UniProtKB/SwissProt variant VAR

Variant information

Variant position:

346

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 Valine (V) to Methionine (M) at position 346 (V346M, p.Val346Met).

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:

Similar physico-chemical property. Both residues are medium size and hydrophobic.

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 VDDR2A; decreased calcitriol receptor activity; decreased affinity for calcitriol; decreased ligand-independent localization to the nucleus; loss of interaction with RXRA; decreased interaction with NCOR1; decreased interaction with NCOA1; decreased sequence-specific DNA-binding.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs267607169 [ dbSNP | Ensembl ]

Sequence information

Variant position:

346

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:

427

The length of the canonical sequence.

Location on the sequence:

HEEEHVLLMAICIVSPDRPG V QDAALIEAIQDRLSNTLQTY

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                         HEEEHVLLMAICIVSPDRPGVQDAALIEAIQDRLSNTLQTY

Mouse                         HEEEHVLLMAICIVSPDRPGVQDAKLVEAIQDRLSNTLQTY

Rat                           HEEEHVLLMAICIVSPDRPGVQDAKLVEAIQDRLSNTLQTY

Pig                           HEEEHVLLMAICIVSPDRPGVQDPTLIEAIQDRLSNTLQTY

Bovine                        HEEEHVLLMAICIVSPDRPGVQDAALVEAIQDRLSNTLQTY

Chicken                       HEEEHVLLMAICILSPDRPGVQDTSLVESIQDRLSDILQTY

Xenopus laevis                HEEEHVLLMAICILSPDRPGLQDKALVESIQDRLSSTLQTY

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	1 – 427	Vitamin D3 receptor
Domain	127 – 423	NR LBD

Literature citations

A novel mutation in the VDR gene in hereditary vitamin D-resistant rickets.
Arita K.; Nanda A.; Wessagowit V.; Akiyama M.; Alsaleh Q.A.; McGrath J.A.;
Br. J. Dermatol. 158:168-171(2008)
Cited for: VARIANT VDDR2A MET-346;

Functional analyses of a novel missense and other mutations of the vitamin D receptor in association with alopecia.
Tamura M.; Ishizawa M.; Isojima T.; Oezen S.; Oka A.; Makishima M.; Kitanaka S.;
Sci. Rep. 7:5102-5102(2017)
Cited for: VARIANT VDDR2A PRO-360; CHARACTERIZATION OF VARIANT VDDR2A 152-GLN--SER-427 DEL; LEU-274; GLN-305; MET-346 AND PRO-360; FUNCTION; INTERACTION WITH NCOA1; NCOR1 AND RXR; SUBCELLULAR LOCATION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P11473: Variant p.Val346Met