UniProtKB/SwissProt variant VAR

Variant information

Variant position:

1472

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 1472 (I1472T, p.Ile1472Thr).

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:

Paroxysmal extreme pain disorder (PEPD) [MIM:167400]: Autosomal dominant paroxysmal disorder of pain and autonomic dysfunction. The distinctive features are paroxysmal episodes of burning pain in the rectal, ocular, and mandibular areas accompanied by autonomic manifestations such as skin flushing. {ECO:0000269|PubMed:17145499, ECO:0000269|PubMed:18945915, ECO:0000269|PubMed:25285947}. 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 PEPD; reduction in fast inactivation leading to persistent sodium current.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121908914 [ dbSNP | Ensembl ]

Sequence information

Variant position:

1472

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:

FIGVIIDNFNQQKKKLGGQD I FMTEEQKKYYNAMKKLGSKK

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                         FIGVIIDNFNQQKKKLGGQDIFMTEEQKKYYNAMKKLGSKK

Mouse                         FIGVIIDNFNQQKKKLGGQDIFMTEEQKKYYNAMKKLGSKK

Rat                           FIGVIIDNFNQQKKKLGGQDIFMTEEQKKYYNAMKKLGSKK

Rabbit                        FIGVIIDNFNQQKKKLGGQDIFMTEEQKKYYNAMKKLGSKK

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
Topological domain	1454 – 1516	Cytoplasmic
Repeat	1180 – 1488	III
Modified residue	1490 – 1490	Phosphoserine; by PKC
Mutagenesis	1490 – 1490	S -> A. Abolishes stimulation by agents that stimulate PKC activity.
Mutagenesis	1490 – 1490	S -> DE. Increases current amplitude.
Beta strand	1472 – 1474

Literature citations

SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes.
Fertleman C.R.; Baker M.D.; Parker K.A.; Moffatt S.; Elmslie F.V.; Abrahamsen B.; Ostman J.; Klugbauer N.; Wood J.N.; Gardiner R.M.; Rees M.;
Neuron 52:767-774(2006)
Cited for: VARIANTS PEPD CYS-1007; PHE-1309; ASP-1309; PHE-1310; THR-1472; VAL-1473; ILE-1475 AND LYS-1638; CHARACTERIZATION OF VARIANTS PEPD THR-1472; ILE-1475 AND LYS-1638; FUNCTION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q15858: Variant p.Ile1472Thr