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UniProtKB/Swiss-Prot P02458: Variant p.Arg904Cys

Collagen alpha-1(II) chain
Gene: COL2A1
Variant information

Variant position:  904
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 Arginine (R) to Cysteine (C) at position 904 (R904C, p.Arg904Cys).
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 large size and basic (R) to medium size and polar (C)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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:  Multiple epiphyseal dysplasia with myopia and conductive deafness (EDMMD) [MIM:132450]: A generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. EDMMD is an autosomal dominant disorder characterized by epiphyseal dysplasia associated with progressive myopia, retinal thinning, crenated cataracts, conductive deafness. {ECO:0000269|PubMed:9800905}. 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.

Involvement in disease:  Stickler syndrome 1 (STL1) [MIM:108300]: An autosomal dominant form of Stickler syndrome, an inherited disorder that associates ocular signs with more or less complete forms of Pierre Robin sequence, bone disorders and sensorineural deafness. Ocular disorders may include juvenile cataract, myopia, strabismus, vitreoretinal or chorioretinal degeneration, retinal detachment, and chronic uveitis. Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate), a large tongue (macroglossia), and a small lower jaw (micrognathia). Bones are affected by slight platyspondylisis and large, often defective epiphyses. Juvenile joint laxity is followed by early signs of arthrosis. The degree of hearing loss varies among affected individuals and may become more severe over time. Syndrome expressivity is variable. {ECO:0000269|PubMed:11007540, ECO:0000269|PubMed:20513134, ECO:0000269|PubMed:7977371}. 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 EDMMD and STL1.
Any additional useful information about the variant.

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



Sequence information

Variant position:  904
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1487
The length of the canonical sequence.

Location on the sequence:   KGARGAQGPPGATGFPGAAG  R VGPPGSNGNPGPPGPPGPSG
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.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         KGARGAQGPPGATGFPGAAGRVGPPGSNGNPGPPGPPGPSG

Mouse                         KGARGAQGPPGATGFPGAAGRVGPPGANGNPGPAGPPGPAG

Rat                           KGARGAQGPPGATGFPGAAGRVGPPGSNGNPGPAGPPGPAG

Bovine                        KGARGAQGPPGATGFPGAAGRVGPPGSNGNPGPPGPPGPSG

Xenopus laevis                KGARGAQGPAGATGFPGAAGRVGTPGPNGNPGPPGPPGSAG

Xenopus tropicalis            KGARGAQGPPGATGFPGAAGRVGPPGPNGNPGPSGAPGSAG

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.

TypePositionsDescription
Chain 182 – 1241 Collagen alpha-1(II) chain
Region 201 – 1214 Triple-helical region
Modified residue 907 – 907 3-hydroxyproline
Modified residue 908 – 908 4-hydroxyproline
Modified residue 914 – 914 4-hydroxyproline
Modified residue 920 – 920 4-hydroxyproline
Alternative sequence 1 – 1219 Missing. In isoform 3.


Literature citations

Stickler-like syndrome due to a dominant negative mutation in the COL2A1 gene.
Ballo R.; Beighton P.H.; Ramesar R.S.;
Am. J. Med. Genet. 80:6-11(1998)
Cited for: VARIANT EDMMD CYS-904;

Stickler syndrome and the vitreous phenotype: mutations in COL2A1 and COL11A1.
Richards A.J.; McNinch A.; Martin H.; Oakhill K.; Rai H.; Waller S.; Treacy B.; Whittaker J.; Meredith S.; Poulson A.; Snead M.P.;
Hum. Mutat. 31:E1461-E1471(2010)
Cited for: VARIANTS STL1 ASP-240; ARG-270; ASP-282; ALA-453; ARG-501; CYS-904 AND ALA-1158;

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.