UniProtKB/SwissProt variant VAR

Variant information

Variant position:

128

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 Phenylalanine (F) to Leucine (L) at position 128 (F128L, p.Phe128Leu).

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 large size and aromatic (F) to medium size and hydrophobic (L)

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

BLOSUM score:

0

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.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs104893696 [ dbSNP | Ensembl ]

Sequence information

Variant position:

128

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:

LEATLSFVAQNKIDSLNLDE F CNCSEHIPSTIAVVGATGSG

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                         LEATLSFVAQNKIDSLNLDEFCNCSEHIPSTIAVVGATGSG

Mouse                         LEATLSFVAQNKIDSLNLDEFCNCSEHIPSTIAVVGATGSG

Rat                           LEATLSFVAQNKIDSLNLDEFCNCSEHIPSTIAVVGATGSG

Pig                           LEATLSFVAQNKIDSLNLDEFCNCSEHIPSTIAVVGATGSG

Bovine                        LEATLSFVAQNKIDSLNLDEFCNCSEHIPSTIAVVGATGSG

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.
Helix	125 – 128

Literature citations

A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor.
Pearce S.H.S.; Williamson C.; Kifor O.; Bai M.; Coulthard M.G.; Davies M.; Lewis-Barned N.; McCredie D.; Powell H.; Kendall-Taylor P.; Brown E.M.; Thakker R.V.;
N. Engl. J. Med. 335:1115-1122(1996)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS HYPOC1 LYS-118; LEU-128; MET-151; LYS-191 AND SER-612; CHARACTERIZATION OF VARIANTS HYPOC1 LEU-128; MET-151 AND LYS-191;

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;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P41180: Variant p.Phe128Leu