HSD17B3

Summary

HSD17B3 (hydroxysteroid 17-beta dehydrogenase 3, HGNC:5212) is a protein-coding gene on chromosome 9q22.32, encoding 17-beta-hydroxysteroid dehydrogenase type 3 (P37058). Catalyzes the conversion of 17-oxosteroids to 17beta-hydroxysteroids.

This isoform of 17 beta-hydroxysteroid dehydrogenase is expressed predominantly in the testis and catalyzes the conversion of androstenedione to testosterone. It preferentially uses NADP as cofactor. Deficiency can result in male pseudohermaphroditism with gynecomastia.

Source: NCBI Gene 3293 — RefSeq curated summary.

At a glance

• Gene–disease (curated): 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency (Definitive, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 304 total — 25 pathogenic, 21 likely-pathogenic
• Phenotypes (HPO): 16
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_000197

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5212
Approved symbol	HSD17B3
Name	hydroxysteroid 17-beta dehydrogenase 3
Location	9q22.32
Locus type	gene with protein product
Status	Approved
Aliases	SDR12C2
Ensembl gene	ENSG00000130948
Ensembl biotype	protein_coding
OMIM	605573
Entrez	3293

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 protein_coding, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000375262, ENST00000375263, ENST00000467499, ENST00000484816, ENST00000494814, ENST00000648146, ENST00000648332, ENST00000648799, ENST00000650005, ENST00000650386

RefSeq mRNA: 1 — MANE Select: NM_000197 NM_000197

CCDS: CCDS6716

Canonical transcript exons

ENST00000375263 — 11 exons

Exon	Start	End
ENSE00000895685	96254868	96254943
ENSE00000895686	96298416	96298462
ENSE00003506291	96245345	96245426
ENSE00003573360	96246556	96246590
ENSE00003600030	96249751	96249786
ENSE00003604146	96240758	96240907
ENSE00003611256	96251418	96251485
ENSE00003636684	96235306	96235570
ENSE00003652031	96244329	96244394
ENSE00003672420	96252803	96252910
ENSE00003839863	96301951	96302176

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 92.40.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0659 / max 45.1085, expressed in 13 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101591	0.0293	7
101590	0.0245	5
101589	0.0121	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	92.40	gold quality
left testis	UBERON:0004533	91.76	gold quality
testis	UBERON:0000473	91.68	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.42	gold quality
right lobe of liver	UBERON:0001114	81.48	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	79.49	gold quality
tibial nerve	UBERON:0001323	76.68	gold quality
substantia nigra	UBERON:0002038	76.29	gold quality
mucosa of stomach	UBERON:0001199	75.96	gold quality
left lobe of thyroid gland	UBERON:0001120	74.89	gold quality
thyroid gland	UBERON:0002046	74.74	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	74.54	gold quality
liver	UBERON:0002107	74.09	gold quality
sural nerve	UBERON:0015488	73.74	gold quality
corpus callosum	UBERON:0002336	73.65	gold quality
right lobe of thyroid gland	UBERON:0001119	72.82	gold quality
Ammon’s horn	UBERON:0001954	72.65	gold quality
right uterine tube	UBERON:0001302	72.10	gold quality
apex of heart	UBERON:0002098	70.90	gold quality
monocyte	CL:0000576	70.59	gold quality
putamen	UBERON:0001874	70.49	gold quality
endocervix	UBERON:0000458	70.27	gold quality
leukocyte	CL:0000738	69.66	gold quality
temporal lobe	UBERON:0001871	69.59	gold quality
amygdala	UBERON:0001876	69.57	gold quality
heart left ventricle	UBERON:0002084	69.31	gold quality
body of pancreas	UBERON:0001150	68.86	gold quality
left uterine tube	UBERON:0001303	68.56	gold quality
primary visual cortex	UBERON:0002436	68.25	gold quality
Brodmann (1909) area 9	UBERON:0013540	67.59	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.10

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, PAX1

miRNA regulators (miRDB)

11 targeting HSD17B3, 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-4470	99.66	69.35	1767
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-3199	99.17	65.19	696
HSA-MIR-8052	99.17	65.01	719
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-4515	95.70	65.73	716

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 27)

• XY sex reversal is sufficiently variable in 17betaHSD3 deficiency to cause problems in accurate diagnosis, particularly in distinguishing it from Androgen Insentitivity Syndrome in undervirilized males.. (PMID:17466011)
• present the clinical, biochemical, and genetic features of a male pseudohermaphrodite whose condition was caused by 17beta-HSD3 deficiency. (PMID:17509588)
• compared (+)- and (-)-gossypols in the inhibition of 3beta-HSD and 17beta-HSD3 in human and rat testes (PMID:19429456)
• These results suggest that the HSD17B3 G289S polymorphism may be a potential risk modifier for hypospadias. (PMID:20059664)
• oxazolidinediones and thiazolidinediones are potent 17beta-hydroxysteroid dehydrogenase type 3 inhibitors (PMID:22137341)
• 68 males with testicular 17beta-HSD deficiency were identified among a highly inbred Arab population in Israel as affected with male pseudohermaphroditism. [Review] (PMID:22217844)
• Case Report: rare form of 46,XY disorders of sexual development, associated to a novel gene nonsense mutation of HSD17B3 gene. (PMID:22594312)
• Results demonstrate a cytoplasmic orientation of 17beta-HSD3 and dependence on glucose-6-phosphate dehydrogenase-generated NADPH, explaining the lack of a direct functional coupling with the luminal 11beta-HSD1-mediated glucocorticoid metabolism (PMID:23183177)
• in two sisters with 17beta hydroxysteroid dehydrogenase type 3 deficiency, a heterozygous mutation for both a known splicing mutation and a previously unreported amplification mutation of the HSD17B3 gene were identified (PMID:23375913)
• Circulating testosterone levels were higher in men with early repolarization electrocardiograms. (PMID:23916922)
• Androgen-metaboliizing enzymes, 17betaHSD5 and 5alpha1 immunoreactivity was decreased in metastatic lymph nodes of breast cancers. (PMID:23953348)
• The H8 haplotype of the HSD17B3 gene was significantly associated with increased risks of acne vulgaris in Han Chinese from the Southwest China. (PMID:24157973)
• Expression of the genes HSD3B1, HSD17B3, and SRD5A2 was significantly increased in BPH tissues compared to normal adjacent prostate tissues. (PMID:24810473)
• Missense mutation in HSD17B3 gene in a 46, XY adolescent is associated with primary amenorrhea and virilization at puberty (PMID:25064799)
• 38% of unrelated 46,XY females with unknown diagnosis in the study have HSD17B3 mutations predicted to cause HSD17B3 deficiency. (PMID:25740850)
• Mutations in the HSD17B3 gene is associated with Disorders of Sex Development. (PMID:25879310)
• Mutations in the HSD17B3 gene is associated with Disorders of Sex Development. (PMID:25894637)
• Mutation G133R in HSD17B3 results in almost complete loss of enzyme activity since it interferes with binding of cofactor NADPH. (PMID:26545797)
• analysis of Tunisian patients with mutations in the gene encoding 17beta-hydroxysteroid dehydrogenase type 3 and a founder effect (PMID:26956191)
• The study shows that 17-beta-HSD-3 deficiency is not an uncommon disorder among Egyptian DSD cases. It was evidenced that the mutational profile of the disease is rather heterogeneous, relatively different from those reported in other populations, and has a high degree of novel genetic defects. (PMID:27073926)
• mutations of HSD17B3 in three Chinese patients with 46,XY Disorders of Sex Development (PMID:28774765)
• The 17beta-HSD3 G289S substitution, previously reported in other patients with 46,XY disorders of sex development, is a polymorphism that does not cause the disorder. (PMID:28859874)
• Establishment of HEK293 cells expressing various missense mutations in the HSD17B3 gene associated with 46,XY DSD revealed that this system is effective to evaluate the enzymatic activities of mutant proteins. (PMID:31614207)
• The novel founder homozygous V225M mutation in the HSD17B3 gene causes aberrant splicing and XY-DSD. (PMID:32372306)
• Substituted Aryl Benzylamines as Potent and Selective Inhibitors of 17beta-Hydroxysteroid Dehydrogenase Type 3. (PMID:34885749)
• Lessons from 17beta-HSD3 deficiency: Clinical spectrum and complex molecular basis in Chinese patients. (PMID:36154887)
• Molecular mechanisms underlying the defects of two novel mutations in the HSD17B3 gene found in the Tunisian population. (PMID:36563763)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	hsd17b3	ENSDARG00000023287
mus_musculus	Hsd17b3	ENSMUSG00000033122
rattus_norvegicus	Hsd17b3	ENSRNOG00000019096

