SRD5A2

Summary

SRD5A2 (steroid 5 alpha-reductase 2, HGNC:11285) is a protein-coding gene on chromosome 2p23.1, encoding 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (P31213). Converts testosterone (T) into 5-alpha-dihydrotestosterone (DHT) and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids.

This gene encodes a microsomal protein expressed at high levels in androgen-sensitive tissues such as the prostate. The encoded protein is active at acidic pH and is sensitive to the 4-azasteroid inhibitor finasteride. Deficiencies in this gene can result in male pseudohermaphroditism, specifically pseudovaginal perineoscrotal hypospadias (PPSH).

Source: NCBI Gene 6716 — RefSeq curated summary.

At a glance

• Gene–disease (curated): 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency (Strong, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 348 total — 71 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 16
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000348

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11285
Approved symbol	SRD5A2
Name	steroid 5 alpha-reductase 2
Location	2p23.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000277893
Ensembl biotype	protein_coding
OMIM	607306
Entrez	6716

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000622030, ENST00000882642, ENST00000882643

RefSeq mRNA: 1 — MANE Select: NM_000348 NM_000348

CCDS: CCDS74503

Canonical transcript exons

ENST00000622030 — 5 exons

Exon	Start	End
ENSE00003717051	31533603	31533766
ENSE00003731183	31529307	31529457
ENSE00003740557	31522480	31526262
ENSE00003740686	31531371	31531472
ENSE00003751995	31580620	31580938

Expression profiles

Bgee: expression breadth broad, 66 present calls, max score 88.24.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2102 / max 62.9450, expressed in 21 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27692	0.1361	20
27693	0.0307	6
27691	0.0207	12
27695	0.0119	4
27694	0.0108	5

Top tissues by expression

273 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	88.24	gold quality
bronchial epithelial cell	CL:0002328	87.93	gold quality
epithelium of bronchus	UBERON:0002031	87.49	gold quality
bronchus	UBERON:0002185	86.33	gold quality
right uterine tube	UBERON:0001302	86.17	gold quality
liver	UBERON:0002107	85.14	gold quality
buccal mucosa cell	CL:0002336	84.84	gold quality
right lobe of liver	UBERON:0001114	84.24	gold quality
caput epididymis	UBERON:0004358	83.08	gold quality
prostate gland	UBERON:0002367	81.82	gold quality
seminal vesicle	UBERON:0000998	81.34	gold quality
mucosa of paranasal sinus	UBERON:0005030	81.25	gold quality
heart right ventricle	UBERON:0002080	81.13	gold quality
olfactory bulb	UBERON:0002264	80.58	gold quality
type B pancreatic cell	CL:0000169	80.27	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.36	gold quality
oviduct epithelium	UBERON:0004804	76.50	gold quality
cauda epididymis	UBERON:0004360	75.70	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	75.67	gold quality
nasal cavity epithelium	UBERON:0005384	74.27	silver quality
diaphragm	UBERON:0001103	73.79	gold quality
epithelium of nasopharynx	UBERON:0001951	73.53	gold quality
fallopian tube	UBERON:0003889	72.93	gold quality
urethra	UBERON:0000057	70.54	gold quality
tongue squamous epithelium	UBERON:0006919	69.91	gold quality
male germ cell	CL:0000015	69.42	gold quality
vastus lateralis	UBERON:0001379	69.03	gold quality
sperm	CL:0000019	68.13	gold quality
quadriceps femoris	UBERON:0001377	67.90	gold quality
myocardium	UBERON:0002349	67.88	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.17

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXC1, SREBF2

miRNA regulators (miRDB)

83 targeting SRD5A2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-7157-5P	99.66	69.33	1829

