UniProtKB/SwissProt variant VAR

Variant information

Variant position:

604

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 Glutamate (E) to Lysine (K) at position 604 (E604K, p.Glu604Lys).

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 acidic (E) to large size and basic (K)

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:

In HYPOC1; there is a significant leftward shift in the concentration response curves for the effects of extracellular calcium on both intracellular calcium mobilization and MAPK activity.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs104893712 [ dbSNP | Ensembl ]

Sequence information

Variant position:

604

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:

KCPDDFWSNENHTSCIAKEI E FLSWTEPFGIALTLFAVLGI

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                         KCPDDFWSNENHTSCIAKEIEFLSWTEPFGIALTLFAVLGI

Mouse                         KCPDDFWSNENHTSCIAKEIEFLAWTEPFGIALTLFAVLGI

Rat                           KCPDDFWSNENHTSCIAKEIEFLAWTEPFGIALTLFAVLGI

Pig                           KCPDDFWSNENHTSCIAKEIEFLSWTEPFGIALTLFAVLGI

Bovine                        KCPDDFWSNENHTSCIAKEIEFLSWTEPFGIALTLFAVLGI

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	542 – 612	Cysteine-rich (CR)
Glycosylation	594 – 594	N-linked (GlcNAc...) asparagine
Beta strand	602 – 604

Literature citations

Autosomal dominant hypocalcemia: a novel activating mutation (E604K) in the cysteine-rich domain of the calcium-sensing receptor.
Tan Y.M.; Cardinal J.; Franks A.H.; Mun H.-C.; Lewis N.; Harris L.B.; Prins J.B.; Conigrave A.D.;
J. Clin. Endocrinol. Metab. 88:605-610(2003)
Cited for: VARIANT HYPOC1 LYS-604; CHARACTERIZATION OF VARIANT HYPOC1 LYS-604;

Calcium-sensing receptor mutations and denaturing high performance liquid chromatography.
Cole D.E.; Yun F.H.; Wong B.Y.; Shuen A.Y.; Booth R.A.; Scillitani A.; Pidasheva S.; Zhou X.; Canaff L.; Hendy G.N.;
J. Mol. Endocrinol. 42:331-339(2009)
Cited for: VARIANTS HHC1 SER-42; LEU-55; HIS-66; MET-81; MET-138; ARG-143; ARG-158; GLY-166; TRP-220; ARG-549; TYR-562; GLY-565; TYR-582; 583-ASN--SER-1078 DEL; TYR-661; HIS-680; ILE-761 DEL AND TRP-795; VARIANTS HYPOC1 LYS-118; PHE-125; ARG-129; LYS-228; LYS-604; ILE-802; SER-830; LEU-832 AND SER-832;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P41180: Variant p.Glu604Lys