Paralogs (25): HSD17B6 (ENSG00000025423), RDH11 (ENSG00000072042), HSD17B10 (ENSG00000072506), DHRS9 (ENSG00000073737), HSD17B2 (ENSG00000086696), HSD17B14 (ENSG00000087076), DHRS12 (ENSG00000102796), HSDL1 (ENSG00000103160), HSD17B1 (ENSG00000108786), RDH10 (ENSG00000121039), HSD17B7 (ENSG00000132196), HSD17B4 (ENSG00000133835), RDH5 (ENSG00000135437), RDH16 (ENSG00000139547), RDH12 (ENSG00000139988), HSD17B12 (ENSG00000149084), BDH1 (ENSG00000161267), DHRS3 (ENSG00000162496), SDR9C7 (ENSG00000170426), HSD17B13 (ENSG00000170509), SDR16C5 (ENSG00000170786), HSD11B2 (ENSG00000176387), WWOX (ENSG00000186153), HSD17B11 (ENSG00000198189), HSD17B8 (ENSG00000204228)

Protein

Protein identifiers

17-beta-hydroxysteroid dehydrogenase type 3 — P37058 (reviewed: P37058)

Alternative names: Estradiol 17-beta-dehydrogenase 2, Short chain dehydrogenase/reductase family 12C member 2, Testicular 17-beta-hydroxysteroid dehydrogenase, Testosterone 17-beta-dehydrogenase 3

All UniProt accessions (8): P37058, A0A0S2Z3U6, A0A0S2Z3V7, A0A0S2Z406, A0A0S2Z413, A0A3B3ITT4, A0A3B3ITW2, Q6FH62

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the conversion of 17-oxosteroids to 17beta-hydroxysteroids. Favors the reduction of androstenedione to testosterone. Testosterone is the key androgen driving male development and function. Uses NADPH while the two other EDH17B enzymes use NADH. Androgens such as epiandrosterone, dehydroepiandrosterone, androsterone and androstanedione are accepted as substrates and reduced at C-17. Can reduce 11-ketoandrostenedione as well as 11beta-hydroxyandrostenedione at C-17 to the respective testosterone forms.

Subcellular location. Endoplasmic reticulum.

Tissue specificity. Testis.

Disease relevance. Male pseudohermaphrodism with gynecomastia (MPH) [MIM:264300] An autosomal recessive disorder that manifests, in males, as undermasculinization characterized by hypoplastic-to-normal internal genitalia (epididymis, vas deferens, seminal vesicles, and ejaculatory ducts) but female external genitalia and the absence of a prostate. This phenotype is caused by inadequate testicular synthesis of testosterone, which, in turn, results in insufficient formation of dihydrotestosterone in the anlage of the external genitalia and prostate during fetal development. At the expected time of puberty, there is a marked increase in plasma leuteinizing hormone and, consequently, in testicular secretion of androstenedione. Hence, a diagnostic hallmark of this disorder is a decreased plasma testosterone-to-androstenedione ratio. Significant amounts of the circulating androstenedione are, however, converted to testosterone, in peripheral tissues, thereby causing virilization. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Hormone biosynthesis; testosterone biosynthesis. Steroid metabolism.

Similarity. Belongs to the short-chain dehydrogenases/reductases (SDR) family. 17-beta-HSD 3 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P37058-1	1	yes
P37058-2	2

RefSeq proteins (1): NP_000188* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002347	SDR_fam	Family
IPR020904	Sc_DH/Rdtase_CS	Conserved_site
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR051019	VLCFA-Steroid_DH	Family

Pfam: PF00106

Enzyme classification (BRENDA):

• EC 1.1.1.51 — 3(or 17)beta-hydroxysteroid dehydrogenase (BRENDA: 18 organisms, 150 substrates, 207 inhibitors, 72 Km, 42 kcat entries)
• EC 1.1.1.64 — testosterone 17beta-dehydrogenase (NADP+) (BRENDA: 9 organisms, 60 substrates, 221 inhibitors, 29 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
TESTOSTERONE	0.0006–0.31	7
NAD+	0.023–0.26	5
NADP+	0.0046–0.047	5
NADH	0.0053–0.642	4
NADP+	0.0082–9.6	4
TESTOSTERONE	0.0015–0.27	4
5ALPHA-ANDROST-16-EN-3-ONE	0.068–0.176	3
5ALPHA-DIHYDROTESTOSTERONE	0.0076–0.2	3
ANDROSTENEDIONE	0.0007–0.04	3
NADPH	0.0083–0.011	3
5ALPHA-PREGNAN-3BETA-OL-20-ONE	0.0039–0.116	2
5BETA-PREGNAN-3,20-DIONE	0.21–1.725	2
5BETA-PREGNAN-3BETA-OL-20-ONE	0.0068–0.314	2
DEHYDROEPIANDROSTERONE	—	2
NADPH	0.0018–0.0021	2