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• The expression of 5 alpha-reductase type 2 was localized to the stroma surrounding the urethra, especially along the urethral seam area in the ventral portion of the remodeling urethra. (PMID:11845321)
• despite a complete loss of function of 5alpha-reductase type 2, marked virilization is possible, most likely the result of a testosterone (T) effect during foetal life. (PMID:11869378)
• role in blood pressure (PMID:11903314)
• no substantial association seen between V89L variant and risk of prostate cancer (PMID:11927504)
• 5alpha-reductase 2 polymorphisms are associated with prostate cancer (PMID:12042668)
• Polymorphisms within the gene are biomarkers for the development of benign prostatic hyperplasia and benign prostatic enlargement(SRD5A2) (PMID:12111704)
• DHT may play more important roles than testosterone in the regulation of androgen action in endometrial cancer and normal human endometrium, especially in the secretory phase, in which both AR and 5alpha-reductase are increased (PMID:12115497)
• LL genotype at codon 89 of SRD5A2 associated with poor prognosis in men with prostate cancer (PMID:12210487)
• polymorphisms of SRD5A1 and SRD5A2 genes may not be directly associated with the development of baldness or generation of different clinical phenotypes. (PMID:12670724)
• Our results do not support the hypothesis that the V89L and A49T polymorphisms in the SRD5A2 gene are related to the risk of prostate cancer (PMID:12712437)
• Loss of 5alpha-reductase type II expression is associated with metastatic prostate cancer (PMID:12738739)
• Polymorphisms of SRD5A2 are unlikely to significantly increase susceptibility to hereditary or sporadic prostate cancer in the study populations. (PMID:12746845)
• SRD5A2 gene codes the steroid 5-reductase type II, a critical mediator of androgen action, and the V89L and A49T polymorphisms of this gene may be associated risk of prostate cancer or benign prostatic hyperplasia (PMID:12771801)
• Enhanced peripheral 5 alpha-reductase activity in PCOS. (PMID:12788885)
• The SRD5A2 (TA)(n) repeat polymorphism was not associated with androgen levels. (PMID:12815006)
• in Japanese patients, micropenis can be caused by SRD5A2 gene mutations, especially by R227Q which has been shown to retain approximately 3.2% of normal enzyme activity and appears relatively frequent in Asian populations (PMID:12843198)
• Association of prostate cancer with reduced 5alpha-reductase enzymatic activity as result of remarkably decreased expression of the SRD5A2 gene. Implications for finasteride therapy of prostate cancer. (PMID:12949937)
• Mutational analysis revealed [in the proband] a homozygous mutation in exon 4 of SRD5A2 gene changing codon 227 from CGA (for arginine) to CAA (for glutamine). (PMID:14594182)
• Candidate gene for benign prostatic hyperplasia. (PMID:15136785)
• Expression of SRD5A1 (5alphaR1) and SRD5A2 (5alphaR2) is elevated, and expression of AKR1C1 (20alpha-HSO), AKR1C2 (3alpha-HSO3) and AKR1C3 (3alpha-HSO2) is reduced in tumorous as compared to normal breast tissue. (PMID:15212687)
• Various types of mutation exist in prostate cancer. (PMID:15326487)
• This is the first demonstration of an alteration of 5alpha-reductase isoform 2 gene expression in X-ALD, that may be related to the steroidogenesis impairment and to the specific organ malfunction. (PMID:15337247)
• Polymorphisms of SRD5A2 is associated with prostate cancer risk (PMID:15477877)
• 5alpha-reductase type 1 (5alphaR1) immunostaining is increased and 5alpha-reductase type 2(5alphaR2) immunostaining is decreased during development of prostate cancer and there is increased expression of both in recurrent and metastatic cancers (PMID:15538746)
• Mutations of the steroid 5alpha-reductase type 2 (SRD5A2) gene in 46,XY subjects cause masculinization defects of varying degrees. This is the first report of a single-nucleotide insertion in the coding sequence of the SRD5A2 gene. (PMID:15770495)
• the SRD5A2 gene may play an important role in both BPH and prostate cancer (PMID:16018939)
• Point mutation in SRD5A2 gene, responsible for higher conversion of testosterone to DHT, seem to be more common in men with prostate cancer than men from the general population. (PMID:16039774)
• In 37 cases of more severe hypospadias we have found only two previously described mutations, one in the androgen receptor and one in the SRD5A2 gene. (PMID:16174723)
• SRD5A2 gene variants were associated with sperm concentration and motility, but not with epididymal and accessory sex gland markers. (PMID:16487406)
• Exon 4 is a hot spot region of mutation within SRD5A2 in patients with hypospadias. (PMID:16736621)
• The SRD5A2 mRNA expression in human prostatic tissue is 4-fold lower than normal rat. (PMID:16818707)
• 5alpha-Reductase type 2 gene variant is associated with prostate cancer (PMID:17136762)
• Distribution of polymorphisms in SRD5A2 and androgen receptor differed between prostate cancer low-risk population from Greenland and relatively high-risk Swedish male population. (PMID:17376218)
• Low activity of an amino acid substituted variant is assoiated with increased risk of aggressive prostatic cancer. (PMID:17448593)
• 5alphaR deficiency in subjects without parental consanguinity and the presence of compound heterozygotic patients suggest that SRD5A2 mutations carrier frequency may be higher than previously thought (PMID:17609295)
• the number of TA repeats and the V89L variant of SRD5A2 failed to show a statistical influence on either macroscopic or microscopic prostate anatomy (PMID:17669147)
• SRD5A2 V89L polymorphism may modify the prostate cancer risk conferred by polymorphism of HSD3B2. (PMID:17823934)
• The SRD5A2 Val89Leu SNP is not associated with transsexualism, refuting SRD5A2 as a candidate gene of transsexualism. (PMID:18000232)
• Identification of the R246Q mutation of the SRD5A2 gene from two unrelated Indian families possibly extends the founder gene effect in pseudohermaphroditism (PMID:18097518)
• Our results demonstrate that the 5alphaR activities of either bDPCs or sDPCs are stronger than that of dermal fibroblasts, despite the fact that the major steroidogenic activity is attributed to 17beta-HSD rather than 5alphaR among the three cell types. (PMID:18258185)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	srd5a2b	ENSDARG00000039067
danio_rerio	srd5a2a	ENSDARG00000043587
mus_musculus	Srd5a2	ENSMUSG00000038541
rattus_norvegicus	Srd5a2	ENSRNOG00000027042
caenorhabditis_elegans		WBGENE00008959
caenorhabditis_elegans		WBGENE00009635
caenorhabditis_elegans		WBGENE00014241

Paralogs (3): TECR (ENSG00000099797), SRD5A1 (ENSG00000145545), TECRL (ENSG00000205678)

Protein

Protein identifiers

3-oxo-5-alpha-steroid 4-dehydrogenase 2 — P31213 (reviewed: P31213)

Alternative names: 5 alpha-SR2, SR type 2, Steroid 5-alpha-reductase 2, Type II 5-alpha reductase

All UniProt accessions (1): P31213

UniProt curated annotations — full annotation on UniProt →

Function. Converts testosterone (T) into 5-alpha-dihydrotestosterone (DHT) and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology.

Subcellular location. Microsome membrane. Endoplasmic reticulum membrane.

Tissue specificity. Expressed in high levels in the prostate and many other androgen-sensitive tissues.

Disease relevance. Pseudovaginal perineoscrotal hypospadias (PPSH) [MIM:264600] A form of male pseudohermaphroditism in which 46,XY males show ambiguous genitalia at birth, including perineal hypospadias and a blind perineal pouch, and develop masculinization at puberty. The name of the disorder stems from the finding of a blind-ending perineal opening resembling a vagina and a severely hypospadiac penis with the urethra opening onto the perineum. The disease is caused by variants affecting the gene represented in this entry.

Polymorphism. Individuals with Thr-49 have an increased risk of prostate cancer. The enzyme with Thr-49 has a higher in vitro V(max) than the Ala-49 enzyme.

Similarity. Belongs to the steroid 5-alpha reductase family.

