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UniProtKB/Swiss-Prot Q7Z333: Variant p.Ile331Lys

Probable helicase senataxin
Gene: SETX
Chromosomal location: 9q34.3
Variant information

Variant position:  331
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 Lysine (K) at position 331 (I331K, p.Ile331Lys).
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 large size and basic (K)
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

Involvement in disease:  Spinocerebellar ataxia, autosomal recessive, 1 (SCAR1) [MIM:606002]: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR1 is an autosomal recessive form associated with peripheral neuropathy and elevated serum alpha-fetoprotein, immunoglobulins and, less commonly, creatine kinase levels. Some SCAR1 patients manifest oculomotor apraxia. {ECO:0000269|PubMed:14770181, ECO:0000269|PubMed:16644229, ECO:0000269|PubMed:16717225, ECO:0000269|PubMed:17096168, ECO:0000269|PubMed:23566282, ECO:0000269|PubMed:23786967, ECO:0000269|PubMed:23941260, ECO:0000269|PubMed:24105744}. 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 SCAR1.
Any additional useful information about the variant.



Sequence information

Variant position:  331
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  2677
The length of the canonical sequence.

Location on the sequence:   PIVAFQTIINNASYNREIRH  I RNSSVRTKLEPESYLDDMVT
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                         PIVAFQTIINNASYNREIRHIRNSSVRTKLEPESYLDDMVT

Mouse                         PIEAFQTIINNESYNREIQNIRNSSIRTKLEPEPHFDDMVT

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 – 2677 Probable helicase senataxin
Cross 339 – 339 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)


Literature citations

SETX mutations are a frequent genetic cause of juvenile and adult onset cerebellar ataxia with neuropathy and elevated serum alpha-fetoprotein.
Nanetti L.; Cavalieri S.; Pensato V.; Erbetta A.; Pareyson D.; Panzeri M.; Zorzi G.; Antozzi C.; Moroni I.; Gellera C.; Brusco A.; Mariotti C.;
Orphanet J. Rare Dis. 8:123-123(2013)
Cited for: VARIANTS SCAR1 LYS-331; LEU-496 AND THR-2229; VARIANT ARG-992;

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.