Catalyzed reactions (Rhea), 9 shown:

• testosterone + NADP(+) = androst-4-ene-3,17-dione + NADPH + H(+) (RHEA:14981)
• 17beta-estradiol + NADP(+) = estrone + NADPH + H(+) (RHEA:24616)
• 17beta-hydroxy-5alpha-androstan-3-one + NADP(+) = 5alpha-androstan-3,17-dione + NADPH + H(+) (RHEA:42120)
• androsterone + NADPH + H(+) = 5alpha-androstane-3alpha,17beta-diol + NADP(+) (RHEA:42156)
• 3beta-hydroxyandrost-5-en-17-one + NADPH + H(+) = androst-5-en-3beta,17beta-diol + NADP(+) (RHEA:46628)
• 3beta-hydroxy-5alpha-androstan-17-one + NADPH + H(+) = 5alpha-androstane-3beta,17beta-diol + NADP(+) (RHEA:53480)
• androst-4-ene-3,11,17-trione + NADPH + H(+) = 17beta-hydroxyandrost-4-ene-3,11-dione + NADP(+) (RHEA:53484)
• 11beta-hydroxyandrost-4-ene-3,17-dione + NADPH + H(+) = 11beta,17beta-dihydroxyandrost-4-ene-3-one + NADP(+) (RHEA:53488)
• a 17beta-hydroxy steroid + NADP(+) = a 17-oxo steroid + NADPH + H(+) (RHEA:69284)

UniProt features (27 total): sequence variant 19, mutagenesis site 3, binding site 2, chain 1, active site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P37058-F1	93.59	0.85

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 198 (proton acceptor)

Ligand- & substrate-binding residues (2): 48–77; 185

Mutagenesis-validated functional residues (3):

Position	Phenotype
133	has 70% of wild-type testosterone 17-beta-dehydrogenase (nadp(+)) activity.
133	almost complete loss of testosterone 17-beta-dehydrogenase (nadp(+)) activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-193048	Androgen biosynthesis
R-HSA-75876	Synthesis of very long-chain fatty acyl-CoAs

MSigDB gene sets: 167 (showing top): REACTOME_SYNTHESIS_OF_VERY_LONG_CHAIN_FATTY_ACYL_COAS, MORF_FLT1, GOBP_MALE_GENITALIA_DEVELOPMENT, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_KETONE_METABOLIC_PROCESS, 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, GOBP_REPRODUCTIVE_SYSTEM_DEVELOPMENT, DELYS_THYROID_CANCER_DN, GOBP_HORMONE_BIOSYNTHETIC_PROCESS, GOBP_STEROID_BIOSYNTHETIC_PROCESS, GOBP_ANDROGEN_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_KETONE_BIOSYNTHETIC_PROCESS

GO Biological Process (5): steroid biosynthetic process (GO:0006694), androgen biosynthetic process (GO:0006702), male genitalia development (GO:0030539), testosterone biosynthetic process (GO:0061370), lipid metabolic process (GO:0006629)

GO Molecular Function (6): estradiol 17-beta-dehydrogenase [NAD(P)+] activity (GO:0004303), testosterone dehydrogenase (NADP+) activity (GO:0047045), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), obsolete testosterone dehydrogenase [NAD(P)+] activity (GO:0030283), 17-beta-hydroxysteroid dehydrogenase (NADP+) activity (GO:0072582)

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), intracellular membrane-bounded organelle (GO:0043231)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of steroid hormones	1
Fatty acyl-CoA biosynthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	2
steroid metabolic process	1
lipid biosynthetic process	1
androgen metabolic process	1
hormone biosynthetic process	1
steroid hormone biosynthetic process	1
male sex differentiation	1
genitalia development	1
reproductive system development	1
steroid biosynthetic process	1
ketone biosynthetic process	1
olefinic compound biosynthetic process	1
primary metabolic process	1
17-beta-hydroxysteroid dehydrogenase (NADP+) activity	1
binding	1
catalytic activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
intracellular anatomical structure	1
membrane-bounded organelle	1
intracellular organelle	1

Protein interactions and networks

STRING

1912 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSD17B3	HSD17B2	P37059	979
HSD17B3	HSD17B1	P14061	976
HSD17B3	HSD17B4	P51659	953
HSD17B3	CYP17A1	P05093	905
HSD17B3	HSD3B2	P26439	875
HSD17B3	AKR1C3	P42330	858
HSD17B3	HSD3B1	P14060	839
HSD17B3	CYP11A1	P05108	816
HSD17B3	SRD5A2	P31213	800
HSD17B3	INSL3	P51460	796
HSD17B3	SRD5A1	P18405	792
HSD17B3	LHCGR	P22888	761
HSD17B3	STAR	P49675	756
HSD17B3	AKR1C2	P52895	742
HSD17B3	NR5A1	Q13285	691

IntAct

16 interactions, top by confidence:

A	B	Type	Score
HSD17B3	NCS1	psi-mi:“MI:0915”(physical association)	0.620
HSD17B3	MLH1	psi-mi:“MI:0915”(physical association)	0.370
BRAF	HSD17B3	psi-mi:“MI:0915”(physical association)	0.370
HSD17B3	BUB1	psi-mi:“MI:0915”(physical association)	0.370
HSD17B3	CDH1	psi-mi:“MI:0915”(physical association)	0.370
HSD17B3	CTNNA1	psi-mi:“MI:0915”(physical association)	0.370
DLC1	HSD17B3	psi-mi:“MI:0915”(physical association)	0.370
ERBB2	HSD17B3	psi-mi:“MI:0915”(physical association)	0.370
MCC	HSD17B3	psi-mi:“MI:0915”(physical association)	0.370
MLH3	HSD17B3	psi-mi:“MI:0915”(physical association)	0.370
HSD17B3	SMAD2	psi-mi:“MI:0915”(physical association)	0.370
HSD17B3	POTEI	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.350
HSD17B3	UBB	psi-mi:“MI:0914”(association)	0.350