RefSeq proteins (1): NP_000339* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001104	3-oxo-5_a-steroid_4-DH_C	Domain
IPR016636	3-oxo-5-alpha-steroid_4-DH	Family
IPR039357	SRD5A/TECR	Family

Pfam: PF02544

Enzyme classification (BRENDA):

• EC 1.3.1.22 — 3-oxo-5alpha-steroid 4-dehydrogenase (NADP+) (BRENDA: 19 organisms, 63 substrates, 409 inhibitors, 93 Km, 0 kcat entries)
• EC 1.3.99.5 — 3-oxo-5alpha-steroid 4-dehydrogenase (acceptor) (BRENDA: 11 organisms, 23 substrates, 497 inhibitors, 9 Km, 3 kcat entries)

Substrate kinetics (BRENDA)

16 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
TESTOSTERONE	—	36
NADPH	0.001–0.65	17
PROGESTERONE	0.0001–0.12	15
ANDROSTENEDIONE	0.0004–0.0263	7
CORTICOSTERONE	0.0006–0.018	5
20ALPHA-HYDROXYPROGESTERONE	0.0002–0.0005	3
(5ALPHA)-ANDROST-1-EN-3,17-DIONE	0.01–0.17	3
TESTOSTERONE	0.0004–0.01	3
17-EPITESTOSTERONE	0.0006–0.0008	2
17ALPHA-HYDROXYPROGESTERONE	0.0061–0.0088	2
20ALPHA-HYDROXYPREGN-4-EN-3-ONE	0.0009	1
3-KETO-DELTA4-ABIRATERONE	0.003	1
CORTISONE	0.14	1
DIHYDROTESTOSTERONE	0.0014	1
1-ANDROSTENE-3,17-DIONE	0.0066	1

Catalyzed reactions (Rhea), 3 shown:

• 5alpha-pregnane-3,20-dione + NADP(+) = progesterone + NADPH + H(+) (RHEA:21952)
• 17beta-hydroxy-5alpha-androstan-3-one + NADP(+) = testosterone + NADPH + H(+) (RHEA:50820)
• a 3-oxo-5alpha-steroid + NADP(+) = a 3-oxo-Delta(4)-steroid + NADPH + H(+) (RHEA:54384)

UniProt features (56 total): sequence variant 37, helix 9, transmembrane region 4, strand 3, turn 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7BW1	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P31213-F1	94.56	0.88

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-193048	Androgen biosynthesis
R-HSA-1430728	Metabolism
R-HSA-196071	Metabolism of steroid hormones
R-HSA-556833	Metabolism of lipids
R-HSA-8957322	Metabolism of steroids

MSigDB gene sets: 180 (showing top): MODULE_93, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BENPORATH_ES_WITH_H3K27ME3, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, GOBP_MALE_GENITALIA_DEVELOPMENT, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_KETONE_METABOLIC_PROCESS, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_CELL_CELL_SIGNALING, SRF_Q5_01, GOBP_HYPOTHALAMUS_DEVELOPMENT, GOMF_STEROID_DEHYDROGENASE_ACTIVITY_ACTING_ON_THE_CH_OH_GROUP_OF_DONORS_NAD_OR_NADP_AS_ACCEPTOR, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_ANDROGEN_BIOSYNTHETIC_PROCESS

GO Biological Process (26): androgen biosynthetic process (GO:0006702), steroid catabolic process (GO:0006706), cell-cell signaling (GO:0007267), androgen metabolic process (GO:0008209), male gonad development (GO:0008584), response to xenobiotic stimulus (GO:0009410), biphenyl metabolic process (GO:0018879), dibenzo-p-dioxin metabolic process (GO:0018894), phthalate metabolic process (GO:0018963), hippocampus development (GO:0021766), hypothalamus development (GO:0021854), cell differentiation (GO:0030154), male genitalia development (GO:0030539), female genitalia development (GO:0030540), response to nutrient levels (GO:0031667), response to follicle-stimulating hormone (GO:0032354), response to testosterone (GO:0033574), response to peptide hormone (GO:0043434), response to steroid hormone (GO:0048545), bone development (GO:0060348), testosterone biosynthetic process (GO:0061370), response to biphenyl (GO:1904614), lipid metabolic process (GO:0006629), steroid biosynthetic process (GO:0006694), sex differentiation (GO:0007548), steroid metabolic process (GO:0008202)

GO Molecular Function (8): 3-oxo-5-alpha-steroid 4-dehydrogenase activity (GO:0003865), obsolete amide binding (GO:0033218), testosterone dehydrogenase (NADP+) activity (GO:0047045), 3-oxo-5-alpha-steroid 4-dehydrogenase (NADP+) activity (GO:0047751), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-CH group of donors (GO:0016627), obsolete testosterone dehydrogenase [NAD(P)+] activity (GO:0030283)

GO Cellular Component (5): endoplasmic reticulum membrane (GO:0005789), neuronal cell body (GO:0043025), cell body fiber (GO:0070852), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Metabolism of steroid hormones	1
Metabolism of steroids	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
steroid metabolic process	2
benzene-containing compound metabolic process	2
limbic system development	2
anatomical structure development	2
genitalia development	2
response to lipid	2
response to hormone	2
androgen metabolic process	1
hormone biosynthetic process	1
steroid hormone biosynthetic process	1
lipid catabolic process	1
cell communication	1
signaling	1
hormone metabolic process	1
gonad development	1
development of primary male sexual characteristics	1
response to chemical	1
small molecule metabolic process	1
dicarboxylic acid metabolic process	1
pallium development	1
diencephalon development	1
cellular developmental process	1
male sex differentiation	1
reproductive system development	1
female sex differentiation	1
response to stimulus	1
response to gonadotropin	1
response to ketone	1
response to nitrogen compound	1
response to oxygen-containing compound	1
skeletal system development	1
animal organ development	1
steroid dehydrogenase activity, acting on the CH-CH group of donors	1
17-beta-hydroxysteroid dehydrogenase (NADP+) activity	1
3-oxo-5-alpha-steroid 4-dehydrogenase activity	1
enone reductase activity	1
binding	1
catalytic activity	1
oxidoreductase activity	1
organelle membrane	1

Protein interactions and networks

STRING

1088 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SRD5A2	CYP17A1	P05093	866
SRD5A2	AR	P10275	816
SRD5A2	HSD17B3	P37058	800
SRD5A2	HSD3B2	P26439	723
SRD5A2	MAMLD1	Q13495	719
SRD5A2	SULT2A1	Q06520	703
SRD5A2	AKR1C3	P42330	702
SRD5A2	TMPRSS2	O15393	687
SRD5A2	CYP3A4	P05184	670
SRD5A2	STAR	P49675	647
SRD5A2	AKR1C2	P52895	647
SRD5A2	HSD3B1	P14060	645
SRD5A2	ELAC2	Q9BQ52	643
SRD5A2	CYP19A1	P11511	627
SRD5A2	CYP11A1	P05108	619

IntAct

10 interactions, top by confidence:

A	B	Type	Score
CYSRT1	SRD5A2	psi-mi:“MI:0915”(physical association)	0.560
SRD5A2	GNMT	psi-mi:“MI:0915”(physical association)	0.560
SRD5A2	CLPTM1	psi-mi:“MI:0915”(physical association)	0.500
SRD5A2	CLPTM1	psi-mi:“MI:0914”(association)	0.500
SRD5A2	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
GNMT	SRD5A2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): SRD5A2 (Two-hybrid), SRD5A2 (Two-hybrid), CLPTM1 (Affinity Capture-MS), PTX3 (Affinity Capture-MS), PKLR (Affinity Capture-MS)

ESM2 similar proteins: A2XWN6, B4FHU1, B8B6G5, C7T2J9, F4J4C8, O08984, O12947, O18765, O70536, O77760, O77761, P18405, P23913, P24008, P31213, P31214, P35610, Q0P4J9, Q0WVZ1, Q14739, Q17428, Q28891, Q28892, Q5R7H4, Q5RIU9, Q60457, Q61263, Q651J5, Q657S5, Q6K991, Q7F0Q2, Q7XUH5, Q84N34, Q8AVI9, Q8BFZ1, Q8GW19, Q8L718, Q8L7R3, Q8S403, Q93YU2

Diamond homologs: A2XWN6, A5PJS2, A8X8R3, B8B6G5, C7T2J9, D2HBV9, I1HTF7, O18765, O94511, P18405, P24008, P31213, P31214, Q17428, Q28891, Q28892, Q2QDF6, Q38944, Q55C17, Q5K2N1, Q5RJM1, Q68FF9, Q7F0Q2, Q7XUH5, Q99N99, Q9CAH5, Q9H8P0, Q9N5Y2, Q9SI62, Q9UT20, Q9WUP4, Q9M2U2, Q9VLP9, P40526, Q0P4J9, Q5RIU9, Q8AVI9, Q3SZ89, Q3ZCD7, Q57ZC7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

348 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	71
Likely pathogenic	11
Uncertain significance	64
Likely benign	112
Benign	33

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1298363	NM_000348.4(SRD5A2):c.169G>T (p.Glu57Ter)	Pathogenic
1410942	NM_000348.4(SRD5A2):c.357del (p.Phe118_Cys119insTer)	Pathogenic
1454899	NC_000002.11:g.(?31751266)(31758856_?)del	Pathogenic
1457456	NC_000002.11:g.(?31751266)(31751352_?)del	Pathogenic
1703543	GRCh37/hg19 2p25.3-q37.3(chr2:1-243199373)	Pathogenic
1802209	NM_000348.4(SRD5A2):c.10C>T (p.Gln4Ter)	Pathogenic
2444013	NM_000348.4(SRD5A2):c.383_384delinsGA (p.Tyr128Ter)	Pathogenic
265705	NM_000348.4(SRD5A2):c.2T>C (p.Met1Thr)	Pathogenic
2674673	NM_000348.4(SRD5A2):c.80_87del (p.Val27fs)	Pathogenic
2674674	NM_000348.4(SRD5A2):c.311G>A (p.Gly104Glu)	Pathogenic
2674675	NM_000348.4(SRD5A2):c.383A>G (p.Tyr128Cys)	Pathogenic
2674676	NM_000348.4(SRD5A2):c.574G>A (p.Ala192Thr)	Pathogenic
2674677	NM_000348.4(SRD5A2):c.587G>A (p.Gly196Asp)	Pathogenic
2674678	NM_000348.4(SRD5A2):c.699-1G>A	Pathogenic
2674681	NM_000348.4(SRD5A2):c.743C>A (p.Ala248Asp)	Pathogenic
2734142	NM_000348.4(SRD5A2):c.689A>C (p.His230Pro)	Pathogenic
2734143	NM_000348.4(SRD5A2):c.418del (p.Trp140fs)	Pathogenic
2734145	NM_000348.4(SRD5A2):c.158G>A (p.Trp53Ter)	Pathogenic
2735335	NM_000348.4(SRD5A2):c.82_88del (p.Ala28fs)	Pathogenic
2756480	NM_000348.4(SRD5A2):c.564del (p.Thr187_Tyr188insTer)	Pathogenic
2762010	NM_000348.4(SRD5A2):c.687del (p.His230fs)	Pathogenic
2764310	NM_000348.4(SRD5A2):c.602G>A (p.Trp201Ter)	Pathogenic
2790633	NM_000348.4(SRD5A2):c.544C>T (p.Gln182Ter)	Pathogenic
2810971	NM_000348.4(SRD5A2):c.547+1G>C	Pathogenic
2858235	NM_000348.4(SRD5A2):c.144del (p.Ala49fs)	Pathogenic
2862678	NM_000348.4(SRD5A2):c.431dup (p.Arg145fs)	Pathogenic
2863404	NM_000348.4(SRD5A2):c.115_137del (p.Ser39fs)	Pathogenic
2879647	NM_000348.4(SRD5A2):c.19C>T (p.Gln7Ter)	Pathogenic
2882755	NM_000348.4(SRD5A2):c.102del (p.Lys35fs)	Pathogenic
2887434	NM_000348.4(SRD5A2):c.492_493insGA (p.Tyr165fs)	Pathogenic

SpliceAI

1118 predictions. Top by Δscore:

Variant	Effect	Δscore
2:31526222:T:A	donor_gain	1.0000
2:31529973:T:A	donor_gain	1.0000
2:31526128:A:AC	donor_gain	0.9900
2:31526129:C:CC	donor_gain	0.9900
2:31526143:TG:T	donor_gain	0.9900
2:31531963:T:TA	donor_gain	0.9900
2:31533601:AC:A	donor_gain	0.9900
2:31533602:CC:C	donor_gain	0.9900
2:31526192:T:TA	donor_gain	0.9800
2:31529196:C:A	donor_gain	0.9800
2:31533763:TGTC:T	acceptor_gain	0.9800
2:31531474:T:C	acceptor_gain	0.9700
2:31580523:T:TA	donor_gain	0.9700
2:31526261:ACCT:A	acceptor_loss	0.9600
2:31526262:CCTAA:C	acceptor_loss	0.9600
2:31526263:CTAA:C	acceptor_loss	0.9600
2:31526264:T:A	acceptor_loss	0.9600
2:31531964:C:A	donor_gain	0.9600
2:31533595:TCAC:T	donor_loss	0.9600
2:31533596:CACT:C	donor_loss	0.9600
2:31533597:ACTTA:A	donor_loss	0.9600
2:31533598:CTTAC:C	donor_loss	0.9600
2:31533599:TTACC:T	donor_loss	0.9600
2:31533600:TAC:T	donor_loss	0.9600
2:31533601:A:T	donor_loss	0.9600
2:31533602:C:G	donor_loss	0.9600
2:31533628:C:CT	donor_gain	0.9600
2:31526271:C:CT	acceptor_loss	0.9500
2:31526272:A:T	acceptor_loss	0.9500
2:31531923:C:CT	donor_gain	0.9500

