AR androgen receptor [Homo sapiens (human)] - Gene

Summary

Official Symbol: ARprovided by HGNC
Official Full Name: androgen receptorprovided by HGNC
Primary source: HGNC:HGNC:644
See related: Ensembl:ENSG00000169083 MIM:313700; AllianceGenome:HGNC:644
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: KD; AIS; AR8; TFM; DHTR; SBMA; HYSP1; NR3C4; SMAX1; HUMARA
Summary: 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]
Expression: Biased expression in liver (RPKM 12.9), endometrium (RPKM 10.8) and 13 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: Xq12

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (67544021..67730619)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (65973852..66160479)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (66763863..66950461)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The androgen receptor interacts with GATA3 to transcriptionally regulate a luminal epithelial cell phenotype in breast cancer.
Title: The androgen receptor interacts with GATA3 to transcriptionally regulate a luminal epithelial cell phenotype in breast cancer.
Loss of feedback regulation between FAM3B and androgen receptor driving prostate cancer progression.
Title: Loss of feedback regulation between FAM3B and androgen receptor driving prostate cancer progression.
Modelling the distinct roles of epithelial and stromal androgen receptor in the regulation of prostate epithelial dynamics.
Title: Modelling the distinct roles of epithelial and stromal androgen receptor in the regulation of prostate epithelial dynamics.
Implication of androgen receptor gene dysfunction in human Mullerian duct anomalies.
Title: Implication of androgen receptor gene dysfunction in human Müllerian duct anomalies.
Structural insights into the mechanism of resistance to bicalutamide by the clinical mutations in androgen receptor in chemo-treatment resistant prostate cancer.
Title: Structural insights into the mechanism of resistance to bicalutamide by the clinical mutations in androgen receptor in chemo-treatment resistant prostate cancer.
A plasma membrane-associated form of the androgen receptor enhances nuclear androgen signaling in osteoblasts and prostate cancer cells.
Title: A plasma membrane-associated form of the androgen receptor enhances nuclear androgen signaling in osteoblasts and prostate cancer cells.
ANKRD1 is a mesenchymal-specific driver of cancer-associated fibroblast activation bridging androgen receptor loss to AP-1 activation.
Title: ANKRD1 is a mesenchymal-specific driver of cancer-associated fibroblast activation bridging androgen receptor loss to AP-1 activation.
Two somatic mutations in the androgen receptor N-terminal domain are oncogenic drivers in hepatocellular carcinoma.
Title: Two somatic mutations in the androgen receptor N-terminal domain are oncogenic drivers in hepatocellular carcinoma.
CAG and GGN repeat polymorphisms in the androgen receptor gene of a Chilean pediatric cohort with idiopathic inguinal cryptorchidism.
Title: CAG and GGN repeat polymorphisms in the androgen receptor gene of a Chilean pediatric cohort with idiopathic inguinal cryptorchidism.
Small Indels in the Androgen Receptor Gene: Phenotype Implications and Mechanisms of Mutagenesis.
Title: Small Indels in the Androgen Receptor Gene: Phenotype Implications and Mechanisms of Mutagenesis.

Submit: New GeneRIF Correction See all GeneRIFs (2021)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Androgen resistance syndrome MedGen: C0039585 OMIM: 300068 GeneReviews: Androgen Insensitivity Syndrome	Compare labs
Hypospadias 1, X-linked MedGen: C2678098 OMIM: 300633 GeneReviews: Not available	Compare labs
Kennedy disease MedGen: C1839259 OMIM: 313200 GeneReviews: Spinal and Bulbar Muscular Atrophy	Compare labs
Malignant tumor of prostate MedGen: C0376358 OMIM: 176807 GeneReviews: Not available	Compare labs
Partial androgen insensitivity syndrome MedGen: C0268301 OMIM: 312300 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2020-12-08) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2020-12-08) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
Genome-wide association analysis of metabolic traits in a birth cohort from a founder population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Male-pattern baldness susceptibility locus at 20p11. EBI GWAS Catalog EBI GWAS CatalogPubMed
Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Six novel susceptibility Loci for early-onset androgenetic alopecia and their unexpected association with common diseases. EBI GWAS Catalog EBI GWAS CatalogPubMed
Susceptibility variants on chromosome 7p21.1 suggest HDAC9 as a new candidate gene for male-pattern baldness. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AF020219 (e-PCR)
- UniSTS:28673

