UniProtKB/SwissProt variant VAR

Variant information

Variant position:

780

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

Type of variant:

Disease [Disclaimer]

The variants are classified into three categories: Disease, Polymorphism and Unclassified.

Disease: Variants implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Arginine (R) to Tryptophan (W) at position 780 (R780W, p.Arg780Trp).

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 basic (R) to large size and aromatic (W)

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

BLOSUM score:

-3

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

Involvement in disease:

Androgen insensitivity syndrome (AIS) [MIM:300068]: An X-linked recessive form of pseudohermaphroditism due end-organ resistance to androgen. Affected males have female external genitalia, female breast development, blind vagina, absent uterus and female adnexa, and abdominal or inguinal testes, despite a normal 46,XY karyotype. {ECO:0000269|PubMed:10022458, ECO:0000269|PubMed:10221692, ECO:0000269|PubMed:10221770, ECO:0000269|PubMed:10404311, ECO:0000269|PubMed:10458483, ECO:0000269|PubMed:10571951, ECO:0000269|PubMed:10590024, ECO:0000269|PubMed:10690872, ECO:0000269|PubMed:11587068, ECO:0000269|PubMed:11744994, ECO:0000269|PubMed:1307250, ECO:0000269|PubMed:1316540, ECO:0000269|PubMed:1426313, ECO:0000269|PubMed:1430233, ECO:0000269|PubMed:1464650, ECO:0000269|PubMed:14756668, ECO:0000269|PubMed:1480178, ECO:0000269|PubMed:1487249, ECO:0000269|PubMed:1569163, ECO:0000269|PubMed:1609793, ECO:0000269|PubMed:16129672, ECO:0000269|PubMed:16595706, ECO:0000269|PubMed:1775137, ECO:0000269|PubMed:1999491, ECO:0000269|PubMed:2082179, ECO:0000269|PubMed:2594783, ECO:0000269|PubMed:7537149, ECO:0000269|PubMed:7581399, ECO:0000269|PubMed:7633398, ECO:0000269|PubMed:7641413, ECO:0000269|PubMed:7671849, ECO:0000269|PubMed:7929841, ECO:0000269|PubMed:7962294, ECO:0000269|PubMed:7970939, ECO:0000269|PubMed:7981687, ECO:0000269|PubMed:7981689, ECO:0000269|PubMed:7993455, ECO:0000269|PubMed:8040309, ECO:0000269|PubMed:8096390, ECO:0000269|PubMed:8103398, ECO:0000269|PubMed:8162033, ECO:0000269|PubMed:8224266, ECO:0000269|PubMed:8281140, ECO:0000269|PubMed:8325950, ECO:0000269|PubMed:8339746, ECO:0000269|PubMed:8413310, ECO:0000269|PubMed:8446106, ECO:0000269|PubMed:8626869, ECO:0000269|PubMed:8647313, ECO:0000269|PubMed:8683794, ECO:0000269|PubMed:8723113, ECO:0000269|PubMed:8768864, ECO:0000269|PubMed:8809734, ECO:0000269|PubMed:8830623, ECO:0000269|PubMed:8918984, ECO:0000269|PubMed:8990010, ECO:0000269|PubMed:9001799, ECO:0000269|PubMed:9007482, ECO:0000269|PubMed:9039340, ECO:0000269|PubMed:9106550, ECO:0000269|PubMed:9160185, ECO:0000269|PubMed:9252933, ECO:0000269|PubMed:9255042, ECO:0000269|PubMed:9302173, ECO:0000269|PubMed:9328206, ECO:0000269|PubMed:9544375, ECO:0000269|PubMed:9554754, ECO:0000269|PubMed:9610419, ECO:0000269|PubMed:9627582, ECO:0000269|PubMed:9698822, ECO:0000269|PubMed:9851768, ECO:0000269|PubMed:9856504, ECO:0000269|Ref.113, ECO:0000269|Ref.179}. Note=The disease is caused by mutations affecting the gene represented in this entry.

The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:

In AIS.

Any additional useful information about the variant.

Sequence information

Variant position:

780

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

Protein sequence length:

920

The length of the canonical sequence.

Location on the sequence:

SRMLYFAPDLVFNEYRMHKS R MYSQCVRMRHLSQEFGWLQI

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                         SRMLYFAPDLVFNEYRMHKSRMYSQCVRMRHLSQEFGWLQI

                              SRMLYFAPDLVFNEYRMHKSRMYSQCVRMRHLSQEFGWLQI

Rhesus macaque                SRMLYFAPDLVFNEYRMHKSRMYSQCVRMRHLSQEFGWLQI

Chimpanzee                    SRMLYFAPDLVFNEYRMHKSRMYSQCVRMRHLSQEFGWLQI

Mouse                         SRMLYFAPDLVFNEYRMHKSRMYSQCVRMRHLSQEFGWLQI

Rat                           SRMLYFAPDLVFNEYRMHKSRMYSQCVRMRHLSQEFGWLQI

Pig                           SRMLYFAPDLVFNEYRMHKSRMYSQCVRMRHLSQEFGWLQI

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 – 920	Androgen receptor
Domain	669 – 900	NR LBD
Region	552 – 919	Interaction with LPXN
Region	592 – 919	Interaction with CCAR1
Region	625 – 919	Interaction with KAT7
Alternative sequence	645 – 920	Missing. In isoform 3.
Alternative sequence	649 – 920	Missing. In isoform 4.

Literature citations

Detection of point mutations in the androgen receptor gene using non-isotopic single strand conformation polymorphism analysis.
Hiort O.; Wodtke A.; Struve D.; Zoellner A.; Sinnecker G.H.;
Hum. Mol. Genet. 3:1163-1166(1994)
Cited for: VARIANTS PAIS SER-583; TYR-605; ALA-709; LEU-755 AND HIS-772; VARIANT AIS TRP-780;

Human androgen insensitivity due to point mutations encoding amino acid substitutions in the androgen receptor steroid-binding domain.
Murono K.; Mendonca B.B.; Arnhold I.J.P.; Rigon A.C.M.M.; Migeon C.J.; Brown T.R.;
Hum. Mutat. 6:152-162(1995)
Cited for: VARIANT PAIS CYS-764; VARIANTS AIS TRP-780; VAL-808 AND CYS-856;

Functional assessment and clinical classification of androgen sensitivity in patients with mutations of the androgen receptor gene.
Sinnecker G.H.; Hiort O.; Nitsche E.M.; Holterhus P.M.; Kruse K.;
Eur. J. Pediatr. 156:7-14(1997)
Cited for: VARIANT AIS TRP-780;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P10275: Variant p.Arg780Trp