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UniProtKB/Swiss-Prot Q15858: Variant p.Ile859Thr

Sodium channel protein type 9 subunit alpha
Gene: SCN9A
Variant information

Variant position:  859
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 Isoleucine (I) to Threonine (T) at position 859 (I859T, p.Ile859Thr).
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 (I) to medium size and polar (T)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
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; sporadic; 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.



Sequence information

Variant position:  859
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:   LLRVFKLAKSWPTLNMLIKI  I GNSVGALGNLTLVLAIIVFI
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                         LLRVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAIIVFI

Mouse                         LLRVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAIIVFI

Rat                           LLRVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAIIVFI

Rabbit                        LLRVFKLAKSWPTLNMLIKIIGNSVGPLGNLTLVLAIIVFI

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.

TypePositionsDescription
Chain 1 – 1988 Sodium channel protein type 9 subunit alpha
Topological domain 849 – 864 Cytoplasmic
Repeat 726 – 989 II
Helix 850 – 863


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;

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;

Early- and late-onset inherited erythromelalgia: genotype-phenotype correlation.
Han C.; Dib-Hajj S.D.; Lin Z.; Li Y.; Eastman E.M.; Tyrrell L.; Cao X.; Yang Y.; Waxman S.G.;
Brain 132:1711-1722(2009)
Cited for: VARIANT PERYTHM ARG-10; CHARACTERIZATION OF VARIANTS PERYTHM ARG-10 AND THR-859; FUNCTION; SUBCELLULAR LOCATION;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.