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UniProtKB/Swiss-Prot Q9H9E3: Variant p.Gly512Arg

Conserved oligomeric Golgi complex subunit 4
Gene: COG4
Variant information

Variant position:  512
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Glycine (G) to Arginine (R) at position 512 (G512R, p.Gly512Arg).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from glycine (G) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Involvement in disease:  Saul-Wilson syndrome (SWILS) [MIM:618150]: A rare skeletal dysplasia with characteristic dysmorphic and radiographic findings, as well as early developmental delay, primarily involving speech, with eventual normal cognition. Clinical findings include marked short stature, prominent forehead with an enlarged anterior fontanel, prominent eyes with cataracts, narrow nasal bridge with a convex nasal ridge, micrognathia, clubfoot, brachydactyly, and short distal phalanges of fingers. Radiographic changes include platyspondyly, irregular end plates of vertebral bodies, and hypoplasia of the odontoid process with cervical instability in the spine, coxa valga, overtubulation, metaphyseal flaring and megaepiphyses in the long bones, while the hands and feet exhibit short phalanges, metacarpals and metatarsals, cone-shaped epiphyses of phalanges, and accessory ossification centers of metacarpals and metatarsals. {ECO:0000269|PubMed:30290151}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In SWILS; delayed anterograde vesicular trafficking from the ER to the Golgi and accelerated retrograde vesicular recycling from the Golgi to the ER, leading to a decrease in Golgi volume, as well as morphologic abnormalities with collapse of the Golgi stacks in affected fibroblasts; altered decorin/DCN Golgi-dependent glycosylation; no effect on protein expression.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.

Sequence information

Variant position:  512
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  785
The length of the canonical sequence.

The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

Chain 2 – 785 Conserved oligomeric Golgi complex subunit 4
Alternative sequence 338 – 785 Missing. In isoform 2.

Literature citations

A recurrent de novo heterozygous COG4 substitution leads to Saul-Wilson syndrome, disrupted vesicular trafficking, and altered proteoglycan glycosylation.
Ferreira C.R.; Xia Z.J.; Clement A.; Parry D.A.; Davids M.; Taylan F.; Sharma P.; Turgeon C.T.; Blanco-Sanchez B.; Ng B.G.; Logan C.V.; Wolfe L.A.; Solomon B.D.; Cho M.T.; Douglas G.; Carvalho D.R.; Bratke H.; Haug M.G.; Phillips J.B.; Wegner J.; Tiemeyer M.; Aoki K.; Nordgren A.; Hammarsjoe A.; Duker A.L.; Rohena L.; Hove H.B.; Ek J.; Adams D.; Tifft C.J.; Onyekweli T.; Weixel T.; Macnamara E.; Radtke K.; Powis Z.; Earl D.; Gabriel M.; Russi A.H.S.; Brick L.; Kozenko M.; Tham E.; Raymond K.M.; Phillips J.A. III; Tiller G.E.; Wilson W.G.; Hamid R.; Malicdan M.C.V.; Nishimura G.; Grigelioniene G.; Jackson A.; Westerfield M.; Bober M.B.; Gahl W.A.; Freeze H.H.;
Am. J. Hum. Genet. 103:553-567(2018)

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.