G64113 (e-PCR)
- UniSTS:146703

G64112 (e-PCR)
- UniSTS:146710

G64114 (e-PCR)
- UniSTS:146713

G64115 (e-PCR)
- UniSTS:146715

RH99038 (e-PCR)
- UniSTS:85019

G64116 (e-PCR)
- UniSTS:146716

DXS7498 (e-PCR)
- UniSTS:38944

DXS9736 (e-PCR)
- UniSTS:49952

RH11082 (e-PCR)
- UniSTS:78379

WI-20403 (e-PCR)
- UniSTS:20793

GDB:185508 (e-PCR)
- UniSTS:155454

GDB:511610 (e-PCR)
- UniSTS:157514

GDB:197027 (e-PCR)
- UniSTS:99693

DXS7751 (e-PCR)
- UniSTS:75647

AR_1980 (e-PCR)
- UniSTS:280451

PMC20963P1 (e-PCR)
- UniSTS:272005

PMC20963P2 (e-PCR)
- UniSTS:272006

PMC20963P3 (e-PCR)
- UniSTS:272007

GDB:194743 (e-PCR)
- UniSTS:155799

DXS1397 (e-PCR)
- UniSTS:99735

GDB:176283 (e-PCR)
- UniSTS:154785

GDB:176286 (e-PCR)
- UniSTS:154787

STS-N64522 (e-PCR)
- UniSTS:29859

GDB:176287 (e-PCR)
- UniSTS:154788

GDB:176288 (e-PCR)
- UniSTS:154789

GDB:176322 (e-PCR)
- UniSTS:154796

GDB:176323 (e-PCR)
- UniSTS:154797

GDB:176324 (e-PCR)
- UniSTS:154798

GDB:176326 (e-PCR)
- UniSTS:154800

GDB:176327 (e-PCR)
- UniSTS:154801

GDB:176328 (e-PCR)
- UniSTS:154802

GDB:176329 (e-PCR)
- UniSTS:154803

STS-M20132 (e-PCR)
- UniSTS:27060

GDB:600694 (e-PCR)
- UniSTS:99252

GDB:188670 (e-PCR)
- UniSTS:155574

G64286 (e-PCR)
- UniSTS:158668

AR (e-PCR)
- UniSTS:262096

GDB:196546 (e-PCR)
- UniSTS:155864

GDB:555517 (e-PCR)
- UniSTS:157676

PMC137585P1 (e-PCR)
- UniSTS:270846

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATPase binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
enables G protein-coupled receptor activity	IC Inferred by Curator more info	PubMed
enables POU domain binding	IEA Inferred from Electronic Annotation more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II general transcription initiation factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables RNA polymerase II-specific DNA-binding transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables androgen binding	IDA Inferred from Direct Assay more info	PubMed
enables beta-catenin binding	IDA Inferred from Direct Assay more info	PubMed
enables beta-catenin binding	IPI Inferred from Physical Interaction more info	PubMed
enables beta-catenin binding	TAS Traceable Author Statement more info	PubMed
enables chromatin binding	IDA Inferred from Direct Assay more info	PubMed
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables estrogen response element binding	IBA Inferred from Biological aspect of Ancestor more info
enables molecular adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables molecular condensate scaffold activity	IDA Inferred from Direct Assay more info	PubMed
enables nuclear receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables nuclear receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables nuclear receptor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables nuclear receptor activity	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables steroid binding	IEA Inferred from Electronic Annotation more info
enables transcription cis-regulatory region binding	IDA Inferred from Direct Assay more info	PubMed
enables transcription coactivator binding	IDA Inferred from Direct Assay more info	PubMed
enables transcription coactivator binding	IPI Inferred from Physical Interaction more info	PubMed
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in G protein-coupled receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in Leydig cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in MAPK cascade	IEA Inferred from Electronic Annotation more info
involved_in activation of prostate induction by androgen receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in androgen receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in animal organ formation	IEA Inferred from Electronic Annotation more info
involved_in cell-cell signaling	TAS Traceable Author Statement more info	PubMed
involved_in cellular response to estrogen stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to steroid hormone stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to testosterone stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in epithelial cell differentiation involved in prostate gland development	IEA Inferred from Electronic Annotation more info
involved_in epithelial cell morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in epithelial cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in in utero embryonic development	IEA Inferred from Electronic Annotation more info