BioGRID (34): POTEI (Affinity Capture-MS), ACTB (Affinity Capture-MS), PYGB (Affinity Capture-MS), TAX1BP1 (Affinity Capture-MS), HERC3 (Affinity Capture-MS), NCS1 (Affinity Capture-MS), HSD17B3 (Affinity Capture-MS), POTEI (Affinity Capture-MS), PCP2 (Affinity Capture-MS), HERC3 (Affinity Capture-MS), AHNAK (Affinity Capture-MS), ACTBL2 (Affinity Capture-MS), AMFR (Affinity Capture-MS), NCS1 (Affinity Capture-MS), ACTB (Affinity Capture-MS)

ESM2 similar proteins: A0A140FAN3, A4IGM4, A5PJF6, A5PJJ7, A7LB60, O54939, O70503, P0DKC5, P0DKC6, P0DKC7, P16232, P28845, P37058, P50172, P51975, P70385, Q05A13, Q29608, Q3SXM5, Q4JK73, Q4V8B7, Q5NVG2, Q5R7K0, Q5ZJG8, Q6AYS8, Q6P3L6, Q6P7J1, Q6PUF3, Q6PUF4, Q6QA32, Q6QLL4, Q6R0J2, Q7M3I4, Q7SYS6, Q7TQA3, Q7Z5P4, Q80ZF7, Q8AVY8, Q8BTX9, Q8HZJ8

Diamond homologs: A0A1U8QWA2, A1C6J8, A1DH66, A2QCH3, A3LXZ3, A4QTE3, A5DND6, A5E0R1, A5PJF6, A6RBW9, A6SG70, A6ZLA1, A7F8T1, A7IQF2, A7TMJ2, A8N6B4, A8Q1U2, B0D8R3, B0XSI3, B2B3L4, B2WMJ3, B3LN00, G0RNA2, O16925, O17795, O31767, O54939, O57314, O70503, P0CR34, P0CR35, P14802, P37058, P38286, P41177, P51831, P70385, Q09517, Q0CY11, Q0IH28

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	25
Likely pathogenic	21
Uncertain significance	54
Likely benign	156
Benign	32

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1202595	NM_000197.2(HSD17B3):c.679A>G (p.Thr227Ala)	Pathogenic
1943775	NM_000197.2(HSD17B3):c.159_160insT (p.Thr54fs)	Pathogenic
208587	NM_000197.2(HSD17B3):c.277+4A>T	Pathogenic
2200699	NM_000197.2(HSD17B3):c.729_735del (p.Ile244fs)	Pathogenic
2674664	NM_000197.2(HSD17B3):c.201+1G>A	Pathogenic
2735299	NM_000197.2(HSD17B3):c.761_762del (p.Glu254fs)	Pathogenic
2735655	NM_000197.2(HSD17B3):c.663_664insCAGGTGAGGTGGGCAGCTGTGGAGTCCTTGTCATCGTCCAGGTGAGGTGGGCAGCTGTGGAGTCCTTGTC (p.Ile222delinsGlnValArgTrpAlaAlaValGluSerLeuSerSerSerArgTer)	Pathogenic
2785248	NM_000197.2(HSD17B3):c.541_554dup (p.Ser185_Gly186insTer)	Pathogenic
2797144	NM_000197.2(HSD17B3):c.352G>T (p.Glu118Ter)	Pathogenic
2799296	NM_000197.2(HSD17B3):c.822+1G>A	Pathogenic
2884604	NM_000197.2(HSD17B3):c.383T>G (p.Leu128Ter)	Pathogenic
2884763	NM_000197.2(HSD17B3):c.105C>A (p.Tyr35Ter)	Pathogenic
2969610	NM_000197.2(HSD17B3):c.199G>T (p.Glu67Ter)	Pathogenic
2998160	NM_000197.2(HSD17B3):c.799G>A (p.Gly267Ser)	Pathogenic
3245281	NC_000009.11:g.(?99064213)(99064386_?)del	Pathogenic
3642919	NM_000197.2(HSD17B3):c.415dup (p.Leu139fs)	Pathogenic
4079685	NM_000197.2(HSD17B3):c.673-1G>C	Pathogenic
4294008	NM_000197.2(HSD17B3):c.150G>A (p.Trp50Ter)	Pathogenic
4532134	NM_000197.2(HSD17B3):c.302dup (p.Ile102fs)	Pathogenic
4538410	NM_000197.2(HSD17B3):c.525-2del	Pathogenic
4874	NM_000197.2(HSD17B3):c.239G>A (p.Arg80Gln)	Pathogenic
488878	NM_000197.2(HSD17B3):c.202-1G>A	Pathogenic
492760	NM_000197.2(HSD17B3):c.121_122del (p.Lys41fs)	Pathogenic
492761	NM_000197.2(HSD17B3):c.278-1G>C	Pathogenic
492765	NM_000197.2(HSD17B3):c.454-1G>A	Pathogenic
1342170	NM_000197.2(HSD17B3):c.3G>A (p.Met1Ile)	Likely pathogenic
2674663	NM_000197.2(HSD17B3):c.1A>G (p.Met1Val)	Likely pathogenic
2674666	NM_000197.2(HSD17B3):c.277+5G>A	Likely pathogenic
2674667	NM_000197.2(HSD17B3):c.590T>A (p.Met197Lys)	Likely pathogenic
2690623	NM_000197.2(HSD17B3):c.252del (p.Lys84fs)	Likely pathogenic

SpliceAI

1871 predictions. Top by Δscore:

Variant	Effect	Δscore
9:96251486:C:CC	acceptor_gain	1.0000
9:96252797:ACTC:A	donor_loss	1.0000
9:96252799:TCAC:T	donor_loss	1.0000
9:96252800:CAC:C	donor_loss	1.0000
9:96252801:A:C	donor_loss	1.0000
9:96252802:CCTAA:C	donor_gain	1.0000
9:96252906:CCGCT:C	acceptor_gain	1.0000
9:96252907:CGCT:C	acceptor_gain	1.0000
9:96252907:CGCTC:C	acceptor_gain	1.0000
9:96252909:CT:C	acceptor_gain	1.0000
9:96252911:C:CA	acceptor_loss	1.0000
9:96252911:C:CC	acceptor_gain	1.0000
9:96252912:T:C	acceptor_loss	1.0000
9:96301946:CTTA:C	donor_loss	1.0000
9:96301947:TTA:T	donor_loss	1.0000
9:96301948:TACC:T	donor_loss	1.0000
9:96301996:T:A	donor_gain	1.0000
9:96235568:CGCCT:C	acceptor_gain	0.9900
9:96235572:T:C	acceptor_gain	0.9900
9:96249459:G:A	donor_gain	0.9900
9:96251491:A:T	acceptor_gain	0.9900
9:96252802:CCTA:C	donor_gain	0.9900
9:96252908:GCT:G	acceptor_gain	0.9900
9:96252909:CTC:C	acceptor_gain	0.9900
9:96252910:TCTAC:T	acceptor_gain	0.9900
9:96252911:C:G	acceptor_gain	0.9900
9:96252914:C:CT	acceptor_gain	0.9900
9:96298460:TCA:T	acceptor_gain	0.9900
9:96298461:CA:C	acceptor_gain	0.9900
9:96298461:CAC:C	acceptor_gain	0.9900

