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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P41180: Variant p.Arg227Leu

Extracellular calcium-sensing receptor
Gene: CASR
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Variant information Variant position: help 227 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 Arginine (R) to Leucine (L) at position 227 (R227L, p.Arg227Leu). 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 large size and basic (R) to medium size and hydrophobic (L) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 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 NSHPT; decreased G-protein coupled receptor signaling pathway; does not affect cell membrane localization. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 227 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 NWVGTIAADDDYGRPGIEKF R EEAEERDICIDFSELISQYS 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                         NWVGTIAADDDYGRPGIEKFREEAEERDICIDFSELISQYS

Mouse                         NWVGTIAADDDYGRPGIEKFREEAEERDICIDFSELISQYS

Rat                           NWVGTIAADDDYGRPGIEKFREEAEERDICIDFSELISQYS

Pig                           NWVGTIAADDDYGRPGIEKFREEAEERDICIDFSELISQYS

Bovine                        NWVGTIAADDDYGRPGIEKFREEAEERDICIDFSELISQYS
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 189 – 324 Ligand-binding 2 (LB2)
Binding site 231 – 231
Binding site 234 – 234
Mutagenesis 218 – 218 Y -> S. Abolishes G-protein coupled receptor activity.
Helix 219 – 232



Literature citations
Structural mechanism of ligand activation in human calcium-sensing receptor.
Geng Y.; Mosyak L.; Kurinov I.; Zuo H.; Sturchler E.; Cheng T.C.; Subramanyam P.; Brown A.P.; Brennan S.C.; Mun H.C.; Bush M.; Chen Y.; Nguyen T.X.; Cao B.; Chang D.D.; Quick M.; Conigrave A.D.; Colecraft H.M.; McDonald P.; Fan Q.R.;
Elife 5:0-0(2016)
Cited for: X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 20-607 IN COMPLEX WITH CALCIUM; PHOSPHATE AND SULFATE ANIONS AND TRYPTOPHAN; FUNCTION; ACTIVITY REGULATION; DOMAIN; DISULFIDE BONDS; GLYCOSYLATION AT ASN-261; ASN-287; ASN-446; ASN-468; ASN-488; ASN-541 AND ASN-594; MUTAGENESIS OF ARG-69; ASN-102; THR-145; SER-147; SER-170; TYR-218; SER-417 AND TRP-458; CHARACTERIZATION OF VARIANTS NSHPT ILE-100; LEU-227 AND LYS-551; CHARACTERIZATION OF VARIANTS HHC1 HIS-66; MET-81; PRO-159; GLY-172; GLY-215; LYS-297 AND GLU-557; Calcium-sensing receptor mutations in familial benign hypercalcemia and neonatal hyperparathyroidism.
Pearce S.H.S.; Trump D.; Wooding C.; Besser G.M.; Chew S.L.; Grant D.B.; Heath D.A.; Hughes I.A.; Paterson C.R.; Whyte M.P.; Thakker R.V.;
J. Clin. Invest. 96:2683-2692(1995)
Cited for: VARIANTS NSHPT LEU-227 AND TYR-582; Functional characterization of calcium-sensing receptor mutations expressed in human embryonic kidney cells.
Pearce S.H.S.; Bai M.; Quinn S.J.; Kifor O.; Brown E.M.; Thakker R.V.;
J. Clin. Invest. 98:1860-1866(1996)
Cited for: VARIANTS HHC1 LEU-55; ASP-178; SER-221 AND ILE-817; VARIANTS HYPOC1 LEU-128; MET-151 AND LYS-191; VARIANT NSHPT LEU-227; CHARACTERIZATION OF VARIANTS HHC1 LEU-55; ASP-178; SER-221 AND ILE-817; FUNCTION; CHARACTERIZATION OF VARIANTS HYPOC1 LEU-128; MET-151 AND LYS-191; CHARACTERIZATION OF VARIANT NSHPT LEU-227; Functional characterization of calcium-sensing receptor codon 227 mutations presenting as either familial (benign) hypocalciuric hypercalcemia or neonatal hyperparathyroidism.
Wystrychowski A.; Pidasheva S.; Canaff L.; Chudek J.; Kokot F.; Wiecek A.; Hendy G.N.;
J. Clin. Endocrinol. Metab. 90:864-870(2005)
Cited for: VARIANT HHC1 GLN-227; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANT NSHPT LEU-227; CHARACTERIZATION OF VARIANT HHC1 GLN-227;
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.