UniProtKB/SwissProt variant VAR

Variant information

Variant position:

869

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 Leucine (L) to Phenylalanine (F) at position 869 (L869F, p.Leu869Phe).

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 hydrophobic (L) to large size and aromatic (F)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

0

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:

Primary erythermalgia (PERYTHM) [MIM:133020]: Autosomal dominant disease characterized by recurrent episodes of severe pain associated with redness and warmth in the feet or hands. {ECO:0000269|PubMed:14985375, ECO:0000269|PubMed:15385606, ECO:0000269|PubMed:15955112, ECO:0000269|PubMed:15958509, ECO:0000269|PubMed:16216943, ECO:0000269|PubMed:16392115, ECO:0000269|PubMed:16702558, ECO:0000269|PubMed:16988069, ECO:0000269|PubMed:18945915, ECO:0000269|PubMed:19369487, ECO:0000269|PubMed:24311784}. 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 PERYTHM; causes a hyperpolarizing shift in channel activation, a depolarizing shift of inactivation and an 18-fold increase in deactivation time compared to wild-type; the mean ramp current amplitude in response to slow depolarization is higher in the mutant channels.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs80356476 [ dbSNP | Ensembl ]

Sequence information

Variant position:

869

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

Protein sequence length:

1988

The length of the canonical sequence.

Location on the sequence:

WPTLNMLIKIIGNSVGALGN L TLVLAIIVFIFAVVGMQLFG

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                         WPTLNMLIKIIGNSVGALGNLTLVLAIIVFIFAVVGMQLFG

Mouse                         WPTLNMLIKIIGNSVGALGNLTLVLAIIVFIFAVVGMQLFG

Rat                           WPTLNMLIKIIGNSVGALGNLTLVLAIIVFIFAVVGMQLFG

Rabbit                        WPTLNMLIKIIGNSVGPLGNLTLVLAIIVFIFAVVGMQLFG

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 – 1988	Sodium channel protein type 9 subunit alpha
Transmembrane	865 – 883	Helical; Name=S5 of repeat II
Repeat	726 – 989	II
Helix	867 – 895

Literature citations

SCN9A mutations define primary erythermalgia as a neuropathic disorder of voltage gated sodium channels.
Drenth J.P.; te Morsche R.H.; Guillet G.; Taieb A.; Kirby R.L.; Jansen J.B.;
J. Invest. Dermatol. 124:1333-1338(2005)
Cited for: VARIANTS PERYTHM SER-216; LYS-395; THR-859 AND PHE-869; VARIANT ARG-1161;

Sporadic onset of erythermalgia: a gain-of-function mutation in Nav1.7.
Han C.; Rush A.M.; Dib-Hajj S.D.; Li S.; Xu Z.; Wang Y.; Tyrrell L.; Wang X.; Yang Y.; Waxman S.G.;
Ann. Neurol. 59:553-558(2006)
Cited for: VARIANT PERYTHM PHE-869; CHARACTERIZATION OF VARIANT PERYTHM PHE-869;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q15858: Variant p.Leu869Phe