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The androgen receptor gene is more than 90 kb long and codes for a protein that has 3 major functional domains: the N-terminal domain, DNA-binding domain, and androgen-binding domain. The protein functions as a steroid-hormone activated transcription factor. Upon binding the hormone ligand, the receptor dissociates from accessory proteins, translocates into the nucleus, dimerizes, and then stimulates transcription of androgen responsive genes. This gene contains 2 polymorphic trinucleotide repeat segments that encode polyglutamine and polyglycine tracts in the N-terminal transactivation domain of its protein. Expansion of the polyglutamine tract from the normal 9-34 repeats to the pathogenic 38-62 repeats causes spinal bulbar muscular atrophy (SBMA, also known as Kennedy's disease). Mutations in this gene are also associated with complete androgen insensitivity (CAIS). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017]
AR (Androgen Receptor) is a Protein Coding gene. Diseases associated with AR include Androgen Insensitivity, Partial and Spinal And Bulbar Muscular Atrophy, X-Linked 1. Among its related pathways are Regulation of Wnt-mediated beta catenin signaling and target gene transcription and Signal transduction_PKA signaling. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and chromatin binding. An important paralog of this gene is NR3C2.
Androgen receptors (ARs) (dihydrotestosterone receptors) are nuclear hormone receptors of the NR3C class, which includes mineralocorticoid, progesterone and glucocorticoid receptors. ARs are expressed in bone marrow, mammary gland and prostate tissues.
GeneHancer (GH) Identifier | GH Type | GH Score |
GH Sources | Gene Association Score | Total Score | TSS distance (kb) | Number of Genes Away | Size (kb) | Transcription Factor Binding Sites |
Gene Targets |
---|---|---|---|---|---|---|---|---|---|---|
GH0XJ067543 | Promoter/Enhancer | 1.6 | EPDnew Ensembl ENCODE CraniofacialAtlas | 606.3 | +3.7 | 3669 | 8.6 | SCRT2 ZBTB44 SP2 ZBTB26 ZFP69B RAD21 EZH2 RXRA ZBTB33 SP3 | AR 5MWI_A-193 piR-61532-355 OPHN1 | |
GH0XJ066728 | Promoter/Enhancer | 1.2 | ENCODE CraniofacialAtlas | 5.1 | -815.1 | -815134 | 1.1 | CREB1 CTCF ZNF629 ZHX2 REST HDAC1 YY1 SCRT2 KLF9 RAD21 | AR piR-61240-322 L13714-487 EDA2R | |
GH0XJ068163 | Enhancer | 0.5 | Ensembl ENCODE | 9.9 | +619.8 | 619780 | 2.8 | NFE2 JUN | AR piR-30048-046 piR-45012-575 OPHN1 RF00017-8487 | |
GH0XJ067779 | Enhancer | 0.8 | Ensembl ENCODE | 5.5 | +236.4 | 236380 | 3.6 | HDAC1 EP300 HMBOX1 CTCF GABPA FOSL1 NCOR1 NFIC STAT5A TAL1 | AR LOC105373241 piR-52368-179 OPHN1 | |
GH0XJ068114 | Enhancer | 0.7 | Ensembl ENCODE | 6.9 | +571.0 | 570980 | 1.6 | JUND SMARCC2 NFIC SPI1 ATF3 POLR2A LCORL | piR-51878-045 AR RF00026-1174 RNU6-1225P OPHN1 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000976 | transcription regulatory region sequence-specific DNA binding | IDA | 12799378 |
GO:0000978 | RNA polymerase II proximal promoter sequence-specific DNA binding | IDA | 16728402 |
GO:0000981 | DNA-binding transcription factor activity, RNA polymerase II-specific | ISM | 19274049 |
GO:0001085 | RNA polymerase II transcription factor binding | IPI | 16120611 |
GO:0001091 | RNA polymerase II basal transcription factor binding | IPI | 20181722 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000790 | nuclear chromatin | IDA,ISA | -- |
GO:0005634 | nucleus | IEA,IDA | 15572661 |
GO:0005654 | nucleoplasm | TAS | -- |
GO:0005737 | cytoplasm | IEA,IDA | 15572661 |
GO:0005829 | cytosol | TAS | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 | ||
2 | Deubiquitination |
.74
|
|
3 | Gene Expression |
.48
|
|
4 | Metabolism of proteins | ||
5 | Nuclear Receptor transcription pathway |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000122 | negative regulation of transcription by RNA polymerase II | IMP | 12902338 |
GO:0001701 | in utero embryonic development | IEA | -- |
GO:0003073 | regulation of systemic arterial blood pressure | IEA | -- |
GO:0003382 | epithelial cell morphogenesis | IEA | -- |
GO:0006351 | transcription, DNA-templated | IDA | 15572661 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Nilutamide | Approved, Investigational | Pharma | Antagonist, Target, antagonist | Androgen receptor antagonist. Orally active | 13 | |
