UniProtKB/SwissProt variant VAR

Variant information

Variant position:

524

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 Cysteine (C) to Tyrosine (Y) at position 524 (C524Y, p.Cys524Tyr).

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 medium size and polar (C) to large size and aromatic (Y)

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:

Reticulate acropigmentation of Kitamura (RAK) [MIM:615537]: A rare cutaneous pigmentation disorder characterized by reticulate, slightly depressed, sharply demarcated brown macules without hypopigmentation, affecting the dorsa of the hands and feet and appearing in the first or second decade of life. The macules gradually darken and extend to the proximal regions of the extremities. The manifestations tend to progress until middle age, after which progression of the eruptions stops. The pigmentary augmentation is found on the flexor aspects of the wrists, neck, patella and olecranon. Other features include breaks in the epidermal ridges on the palms and fingers, palmoplantar pits, occasionally plantar keratoderma, and partial alopecia. {ECO:0000269|PubMed:23666529}. 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 RAK.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs483352916 [ dbSNP | Ensembl ]

Sequence information

Variant position:

524

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

Protein sequence length:

748

The length of the canonical sequence.

Location on the sequence:

SPSQGPCCTAQCAFKSKSEK C RDDSDCAREGICNGFTALCP

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                         SPSQGPCCTAQ-CAFKSKSEK--CRDDSDCAREGICNGFTALCP

Mouse                         SPSQGPCCTAQ-CAFKSKSEK--CRDDSDCAKEGICNGFTA

Rat                           SPSQGPCCTAQ-CAFKSKSEK--CRDDSDCAKEGICNGFTA

Pig                           SPSQGPCCTAQ-CKFKSKTEK--CRDDSDCAKEGICNGITA

Bovine                        SPSQGPCCTAH-CAFKSKTEK--CRDDSDCAKEGICNGITA

Xenopus laevis                SPSQGPCCTTD-CTFKRASEN--CREESDCAKMGTCNGNSA

Caenorhabditis elegans        SPSQGYCCNPDTCSLHGKNEEKICRQESECSNLQTCDGRNA

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	214 – 748	Disintegrin and metalloproteinase domain-containing protein 10
Topological domain	20 – 672	Extracellular
Domain	457 – 551	Disintegrin
Disulfide bond	510 – 536
Disulfide bond	524 – 543
Beta strand	523 – 525

Literature citations

Whole-exome sequencing identifies ADAM10 mutations as a cause of reticulate acropigmentation of Kitamura, a clinical entity distinct from Dowling-Degos disease.
Kono M.; Sugiura K.; Suganuma M.; Hayashi M.; Takama H.; Suzuki T.; Matsunaga K.; Tomita Y.; Akiyama M.;
Hum. Mol. Genet. 22:3524-3533(2013)
Cited for: VARIANTS RAK SER-139 AND TYR-524;

UniProtKB/Swiss-Prot O14672: Variant p.Cys524Tyr