Atlas of Genetics and Cytogenetics in Oncology and Haematology

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SRD5A2 (steroid-5-alpha-reductase, alpha polypeptide 2 (3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha 2))

Written2013-05Nelson LS Tang, Chen Di Liao
Department of Chemical Pathology, The Chinese University of Hong Kong, China

(Note : for Links provided by Atlas : click)


Alias_namessteroid-5-alpha-reductase, alpha polypeptide 2 (3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha 2)
Other alias
HGNC (Hugo) SRD5A2
LocusID (NCBI) 6716
Atlas_Id 42385
Location 2p23.1  [Link to chromosome band 2p23]
Location_base_pair Starts at 31524586 and ends at 31580971 bp from pter ( according to hg19-Feb_2009)  [Mapping SRD5A2.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
FAM107A (3p14.3) / SRD5A2 (2p23.1)


Description Genomic DNA of SRD5A2 gene spans about 58.6 kbp on chromosome 2p23.
Transcription Five exons with a long 3' UTR.


Description SRD5A2 is a microsomal protein of 254 amino acids in length.
Expression Androgen sensitive tissues, such as prostate.
Localisation Microsome.
Function SRD5A2 protein is an enzyme that converts testosterone to 5-alpha dihydrotestosterone (DHT) and progesterone or corticosterone into 5-alpha-3-oxosteroids. It is active at acidic pH, and is inhibited by finasteride.
Homology 50% homology with human SRD5A1 isoenzyme and 46% homology with rat 5-alpha-reductase.


Note There were over 29 mutations of SRD5A2 gene documented in literature, including 12 single amino acid missense substitutions (Makridakis et al., 2000; Vilchis et al., 2008; Nie et al., 2011). It has been suggested that exon 4 may be a mutation hotspot region on the SRD5A2 gene (Vilchis et al., 2008). Some of the more studied polymorphisms of SRD5A2 included V89L, A49T, and the (TA)n dinucleotide repeat.

Implicated in

Entity Prostate cancer
Note Various genetic studies from multiple ethnic populations have shown genetic variations in the SRD5A2 gene are associated with prostate cancer. Polymorphisms V89L, A29T, and the (TA)n repeat are some of well-known SRD5A2 variation that have been liked to prostate cancer risk. However, these associations are not always consistent. For example, the V89L (rs523349) variant is a missense single nucleotide polymorphism resulting in a valine to leucine substitution at condon 89 that reduced SRD5A2 enzyme activity. More than couple dozen of studies performed genetic association studies between V89L polymorphism and prostate cancer risk since 1997. Although the association has been found significant repeatedly, the results were inconsistent and conflicting (Nam et al., 2001; Salam et al., 2005, Hsing et al., 2001). Recently, a meta-analysis review (Wang et al., 2010) was conducted on 25 genetic studies of SRD5A2 V89L polymorphism and prostate cancer, which included additional subgroup analysis in Asian, African, European and age ≤ 65 group. In overall analysis, no significant association was found between V89L and prostate cancer risk. Subgroup analysis revealed a slight but significant increased risk in European men with at least one L-allele (LL+LV vs VV, OR=1.11; 95%CI=1.03-1.19; P<0.01), and in men younger than 65 with LL genotype when compared to those with VV genotype (OR=1.70; 95%CI=1.14-2.68; P=0.02). The interethnic discrepancy of the effect of V89L may have arisen from a variable influence of the risk allele due to the significantly varied allelic distribution of V89L between the ethnic groups (Zeigler-Johnson et al., 2002). It was concluded that the V89L polymorphism plays a low-penetrant role in the risk of prostate cancer among European and men younger than 65 years of age.
Oncogenesis Androgen levels have been suggested to play an important role in the etiology of prostate cancer. The same SRD5A2 genetic variations linked to prostate cancer has also been repeatedly shown to be associated with various circulating androgen level in the blood, including testosterone, dihydrotestosterone and various forms of their metabolites (Makridakis et al., 2000; Allen et al., 2001; Hsing et al., 2001). Therefore, it is possible that these risk-predisposing polymorphisms may cause changes in the SRD5A2 enzyme functional activity that results in the variation of circulating androgens, and ultimately leads to the development of prostate cancer.