AlphaMissense

1631 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:31529447:A:C	F186L	0.991
2:31529447:A:T	F186L	0.991
2:31529449:A:G	F186L	0.991
2:31529357:A:C	F216L	0.987
2:31529357:A:T	F216L	0.987
2:31529359:A:G	F216L	0.987
2:31529404:A:G	W201R	0.986
2:31529404:A:T	W201R	0.986
2:31531429:A:C	S163R	0.986
2:31531429:A:T	S163R	0.986
2:31531431:T:G	S163R	0.986
2:31580620:C:A	R94M	0.986
2:31526244:A:C	F239L	0.984
2:31526244:A:T	F239L	0.984
2:31526246:A:G	F239L	0.984
2:31529415:T:A	E197V	0.984
2:31580620:C:G	R94T	0.984
2:31529405:T:A	E200D	0.982
2:31529405:T:G	E200D	0.982
2:31529426:A:C	N193K	0.982
2:31529426:A:T	N193K	0.982
2:31529449:A:T	F186I	0.981
2:31533694:G:C	F118L	0.981
2:31533694:G:T	F118L	0.981
2:31533696:A:G	F118L	0.981
2:31533766:C:A	R94S	0.981
2:31533766:C:G	R94S	0.981
2:31531405:C:A	R171S	0.978
2:31531405:C:G	R171S	0.978
2:31531438:G:C	N160K	0.978

dbSNP variants (sampled 300 via entrez): RS1000026776 (2:31539677 T>G), RS1000053580 (2:31619534 T>G), RS1000099002 (2:31527199 C>T), RS1000099687 (2:31597377 T>A,C), RS1000114944 (2:31614914 G>T), RS1000118843 (2:31627950 T>C), RS1000122464 (2:31572256 C>T), RS1000131655 (2:31651993 T>C,G), RS1000187081 (2:31645947 A>T), RS1000199595 (2:31644108 T>A,C), RS1000201117 (2:31650611 C>G,T), RS1000204461 (2:31567860 C>G), RS1000204955 (2:31612335 GCAA>G,GCAACAA), RS1000228769 (2:31620603 C>G), RS1000231704 (2:31609471 T>C)

Disease associations

OMIM: gene MIM:607306 | disease phenotypes: MIM:264600, MIM:603592, MIM:278300

GenCC curated gene-disease

Disease	Classification	Inheritance
46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency	Strong	Autosomal recessive

Mondo (6): 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency (MONDO:0009923), mosaic trisomy 2 (MONDO:0015763), xanthinuria type II (MONDO:0011346), xanthinuria type I (MONDO:0010209), urogenital tract malformation (MONDO:0019356), autism spectrum disorder (MONDO:0005258)

Orphanet (7): 46,XY difference of sex development due to 5-alpha-reductase 2 deficiency (Orphanet:753), Mosaic trisomy 2 syndrome (Orphanet:1723), Hereditary xanthinuria (Orphanet:3467), Xanthinuria type II (Orphanet:93602), Xanthinuria type I (Orphanet:93601), Urogenital tract malformation (Orphanet:83001), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

16 total (16 of 16 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000033	Ambiguous genitalia, male
HP:0000046	Small scrotum
HP:0000048	Bifid scrotum
HP:0000051	Perineal hypospadias
HP:0000054	Micropenis
HP:0000062	Ambiguous genitalia
HP:0000144	Decreased fertility
HP:0000818	Abnormality of the endocrine system
HP:0001595	Abnormal hair morphology
HP:0001608	Abnormality of the voice
HP:0001939	Abnormality of metabolism/homeostasis
HP:0008736	Hypoplasia of penis
HP:0032382	Uniparental disomy
HP:0100779	Urogenital sinus anomaly

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002255_2	Inflammatory biomarkers	3.000000e-19
GCST002934_13	Zinc levels	6.000000e-06
GCST003983_13	Male-pattern baldness	2.000000e-15
GCST004986_1	Idiopathic pulmonary fibrosis	6.000000e-06
GCST005116_39	Male-pattern baldness	2.000000e-26
GCST006661_237	Male-pattern baldness	7.000000e-26
GCST006661_245	Male-pattern baldness	3.000000e-24
GCST90020091_1	Estradiol levels	9.000000e-24

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004812	interleukin-1 beta measurement
EFO:0000768	idiopathic pulmonary fibrosis
EFO:0004697	estradiol measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
C535830	Pseudovaginal Perineoscrotal Hypospadias (supp.)
C562584	Xanthinuria, Type I (supp.)
C566358	Xanthinuria, Type II (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1856 (SINGLE PROTEIN), CHEMBL2363075 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 96,723 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL710	FINASTERIDE	4	51,247
CHEMBL464982	GAMOLENIC ACID	3	26,552
CHEMBL138225	EPRISTERIDE	2	10,015
CHEMBL1908332	TUROSTERIDE	2	8,168
CHEMBL24955	BEXLOSTERIDE	2	741

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs523349	Efficacy	3	abiraterone	Prostatic Neoplasms

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs523349	SRD5A2	3	2.25	1	abiraterone

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 1.-.-.- Oxidoreductases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
finasteride	Inhibition	7.84	pIC50

Binding affinities (BindingDB)

