UniProtKB/SwissProt variant VAR

Variant information

Variant position:

907

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 Arginine (R) to Glutamine (Q) at position 907 (R907Q, p.Arg907Gln).

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 basic (R) to medium size and polar (Q)

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:

Indifference to pain, congenital, autosomal recessive (CIP) [MIM:243000]: A disorder characterized by congenital inability to perceive any form of pain, in any part of the body. All other sensory modalities are preserved and the peripheral and central nervous systems are apparently intact. Patients perceive the sensations of touch, warm and cold temperature, proprioception, tickle and pressure, but not painful stimuli. There is no evidence of a motor or sensory neuropathy, either axonal or demyelinating. {ECO:0000269|PubMed:20635406}. 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 CIP; significant reduction in membrane localization of the mutant protein compared to the wild-type; complete loss of function of the sodium channel.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs1024152367 [ dbSNP | Ensembl ]

Sequence information

Variant position:

907

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:

LFGKSYKECVCKINDDCTLP R WHMNDFFHSFLIVFRVLCGE

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                         LFGKSYKECVCKINDDCTLPRWHMNDFFHSFLIVFRVLCGE

Mouse                         LFGKSYKECVCKINENCKLPRWHMNDFFHSFLIVFRVLCGE

Rat                           LFGKSYKECVCKINVDCKLPRWHMNDFFHSFLIVFRVLCGE

Rabbit                        LFGKSYKECVCKINDDCSLPRWHMNDFFHSFLIVFRVLCGE

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	884 – 912	Extracellular
Repeat	726 – 989	II
Disulfide bond	895 – 895	Interchain; with SCN2B or SCN4B
Disulfide bond	895 – 895	Interchain; with the conotoxin GVIIJ (when the channel is not linked to SCN2B or SCN4B; the bond to SCN2B or SCN4B protects the channel from the inhibition by toxin)

Literature citations

Congenital insensitivity to pain: novel SCN9A missense and in-frame deletion mutations.
Cox J.J.; Sheynin J.; Shorer Z.; Reimann F.; Nicholas A.K.; Zubovic L.; Baralle M.; Wraige E.; Manor E.; Levy J.; Woods C.G.; Parvari R.;
Hum. Mutat. 31:E1670-E1686(2010)
Cited for: VARIANTS CIP GLN-907 AND 1381-ARG--LEU-1385 DEL; CHARACTERIZATION OF VARIANTS CIP GLN-907 AND 1381-ARG--LEU-1385 DEL;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q15858: Variant p.Arg907Gln