The association between polymorphisms in the CYP17 and 5alpha-reductase (SRD5A2) genes and serum androgen concentrations in men.
Allen NE, Forrest MS, Key TJ.
Cancer Epidemiol Biomarkers Prev. 2001 Mar;10(3):185-9.
PMID 11303586
Polymorphic markers in the SRD5A2 gene and prostate cancer risk: a population-based case-control study.
Hsing AW, Chen C, Chokkalingam AP, Gao YT, Dightman DA, Nguyen HT, Deng J, Cheng J, Sesterhenn IA, Mostofi FK, Stanczyk FZ, Reichardt JK.
Cancer Epidemiol Biomarkers Prev. 2001 Oct;10(10):1077-82.
PMID 11588134
International trends and patterns of prostate cancer incidence and mortality.
Hsing AW, Tsao L, Devesa SS.
Int J Cancer. 2000 Jan 1;85(1):60-7.
PMID 10585584
Association of SRD5A2 variants and serum androstane-3alpha,17beta-diol glucuronide concentration in Chinese elderly men.
Jiang J, Tang NL, Ohlsson C, Eriksson AL, Vandenput L, Liao C, Wang X, Chan FW, Kwok A, Orwoll E, Kwok TC, Woo J, Leung PC.
Clin Chem. 2010 Nov;56(11):1742-9. doi: 10.1373/clinchem.2010.150607. Epub 2010 Sep 20.
PMID 20855474
Biochemical and pharmacogenetic dissection of human steroid 5 alpha-reductase type II.
Makridakis NM, di Salle E, Reichardt JK.
Pharmacogenetics. 2000 Jul;10(5):407-13.
PMID 10898110
V89L polymorphism of type-2, 5-alpha reductase enzyme gene predicts prostate cancer presence and progression.
Nam RK, Toi A, Vesprini D, Ho M, Chu W, Harvie S, Sweet J, Trachtenberg J, Jewett MA, Narod SA.
Urology. 2001 Jan;57(1):199-204.
PMID 11164181
Five novel mutations of SRD5A2 found in eight Chinese patients with 46,XY disorders of sex development.
Nie M, Zhou Q, Mao J, Lu S, Wu X.
Mol Hum Reprod. 2011 Jan;17(1):57-62. doi: 10.1093/molehr/gaq072. Epub 2010 Aug 24.
PMID 20736251
Associations between polymorphisms in the steroid 5-alpha reductase type II (SRD5A2) gene and benign prostatic hyperplasia and prostate cancer.
Salam MT, Ursin G, Skinner EC, Dessissa T, Reichardt JK.
Urol Oncol. 2005 Jul-Aug;23(4):246-53.
PMID 16018939
Novel compound heterozygous mutations in the SRD5A2 gene from 46,XY infants with ambiguous external genitalia.
Vilchis F, Valdez E, Ramos L, Garcia R, Gomez R, Chavez B.
J Hum Genet. 2008;53(5):401-6. doi: 10.1007/s10038-008-0274-2. Epub 2008 Mar 19.
PMID 18350250
SRD5A2 V89L polymorphism and prostate cancer risk: a meta-analysis.
Wang C, Tao W, Chen Q, Hu H, Wen XY, Han R.
Prostate. 2010 Feb 1;70(2):170-8. doi: 10.1002/pros.21050.
PMID 19760631
Ethnic differences in the frequency of prostate cancer susceptibility alleles at SRD5A2 and CYP3A4.
Zeigler-Johnson CM, Walker AH, Mancke B, Spangler E, Jalloh M, McBride S, Deitz A, Malkowicz SB, Ofori-Adjei D, Gueye SM, Rebbeck TR.
Hum Hered. 2002;54(1):13-21.
PMID 12446983


This paper should be referenced as such :
Tang, NLS ; Liao, CD
SRD5A2 (steroid-5-alpha-reductase, alpha polypeptide 2 (3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha 2))
Atlas Genet Cytogenet Oncol Haematol. 2013;17(11):757-758.
Free journal version : [ pdf ]   [ DOI ]
On line version :

