U.S. flag

An official website of the United States government

NM_015386.3(COG4):c.2197C>T (p.Arg733Trp) AND COG4-congenital disorder of glycosylation

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 1, 2009
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000003837.3

Allele description [Variation Report for NM_015386.3(COG4):c.2197C>T (p.Arg733Trp)]

NM_015386.3(COG4):c.2197C>T (p.Arg733Trp)

Gene:
COG4:component of oligomeric golgi complex 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16q22.1
Genomic location:
Preferred name:
NM_015386.3(COG4):c.2197C>T (p.Arg733Trp)
Other names:
R729W
HGVS:
  • NC_000016.10:g.70481397G>A
  • NG_027529.1:g.47158C>T
  • NM_001195139.2:c.2122C>T
  • NM_001365426.1:c.1771C>T
  • NM_015386.3:c.2197C>TMANE SELECT
  • NP_001182068.2:p.Arg708Trp
  • NP_001352355.1:p.Arg591Trp
  • NP_056201.2:p.Arg733Trp
  • NC_000016.9:g.70515300G>A
  • NM_015386.2:c.2197C>T
  • NR_158212.1:n.2156C>T
Protein change:
R591W; ARG729TRP
Links:
OMIM: 606976.0001; dbSNP: rs267606740
NCBI 1000 Genomes Browser:
rs267606740
Molecular consequence:
  • NM_001195139.2:c.2122C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365426.1:c.1771C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015386.3:c.2197C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_158212.1:n.2156C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
COG4-congenital disorder of glycosylation
Synonyms:
CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIj; CDG IIj; Congenital disorder of glycosylation type 2J; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0013281; MedGen: C4303552; Orphanet: 263501; OMIM: 613489

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000024002OMIM
no assertion criteria provided
Pathogenic
(Sep 1, 2009)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Golgi function and dysfunction in the first COG4-deficient CDG type II patient.

Reynders E, Foulquier F, Leão Teles E, Quelhas D, Morelle W, Rabouille C, Annaert W, Matthijs G.

Hum Mol Genet. 2009 Sep 1;18(17):3244-56. doi: 10.1093/hmg/ddp262. Epub 2009 Jun 3.

PubMed [citation]
PMID:
19494034
PMCID:
PMC2722986

Structural basis for a human glycosylation disorder caused by mutation of the COG4 gene.

Richardson BC, Smith RD, Ungar D, Nakamura A, Jeffrey PD, Lupashin VV, Hughson FM.

Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13329-34. doi: 10.1073/pnas.0901966106. Epub 2009 Jul 27.

PubMed [citation]
PMID:
19651599
PMCID:
PMC2716380

Details of each submission

From OMIM, SCV000024002.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

Reynders et al. (2009) reported a Portuguese boy with congenital disorder of glycosylation type IIj (CDG2J; 613489) and identified compound heterozygosity for a 2185C-T transition in exon 18 of the COG4 gene, resulting in an arg729-to-trp (R729W) substitution at a conserved residue, and a large deletion (606976.0002) of approximately 400 kb with the distal breakpoint between intron 2 and exon 5 of the COG4 gene and the proximal breakpoint upstream of the FUK gene (608675). The FUK gene encodes L-fucose kinase, which is necessary for the reutilization of fucose after the degradation of oligosaccharides. Because no decreased fucosylation was observed in the N-glycans of the patient, the authors concluded that the 'partial monosomy' of this gene was not pathogenic. The R729W mutation was not identified in over 100 European control alleles. Western blot analysis of patient fibroblasts showed reduced COG4 protein levels compared to control, and downregulation of COG4 expression additionally affected expression or stability of other lobe A subunits. Despite this, full complex formation was maintained albeit to a lower extent. Subunits were present in a cytosolic pool and full complex formation assisted tethering preceding membrane fusion. The unrelated father and mother were heterozygous for the R729W mutation or the deletion, respectively, and Western blot analysis of parental fibroblasts showed normal COG4 protein levels.

By determining the crystal structure of a COG4 C-terminal fragment, Richardson et al. (2009) determined that the R729 residue occupies a key position at the center of a salt bridge network, thereby stabilizing the small C-terminal domain. Knockdown of COG4 in HeLa cells by use of a COG4-specific shRNA plasmid resulted in disruption of glycosylation of cell surface proteins. A full-length COG4 containing the R729W mutation failed to rescue the glycosylation defect in these knockdown cells.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2024