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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q13936: Variant p.Glu1135Lys

Voltage-dependent L-type calcium channel subunit alpha-1C
Gene: CACNA1C
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Variant information Variant position: help 1135 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 Glutamate (E) to Lysine (K) at position 1135 (E1135K, p.Glu1135Lys). 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 medium size and acidic (E) to large size and basic (K) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 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
Variant description: help In TS and BRGDA3; likely pathogenic; affects voltage-gated calcium channel activity resulting in loss of selectivity for Ca(2+) and other divalent cations over monovalent cations; mutant channels show a marked increase in sodium-mediated inward currents and potassium-mediated outward currents. Any additional useful information about the variant.


Sequence information Variant position: help 1135 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 2221 The length of the canonical sequence.
Location on the sequence: help KFDFDNVLAAMMALFTVSTF E GWPELLYRSIDSHTEDKGPI 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                         KFDFDNVLAAMMALFTVSTFEGWPELLYRSIDSHTEDKGPI

Mouse                         KFDFDNVLAAMMALFTVSTFEGWPELLYRSIDSHTEDKGPI

Rat                           KFDFDNVLAAMMALFTVSTFEGWPELLYRSIDSHTEDKGPI

Rabbit                        KFDFDNVLAAMMALFTVSTFEGWPELLYRSIDSHTEDKGPI
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 – 2221 Voltage-dependent L-type calcium channel subunit alpha-1C
Intramembrane 1122 – 1142 Pore-forming
Repeat 887 – 1189 III
Region 1109 – 1198 Dihydropyridine binding
Motif 1133 – 1136 Selectivity filter of repeat III
Binding site 1135 – 1135
Site 1135 – 1135 Calcium ion selectivity and permeability
Mutagenesis 1135 – 1135 E -> Q. Decreased selectivity for divalent over monovalent cations.
Beta strand 1133 – 1136



Literature citations
Molecular localization of ion selectivity sites within the pore of a human L-type cardiac calcium channel.
Tang S.; Mikala G.; Bahinski A.; Yatani A.; Varadi G.; Schwartz A.;
J. Biol. Chem. 268:13026-13029(1993)
Cited for: FUNCTION; SUBCELLULAR LOCATION; ACTIVITY REGULATION; MUTAGENESIS OF GLU-363; GLU-1135 AND GLU-1464; CALCIUM-BINDING; SITE; TRANSPORTER ACTIVITY; CHARACTERIZATION OF VARIANT TS LYS-1135; Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death.
Burashnikov E.; Pfeiffer R.; Barajas-Martinez H.; Delpon E.; Hu D.; Desai M.; Borggrefe M.; Haeissaguerre M.; Kanter R.; Pollevick G.D.; Guerchicoff A.; Laino R.; Marieb M.; Nademanee K.; Nam G.B.; Robles R.; Schimpf R.; Stapleton D.D.; Viskin S.; Winters S.; Wolpert C.; Zimmern S.; Veltmann C.; Antzelevitch C.;
Heart Rhythm 7:1872-1882(2010)
Cited for: VARIANTS BRGDA3 VAL-39; ARG-490; LYS-1135; GLU-GLU-THR-SER-GLN-1916 INS; CYS-1920; GLN-1963; ILE-2097 AND ASN-2213; CHARACTERIZATION OF VARIANT BRGDA3 ILE-2097; VARIANTS ARG-37; SER-817; GLU-850 DEL; GLY-1765; MET-1835 AND GLN-2056; A pore-localizing CACNA1C-E1115K missense mutation, identified in a patient with idiopathic QT prolongation, bradycardia, and autism spectrum disorder, converts the L-type calcium channel into a hybrid nonselective monovalent cation channel.
Ye D.; Tester D.J.; Zhou W.; Papagiannis J.; Ackerman M.J.;
Heart Rhythm 16:270-278(2019)
Cited for: VARIANT TS LYS-1135; CHARACTERIZATION OF VARIANT TS LYS-1135; 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.