17 measured of 20 human assays (20 total across all organisms); most potent 17 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL2282783	IC50	0.04 nM
CHEMBL2282782	IC50	0.07 nM
(1S,9aR,11aS)-5,9a,11a-Trimethyl-7-oxo-2,3,3a,3b,4,5,7,9a,9b,10,11,11a-dodecahydro-1H-cyclopenta[i]phenanthridine-1-carboxylic acid adamantan-1-ylamide	IC50	0.3 nM
CHEMBL2282647	IC50	0.3 nM
(1S,9aR,11aS)-5,6,9a,11a-Tetramethyl-7-oxo-2,3,3a,3b,4,5,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[i]phenanthridine-1-carboxylic acid adamantan-1-ylamide	IC50	0.4 nM
CHEMBL2282645	IC50	0.4 nM
(1S,9aR,11aS)-6-Bromo-5,9a,11a-trimethyl-7-oxo-2,3,3a,3b,4,5,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-cyclopenta[i]phenanthridine-1-carboxylic acid adamantan-1-ylamide	IC50	1.7 nM
CHEMBL2282646	IC50	1.7 nM
Steroid, 10b	IC50	4.9 nM
Finasteride, 3	IC50	8.5 nM
Steroid, 10a	IC50	13 nM
4-[1-(Adamantane-1-carbonyl)-piperidin-4-ylidenemethyl]-benzoic acid	IC50	260 nM
Steroid, 9a	IC50	360 nM
Steroid, 9b	IC50	370 nM
4-[1-(Adamantane-1-carbonyl)-piperidin-4-yloxy]-benzoic acid	IC50	430 nM
4-[1-(Adamantane-1-carbonyl)-piperidin-4-ylidenemethyl]-3-methoxy-benzoic acid	IC50	1200 nM
(6Z,9Z,12Z)-octadeca-6,9,12-trienoic acid	IC50	14000 nM	US-9061023: Management and treatment of benign prostatic hyperplasia

ChEMBL bioactivities

505 potent at pChembl≥5 of 515 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.40	IC50	0.04	nM	CHEMBL138173
10.40	IC50	0.04	nM	CHEMBL2282783
10.15	IC50	0.07	nM	CHEMBL137733
10.15	IC50	0.07	nM	CHEMBL2282782
10.10	IC50	0.08	nM	CHEMBL420020
10.10	IC50	0.08	nM	CHEMBL2282766
10.10	Ki	0.08	nM	CHEMBL420020
10.05	IC50	0.09	nM	CHEMBL308258
10.05	IC50	0.09	nM	CHEMBL24088
10.05	IC50	0.09	nM	CHEMBL2282775
10.05	IC50	0.09	nM	CHEMBL2282776
10.00	IC50	0.1	nM	CHEMBL2282649
10.00	IC50	0.1	nM	CHEMBL108625
10.00	IC50	0.1	nM	CHEMBL432439
10.00	IC50	0.1	nM	CHEMBL322592
10.00	IC50	0.1	nM	CHEMBL445627
10.00	IC50	0.1	nM	CHEMBL80160
9.92	IC50	0.12	nM	CHEMBL412425
9.92	IC50	0.12	nM	CHEMBL2282773
9.89	IC50	0.13	nM	CHEMBL436215
9.89	IC50	0.13	nM	CHEMBL2282777
9.80	IC50	0.16	nM	CHEMBL306722
9.80	IC50	0.16	nM	CHEMBL2282774
9.74	IC50	0.18	nM	FINASTERIDE
9.74	IC50	0.18	nM	EPRISTERIDE
9.74	IC50	0.18	nM	CHEMBL420415
9.70	Ki	0.2	nM	EPRISTERIDE
9.70	IC50	0.2	nM	CHEMBL2282644
9.70	IC50	0.2	nM	CHEMBL2282763
9.70	IC50	0.2	nM	CHEMBL2282765
9.70	IC50	0.2	nM	CHEMBL285599
9.70	IC50	0.2	nM	CHEMBL25072
9.70	IC50	0.2	nM	CHEMBL324210
9.70	IC50	0.2	nM	CHEMBL107719
9.70	IC50	0.2	nM	CHEMBL321617
9.70	IC50	0.2	nM	CHEMBL323788
9.70	IC50	0.2	nM	CHEMBL107654
9.70	IC50	0.2	nM	CHEMBL109170
9.70	IC50	0.2	nM	CHEMBL110398
9.70	IC50	0.2	nM	CHEMBL89240
9.70	IC50	0.2	nM	CHEMBL88494
9.70	IC50	0.2	nM	CHEMBL306554
9.64	IC50	0.23	nM	CHEMBL312531
9.64	IC50	0.23	nM	CHEMBL2282771
9.64	IC50	0.23	nM	CHEMBL2298601
9.57	IC50	0.27	nM	CHEMBL86832
9.52	IC50	0.3	nM	CHEMBL2282640
9.52	IC50	0.3	nM	CHEMBL2282647
9.52	IC50	0.3	nM	CHEMBL108151
9.52	IC50	0.3	nM	CHEMBL311577

