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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P41180: Variant p.Glu127Ala

Extracellular calcium-sensing receptor
Gene: CASR
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Variant information Variant position: help 127 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 Alanine (A) at position 127 (E127A, p.Glu127Ala). 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 small size and hydrophobic (A) 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 HYPOC1; increased G-protein coupled receptor signaling pathway. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 127 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1078 The length of the canonical sequence.
Location on the sequence: help ALEATLSFVAQNKIDSLNLD E FCNCSEHIPSTIAVVGATGS 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                         ALEATLSFVAQNKIDSLNLDEFCNCSEHIPSTIAVVGATGS

Mouse                         ALEATLSFVAQNKIDSLNLDEFCNCSEHIPSTIAVVGATGS

Rat                           ALEATLSFVAQNKIDSLNLDEFCNCSEHIPSTIAVVGATGS

Pig                           ALEATLSFVAQNKIDSLNLDEFCNCSEHIPSTIAVVGATGS

Bovine                        ALEATLSFVAQNKIDSLNLDEFCNCSEHIPSTIAVVGATGS
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 20 – 1078 Extracellular calcium-sensing receptor
Topological domain 20 – 612 Extracellular
Region 22 – 188 Ligand-binding 1 (LB1)
Binding site 145 – 145
Binding site 147 – 147
Glycosylation 130 – 130 N-linked (GlcNAc...) asparagine
Disulfide bond 129 – 129 Interchain
Disulfide bond 131 – 131 Interchain
Mutagenesis 145 – 145 T -> A. Abolishes G-protein coupled receptor activity.
Mutagenesis 147 – 147 S -> A. Nearly abolished G-protein coupled receptor activity.
Helix 125 – 128



Literature citations
Autosomal dominant hypocalcaemia caused by a Ca(2+)-sensing receptor gene mutation.
Pollak M.R.; Brown E.M.; Estep H.L.; McLaine P.N.; Kifor O.; Park J.; Hebert S.C.; Seidman C.E.; Seidman J.G.;
Nat. Genet. 8:303-307(1994)
Cited for: VARIANT HYPOC1 ALA-127; Expression and characterization of inactivating and activating mutations in the human Ca2+o-sensing receptor.
Bai M.; Quinn S.; Trivedi S.; Kifor O.; Pearce S.H.S.; Pollak M.R.; Krapcho K.; Hebert S.C.; Brown E.M.;
J. Biol. Chem. 271:19537-19545(1996)
Cited for: VARIANTS HHC1 MET-62; CYS-66; MET-138; GLU-143; GLN-185; LYS-297 AND TRP-795; VARIANT HYPOC1 ALA-127; FUNCTION; SUBCELLULAR LOCATION; GLYCOSYLATION; CHARACTERIZATION OF VARIANTS HHC1 MET-62; CYS-66; MET-138; GLU-143; GLN-185; LYS-297 AND TRP-795; CHARACTERIZATION OF VARIANT HYPOC1 ALA-127;
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.