
SQ SEQUENCE 456 AA; 50801 MW; 2707ABAC8FF158CB CRC64;
MGYFRCARAG SFGRRRKMEP STAARAWALF WLLLPLLGAV CASGPRTLVL LDNLNVRETH
SLFFRSLKDR GFELTFKTAD DPSLSLIKYG EFLYDNLIIF SPSVEDFGGN INVETISAFI
DGGGSVLVAA SSDIGDPLRE LGSECGIEFD EEKTAVIDHH NYDISDLGQH TLIVADTENL
LKAPTIVGKS SLNPILFRGV GMVADPDNPL VLDILTGSST SYSFFPDKPI TQYPHAVGKN
TLLIAGLQAR NNARVIFSGS LDFFSDSFFN SAVQKAAPGS QRYSQTGNYE LAVALSRWVF
KEEGVLRVGP VSHHRVGETA PPNAYTVTDL VEYSIVIQQL SNGKWVPFDG DDIQLEFVRI
DPFVRTFLKK KGGKYSVQFK LPDVYGVFQF KVDYNRLGYT HLYSSTQVSV RPLQHTQYER
FIPSAYPYYA SAFSMMLGLF IFSIVFLHMK EKEKSD
//

MIM 602202
*RECORD*
*FIELD* NO
602202
*FIELD* TI
*602202 DOLICHYL-DIPHOSPHOOLIGOSACCHARIDE-PROTEIN GLYCOSYLTRANSFERASE; DDOST
;;OLIGOSACCHARYLTRANSFERASE; OST;;
read moreOLIGOSACCHARYLTRANSFERASE, 48-KD; OST48
*FIELD* TX

DESCRIPTION

The DDOST gene encodes the enzyme oligosaccharyltransferase
(dolichyl-diphosphooligosaccharide-protein glycosyltransferase (EC
2.4.1.119)), which catalyzes the transfer of a high-mannose
oligosaccharide from a dolichyl-linked oligosaccharide donor onto the
asparagine acceptor site in nascent polypeptide chains across the
membrane of the rough endoplasmic reticulum (Yamagata et al., 1997).

CLONING

Kelleher et al. (1992) reported that mammalian oligosaccharyltransferase
activity is associated with a protein complex composed of ribophorin I
(180470), ribophorin II (180490), and a 48-kD protein, OST48.

Yamagata et al. (1997) isolated mouse and human DDOST cDNAs from
retinoic acid-treated mouse and human cells. DDOST mRNA was expressed
intensely in heart and pancreas, but at lower levels in brain.

GENE STRUCTURE

Yamagata et al. (1997) showed that the gene encoding the human DDOST
48-kD gene is organized into 11 exons spanning about 9 kb.

MAPPING

By fluorescence in situ hybridization, Yamagata et al. (1997) assigned
the DDOST gene to chromosome 1p36.1.

GENE FUNCTION

Advanced glycosylation end products (AGE) contribute to kidney disease
due to diabetes or aging by means of mesangial cell receptors, such as
receptor for AGE (RAGE; 600214), which promote oxidant stress-dependent
activation of NF-kappa-B (see 164011) and inflammatory gene expression.
Lu et al. (2004) found that DDOST, which they referred to as AGE
receptor-1 (AGE-R1), enhances AGE removal, but is also a distinct
receptor in that it suppresses AGE-mediated mesangial cell inflammatory
injury through negative regulation of RAGE, a previously uncharacterized
pathway that may protect from renal and other tissue injury due to
diabetes and aging.

MOLECULAR GENETICS

By whole-exome sequencing of a European boy with congenital disorder of
glycosylation type 1r (CDG1R; 614507), Jones et al. (2012) identified
compound heterozygosity for 2 mutations in the DDOST gene (602202.0001
and 602202.0002). The patient presented in infancy with failure to
thrive, gastroesophageal reflux, developmental delay, and oromotor
dysfunction. He later showed hypotonia, external strabismus, and mild to
moderate liver dysfunction. He had delayed psychomotor development with
walking acquired at age 3 years, and never developed speech.

*FIELD* AV
.0001
CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ir
DDOST, 22-BP DEL, NT1265

By whole-exome sequencing of a European boy with congenital disorder of
glycosylation type 1r (CDG1R; 614507), Jones et al. (2012) identified
compound heterozygosity for 2 mutations in the DDOST gene: a 22-bp
deletion in exon 11 (1265_1286del22) resulting in a frameshift,
truncation of 29 C-terminal residues, and a presumably nonfunctional
protein, and a 650G-A transition in exon 6, resulting in a gly217-to-asp
(G217D) substitution in a highly conserved residue in the luminal domain
of the endoplasmic reticulum. Neither mutation was found in the 1000
Genomes Project or in 100 controls, and each unaffected parent was
heterozygous for 1 of the mutations. Immunoblot analysis of patient
fibroblasts showed a 50% reduction in DDOST protein expression. Several
biochemical studies showed that the patient's fibroblasts had an
N-glycosylation defect, which could be corrected by transfection with
wildtype DDOST. The patient presented in infancy with failure to thrive,
gastroesophageal reflux, developmental delay, and oromotor dysfunction.
He later showed hypotonia, external strabismus, and mild to moderate
liver dysfunction. He had delayed psychomotor development with walking
acquired at age 3 years, and never developed speech.

.0002
CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ir
DDOST, GLY217ASP

See Jones et al. (2012) and 602202.0001.

