UniProtKB/SwissProt variant VAR

Variant information

Variant position:

285

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 Cysteine (C) at position 285 (G285C, p.Gly285Cys).

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 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:

Deafness, autosomal dominant, 2A (DFNA2A) [MIM:600101]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:10025409, ECO:0000269|PubMed:10369879, ECO:0000269|PubMed:10571947, ECO:0000269|PubMed:10925378, ECO:0000269|PubMed:21242547}. 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 DFNA2A; loss of potassium selectivity of the pore.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs28937588 [ dbSNP | Ensembl ]

Sequence information

Variant position:

285

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

Protein sequence length:

695

The length of the canonical sequence.

Location on the sequence:

SDFSSYADSLWWGTITLTTI G YGDKTPHTWLGRVLAAGFAL

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                         SDFSSYADSLWWGTITLTTIGYGDKTPHTWLGRVLAAGFAL

Mouse                         SDFSSYADSLWWGTITLTTIGYGDKTPHTWLGRVLAAGFAL

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 – 695	Potassium voltage-gated channel subfamily KQT member 4
Intramembrane	271 – 292	Pore-forming; Name=Segment H5
Motif	283 – 288	Selectivity filter
Mutagenesis	266 – 266	D -> G. Resistant to inhibition by potassium channel toxin SsTX. Normal voltage activation.
Mutagenesis	268 – 268	S -> G. No effect on inhibition by potassium channel toxin SsTX.
Mutagenesis	272 – 272	D -> G. No effect on inhibition by potassium channel toxin SsTX.
Mutagenesis	288 – 288	D -> G. Resistant to inhibition by potassium channel toxin SsTX. Normal voltage activation.
Mutagenesis	290 – 290	T -> V. No effect on inhibition by potassium channel toxin SsTX.
Mutagenesis	292 – 292	H -> G. No effect on inhibition by potassium channel toxin SsTX.
Mutagenesis	295 – 295	L -> V. No effect on inhibition by potassium channel toxin SsTX.
Mutagenesis	298 – 298	V -> T. No effect on inhibition by potassium channel toxin SsTX.

Literature citations

Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families.
Coucke P.J.; Van Hauwe P.; Kelley P.M.; Kunst H.; Schatteman I.; Van Velzen D.; Meyers J.; Ensink R.J.; Verstreken M.; Declau F.; Marres H.; Kastury K.; Bhasin S.; McGuirt W.T.; Smith R.J.H.; Cremers C.W.R.J.; Van de Heyning P.; Willems P.J.; Smith S.D.; Van Camp G.;
Hum. Mol. Genet. 8:1321-1328(1999)
Cited for: VARIANTS DFNA2A SER-276; CYS-285 AND SER-321;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P56696: Variant p.Gly285Cys