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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q92736: Variant p.Ala4860Gly

Ryanodine receptor 2
Gene: RYR2
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Variant information Variant position: help 4860 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Alanine (A) to Glycine (G) at position 4860 (A4860G, p.Ala4860Gly). 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: help Change from small size and hydrophobic (A) to glycine (G) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 0 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
Variant description: help In VACRDS; decreased function in release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; changed ryanodine-sensitive calcium-release channel activity; diminishes the response to activation by luminal Ca(2+) but has little effect on the sensitivity of the channel to activation by cytosolic Ca(2+); shows caffeine-induced Ca(2+) release but exhibits no store-overload-induced Ca(2+) release (SOICR); HL1 cardiac cells transfected with the G-4860 mutant displayed attenuated SOICR activity compared to cells transfected with wild-type RYR2. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 4860 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 4967 The length of the canonical sequence.
Location on the sequence: help EIYRIIFDITFFFFVIVILL A IIQGLIIDAFGELRDQQEQV 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         EIYRIIFDITFFFFVIVILLAIIQGLIIDAFGELRDQQEQV

Mouse                         EIYRIIFDITFFFFVIVILLAIIQGLIIDAFGELRDQQEQV

Rat                           EIYRIIFDITFFFFVIVILLAIIQGLIIDAFGELRDQQEQV

Rabbit                        EIYRIIFDITFFFFVIVILLAIIQGLIIDAFGELRDQQEQV
Sequence annotation in neighborhood: help 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 – 4967 Ryanodine receptor 2
Transmembrane 4850 – 4870 Helical
Mutagenesis 4855 – 4855 I -> M. Decreased function in release of sequestered calcium ion into cytosol by sarcoplasmic reticulum. Changed ryanodine-sensitive calcium-release channel activity. Mutant channels are less respositive to activation by caffeine and store calcium overload. Affects channel sensitivity to cytosolic and luminal calcium activation.
Mutagenesis 4879 – 4879 Q -> H. Decreased function in release of sequestered calcium ion into cytosol by sarcoplasmic reticulum. Changed ryanodine-sensitive calcium-release channel activity. Mutant channels are less respositive to activation by caffeine and store calcium overload. Affects channel sensitivity to cytosolic and luminal calcium activation.



Literature citations
Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia.
Priori S.G.; Napolitano C.; Memmi M.; Colombi B.; Drago F.; Gasparini M.; DeSimone L.; Coltorti F.; Bloise R.; Keegan R.; Cruz Filho F.E.S.; Vignati G.; Benatar A.; DeLogu A.;
Circulation 106:69-74(2002)
Cited for: VARIANTS CPVT1 LEU-2246; ASP-2311; SER-2474; PHE-3778; SER-3946; SER-3946; LYS-4104; CYS-4497; ILE-4771; MET-4867; ASP-4895 AND LYS-4950; VARIANT VACRDS GLY-4860; Loss of luminal Ca(2+) activation in the cardiac ryanodine receptor is associated with ventricular fibrillation and sudden death.
Jiang D.; Chen W.; Wang R.; Zhang L.; Chen S.R.W.;
Proc. Natl. Acad. Sci. U.S.A. 104:18309-18314(2007)
Cited for: CHARACTERIZATION OF VARIANT VACRDS GLY-4860; FUNCTION; TRANSPORTER ACTIVITY; Cardiac ryanodine receptor calcium release deficiency syndrome.
Sun B.; Yao J.; Ni M.; Wei J.; Zhong X.; Guo W.; Zhang L.; Wang R.; Belke D.; Chen Y.X.; Lieve K.V.V.; Broendberg A.K.; Roston T.M.; Blankoff I.; Kammeraad J.A.; von Alvensleben J.C.; Lazarte J.; Vallmitjana A.; Bohne L.J.; Rose R.A.; Benitez R.; Hove-Madsen L.; Napolitano C.; Hegele R.A.; Fill M.; Sanatani S.; Wilde A.A.M.; Roberts J.D.; Priori S.G.; Jensen H.K.; Chen S.R.W.;
Sci. Transl. Med. 13:0-0(2021)
Cited for: VARIANTS VACRDS LEU-3774; ILE-4196; ALA-4646; GLY-4860 AND PHE-4938; INVOLVEMENT IN VACRDS; CHARACTERIZATION OF VARIANTS VACRDS LEU-3774; ILE-4196; ALA-4646; GLY-4860 AND PHE-4938; MUTAGENESIS OF ILE-3995; ASP-4112; ILE-4855 AND GLN-4879; FUNCTION; TRANSPORTER ACTIVITY;
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.