UniProtKB/SwissProt variant VAR

Variant information

Variant position:

131

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 Cysteine (C) to Tryptophan (W) at position 131 (C131W, p.Cys131Trp).

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 polar (C) to large size and aromatic (W)

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; associated with clinical features of Bartter syndrome.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121909267 [ dbSNP | Ensembl ]

Sequence information

Variant position:

131

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:

TLSFVAQNKIDSLNLDEFCN C SEHIPSTIAVVGATGSGVST

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                         TLSFVAQNKIDSLNLDEFCNCSEHIPSTIAVVGATGSGVST

Mouse                         TLSFVAQNKIDSLNLDEFCNCSEHIPSTIAVVGATGSGVST

Rat                           TLSFVAQNKIDSLNLDEFCNCSEHIPSTIAVVGATGSGVST

Pig                           TLSFVAQNKIDSLNLDEFCNCSEHIPSTIAVVGATGSGIST

Bovine                        TLSFVAQNKIDSLNLDEFCNCSEHIPSTIAVVGATGSGIST

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	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.
Beta strand	129 – 131

Literature citations

Association between activating mutations of calcium-sensing receptor and Bartter's syndrome.
Watanabe S.; Fukumoto S.; Chang H.; Takeuchi Y.; Hasegawa Y.; Okazaki R.; Chikatsu N.; Fujita T.;
Lancet 360:692-694(2002)
Cited for: VARIANTS HYPOC1 TRP-131 AND GLU-843;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P41180: Variant p.Cys131Trp