involved_in insulin-like growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in intracellular estrogen receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in intracellular receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in intracellular steroid hormone receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in lateral sprouting involved in mammary gland duct morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in male genitalia morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in male gonad development	IBA Inferred from Biological aspect of Ancestor more info
involved_in male somatic sex determination	IEA Inferred from Electronic Annotation more info
involved_in mammary gland alveolus development	IEA Inferred from Electronic Annotation more info
involved_in morphogenesis of an epithelial fold	IEA Inferred from Electronic Annotation more info
involved_in multicellular organism growth	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of epithelial cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of extrinsic apoptotic signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of integrin biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in non-membrane-bounded organelle assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of MAPK cascade	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of NF-kappaB transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of epithelial cell proliferation involved in prostate gland development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of gene expression	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of insulin-like growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of integrin biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of intracellular estrogen receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of miRNA transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase III	IDA Inferred from Direct Assay more info	PubMed
involved_in prostate gland epithelium morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in prostate gland growth	IEA Inferred from Electronic Annotation more info
involved_in regulation of developmental growth	IEA Inferred from Electronic Annotation more info
involved_in regulation of protein localization to plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of systemic arterial blood pressure	IEA Inferred from Electronic Annotation more info
involved_in seminiferous tubule development	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in single fertilization	IEA Inferred from Electronic Annotation more info
involved_in spermatogenesis	IEA Inferred from Electronic Annotation more info
involved_in tertiary branching involved in mammary gland duct morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of chromatin	IBA Inferred from Biological aspect of Ancestor more info
part_of chromatin	IDA Inferred from Direct Assay more info	PubMed
part_of chromatin	ISA Inferred from Sequence Alignment more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in nuclear speck	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: androgen receptor

Names: dihydrotestosterone receptor; nuclear receptor subfamily 3 group C member 4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009014.2 RefSeqGene

Range

4990..191588

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1406

mRNA and Protein(s)

NM_000044.6 → NP_000035.2 androgen receptor isoform 1

See identical proteins and their annotated locations for NP_000035.2

Status: REVIEWED

Description

Transcript Variant: This variant (1, also known as AR-FL in PMID:20823238) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AA505591, AF321915, AL049564, AL356358, BC132975, M20132

Consensus CDS

CCDS14387.1

UniProtKB/Swiss-Prot

A0A0B4J1T2, A2RUN2, B1AKD7, C0JKD3, C0JKD4, E7EVX6, P10275, Q9UD95

UniProtKB/TrEMBL

D2Y6K2, D3YPP9, D3YPQ0, D3YPQ1, D3YPQ2, D3YPQ3

Related

ENSP00000363822.3, ENST00000374690.9

Conserved Domains (3) summary

cd07073
Location:673 → 918

NR_LBD_AR; Ligand binding domain of the nuclear receptor androgen receptor, ligand activated transcription regulator

cd07173
Location:555 → 636

NR_DBD_AR; DNA-binding domain of androgen receptor (AR) is composed of two C4-type zinc fingers

pfam02166
Location:6 → 449

Androgen_recep; Androgen receptor
NM_001011645.3 → NP_001011645.1 androgen receptor isoform 2

