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UniProtKB/Swiss-Prot P10275: Variant p.Ile738Thr

Androgen receptor
Gene: AR
Variant information

Variant position:  738
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 Isoleucine (I) to Threonine (T) at position 738 (I738T, p.Ile738Thr).
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 hydrophobic (I) to medium size and polar (T)
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.



Sequence information

Variant position:  738
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:   KWAKALPGFRNLHVDDQMAV  I QYSWMGLMVFAMGWRSFTNV
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                         KWAKALPGFRNLHVDDQMAVIQYSWMGLMVFAMGWRSFTNV

                              KWAKALPGFRNLHVDDQMAVIQYSWMGLMVFAMGWRSFTNV

Rhesus macaque                KWAKALPGFRNLHVDDQMAVIQYSWMGLMVFAMGWRSFTNV

Chimpanzee                    KWAKALPGFRNLHVDDQMAVIQYSWMGLMVFAMGWRSFTNV

Mouse                         KWAKALPGFRNLHVDDQMAVIQYSWMGLMVFAMGWRSFTNV

Rat                           KWAKALPGFRNLHVDDQMAVIQYSWMGLMVFAMGWRSFTNV

Pig                           KWAKALPGFRNLHVDDQMAVIQYSWMGLMVFAMGWRSFTNV

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 753 – 753 Androgen
Site 721 – 721 Interaction with coactivator LXXL and FXXFY motifs
Alternative sequence 645 – 920 Missing. In isoform 3.
Alternative sequence 649 – 920 Missing. In isoform 4.
Mutagenesis 721 – 721 K -> A. Loss of transcription activation in the presence of androgen and of interaction with NCOA2.
Mutagenesis 742 – 742 W -> L. Strongly decreased transcription activation in the presence of androgen.
Helix 731 – 758


Literature citations

Androgen receptor defects: historical, clinical, and molecular perspectives.
Quigley C.A.; De Bellis A.; Marschke K.B.; el-Awady M.K.; Wilson E.M.; French F.S.;
Endocr. Rev. 16:271-321(1995)
Cited for: VARIANTS AIS SER-706 AND HIS-764; VARIANTS PAIS LEU-726; THR-738; HIS-775 AND GLU-799;

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.