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UniProtKB/Swiss-Prot O95859: Variant p.Tyr138Cys

Gene: TSPAN12
Variant information

Variant position:  138
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 Tyrosine (Y) to Cysteine (C) at position 138 (Y138C, p.Tyr138Cys).
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 aromatic (Y) to medium size and polar (C)
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:  Vitreoretinopathy, exudative 5 (EVR5) [MIM:613310]: A disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery. {ECO:0000269|PubMed:20159111, ECO:0000269|PubMed:20159112, ECO:0000269|PubMed:22427576}. Note=The disease is caused by mutations affecting the gene represented in this entry. TSPAN12 dominant and recessive mutations have been identified in patients with exudative vitreoretinopathy. Patients with mutations in both alleles of TSPAN12 have severe exudative vitreoretinopathy or retinal dysplasia. These mutations appear to result in a milder phenotype in heterozygous mutation carriers (PubMed:22427576). {ECO:0000269|PubMed:22427576}.
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 EVR5.
Any additional useful information about the variant.

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

Sequence information

Variant position:  138
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  305
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.

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






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 1 – 305 Tetraspanin-12
Topological domain 111 – 224 Extracellular

Literature citations

Recessive mutations in TSPAN12 cause retinal dysplasia and severe familial exudative vitreoretinopathy (FEVR).
Poulter J.A.; Davidson A.E.; Ali M.; Gilmour D.F.; Parry D.A.; Mintz-Hittner H.A.; Carr I.M.; Bottomley H.M.; Long V.W.; Downey L.M.; Sergouniotis P.I.; Wright G.A.; MacLaren R.E.; Moore A.T.; Webster A.R.; Inglehearn C.F.; Toomes C.;
Invest. Ophthalmol. Vis. Sci. 53:2873-2879(2012)
Cited for: VARIANTS EVR5 MET-49; CYS-138 AND PRO-223;

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.