UniProtKB/SwissProt variant VAR

Variant information

Variant position:

727

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 Leucine (L) to Glutamine (Q) at position 727 (L727Q, p.Leu727Gln).

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 hydrophobic (L) to medium size and polar (Q)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-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:

In HYPOC1; increased G-protein coupled receptor signaling pathway; does not affect cell membrane localization.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs104893718 [ dbSNP | Ensembl ]

Sequence information

Variant position:

727

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:

EAKIPTSFHRKWWGLNLQFL L VFLCTFMQIVICVIWLYTAP

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                         EAKIPTSFHRKWWGLNLQFLLVFLCTFMQIVICVIWLYTAP

Mouse                         EAKIPTSFHRKWWGLNLQFLLVFLCTFMQIVICIIWLYTAP

Rat                           EAKIPTSFHRKWWGLNLQFLLVFLCTFMQILICIIWLYTAP

Pig                           EAKIPTSFHRKWWGLNLQFLLVFLCTFMQIVICAIWLYTAP

Bovine                        EAKIPTSFHRKWWGLNLQFLLVFLCTFMQIVICAIWLNTAP

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
Transmembrane	725 – 745	Helical; Name=4
Helix	725 – 745

Literature citations

A hypocalcemic child with a novel activating mutation of the calcium-sensing receptor gene: successful treatment with recombinant human parathyroid hormone.
Mittelman S.D.; Hendy G.N.; Fefferman R.A.; Canaff L.; Mosesova I.; Cole D.E.; Burkett L.; Geffner M.E.;
J. Clin. Endocrinol. Metab. 91:2474-2479(2006)
Cited for: VARIANT HYPOC1 GLN-727; CHARACTERIZATION OF VARIANT HYPOC1 GLN-727;

CASR gene activating mutations in two families with autosomal dominant hypocalcemia.
Guarnieri V.; Valentina D'Elia A.; Baorda F.; Pazienza V.; Benegiamo G.; Stanziale P.; Copetti M.; Battista C.; Grimaldi F.; Damante G.; Pellegrini F.; D'Agruma L.; Zelante L.; Carella M.; Scillitani A.;
Mol. Genet. Metab. 107:548-552(2012)
Cited for: VARIANTS HYPOC1 LEU-221; ARG-681 AND GLN-727; FUNCTION; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS HYPOC1 ARG-681 AND GLN-727;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P41180: Variant p.Leu727Gln