UniProtKB/SwissProt variant VAR

Variant information

Variant position:

216

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 Phenylalanine (F) to Serine (S) at position 216 (F216S, p.Phe216Ser).

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 aromatic (F) to small size and polar (S)

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

Variant description:

In PERYTHM; hyperpolarizes the voltage dependence of activation by 11 mV, accelerates activation, slows deactivation and enhances the response to slow, small depolarizations.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs80356469 [ dbSNP | Ensembl ]

Sequence information

Variant position:

216

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:

IVFAYLTEFVNLGNVSALRT F RVLRALKTISVIPGLKTIVG

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                         IVFAYLTEFVNLGNVSALRTFRVLRALKTISVIPGLKTIVG

Mouse                         IVFAYLTEFVNLGNVSALRTFRVLRALKTISVIPGLKTIVG

Rat                           IVFAYLTEFVNLGNVSALRTFRVLRALKTISVIPGLKTIVG

Rabbit                        IVFAYLTEFVNLGNVSALRTFRVLRALKTISVIPGLKTIVG

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	212 – 228	Helical; Name=S4 of repeat I
Repeat	112 – 410	I
Glycosylation	209 – 209	N-linked (GlcNAc...) asparagine
Alternative sequence	200 – 229	YLTEFVNLGNVSALRTFRVLRALKTISVIP -> YVTEFVDLGNVSALRTFRVLRALKTISVIP. In isoform 2 and isoform 4.
Helix	215 – 218

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;

Inherited erythermalgia: limb pain from an S4 charge-neutral Na channelopathy.
Choi J.S.; Dib-Hajj S.D.; Waxman S.G.;
Neurology 67:1563-1567(2006)
Cited for: CHARACTERIZATION OF VARIANT PERYTHM SER-216; FUNCTION; SUBCELLULAR LOCATION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q15858: Variant p.Phe216Ser