AlphaMissense

2007 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:96240827:A:C	F251L	0.986
9:96240827:A:T	F251L	0.986
9:96240829:A:G	F251L	0.986
9:96301957:A:G	W50R	0.986
9:96301957:A:T	W50R	0.986
9:96244389:A:C	F204L	0.985
9:96244389:A:T	F204L	0.985
9:96244391:A:G	F204L	0.985
9:96240888:A:T	V231D	0.984
9:96251481:G:C	N130K	0.984
9:96251481:G:T	N130K	0.984
9:96245345:C:A	K202N	0.983
9:96245345:C:G	K202N	0.983
9:96245405:G:C	N182K	0.983
9:96245405:G:T	N182K	0.983
9:96254918:A:T	V76D	0.982
9:96251485:A:T	V129D	0.980
9:96244375:G:A	S209F	0.978
9:96245415:A:G	L179P	0.978
9:96252867:A:C	F107L	0.978
9:96252867:A:T	F107L	0.978
9:96252869:A:G	F107L	0.978
9:96244366:A:G	L212P	0.974
9:96245359:A:G	Y198H	0.974
9:96240817:A:G	S255P	0.973
9:96245400:G:A	S184F	0.973
9:96254942:A:G	L68P	0.973
9:96245349:G:A	S201F	0.972
9:96249772:A:C	C156W	0.971
9:96301954:C:G	A51P	0.970

dbSNP variants (sampled 300 via entrez): RS1000099921 (9:96308991 G>A), RS1000120482 (9:96263016 G>A,C), RS1000139033 (9:96274444 G>C), RS1000184635 (9:96285019 A>T), RS1000192138 (9:96274239 G>A), RS1000229628 (9:96281402 T>C), RS1000331298 (9:96281185 T>C), RS1000432648 (9:96288409 G>C), RS1000481704 (9:96295075 C>T), RS1000497811 (9:96267738 A>C), RS1000522832 (9:96272875 C>A,T), RS1000636489 (9:96279960 G>A), RS1000681290 (9:96236208 C>A,T), RS1000701651 (9:96281551 A>G), RS1000734641 (9:96235869 G>A,C)

Disease associations

OMIM: gene MIM:605573 | disease phenotypes: MIM:264300

GenCC curated gene-disease

Disease	Classification	Inheritance
46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency	Definitive	Autosomal recessive

Mondo (3): disorder of sexual differentiation (MONDO:0002145), 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency (MONDO:0009916), pseudohermaphroditism (MONDO:0005518)

Orphanet (2): Difference of sex development (Orphanet:90771), 46,XY difference of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency (Orphanet:752)

HPO phenotypes

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

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000037	Male pseudohermaphroditism
HP:0000047	Hypospadias
HP:0000048	Bifid scrotum
HP:0000062	Ambiguous genitalia
HP:0000771	Gynecomastia
HP:0000789	Infertility
HP:0000821	Hypothyroidism
HP:0001939	Abnormality of metabolism/homeostasis
HP:0008665	Clitoral hypertrophy
HP:0008730	Female external genitalia in individual with 46,XY karyotype
HP:0008736	Hypoplasia of penis
HP:0025380	Increased circulating androstenedione concentration
HP:0100779	Urogenital sinus anomaly

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003072_5	Cerebrospinal fluid AB1-42 levels	9.000000e-07
GCST003139_10	Glomerular filtration rate in chronic kidney disease	9.000000e-06
GCST009311_1	Letter-number span reordering	3.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0004874	memory performance

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D012734	Disorders of Sex Development	C12.050.351.875.253; C12.200.706.316; C12.800.316; C16.131.939.316; C19.391.119
C537805	17-Hydroxysteroid Dehydrogenase Deficiency (supp.)
C564868	Polycystic Ovarian Disease due to 17-Ketosteroid Reductase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4234 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 112,245 (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
CHEMBL140	CURCUMIN	3	93,882
CHEMBL12208	HYMECROMONE	2	18,363

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

Binding affinities (BindingDB)

4 measured of 15 human assays (16 total across all organisms); most potent 4 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
5,7-dihydroxy-3-(4-methoxyphenyl)-4H-chromen-4-one	EC50	0.00334 nM
N-Adamantan-2-ylmethyl-N-(3-hydroxy-10,13-dimethyl-17-oxo-hexadecahydro-cyclopenta[a]phenanthren-3-ylmethyl)-butyramide	IC50	57 nM
3-[(Adamantan-2-ylmethyl-butyl-amino)-methyl]-3-hydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-one	IC50	80 nM
5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one	IC50	64300 nM

ChEMBL bioactivities

251 potent at pChembl≥5 of 258 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	IC50	0.02	nM	CHEMBL206167
10.70	IC50	0.02	nM	CHEMBL206384
10.70	IC50	0.02	nM	CHEMBL206432
9.30	IC50	0.5	nM	CHEMBL206167
9.30	IC50	0.5	nM	CHEMBL206384
9.15	IC50	0.7	nM	CHEMBL204882
9.05	IC50	0.9	nM	CHEMBL206405
9.00	IC50	1	nM	CHEMBL2018254
9.00	IC50	1	nM	CHEMBL204882
8.85	IC50	1.4	nM	CHEMBL383546
8.82	IC50	1.5	nM	CHEMBL589158
8.70	IC50	2	nM	CHEMBL2018139
8.70	IC50	2	nM	CHEMBL2018141
8.70	IC50	2	nM	CHEMBL2018249
8.70	IC50	2	nM	CHEMBL382563
8.70	IC50	2	nM	CHEMBL206331
8.70	IC50	2	nM	CHEMBL206405
8.70	IC50	2	nM	CHEMBL383546
8.52	IC50	3	nM	CHEMBL2018131
8.52	IC50	3	nM	CHEMBL2018142
8.52	IC50	3	nM	CHEMBL204349
8.52	IC50	3	nM	CHEMBL205426
8.52	IC50	3	nM	CHEMBL206217
8.52	IC50	3	nM	CHEMBL590129
8.40	IC50	4	nM	CHEMBL2018238
8.40	IC50	4	nM	CHEMBL2018242
8.40	IC50	4	nM	CHEMBL2018250
8.40	IC50	4	nM	CHEMBL205666
8.40	IC50	4	nM	CHEMBL206432
8.40	IC50	4	nM	CHEMBL202916
8.30	IC50	5	nM	CHEMBL2018251
8.30	IC50	5	nM	CHEMBL2018253
8.30	IC50	5	nM	CHEMBL205915
8.30	IC50	5	nM	CHEMBL206331
8.22	IC50	6	nM	CHEMBL2018135
8.22	IC50	6	nM	CHEMBL2018140
8.22	IC50	6	nM	CHEMBL1813731
8.22	IC50	6	nM	CHEMBL1934493
8.15	IC50	7	nM	CHEMBL2018136
8.15	IC50	7	nM	CHEMBL205144
8.10	IC50	8	nM	CHEMBL206250
8.10	IC50	8	nM	CHEMBL202916
8.10	IC50	8	nM	CHEMBL589396
8.05	IC50	9	nM	CHEMBL203947
8.05	IC50	9	nM	CHEMBL382563
8.00	IC50	10	nM	CHEMBL204051
8.00	IC50	10	nM	CHEMBL589156
7.92	IC50	12	nM	CHEMBL2018138
7.92	IC50	12	nM	CHEMBL2018252
7.89	IC50	13	nM	CHEMBL1934492