See identical proteins and their annotated locations for NP_001011645.1

Status: REVIEWED

Description

Transcript Variant: This variant (2, also known as AR45 in PMID:15634333) contains an alternate exon in the 5' region and initiates translation at an alternate start codon compared to variant 1. The encoded isoform (2) has a distinct and shorter N-terminus than isoform 1.

Source sequence(s)

AA505591, AF321915, AL049564, AL356358, BC132975, M20132, M23263

UniProtKB/TrEMBL

F1D8N5

Conserved Domains (2) summary

cd07073
Location:141 → 386

NR_LBD_AR; Ligand binding domain of the nuclear receptor androgen receptor, ligand activated transcription regulator

cd07173
Location:23 → 104

NR_DBD_AR; DNA-binding domain of androgen receptor (AR) is composed of two C4-type zinc fingers
NM_001348061.1 → NP_001334990.1 androgen receptor isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3, also known as AR-V7 in PMID:19117982 and AR3 in PMID:19244107) lacks multiple exons and includes an alternate 3' terminal exon, compared to variant 1. The encoded isoform (3) has a distinct and shorter C-terminus than isoform 1. This variant has been shown to be expressed at higher levels in castration-resistant prostate cancer samples (PMID:20823238).

Source sequence(s)

AF321915, AL356358, BC132975, FJ235916, M23263

Consensus CDS

CCDS87754.1

UniProtKB/TrEMBL

C0JKD5

Related

ENSP00000421155.1, ENST00000504326.5

Conserved Domains (2) summary

cd07173
Location:555 → 630

NR_DBD_AR; DNA-binding domain of androgen receptor (AR) is composed of two C4-type zinc fingers

pfam02166
Location:6 → 449

Androgen_recep; Androgen receptor
NM_001348063.1 → NP_001334992.1 androgen receptor isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4, also known as AR-V1 in PMID:20823238 and AR4 in PMID:19244107) lacks multiple exons and includes an alternate 3' terminal exon, compared to variant 1. The encoded isoform (4) has a distinct and shorter C-terminus than isoform 1.

Source sequence(s)

AF321915, AL356358, BC132975, FJ235917, M23263

UniProtKB/TrEMBL

C0JKD5

Related

ENST00000513847.5

Conserved Domains (2) summary

cd07173
Location:555 → 629

NR_DBD_AR; DNA-binding domain of androgen receptor (AR) is composed of two C4-type zinc fingers

pfam02166
Location:6 → 449

Androgen_recep; Androgen receptor
NM_001348064.1 → NP_001334993.1 androgen receptor isoform 5

Status: REVIEWED

Description

Transcript Variant: This variant (5, also known as AR8 in PMID:21878636) lacks alternate exons in the central and 3' coding regions, uses an alternate splice site, resulting in a frameshift, and contains an alternate 3' terminal exon, compared to variant 1. The encoded isoform (5) has a distinct and shorter C-terminus than isoform 1. Although this variant is predicted to be a candidate for nonsense-mediated mRNA decay (NMD), Western blot data with variant-specific antibodies in PMID:21878636 indicate that it is translated.

Source sequence(s)

AF321915, AL356358, BC132975, FJ235916, HM055487, M23263

Consensus CDS

CCDS87755.1

UniProtKB/TrEMBL

A0A087WUX9, G4VV16

Related

ENSP00000479013.1, ENST00000613054.2

Conserved Domains (1) summary

pfam02166
Location:6 → 449

Androgen_recep; Androgen receptor
NM_001424175.1 → NP_001411104.1 androgen receptor isoform 6

Status: REVIEWED

Source sequence(s)

CP068255