UniProtKB/Swiss-Prot Q9Y698: Variant p.Val143Leu

Voltage-dependent calcium channel gamma-2 subunit
Gene: CACNG2
Chromosomal location: 22q13.1
Variant information

Variant position:  143
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 Valine (V) to Leucine (L) at position 143 (V143L, p.Val143Leu).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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:  Mental retardation, autosomal dominant 10 (MRD10) [MIM:614256]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:21376300}. 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 MRD10; significantly reduced ability to bind GRIA1 or GRIA2 AMPARs; cell surface expression of GRIA1 is reduced in transfected hippocampal neurons and HEK293 cells producing mutant protein compared to cells producing the wild-type.
Any additional useful information about the variant.

Sequence information

Variant position:  143
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  323
The length of the canonical sequence.

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.




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.

Chain 1 – 323 Voltage-dependent calcium channel gamma-2 subunit
Transmembrane 134 – 154 Helical

Literature citations

Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability.
Hamdan F.F.; Gauthier J.; Araki Y.; Lin D.T.; Yoshizawa Y.; Higashi K.; Park A.R.; Spiegelman D.; Dobrzeniecka S.; Piton A.; Tomitori H.; Daoud H.; Massicotte C.; Henrion E.; Diallo O.; Shekarabi M.; Marineau C.; Shevell M.; Maranda B.; Mitchell G.; Nadeau A.; D'Anjou G.; Vanasse M.; Srour M.; Lafreniere R.G.; Drapeau P.; Lacaille J.C.; Kim E.; Lee J.R.; Igarashi K.; Huganir R.L.; Rouleau G.A.; Michaud J.L.;
Am. J. Hum. Genet. 88:306-316(2011)

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.