PubChem BioAssay actives

256 with measured affinity, of 833 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
methyl 2-(5-acetyl-2-chloro-11,12-dihydro-6H-benzo[c][1]benzazocin-8-yl)benzoate	262177: Inhibition of 17beta-HSD3	ic50	<0.0001	uM
1-[2-(5-acetyl-2-chloro-11,12-dihydro-6H-benzo[c][1]benzazocin-8-yl)phenyl]ethanone	262177: Inhibition of 17beta-HSD3	ic50	<0.0001	uM
1-(8-phenyl-11,12-dihydro-6H-benzo[c][1]benzazocin-5-yl)ethanone	262177: Inhibition of 17beta-HSD3	ic50	<0.0001	uM
methyl 2-(5-acetyl-2-bromo-11,12-dihydro-6H-benzo[c][1]benzazocin-8-yl)benzoate	262177: Inhibition of 17beta-HSD3	ic50	0.0007	uM
1-[2-chloro-8-[2-(hydroxymethyl)phenyl]-11,12-dihydro-6H-benzo[c][1]benzazocin-5-yl]ethanone	262177: Inhibition of 17beta-HSD3	ic50	0.0009	uM
(5Z)-5-[(3-chloro-5-fluoro-4-hydroxyphenyl)methylidene]-3-(4-methoxyphenyl)-2-sulfanylidene-1,3-oxazolidin-4-one	657618: Inhibition of human recombinant 17-beta-HSD3 expressed in human HeLa cells using androstenedione as substrate preincubated for 30 mins prior substrate addition measured after 120 mins by spectrophotometry	ic50	0.0010	uM
methyl 3-(5-acetyl-2-chloro-11,12-dihydro-6H-benzo[c][1]benzazocin-8-yl)benzoate	262177: Inhibition of 17beta-HSD3	ic50	0.0014	uM
7-hydroxy-4-[(6-methyl-2-pyridinyl)sulfanylmethyl]chromen-2-one	452459: Inhibition of human 17beta-HSD3 expressed in HeLa cells	ic50	0.0015	uM
N-[2-(5-acetyl-2-chloro-11,12-dihydro-6H-benzo[c][1]benzazocin-8-yl)phenyl]methanesulfonamide	262177: Inhibition of 17beta-HSD3	ic50	0.0020	uM
1-[2-chloro-8-(2-methoxyphenyl)-11,12-dihydro-6H-benzo[c][1]benzazocin-5-yl]ethanone	262177: Inhibition of 17beta-HSD3	ic50	0.0020	uM
(5Z)-5-[(3-bromo-4-hydroxyphenyl)methylidene]-3-(4-fluorophenyl)-2-sulfanylidene-1,3-oxazolidin-4-one	657618: Inhibition of human recombinant 17-beta-HSD3 expressed in human HeLa cells using androstenedione as substrate preincubated for 30 mins prior substrate addition measured after 120 mins by spectrophotometry	ic50	0.0020	uM
(5Z)-5-[(3-bromo-4-hydroxyphenyl)methylidene]-3-(4-methylphenyl)-2-sulfanylidene-1,3-oxazolidin-4-one	657618: Inhibition of human recombinant 17-beta-HSD3 expressed in human HeLa cells using androstenedione as substrate preincubated for 30 mins prior substrate addition measured after 120 mins by spectrophotometry	ic50	0.0020	uM
(5Z)-5-[(3-fluoro-4-hydroxyphenyl)methylidene]-3-(4-methoxyphenyl)-2-sulfanylidene-1,3-oxazolidin-4-one	657618: Inhibition of human recombinant 17-beta-HSD3 expressed in human HeLa cells using androstenedione as substrate preincubated for 30 mins prior substrate addition measured after 120 mins by spectrophotometry	ic50	0.0020	uM
(5Z)-5-[(3-bromo-4-hydroxyphenyl)methylidene]-3-cyclohexyl-2-sulfanylidene-1,3-thiazolidin-4-one	657618: Inhibition of human recombinant 17-beta-HSD3 expressed in human HeLa cells using androstenedione as substrate preincubated for 30 mins prior substrate addition measured after 120 mins by spectrophotometry	ic50	0.0030	uM
1-[2-chloro-8-(4-methoxyphenyl)-11,12-dihydro-6H-benzo[c][1]benzazocin-5-yl]ethanone	262177: Inhibition of 17beta-HSD3	ic50	0.0030	uM
3-(5-acetyl-2-chloro-11,12-dihydro-6H-benzo[c][1]benzazocin-8-yl)benzonitrile	262177: Inhibition of 17beta-HSD3	ic50	0.0030	uM
4-(5-acetyl-2-chloro-11,12-dihydro-6H-benzo[c][1]benzazocin-8-yl)benzonitrile	262177: Inhibition of 17beta-HSD3	ic50	0.0030	uM
7-hydroxy-4-(pyridin-2-ylsulfanylmethyl)chromen-2-one	452459: Inhibition of human 17beta-HSD3 expressed in HeLa cells	ic50	0.0030	uM
(5Z)-5-[(3-bromo-4-hydroxyphenyl)methylidene]-2-sulfanylidene-3-[4-(trifluoromethyl)phenyl]-1,3-oxazolidin-4-one	657618: Inhibition of human recombinant 17-beta-HSD3 expressed in human HeLa cells using androstenedione as substrate preincubated for 30 mins prior substrate addition measured after 120 mins by spectrophotometry	ic50	0.0030	uM
1-[9-(benzylamino)-11,12-dihydro-6H-benzo[c][1]benzazocin-5-yl]ethanone	262178: Inhibition of 17beta-HSD3 by SEAP assay	ic50	0.0040	uM
1-(2-chloro-8-phenyl-11,12-dihydro-6H-benzo[c][1]benzazocin-5-yl)ethanone	262177: Inhibition of 17beta-HSD3	ic50	0.0040	uM
(5Z)-5-[(3-bromo-4-hydroxyphenyl)methylidene]-3-[6-(dimethylamino)-3-pyridinyl]-1,3-oxazolidine-2,4-dione	657618: Inhibition of human recombinant 17-beta-HSD3 expressed in human HeLa cells using androstenedione as substrate preincubated for 30 mins prior substrate addition measured after 120 mins by spectrophotometry	ic50	0.0040	uM
(5Z)-5-[(3-chloro-4-hydroxyphenyl)methylidene]-3-(4-methoxyphenyl)-2-sulfanylidene-1,3-oxazolidin-4-one	657618: Inhibition of human recombinant 17-beta-HSD3 expressed in human HeLa cells using androstenedione as substrate preincubated for 30 mins prior substrate addition measured after 120 mins by spectrophotometry	ic50	0.0040	uM
