UniProtKB/Swiss-Prot Q04671: Variant p.Arg305Trp

P protein
Gene: OCA2
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Variant information Variant position:

305 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Arginine (R) to Tryptophan (W) at position 305 (R305W, p.Arg305Trp). 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 large size and aromatic (W) 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
Polymorphism:

Genetic variants in OCA2 define the skin/hair/eye pigmentation variation locus 1 (SHEP1) [MIM:227220]; also known as skin/hair/eye pigmentation type 1, blue/nonblue eyes or skin/hair/eye pigmentation type 1, blue/brown eyes or skin/hair/eye pigmentation type 1, blond/brown hair or eye color, brown/blue or eye color, blue/nonblue or eye color type 3 (EYCL3) or brown eye color type 2 (BEY2) or hair color type 3 (HCL3). Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair. OCA2 polymorphisms may act as a penetrance modifier of the risk of malignant melanoma. Additional information on the polymorphism described.
Variant description:

Affects eye pigmentation and is correlated with non-blue eye color. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1800401 [ dbSNP | Ensembl ]

Sequence information Variant position:

305 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

838 The length of the canonical sequence.
Location on the sequence:

HSVMSRTFEVLTRETVSISI R ASLQQTQAVPLLMAHQYLRG 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                         HSVMSRTFEVLTRETVSISIRASLQQTQAVPLLMAHQYLRG

Mouse                         HVVVSRTFEIVSREAVSISIQASLQQTRLVPLLLAHQFLGA

Pig                           HTVMSRTFEVLSREPVSINIRASLQQTQIVPLLMAHQYLRA

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.

Type	Positions	Description
Chain	1 – 838	P protein
Topological domain	198 – 330	Extracellular

Literature citations
Organization and sequence of the human P gene and identification of a new family of transport proteins.
Lee S.-T.; Nicholls R.D.; Jong M.T.C.; Fukai K.; Spritz R.A.;
Genomics 26:354-363(1995)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 3); FUNCTION; SUBCELLULAR LOCATION; VARIANTS TRP-305; GLN-419; PHE-440; ARG-615 AND THR-722; Novel and recurrent mutations in the tyrosinase gene and the P gene in the German albino population.
Passmore L.A.; Kaesmann-Kellner B.; Weber B.H.F.;
Hum. Genet. 105:200-210(1999)
Cited for: VARIANTS OCA2 GLY-290; ILE-443; GLU-614; LEU-617; CYS-679; CYS-720; ARG-795 AND VAL-833 DEL; VARIANTS TRP-305 AND GLN-419; P gene as an inherited biomarker of human eye color.
Rebbeck T.R.; Kanetsky P.A.; Walker A.H.; Holmes R.; Halpern A.C.; Schuchter L.M.; Elder D.E.; Guerry D.;
Cancer Epidemiol. Biomarkers Prev. 11:782-784(2002)
Cited for: VARIANTS TRP-305 AND GLN-419; INVOLVEMENT IN DETERMINATION OF EYE COLOR; Allele variations in the OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma.
Jannot A.-S.; Meziani R.; Bertrand G.; Gerard B.; Descamps V.; Archimbaud A.; Picard C.; Ollivaud L.; Basset-Seguin N.; Kerob D.; Lanternier G.; Lebbe C.; Saiag P.; Crickx B.; Clerget-Darpoux F.; Grandchamp B.; Soufir N.;
Eur. J. Hum. Genet. 13:913-920(2005)
Cited for: VARIANTS TRP-305 AND GLN-419; INVOLVEMENT IN SUSCEPTIBILITY TO MELANOMA;

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.