PubChem BioAssay actives

482 with measured affinity, of 818 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(1S,9aR,11aS)-1-(adamantane-2-carbonyl)-9a,11a-dimethyl-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridin-7-one	91252: Inhibition of recombinant human 5-alpha reductase-2 at a concentration of 5 microL after pre-incubation for 10 minutes	ic50	<0.0001	uM
(1S,9aR,11aS)-N-[1-(4-chlorophenyl)cyclopentyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207446: Inhibitory activity measured on human steroid 5-alpha-reductase type 2	ic50	0.0001	uM
2-adamantyl (1S,3aS,3bS,9aR,9bS,11aS)-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxylate	205601: Binding affinity for human 5-alpha reductase 2 isozyme	ic50	0.0001	uM
(1S,9aR,11aS)-N-[2,5-bis(trifluoromethyl)phenyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207446: Inhibitory activity measured on human steroid 5-alpha-reductase type 2	ic50	0.0001	uM
(1S,9aR,11aS)-N-(2,5-ditert-butylphenyl)-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207446: Inhibitory activity measured on human steroid 5-alpha-reductase type 2	ic50	0.0001	uM
(1S,9aR,11aS)-9a,11a-dimethyl-7-oxo-N-(3-phenylphenyl)-1,2,3,3a,3b,4,5,5a,6,9b,10,11-dodecahydroindeno[5,4-f]quinoline-1-carboxamide	205611: Inhibition of human 5-alpha reductase 2 isozyme.	ic50	0.0001	uM
(1S,9aR,11aS)-6-chloro-N-(4-chlorophenyl)-N-cyclopentyl-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	205601: Binding affinity for human 5-alpha reductase 2 isozyme	ic50	0.0001	uM
(1S,9aR,11aS)-9a,11a-dimethyl-7-oxo-N-[2-(trifluoromethyl)phenyl]-1,2,3,3a,3b,4,5,5a,6,9b,10,11-dodecahydroindeno[5,4-f]quinoline-1-carboxamide	205611: Inhibition of human 5-alpha reductase 2 isozyme.	ic50	0.0001	uM
(1S,9aR,11aS)-N-(4-chlorophenyl)-N-cyclopentyl-6,9a,11a-trimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	205601: Binding affinity for human 5-alpha reductase 2 isozyme	ic50	0.0001	uM
(1S,9aR,11aS)-N-[2,5-bis(trifluoromethyl)phenyl]-6-chloro-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	205601: Binding affinity for human 5-alpha reductase 2 isozyme	ic50	0.0001	uM
(1S,9aR,11aS)-9a,11a-dimethyl-7-oxo-N-phenyl-1,2,3,3a,3b,4,5,5a,6,9b,10,11-dodecahydroindeno[5,4-f]quinoline-1-carboxamide	205611: Inhibition of human 5-alpha reductase 2 isozyme.	ic50	0.0001	uM
(1S,9aR,11aS)-N-[2,5-bis(trifluoromethyl)phenyl]-6,9a,11a-trimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	205601: Binding affinity for human 5-alpha reductase 2 isozyme	ic50	0.0001	uM
(1S,9aR,11aS)-N-benzhydryl-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	205601: Binding affinity for human 5-alpha reductase 2 isozyme	ic50	0.0001	uM
(1S,9aR,11aS)-N-[bis(4-chlorophenyl)methyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	205601: Binding affinity for human 5-alpha reductase 2 isozyme	ic50	0.0001	uM
(1S,9aR,11aS)-N-(3,5-ditert-butylphenyl)-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	205601: Binding affinity for human 5-alpha reductase 2 isozyme	ic50	0.0001	uM
(1S,9aR,11aS)-N-[2-tert-butyl-5-(trifluoromethyl)phenyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	205601: Binding affinity for human 5-alpha reductase 2 isozyme	ic50	0.0001	uM
(1S,9aR,11aS)-N-benzhydryl-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,9b,10,11-decahydrocyclopenta[i]phenanthridine-1-carboxamide	205603: In vitro inhibitory activity against human type 2 5-alpha reductase	ic50	0.0001	uM
(1S,9aR,11aS)-9a,11a-dimethyl-7-oxo-N-trityl-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	205603: In vitro inhibitory activity against human type 2 5-alpha reductase	ic50	0.0001	uM
(1S,9aR,11aS)-N-(1-adamantyl)-5,9a,11a-trimethyl-7-oxo-2,3,3a,3b,4,8,9,9b,10,11-decahydro-1H-cyclopenta[i]phenanthridine-1-carboxamide	205603: In vitro inhibitory activity against human type 2 5-alpha reductase	ic50	0.0001	uM
(1S,9aR,11aS)-9a,11a-dimethyl-1-(naphthalene-1-carbonyl)-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridin-7-one	205603: In vitro inhibitory activity against human type 2 5-alpha reductase	ic50	0.0001	uM
(1S,9aR,11aS)-9a,11a-dimethyl-1-nonanoyl-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridin-7-one	205603: In vitro inhibitory activity against human type 2 5-alpha reductase	ic50	0.0001	uM
(1S,9aR,11aS)-1-(2-cyclohexylacetyl)-9a,11a-dimethyl-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridin-7-one	205603: In vitro inhibitory activity against human type 2 5-alpha reductase	ic50	0.0001	uM
(1S,9aR,11aS)-N-(1-adamantyl)-6,9a,11a-trimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	205603: In vitro inhibitory activity against human type 2 5-alpha reductase	ic50	0.0001	uM
(1S,9aR,11aS)-N-(1-adamantyl)-6-bromo-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	205603: In vitro inhibitory activity against human type 2 5-alpha reductase	ic50	0.0001	uM
(1S,9aR,11aS)-N-benzhydryl-6,9a,11a-trimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	205603: In vitro inhibitory activity against human type 2 5-alpha reductase	ic50	0.0001	uM
(1S,9aR,11aS)-5,9a,11a-trimethyl-1-(3-methylbutanoyl)-2,3,3a,3b,4,8,9,9b,10,11-decahydro-1H-cyclopenta[i]phenanthridin-7-one	205603: In vitro inhibitory activity against human type 2 5-alpha reductase	ic50	0.0001	uM
(1S,9aR,11aS)-9a,11a-dimethyl-1-(3-methylbutanoyl)-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridin-7-one	205603: In vitro inhibitory activity against human type 2 5-alpha reductase	ic50	0.0001	uM
(1S,9aR,11aS)-N-(1-adamantyl)-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,9b,10,11-decahydrocyclopenta[i]phenanthridine-1-carboxamide	205603: In vitro inhibitory activity against human type 2 5-alpha reductase	ic50	0.0001	uM
(1S,9aR,11aS)-N-(1-adamantyl)-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	205603: In vitro inhibitory activity against human type 2 5-alpha reductase	ic50	0.0001	uM
(1S,9aR,11aS)-1-(2,6-difluorobenzoyl)-9a,11a-dimethyl-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridin-7-one	205603: In vitro inhibitory activity against human type 2 5-alpha reductase	ic50	0.0001	uM
(1S,9aR,11aS)-N-[2-tert-butyl-5-(4-tert-butylphenyl)phenyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207446: Inhibitory activity measured on human steroid 5-alpha-reductase type 2	ic50	0.0001	uM
(1S,9aR,11aS)-N-(5-bromo-2-tert-butylphenyl)-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207446: Inhibitory activity measured on human steroid 5-alpha-reductase type 2	ic50	0.0001	uM
(1S,9aR,11aS)-N-(2-tert-butyl-5-chlorophenyl)-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207446: Inhibitory activity measured on human steroid 5-alpha-reductase type 2	ic50	0.0001	uM
(10R,13S,17S)-17-[[1-(4-chlorophenyl)cyclopentyl]carbamoyl]-10,13-dimethyl-2,7,8,9,11,12,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthrene-3-carboxylic acid	207446: Inhibitory activity measured on human steroid 5-alpha-reductase type 2	ic50	0.0001	uM
(1S,9aR,11aS)-N-(4-bromo-2-tert-butylphenyl)-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207446: Inhibitory activity measured on human steroid 5-alpha-reductase type 2	ic50	0.0001	uM
(1S,9aR,11aS)-N-[1-(4-tert-butylphenyl)cycloheptyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207446: Inhibitory activity measured on human steroid 5-alpha-reductase type 2	ic50	0.0001	uM
(1S,9aR,11aS)-N-[1-(2,4-dichlorophenyl)cyclopropyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207446: Inhibitory activity measured on human steroid 5-alpha-reductase type 2	ic50	0.0001	uM
(1S,9aR,11aS)-N-[1-(4-chlorophenyl)cyclohexyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207446: Inhibitory activity measured on human steroid 5-alpha-reductase type 2	ic50	0.0001	uM
(1S,9aR,11aS)-N-[1-(4-tert-butylphenyl)cyclopentyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207446: Inhibitory activity measured on human steroid 5-alpha-reductase type 2	ic50	0.0001	uM
(1S,9aR,11aS)-N-[2,6-bis(trifluoromethyl)phenyl]-6,9a,11a-trimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207446: Inhibitory activity measured on human steroid 5-alpha-reductase type 2	ic50	0.0001	uM
(1S,9aR,11aS)-N-[2-tert-butyl-6-(trifluoromethyl)phenyl]-6,9a,11a-trimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207446: Inhibitory activity measured on human steroid 5-alpha-reductase type 2	ic50	0.0001	uM
(1S,9aR,11aS)-N-[1-(4-tert-butylphenyl)cyclohexyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207446: Inhibitory activity measured on human steroid 5-alpha-reductase type 2	ic50	0.0001	uM
(1S,9aR,11aS)-N-[2-tert-butyl-5-(4-chlorophenyl)phenyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207446: Inhibitory activity measured on human steroid 5-alpha-reductase type 2	ic50	0.0001	uM
(1S,9aR,11aS)-N-(2-tert-butyl-5-phenylphenyl)-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,8,9,9b,10,11-dodecahydrocyclopenta[i]phenanthridine-1-carboxamide	207446: Inhibitory activity measured on human steroid 5-alpha-reductase type 2	ic50	0.0001	uM
(9aR,11aS)-9a,11a-dimethyl-7-oxo-N-[3-(trifluoromethyl)phenyl]-1,2,3,3a,3b,4,5,5a,6,9b,10,11-dodecahydroindeno[5,4-f]quinoline-1-carboxamide	207443: Inhibition of recombinant human Steroid 5-alpha-reductase type 2	ic50	0.0001	uM
(9aR,11aS)-N-(3-chlorophenyl)-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,5a,6,9b,10,11-dodecahydroindeno[5,4-f]quinoline-1-carboxamide	207443: Inhibition of recombinant human Steroid 5-alpha-reductase type 2	ic50	0.0001	uM
(9aR,11aS)-N-(2-chlorophenyl)-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,5a,6,9b,10,11-dodecahydroindeno[5,4-f]quinoline-1-carboxamide	207443: Inhibition of recombinant human Steroid 5-alpha-reductase type 2	ic50	0.0001	uM
(9aR,11aS)-N-(2-fluorophenyl)-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,5a,6,9b,10,11-dodecahydroindeno[5,4-f]quinoline-1-carboxamide	207443: Inhibition of recombinant human Steroid 5-alpha-reductase type 2	ic50	0.0001	uM
(9aR,11aS)-9a,11a-dimethyl-7-oxo-N-(3-phenylphenyl)-1,2,3,3a,3b,4,5,5a,6,9b,10,11-dodecahydroindeno[5,4-f]quinoline-1-carboxamide	207443: Inhibition of recombinant human Steroid 5-alpha-reductase type 2	ic50	0.0001	uM
(9aR,11aS)-9a,11a-dimethyl-7-oxo-N-(2-phenylphenyl)-1,2,3,3a,3b,4,5,5a,6,9b,10,11-dodecahydroindeno[5,4-f]quinoline-1-carboxamide	207443: Inhibition of recombinant human Steroid 5-alpha-reductase type 2	ic50	0.0001	uM