(5Z)-5-[(3-bromo-4-hydroxyphenyl)methylidene]-3-(6-methoxy-3-pyridinyl)-1,3-oxazolidine-2,4-dione	657618: Inhibition of human recombinant 17-beta-HSD3 expressed in human HeLa cells using androstenedione as substrate preincubated for 30 mins prior substrate addition measured after 120 mins by spectrophotometry	ic50	0.0040	uM
2-(5-acetyl-2-chloro-11,12-dihydro-6H-benzo[c][1]benzazocin-8-yl)benzonitrile	262177: Inhibition of 17beta-HSD3	ic50	0.0050	uM
(5Z)-5-[(2-chloro-4-hydroxyphenyl)methylidene]-3-(4-methoxyphenyl)-2-sulfanylidene-1,3-oxazolidin-4-one	657618: Inhibition of human recombinant 17-beta-HSD3 expressed in human HeLa cells using androstenedione as substrate preincubated for 30 mins prior substrate addition measured after 120 mins by spectrophotometry	ic50	0.0050	uM
(5Z)-5-[(3,5-difluoro-4-hydroxyphenyl)methylidene]-3-(4-methoxyphenyl)-2-sulfanylidene-1,3-oxazolidin-4-one	657618: Inhibition of human recombinant 17-beta-HSD3 expressed in human HeLa cells using androstenedione as substrate preincubated for 30 mins prior substrate addition measured after 120 mins by spectrophotometry	ic50	0.0050	uM
(5Z)-5-[(3-bromo-4-hydroxyphenyl)methylidene]-3-(4-methoxyphenyl)-2-sulfanylidene-1,3-thiazolidin-4-one	639126: Inhibition of 17beta-HSD3 in human testes homogenate	ic50	0.0060	uM
(3R,5S,8R,9S,10S,13S,14S)-3-[[(2R,5S)-2,5-dimethyl-4-[2-(trifluoromethyl)phenyl]sulfonylpiperazin-1-yl]methyl]-3-hydroxy-10,13-dimethyl-2,4,5,6,7,8,9,11,12,14,15,16-dodecahydro-1H-cyclopenta[a]phenanthren-17-one	1297420: Inhibition of 17betaHSD3 (unknown origin) transfected in HEK293 cells	ic50	0.0060	uM
(5Z)-5-[(3-bromo-4-hydroxyphenyl)methylidene]-3-phenyl-2-sulfanylidene-1,3-oxazolidin-4-one	657618: Inhibition of human recombinant 17-beta-HSD3 expressed in human HeLa cells using androstenedione as substrate preincubated for 30 mins prior substrate addition measured after 120 mins by spectrophotometry	ic50	0.0060	uM
(5Z)-5-[(3-bromo-4-hydroxyphenyl)methylidene]-3-(4-chlorophenyl)-2-sulfanylidene-1,3-oxazolidin-4-one	657618: Inhibition of human recombinant 17-beta-HSD3 expressed in human HeLa cells using androstenedione as substrate preincubated for 30 mins prior substrate addition measured after 120 mins by spectrophotometry	ic50	0.0060	uM
1-(9-bromo-11,12-dihydro-6H-benzo[c][1]benzazocin-5-yl)ethanone	262177: Inhibition of 17beta-HSD3	ic50	0.0070	uM
(5Z)-5-[(3-bromo-4-hydroxyphenyl)methylidene]-3-(3-methoxyphenyl)-2-sulfanylidene-1,3-oxazolidin-4-one	657618: Inhibition of human recombinant 17-beta-HSD3 expressed in human HeLa cells using androstenedione as substrate preincubated for 30 mins prior substrate addition measured after 120 mins by spectrophotometry	ic50	0.0070	uM
7-hydroxy-4-[2-(6-methyl-2-pyridinyl)ethyl]chromen-2-one	452459: Inhibition of human 17beta-HSD3 expressed in HeLa cells	ic50	0.0080	uM
1-[2-chloro-8-(3-methoxyphenyl)-11,12-dihydro-6H-benzo[c][1]benzazocin-5-yl]ethanone	262177: Inhibition of 17beta-HSD3	ic50	0.0080	uM
1-(8-bromo-11,12-dihydro-6H-benzo[c][1]benzazocin-5-yl)ethanone	262177: Inhibition of 17beta-HSD3	ic50	0.0090	uM
7-hydroxy-4-(1,3-thiazol-2-ylsulfanylmethyl)chromen-2-one	452459: Inhibition of human 17beta-HSD3 expressed in HeLa cells	ic50	0.0100	uM
1-(2,3-dichloro-6,11-dihydrobenzo[c][1,6]benzothiazocin-12-yl)ethanone	262177: Inhibition of 17beta-HSD3	ic50	0.0100	uM
(5Z)-5-[(3,5-dichloro-4-hydroxyphenyl)methylidene]-3-(4-methoxyphenyl)-2-sulfanylidene-1,3-oxazolidin-4-one	657618: Inhibition of human recombinant 17-beta-HSD3 expressed in human HeLa cells using androstenedione as substrate preincubated for 30 mins prior substrate addition measured after 120 mins by spectrophotometry	ic50	0.0120	uM
(5Z)-3-(1,3-benzodioxol-5-yl)-5-[(3-bromo-4-hydroxyphenyl)methylidene]-2-sulfanylidene-1,3-oxazolidin-4-one	657618: Inhibition of human recombinant 17-beta-HSD3 expressed in human HeLa cells using androstenedione as substrate preincubated for 30 mins prior substrate addition measured after 120 mins by spectrophotometry	ic50	0.0120	uM
(5Z)-5-[(3-bromo-4-hydroxyphenyl)methylidene]-3-(4-methoxyphenyl)-2-sulfanylidene-1,3-oxazolidin-4-one	639125: Inhibition of human 17beta-HSD3 expressed in HeLa cells assessed as conversion of 4-androstene-3,17-dione to testosterone	ic50	0.0130	uM
4-[(5Z)-5-[(3-bromo-4-hydroxyphenyl)methylidene]-4-oxo-2-sulfanylidene-1,3-oxazolidin-3-yl]benzonitrile	657618: Inhibition of human recombinant 17-beta-HSD3 expressed in human HeLa cells using androstenedione as substrate preincubated for 30 mins prior substrate addition measured after 120 mins by spectrophotometry	ic50	0.0190	uM