*FIELD* RF
1. Jones, M. A.; Ng, B. G.; Bhide, S.; Chin, E.; Rhodenizer, D.; He,
P.; Losfeld, M.-E.; He, M.; Raymond, K.; Berry, G.; Freeze, H. H.;
Hegde, M. R.: DDOST mutations identified by whole-exome sequencing
are implicated in congenital disorders of glycosylation. Am. J. Hum.
Genet. 90: 363-368, 2012.

2. Kelleher, D. J.; Kreibich, G.; Gilmore, R.: Oligosaccharyltransferase
activity is associated with a protein complex composed of ribophorins
I and II and a 48 kd protein. Cell 69: 55-65, 1992.

3. Lu, C.; He, J. C.; Cai, W.; Liu, H.; Zhu, L.; Vlassara, H.: Advanced
glycation endproduct (AGE) receptor 1 is a negative regulator of the
inflammatory response to AGE in mesangial cells. Proc. Nat. Acad.
Sci. 101: 11767-11772, 2004.

4. Yamagata, T.; Tsuru, T.; Momoi, M. Y.; Suwa, K.; Nozaki, Y.; Mukasa,
T.; Ohashi, H.; Fukushima, Y.; Momoi, T.: Genome organization of
human 48-kDa oligosaccharyltransferase (DDOST). Genomics 45: 535-540,
1997.

*FIELD* CN
Cassandra L. Kniffin - updated: 3/1/2012
Victor A. McKusick - updated: 10/11/2004
Jennifer P. Macke - updated: 4/15/1998

*FIELD* CD
Victor A. McKusick: 12/18/1997

*FIELD* ED
carol: 09/16/2013
carol: 3/2/2012
terry: 3/1/2012
ckniffin: 3/1/2012
tkritzer: 10/11/2004
dholmes: 4/15/1998
dholmes: 4/7/1998
mark: 12/20/1997
mark: 12/18/1997

MIM 614507
*RECORD*
*FIELD* NO
614507
*FIELD* TI
#614507 CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Ir; CDG1R
*FIELD* TX
A number sign (#) is used with this entry because this form of
read morecongenital disorder of glycosylation type I, designated here as CDG1R,
can be caused by compound heterozygous mutation in the DDOST gene
(602202) on chromosome 1p36.1.

For a discussion of the classification of CDGs, see CDG1A (212065).

CLINICAL FEATURES

Jones et al. (2012) reported a 6-month-old boy of European descent who
presented with failure to thrive, gastroesophageal reflux, developmental
delay, ear infections, and oromotor dysfunction. At age 1 year, he
showed hypotonia, external strabismus, mild to moderate liver
dysfunction, and constipation. He had delayed psychomotor development
with walking acquired at age 3 years, and never developed speech.
Laboratory studies at age 6 years showed a deficiency of coagulation
factors factor XI (F9; 300746), antithrombin III (SERPINC1; 107300),
protein C (PROC; 612283), and protein S (PROS1; 176880). Brain MRI
suggested disordered myelination. He also had slightly advanced bone age
and mild osteopenia. At age 7 years, he had 2 episodes of tremors
affecting the extremities that were not clearly associated with loss of
consciousness. Biochemical analysis of transferrin revealed a type 1
pattern in which both monoglycosylated and aglycosylated transferrin
were markedly increased.

MOLECULAR GENETICS

By whole-exome sequencing of a European boy with type 1 CDG, Jones et
al. (2012) identified compound heterozygosity for 2 mutations in the
DDOST gene (602202.0001 and 602202.0002). Immunoblot analysis of patient
fibroblasts showed a 50% reduction in DDOST protein expression, and
several biochemical studies showed that the patient's fibroblasts had an
N-glycosylation defect, which could be corrected by transfection with
wildtype DDOST.

*FIELD* RF
1. Jones, M. A.; Ng, B. G.; Bhide, S.; Chin, E.; Rhodenizer, D.; He,
P.; Losfeld, M.-E.; He, M.; Raymond, K.; Berry, G.; Freeze, H. H.;
Hegde, M. R.: DDOST mutations identified by whole-exome sequencing
are implicated in congenital disorders of glycosylation. Am. J. Hum.
Genet. 90: 363-368, 2012.

*FIELD* CS
INHERITANCE:
Autosomal recessive

GROWTH:
[Other];
Failure to thrive

HEAD AND NECK:
[Ears];
Recurrent ear infections;
[Eyes];
Strabismus;
[Mouth];
Oromotor dysfunction

ABDOMEN:
[Liver];
Liver dysfunction, mild;
[Gastrointestinal];
Gastroesophageal reflux;
Constipation

MUSCLE, SOFT TISSUE:
Hypotonia

NEUROLOGIC:
[Central nervous system];
Delayed psychomotor development;
Lack of speech development;
Disordered myelination

HEMATOLOGY:
Deficiency of coagulation factors

LABORATORY ABNORMALITIES:
Abnormal isoelectric focusing of serum transferrin (type 1 pattern)

MISCELLANEOUS:
Onset in infancy;
One patient has been reported (as of February 2012)

MOLECULAR BASIS:
Caused by mutation in the dolichyl-diphosphooligosaccharide-protein
glycosyltransferase gene (DDOST, 602202.0001)

*FIELD* CD
Cassandra L. Kniffin: 2/29/2012

*FIELD* ED
joanna: 04/01/2012
ckniffin: 3/1/2012

*FIELD* CD
Cassandra L. Kniffin: 2/29/2012

*FIELD* ED
carol: 03/02/2012
terry: 3/1/2012
ckniffin: 3/1/2012

RBCC Red Blood Cell Collection

Full text data of DDOST