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:

LP/P [Disclaimer]

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 Leucine (L) to Histidine (H) at position 869 (L869H, p.Leu869His).

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 medium size and polar (H)

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

Variant description:

In PERYTHM; activated at more negative potentials; slower inactivation kinetics than wild-type channels.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs80356475 [ 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

Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia.
Yang Y.; Wang Y.; Li S.; Xu Z.; Li H.; Ma L.; Fan J.; Bu D.; Liu B.; Fan Z.; Wu G.; Jin J.; Ding B.; Zhu X.; Shen Y.;
J. Med. Genet. 41:171-174(2004)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 840-958; VARIANTS PERYTHM THR-859 AND HIS-869;

Electrophysiological properties of mutant Nav1.7 sodium channels in a painful inherited neuropathy.
Cummins T.R.; Dib-Hajj S.D.; Waxman S.G.;
J. Neurosci. 24:8232-8236(2004)
Cited for: CHARACTERIZATION OF VARIANTS PERYTHM THR-859 AND HIS-869; FUNCTION; SUBCELLULAR LOCATION;

A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons.
Rush A.M.; Dib-Hajj S.D.; Liu S.; Cummins T.R.; Black J.A.; Waxman S.G.;
Proc. Natl. Acad. Sci. U.S.A. 103:8245-8250(2006)
Cited for: CHARACTERIZATION OF VARIANT PERYTHM HIS-869;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q15858: Variant p.Leu869His