CTD chemical–gene interactions

48 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Finasteride	decreases reaction, increases activity, increases expression, increases reaction, decreases activity	6
tributyltin	increases expression, increases reaction, decreases activity, decreases reaction	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Testosterone	increases activity, increases expression, increases reaction, decreases reaction	2
Aflatoxin B1	affects expression, decreases expression	2
methyleugenol	decreases expression	1
bis(tri-n-butyltin)oxide	decreases activity	1
mangiferin	decreases activity	1
vinyl fluoride	decreases activity	1
sodium arsenite	increases expression	1
dibutyldichlorotin	decreases activity	1
butylbenzyl phthalate	increases expression	1
androstane-3,17-diol glucuronide	decreases abundance	1
triphenyltin	decreases activity	1
piperidine	decreases activity	1
puerarin	decreases expression	1
fenarimol	decreases activity	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
prochloraz	decreases activity	1
epigallocatechin gallate	decreases expression	1
pomiferin	decreases expression	1
clothianidin	increases expression	1
osajin	decreases expression	1
abrine	increases expression	1
diphlorethohydroxycarmalol	decreases reaction, increases activity	1
rosavin	decreases expression	1
Dutasteride	decreases expression	1
Resveratrol	decreases expression	1
Zoledronic Acid	increases expression	1
Cadmium	increases expression	1

ChEMBL screening assays

119 unique, capped per target: 115 binding, 4 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1106729	Binding	Inhibition of human 5alpha reductase 2 expressed in HEK293 cells assessed as inhibition of conversion of [14C]4-androstene-3,17-dione to [14C]5R-androstane-3,17-dione at 0.3 uM after 3 hrs	Potent and selective steroidal inhibitors of 17beta-hydroxysteroid dehydrogenase type 7, an enzyme that catalyzes the reduction of the key hormones estrone and dihydrotestosterone. — J Med Chem
CHEMBL814231	Functional	In vitro inhibition against Steroid 5-alpha-reductase of benign hyperplastic human prostatic tissue expressed as apparent inhibition constant	Steroidal A ring aryl carboxylic acids: a new class of steroid 5 alpha-reductase inhibitors. — J Med Chem

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder