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UniProtKB/Swiss-Prot P10275: Variant p.Val867Leu

Androgen receptor
Gene: AR
Variant information

Variant position:  867
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 Valine (V) to Leucine (L) at position 867 (V867L, p.Val867Leu).
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

Involvement in disease:  Androgen insensitivity, partial (PAIS) [MIM:312300]: A disorder that is characterized by hypospadias, hypogonadism, gynecomastia, genital ambiguity, normal XY karyotype, and a pedigree pattern consistent with X-linked recessive inheritance. Some patients present azoospermia or severe oligospermia without other clinical manifestations. {ECO:0000269|PubMed:10022458, ECO:0000269|PubMed:10221692, ECO:0000269|PubMed:10470409, ECO:0000269|PubMed:10502786, ECO:0000269|PubMed:10543676, ECO:0000269|PubMed:11587068, ECO:0000269|PubMed:1303262, ECO:0000269|PubMed:1307250, ECO:0000269|PubMed:1316540, ECO:0000269|PubMed:1424203, ECO:0000269|PubMed:1430233, ECO:0000269|PubMed:14756668, ECO:0000269|PubMed:2010552, ECO:0000269|PubMed:7581399, ECO:0000269|PubMed:7649358, ECO:0000269|PubMed:7671849, ECO:0000269|PubMed:7909256, ECO:0000269|PubMed:7910529, ECO:0000269|PubMed:7929841, ECO:0000269|PubMed:7970939, ECO:0000269|PubMed:7981687, ECO:0000269|PubMed:8033918, ECO:0000269|PubMed:8097257, ECO:0000269|PubMed:8126121, ECO:0000269|PubMed:8205256, ECO:0000269|PubMed:8281139, ECO:0000269|PubMed:8325932, ECO:0000269|PubMed:8325950, ECO:0000269|PubMed:8446106, ECO:0000269|PubMed:8550758, ECO:0000269|PubMed:8809734, ECO:0000269|PubMed:8823308, ECO:0000269|PubMed:8824883, ECO:0000269|PubMed:9039340, ECO:0000269|PubMed:9196614, ECO:0000269|PubMed:9302173, ECO:0000269|PubMed:9329414, ECO:0000269|PubMed:9543136, ECO:0000269|PubMed:9607727, ECO:0000269|PubMed:9768671, ECO:0000269|PubMed:9856504, ECO:0000269|Ref.121}. 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 PAIS.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  867
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:   RKNPTSCSRRFYQLTKLLDS  V QPIARELHQFTFDLLIKSHM
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                         RKNPTSCSRRFYQLTKLLDSVQPIARELHQFTFDLLIKSHM

                              RKNPTSCSRRFYQLTKLLDSVQPIARELHQFTFDLLIKSHM

Rhesus macaque                RKNPTSCSRRFYQLTKLLDSVQPIARELHQFTFDLLIKSHM

Chimpanzee                    RKNPTSCSRRFYQLTKLLDSVQPIARELHQFTFDLLIKSHM

Mouse                         RKNPTSCSRRFYQLTKLLDSVQPIARELHQFTFDLLIKSHM

Rat                           RKNPTSCSRRFYQLTKLLDSVQPIARELHQFTFDLLIKSHM

Pig                           RKNPTSCSRRFYQLTKLLDSVQPIARELHQFTFDLLIKSHM

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.

TypePositionsDescription
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
Binding site 878 – 878 Androgen
Cross 848 – 848 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Alternative sequence 645 – 920 Missing. In isoform 3.
Alternative sequence 649 – 920 Missing. In isoform 4.
Mutagenesis 848 – 848 K -> R. Partially prevents ubiquitination by RNF6.
Helix 853 – 883


Literature citations

Point mutations detected in the androgen receptor gene of three men with partial androgen insensitivity syndrome.
Saunders P.T.; Padayachi T.; Tincello D.G.; Shalet S.M.; Wu F.C.;
Clin. Endocrinol. (Oxf.) 37:214-220(1992)
Cited for: VARIANTS PAIS LYS-609 AND LEU-867;

Single strand conformation polymorphism analysis of androgen receptor gene mutations in patients with androgen insensitivity syndromes: application for diagnosis, genetic counseling, and therapy.
Hiort O.; Huang Q.; Sinnecker G.H.; Sadeghi-Nejad A.; Kruse K.; Wolfe H.J.; Yandell D.W.;
J. Clin. Endocrinol. Metab. 77:262-266(1993)
Cited for: VARIANTS AIS LYS-682 AND THR-843; VARIANTS PAIS HIS-841 AND LEU-867;

Substitution of valine-865 by methionine or leucine in the human androgen receptor causes complete or partial androgen insensitivity, respectively with distinct androgen receptor phenotypes.
Kazemi-Esfarjani P.; Beitel L.K.; Trifiro M.A.; Kaufman M.; Rennie P.; Sheppard P.; Matusik R.; Pinsky L.;
Mol. Endocrinol. 7:37-46(1993)
Cited for: VARIANT AIS MET-867; VARIANT PAIS LEU-867;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.