UniProtKB/Swiss-Prot P41180: Variant p.Ala986Ser

Extracellular calcium-sensing receptor
Gene: CASR
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Variant information Variant position:

986 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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 Alanine (A) to Serine (S) at position 986 (A986S, p.Ala986Ser). 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 small size and hydrophobic (A) to small size and polar (S) 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:

Correlated with high serum level of calcium; is also a potential predisposing factor in disorders of bone and mineral metabolism. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1801725 [ dbSNP | Ensembl ]

Sequence information Variant position:

986 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1078 The length of the canonical sequence.
Location on the sequence:

VIFGSGTVTFSLSFDEPQKN A MAHRNSTHQNSLEAQKSSDT 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                         VIFGSGTVTFSLSFDEPQKNAMAHRNSTHQNSLEAQKSSDT

Mouse                         VIFGSGTVTFSLSFDEPQKNAMAHRNSMRQNSLEAQKSNDT

Rat                           VIFGSGTVTFSLSFDEPQKNAMAHRNSMRQNSLEAQRSNDT

Pig                           VIFGSGTVTFSLSFDEPQKSATAHRNSTHQNSLEAQKNNDA

Bovine                        VIFGSGTVTFSLSFDEPQKTAVAHRNSTHQTSLEAQKNNDA

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.

Type	Positions	Description
Chain	20 – 1078	Extracellular calcium-sensing receptor
Topological domain	863 – 1078	Cytoplasmic
Region	986 – 1006	Disordered

Literature citations
Submission
SeattleSNPs variation discovery resource;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS SER-986; GLY-990 AND GLN-1011; Clustered inactivating mutations and benign polymorphisms of the calcium receptor gene in familial benign hypocalciuric hypercalcemia suggest receptor functional domains.
Heath H. III; Odelberg S.; Jackson C.E.; Teh B.T.; Hayward N.; Larsson C.; Buist N.R.; Krapcho K.J.; Hung B.C.; Capuano I.V.; Garrett J.E.; Leppert M.F.;
J. Clin. Endocrinol. Metab. 81:1312-1317(1996)
Cited for: VARIANTS HHC1 PRO-53; LEU-55; GLN-185; GLY-215; TYR-657 AND ARG-748; VARIANTS SER-986; GLY-990 AND GLN-1011; CHARACTERIZATION OF VARIANTS HHC1 PRO-53; LEU-55 AND GLY-215; A986S polymorphism of the calcium-sensing receptor and circulating calcium concentrations.
Cole D.E.C.; Peltekova V.D.; Rubin L.A.; Hawker G.A.; Vieth R.; Liew C.C.; Hwang D.M.; Evrovski J.; Hendy G.N.;
Lancet 353:112-115(1999)
Cited for: VARIANT SER-986; ASSOCIATION WITH SERUM LEVEL OF CALCIUM; Association between total serum calcium and the A986S polymorphism of the calcium-sensing receptor gene.
Cole D.E.C.; Vieth R.; Trang H.M.; Wong B.Y.-L.; Hendy G.N.; Rubin L.A.;
Mol. Genet. Metab. 72:168-174(2001)
Cited for: VARIANT SER-986; ASSOCIATION WITH SERUM LEVEL OF CALCIUM; PREDISPOSING FACTOR IN DISORDERS OF BONE AND MINERAL METABOLISM; Blood ionized calcium is associated with clustered polymorphisms in the carboxyl-terminal tail of the calcium-sensing receptor.
Scillitani A.; Guarnieri V.; De Geronimo S.; Muscarella L.A.; Battista C.; D'Agruma L.; Bertoldo F.; Florio C.; Minisola S.; Hendy G.N.; Cole D.E.C.;
J. Clin. Endocrinol. Metab. 89:5634-5638(2004)
Cited for: VARIANTS SER-986; GLY-990 AND GLN-1011; ASSOCIATION WITH SERUM LEVEL OF CALCIUM; Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications.
Warner J.; Epstein M.; Sweet A.; Singh D.; Burgess J.; Stranks S.; Hill P.; Perry-Keene D.; Learoyd D.; Robinson B.; Birdsey P.; Mackenzie E.; Teh B.T.; Prins J.B.; Cardinal J.;
J. Med. Genet. 41:155-160(2004)
Cited for: VARIANTS NSHPT ILE-100; LYS-336 DEL; PRO-650 AND MET-689; VARIANTS SER-986; GLY-990 AND GLN-1011; Identification of a novel inactivating R465Q mutation of the calcium-sensing receptor.
Leech C.; Lohse P.; Stanojevic V.; Lechner A.; Goeke B.; Spitzweg C.;
Biochem. Biophys. Res. Commun. 342:996-1002(2006)
Cited for: VARIANT HHC1 GLN-465; CHARACTERIZATION OF VARIANT HHC1 GLN-465; VARIANT SER-986; Neonatal severe hyperparathyroidism associated with a novel de novo heterozygous R551K inactivating mutation and a heterozygous A986S polymorphism of the calcium-sensing receptor gene.
Toke J.; Czirjak G.; Patocs A.; Enyedi B.; Gergics P.; Csakvary V.; Enyedi P.; Toth M.;
Clin. Endocrinol. (Oxf.) 67:385-392(2007)
Cited for: VARIANT NSHPT LYS-551; VARIANT SER-986; FUNCTION; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANT NSHPT LYS-551; Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population.
Nissen P.H.; Christensen S.E.; Heickendorff L.; Brixen K.; Mosekilde L.;
J. Clin. Endocrinol. Metab. 92:4373-4379(2007)
Cited for: VARIANTS HHC1 ARG-21; ASN-171; GLN-221; THR-225; PHE-271; ARG-397; ARG-509; ARG-553; VAL-555; TYR-562; PHE-582; TYR-582; ASP-623; ARG-670; PHE-728; ARG-742 AND TRP-886; VARIANTS LYS-250; SER-986; GLY-990 AND GLN-1011; An idiopathic epilepsy syndrome linked to 3q13.3-q21 and missense mutations in the extracellular calcium sensing receptor gene.
Kapoor A.; Satishchandra P.; Ratnapriya R.; Reddy R.; Kadandale J.; Shankar S.K.; Anand A.;
Ann. Neurol. 64:158-167(2008)
Cited for: VARIANTS EIG8 ALA-354; VAL-686; GLN-898; VAL-988 AND GLY-988; VARIANTS SER-986 AND GLY-990; TISSUE SPECIFICITY; A novel loss-of-function mutation, Gln459Arg, of the calcium-sensing receptor gene associated with apparent autosomal recessive inheritance of familial hypocalciuric hypercalcemia.
Lietman S.A.; Tenenbaum-Rakover Y.; Jap T.S.; Yi-Chi W.; De-Ming Y.; Ding C.; Kussiny N.; Levine M.A.;
J. Clin. Endocrinol. Metab. 94:4372-4379(2009)
Cited for: VARIANT HHC1 ARG-459; VARIANTS SER-986 AND GLN-1011; FUNCTION; CHARACTERIZATION OF VARIANT HHC1 ARG-459;

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.