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UniProtKB/Swiss-Prot P0DP23: Variant p.Asp130Gly

Calmodulin-1
Gene: CALM1
Variant information

Variant position:  130
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  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:  From Aspartate (D) to Glycine (G) at position 130 (D130G, p.Asp130Gly).
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 glycine (G)
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

Variant description:  In LQT14; reduction in calcium affinity; not changed protein abundance; not changed structure; significantly decreased thermal stability in presence of calcium; significantly decreased RYR2 interaction; increased ryanodine-sensitive calcium-release channel activity; decreased of KCNN2 calcium-activated potassium channel activity; not changed KCNN2 expression; not changed KCNN2 location at membrane.
Any additional useful information about the variant.

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



Sequence information

Variant position:  130
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  149
The length of the canonical sequence.

Location on the sequence:   MTNLGEKLTDEEVDEMIREA  D IDGDGQVNYEEFVQMMTAK
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                         MTNLGEKLTDEEVDEMIREADIDGDGQVNYEEFVQMMTAK

Mouse                         MTNLGEKLTDEEVDEMIREADIDGDGQVNYEEFVQMMTAK

Rat                           MTNLGEKLTDEEVDEMIREADIDGDGQVNYEEFVQMMTAK

Xenopus laevis                MTNLGEKLTDEEVDEMIREADIDGDGQVNYEEFVQMMTAK

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 2 – 149 Calmodulin-1
Domain 117 – 149 EF-hand 4
Region 77 – 149 Necessary and sufficient for interaction with PCP4
Metal binding 130 – 130 Calcium 4
Metal binding 132 – 132 Calcium 4
Metal binding 134 – 134 Calcium 4
Metal binding 136 – 136 Calcium 4
Metal binding 141 – 141 Calcium 4
Modified residue 111 – 111 Phosphothreonine
Modified residue 116 – 116 N6,N6,N6-trimethyllysine; alternate
Modified residue 116 – 116 N6-methyllysine; alternate
Modified residue 139 – 139 Phosphotyrosine
Turn 130 – 132


Literature citations

Calmodulin mutations associated with recurrent cardiac arrest in infants.
Crotti L.; Johnson C.N.; Graf E.; De Ferrari G.M.; Cuneo B.F.; Ovadia M.; Papagiannis J.; Feldkamp M.D.; Rathi S.G.; Kunic J.D.; Pedrazzini M.; Wieland T.; Lichtner P.; Beckmann B.M.; Clark T.; Shaffer C.; Benson D.W.; Kaab S.; Meitinger T.; Strom T.M.; Chazin W.J.; Schwartz P.J.; George A.L. Jr.;
Circulation 127:1009-1017(2013)
Cited for: INVOLVEMENT IN LQT14; VARIANTS LQT14 GLY-130 AND LEU-142; CHARACTERIZATION OF VARIANTS LQT14 GLY-130 AND LEU-142;

Distinctive malfunctions of calmodulin mutations associated with heart RyR2-mediated arrhythmic disease.
Vassilakopoulou V.; Calver B.L.; Thanassoulas A.; Beck K.; Hu H.; Buntwal L.; Smith A.; Theodoridou M.; Kashir J.; Blayney L.; Livaniou E.; Nounesis G.; Lai F.A.; Nomikos M.;
Biochim. Biophys. Acta 1850:2168-2176(2015)
Cited for: VARIANTS CPVT4 ILE-54 AND SER-98; CHARACTERIZATION OF VARIANTS CPVT4 ILE-54 AND SER-98; VARIANTS LQT14 GLY-130 AND LEU-142; CHARACTERIZATION OF VARIANTS LQT14 GLY-130 AND LEU-142; INTERACTION WITH RYR2;

Arrhythmogenic calmodulin mutations impede activation of small-conductance calcium-activated potassium current.
Yu C.C.; Ko J.S.; Ai T.; Tsai W.C.; Chen Z.; Rubart M.; Vatta M.; Everett T.H. IV; George A.L. Jr.; Chen P.S.;
Heart Rhythm 13:1716-1723(2016)
Cited for: VARIANTS CPVT4 ILE-54 AND SER-98; CHARACTERIZATION OF VARIANTS CPVT4 ILE-54 AND SER-98; VARIANTS LQT14 LEU-90 AND GLY-130; CHARACTERIZATION OF VARIANTS LQT14 LEU-90 AND GLY-130; FUNCTION;

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.