Home  |  Contact

UniProtKB/Swiss-Prot O14958: Variant p.Asp307His

Calsequestrin-2
Gene: CASQ2
Chromosomal location: 1p11-p13.3
Variant information

Variant position:  307
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 Aspartate (D) to Histidine (H) at position 307 (D307H, p.Asp307His).
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 acidic (D) to medium size and polar (H)
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:  Ventricular tachycardia, catecholaminergic polymorphic, 2 (CPVT2) [MIM:611938]: An arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death. Patients present with recurrent syncope, seizures, or sudden death after physical activity or emotional stress. CPVT2 inheritance is autosomal recessive. {ECO:0000269|PubMed:11704930, ECO:0000269|PubMed:15485681, ECO:0000269|PubMed:16908766, ECO:0000269|PubMed:17881003, ECO:0000269|PubMed:18399795, ECO:0000269|PubMed:27157848}. 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 CPVT2; reduces calcium-binding; impairs calcium-dependent oligomerization; causes 50% decrease in calcium-dependent binding to TRDN; causes 50% decrease in calcium-dependent binding to ASPH.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  307
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  399
The length of the canonical sequence.

Location on the sequence:   ILKQVARDNTDNPDLSILWI  D PDDFPLLVAYWEKTFKIDLF
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                         ILKQVARDNTDNPDLSILWIDPDDFPLLVAYWEKTFKIDLF

                              ILKQVARDNTDNPDLSIVWIDPDDFPLLVAYWEKTFKIDLF

Mouse                         ILKQVARDNTDNPDLSILWIDPDDFPLLVAYWEKTFKIDLF

Rat                           ILKQVARDNTDNPDLSILWIDPDDFPLLVAYWEKTFKIDLF

Rabbit                        ILKQVARDNTDNPDLSIVWIDPDDFPLLVAYWEKTFKIDLF

Chicken                       ILKQVARDNTDNPDLSIVWIDPDDFPLLITYWEKTFKIDLF

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 20 – 399 Calsequestrin-2


Literature citations

Characterization of human cardiac calsequestrin and its deleterious mutants.
Kim E.; Youn B.; Kemper L.; Campbell C.; Milting H.; Varsanyi M.; Kang C.;
J. Mol. Biol. 373:1047-1057(2007)
Cited for: X-RAY CRYSTALLOGRAPHY (3.8 ANGSTROMS) OF 22-399; SUBUNIT; FUNCTION; CHARACTERIZATION OF VARIANTS CPVT2 GLN-33; HIS-167 AND HIS-307; CHARACTERIZATION OF VARIANTS ALA-66 AND MET-76;

A missense mutation in a highly conserved region of CASQ2 is associated with autosomal recessive catecholamine-induced polymorphic ventricular tachycardia in Bedouin families from Israel.
Lahat H.; Pras E.; Olender T.; Avidan N.; Ben-Asher E.; Man O.; Levy-Nissenbaum E.; Khoury A.; Lorber A.; Goldman B.; Lancet D.; Eldar M.;
Am. J. Hum. Genet. 69:1378-1384(2001)
Cited for: VARIANT CPVT2 HIS-307;

Calsequestrin mutant D307H exhibits depressed binding to its protein targets and a depressed response to calcium.
Houle T.D.; Ram M.L.; Cala S.E.;
Cardiovasc. Res. 64:227-233(2004)
Cited for: CHARACTERIZATION OF VARIANT CPVT2 HIS-307; INTERACTION WITH ASPH AND TRDN; GLYCOSYLATION; IDENTIFICATION BY MASS SPECTROMETRY;

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.