Bicalutamide | Approved | Pharma | Target, antagonist | Androgen receptor antagonist | 195 | |
Flutamide | Approved, Investigational | Pharma | Target, antagonist | 68 | ||
Testosterone | Approved, Experimental, Investigational | Pharma | Target, agonist | Endogenous androgen receptor agonist | 660 | |
Fluoxymesterone | Approved, Illicit | Pharma | Target, agonist | 37 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
[<sup>3</sup>H]R1881 |
|
Agonist |
|
|
||
Androsterone |
|
53-41-8 |
Compound | Action | Cas Number |
---|---|---|
Cl-4AS-1 | Steroidal androgen receptor agonist | 188589-66-4 |
Nilutamide | Androgen receptor antagonist. Orally active | 63612-50-0 |
Testosterone | Endogenous androgen receptor agonist | 58-22-0 |
TFM-4AS-1 | Selective androgen receptor modulator (SARM) | 188589-61-9 |
Compound | Action | Cas Number |
---|---|---|
17 alpha-propionate | Androgen antagonist | 19608-29-8 |
Andarine | Androgen receptor agonist | 401900-40-1 |
ARN-509 | Androgen receptor inhibitor | 956104-40-8 |
ASC-J9 | AR degradation enhancer,antiumor agent | 52328-98-0 |
AZD3514 | Androgen receptor downregulator | 1240299-33-5 |
Bicalutamide | Androgen receptor antagonist | 90357-06-5 |
CITCO | 338404-52-7 | |
Cl-4AS-1 | 188589-66-4 | |
Cyproterone Acetate | Androgen receptor antagonist | 427-51-0 |
Epiandrosterone | 481-29-8 | |
Estradiol valerate | 979-32-8 | |
Flutamide | 13311-84-7 | |
Genistein | AR agonist | 446-72-0 |
MDV3100 (Enzalutamide) | Androgen receptor antagonist | 915087-33-1 |
ODM-201 | new-generation androgen receptor inhibitor | 1297538-32-9 |
Orteronel | For castration-resistant prostate cancer, clinical candidate | 566939-85-3 |
PF 998425 | 1076225-27-8 | |
RU 58841 | Androgen receptor antagonist | 154992-24-2 |
Spironolactone | 1952-01-7 | |
TAK-700 (Orteronel) | Human 17,20-lyase inhibitor | 426219-18-3 |
TFM-4AS-1 | 188589-61-9 | |
TOK-001 | CYP17 inhibitor and androgen receptor (AR) antagonist | 851983-85-2 |
This gene was present in the common ancestor of chordates.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | AR 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | AR 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | AR 30 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Ar 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Ar 30 17 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | AR 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | AR 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | AR 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | ar 30 |
|
||
African clawed frog (Xenopus laevis) |
Amphibia | Xl.426 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | ar 31 |
|
OneToOne | |
Rainbow Trout (Oncorhynchus mykiss) |
Actinopterygii | Omy.12054 30 |
|
SNP ID | Clinical significance and condition | Chr 0X pos | Variation | AA Info | Type |
---|---|---|---|---|---|
417975 | Uncertain Significance: Bulbo-spinal atrophy X-linked | 67,545,316(+) | T/TGCAGCAGCAGCAG | INFRAME_INSERTION,FIVE_PRIME_UTR_VARIANT | |
638387 | Conflicting Interpretations: Androgen resistance syndrome; not provided | 67,546,514(+) | T/TGGCGGCGGC | INFRAME_INSERTION,FIVE_PRIME_UTR_VARIANT | |
642559 | Uncertain Significance: Androgen resistance syndrome; Bulbo-spinal atrophy X-linked | 67,723,828(+) | TC/T | FRAMESHIFT_VARIANT | |
643319 | Pathogenic: Androgen resistance syndrome; Bulbo-spinal atrophy X-linked | 67,545,318(+) | C/CAGT | NONSENSE,FIVE_PRIME_UTR_VARIANT | |
644458 | Pathogenic: Androgen resistance syndrome; Bulbo-spinal atrophy X-linked | 67,545,901(+) | AGGCGTTGGAG/A | FRAMESHIFT_VARIANT,FIVE_PRIME_UTR_VARIANT |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
esv1584074 | OTHER | inversion | 17803354 |
esv2740196 | CNV | deletion | 23290073 |
esv2758871 | CNV | gain | 17122850 |
esv3558939 | CNV | deletion | 23714750 |
esv3574017 | CNV | loss | 25503493 |
nsv818030 | CNV | gain | 17921354 |
Disorder | Aliases | PubMed IDs |
---|---|---|
androgen insensitivity, partial |
|
|
spinal and bulbar muscular atrophy, x-linked 1 |
|
|
androgen insensitivity syndrome |
|
|
hypospadias 1, x-linked |
|
|
prostate cancer |
|