External links

HGNC (Hugo)SRD5A2   11285
Entrez_Gene (NCBI)SRD5A2  6716  steroid 5 alpha-reductase 2
GeneCards (Weizmann)SRD5A2
Ensembl hg19 (Hinxton)ENSG00000277893 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000277893 [Gene_View]  ENSG00000277893 [Sequence]  chr2:31524586-31580971 [Contig_View]  SRD5A2 [Vega]
ICGC DataPortalENSG00000277893
TCGA cBioPortalSRD5A2
AceView (NCBI)SRD5A2
Genatlas (Paris)SRD5A2
SOURCE (Princeton)SRD5A2
Genetics Home Reference (NIH)SRD5A2
Genomic and cartography
GoldenPath hg38 (UCSC)SRD5A2  -     chr2:31524586-31580971 -  2p23.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)SRD5A2  -     2p23.1   [Description]    (hg19-Feb_2009)
GoldenPathSRD5A2 - 2p23.1 [CytoView hg19]  SRD5A2 - 2p23.1 [CytoView hg38]
Mapping of homologs : NCBISRD5A2 [Mapview hg19]  SRD5A2 [Mapview hg38]
OMIM264600   607306   
Gene and transcription
Genbank (Entrez)AK307235 AK316597 BC112252 BC113641 EF560740
RefSeq transcript (Entrez)NM_000348
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)SRD5A2
Cluster EST : UnigeneHs.458345 [ NCBI ]
CGAP (NCI)Hs.458345
Alternative Splicing GalleryENSG00000277893
Gene ExpressionSRD5A2 [ NCBI-GEO ]   SRD5A2 [ EBI - ARRAY_EXPRESS ]   SRD5A2 [ SEEK ]   SRD5A2 [ MEM ]
Gene Expression Viewer (FireBrowse)SRD5A2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6716
GTEX Portal (Tissue expression)SRD5A2
Human Protein AtlasENSG00000277893-SRD5A2 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP31213   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP31213  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP31213
Splice isoforms : SwissVarP31213
Catalytic activity : Enzyme1.3.99.5 [ Enzyme-Expasy ] [ IntEnz-EBI ] [ BRENDA ] [ KEGG ]   
Domaine pattern : Prosite (Expaxy)S5A_REDUCTASE (PS50244)   
Domains : Interpro (EBI)3-oxo-5-alpha-steroid_4-DH    3-oxo-5_a-steroid_4-DH_C   
Domain families : Pfam (Sanger)Steroid_dh (PF02544)   
Domain families : Pfam (NCBI)pfam02544   
Conserved Domain (NCBI)SRD5A2
DMDM Disease mutations6716
Blocks (Seattle)SRD5A2
Human Protein Atlas [tissue]ENSG00000277893-SRD5A2 [tissue]
Peptide AtlasP31213
Protein Interaction databases
IntAct (EBI)P31213
Ontologies - Pathways
Ontology : AmiGO3-oxo-5-alpha-steroid 4-dehydrogenase activity  endoplasmic reticulum membrane  androgen biosynthetic process  cell-cell signaling  androgen metabolic process  male gonad development  sterol 5-alpha reductase activity  integral component of membrane  oxidoreductase activity  cell differentiation  testosterone dehydrogenase [NAD(P)] activity  male genitalia development  cholestenone 5-alpha-reductase activity  oxidation-reduction process  testosterone biosynthetic process  
Ontology : EGO-EBI3-oxo-5-alpha-steroid 4-dehydrogenase activity  endoplasmic reticulum membrane  androgen biosynthetic process  cell-cell signaling  androgen metabolic process  male gonad development  sterol 5-alpha reductase activity  integral component of membrane  oxidoreductase activity  cell differentiation  testosterone dehydrogenase [NAD(P)] activity  male genitalia development  cholestenone 5-alpha-reductase activity  oxidation-reduction process  testosterone biosynthetic process  
Pathways : KEGGSteroid hormone biosynthesis    Prostate cancer   
REACTOMEP31213 [protein]
REACTOME PathwaysR-HSA-193048 [pathway]   
NDEx NetworkSRD5A2
Atlas of Cancer Signalling NetworkSRD5A2
Wikipedia pathwaysSRD5A2
Orthology - Evolution
GeneTree (enSembl)ENSG00000277893
Phylogenetic Trees/Animal Genes : TreeFamSRD5A2
Homologs : HomoloGeneSRD5A2
Homology/Alignments : Family Browser (UCSC)SRD5A2
Gene fusions - Rearrangements
Fusion : FusionGDB12467   
Fusion : Fusion_HubC11ORF52--SRD5A2    FAM107A--SRD5A2   
Fusion : QuiverSRD5A2
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSRD5A2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SRD5A2
Exome Variant ServerSRD5A2
ExAC (Exome Aggregation Consortium)ENSG00000277893
GNOMAD BrowserENSG00000277893
Varsome BrowserSRD5A2
Genetic variants : HAPMAP6716
Genomic Variants (DGV)SRD5A2 [DGVbeta]
DECIPHERSRD5A2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisSRD5A2 
ICGC Data PortalSRD5A2 
TCGA Data PortalSRD5A2 
Broad Tumor PortalSRD5A2
OASIS PortalSRD5A2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSRD5A2  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DSRD5A2
Mutations and Diseases : HGMDSRD5A2
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)Zhejiang University Center for Genetic and Genomic Medicine (ZJU-CGGM)
BioMutasearch SRD5A2
DgiDB (Drug Gene Interaction Database)SRD5A2
DoCM (Curated mutations)SRD5A2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SRD5A2 (select a term)
NCG5 (London)SRD5A2
Cancer3DSRD5A2(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM264600    607306   
Orphanet324    903   
Genetic Testing Registry SRD5A2
NextProtP31213 [Medical]
Target ValidationSRD5A2
Huge Navigator SRD5A2 [HugePedia]
snp3D : Map Gene to Disease6716
BioCentury BCIQSRD5A2
ClinGenSRD5A2 (curated)
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD6716
Chemical/Pharm GKB GenePA36113
Clinical trialSRD5A2
canSAR (ICR)SRD5A2 (select the gene name)
DataMed IndexSRD5A2
PubMed236 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Nov 13 22:02:19 CET 2019

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