(8R,9S,13S,14S)-3-[2-[2,5-dimethyl-4-[2-(trifluoromethyl)phenyl]sulfonylpiperazin-1-yl]-1-hydroxyethyl]-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one	1607907: Inhibition of 17beta-HSD3 (unknown origin) expressed in human LNCAP cells assessed as reduction in [14C]-testosterone formation from [14C]-4-androstene-3,17-dione measured after 1 hr	ic50	0.0200	uM
7-hydroxy-4-(2-phenylethyl)chromen-2-one	452459: Inhibition of human 17beta-HSD3 expressed in HeLa cells	ic50	0.0200	uM
(5Z)-5-[(3-bromo-4-hydroxyphenyl)methylidene]-3-(6-chloro-3-pyridinyl)-1,3-oxazolidine-2,4-dione	657618: Inhibition of human recombinant 17-beta-HSD3 expressed in human HeLa cells using androstenedione as substrate preincubated for 30 mins prior substrate addition measured after 120 mins by spectrophotometry	ic50	0.0200	uM
(5Z)-5-[(4-hydroxy-3-methylphenyl)methylidene]-3-(4-methoxyphenyl)-2-sulfanylidene-1,3-oxazolidin-4-one	657618: Inhibition of human recombinant 17-beta-HSD3 expressed in human HeLa cells using androstenedione as substrate preincubated for 30 mins prior substrate addition measured after 120 mins by spectrophotometry	ic50	0.0200	uM
(5Z)-5-[(3-bromo-4-hydroxyphenyl)methylidene]-3-(6-fluoro-3-pyridinyl)-1,3-oxazolidine-2,4-dione	657618: Inhibition of human recombinant 17-beta-HSD3 expressed in human HeLa cells using androstenedione as substrate preincubated for 30 mins prior substrate addition measured after 120 mins by spectrophotometry	ic50	0.0210	uM
N-[4-[(5Z)-5-[(3-bromo-4-hydroxyphenyl)methylidene]-2,4-dioxo-1,3-oxazolidin-3-yl]phenyl]cyclohexanecarboxamide	657618: Inhibition of human recombinant 17-beta-HSD3 expressed in human HeLa cells using androstenedione as substrate preincubated for 30 mins prior substrate addition measured after 120 mins by spectrophotometry	ic50	0.0210	uM
(5Z)-5-[(3-bromo-4-hydroxyphenyl)methylidene]-3-pyridin-3-yl-1,3-oxazolidine-2,4-dione	657618: Inhibition of human recombinant 17-beta-HSD3 expressed in human HeLa cells using androstenedione as substrate preincubated for 30 mins prior substrate addition measured after 120 mins by spectrophotometry	ic50	0.0220	uM
(5Z)-5-[(3-bromo-4-hydroxyphenyl)methylidene]-3-(4-methoxyphenyl)-1,3-oxazolidine-2,4-dione	639125: Inhibition of human 17beta-HSD3 expressed in HeLa cells assessed as conversion of 4-androstene-3,17-dione to testosterone	ic50	0.0230	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects expression, decreases expression, decreases methylation	3
bisphenol A	decreases expression, decreases activity	2
Estradiol	affects expression, affects cotreatment, decreases expression	2
NADP	decreases activity, decreases reaction, affects binding, increases activity	2
Aflatoxin B1	affects expression, decreases expression	2
propionaldehyde	increases expression	1
terbufos	increases methylation	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases activity	1
tobacco tar	decreases expression	1
perfluorooctane sulfonic acid	decreases activity	1
fipronil	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane	decreases activity, decreases reaction	1
nutlin 3	affects cotreatment, increases expression	1
Dutasteride	increases expression	1
Acetaminophen	decreases expression	1
Androstenedione	increases metabolic processing	1
Cadmium	decreases expression, increases abundance	1
Dactinomycin	affects cotreatment, increases expression	1
DEET	decreases expression, affects cotreatment	1
Fonofos	increases methylation	1
N-Nitrosopyrrolidine	decreases expression	1
Parathion	increases methylation	1
Dihydrotestosterone	increases expression	1
Testosterone	increases chemical synthesis	1
Tobacco Smoke Pollution	decreases expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

ChEMBL screening assays

64 unique, capped per target: 62 binding, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1068436	Binding	Inhibition of human 17beta-HSD3 expressed in HeLa cells	Coumarins as novel 17beta-hydroxysteroid dehydrogenase type 3 inhibitors for potential treatment of prostate cancer. — Bioorg Med Chem Lett
CHEMBL4733678	ADMET	Inhibition of human 17-beta-HSD3 expressed in LNCaP cells assessed as reduction in oxidation of [14C]-4-androstene-3,17-dione to [14C]-testosterone at 0.3 uM incubated for 1 hr by thin layer chromatography	Synthesis of 17β-hydroxysteroid dehydrogenase type 10 steroidal inhibitors: Selectivity, metabolic stability and enhanced potency. — Eur J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03718234	PHASE1	COMPLETED	Subcutaneous Hydrocortisone Children With Congenital Adrenal Hyperplasia
NCT00485186	Not specified	WITHDRAWN	Gene Polymorphisms Influencing Steroid Synthesis and Action
NCT01875640	Not specified	COMPLETED	Decision Support for Parents Receiving Information About Child’s Rare Disease
NCT02784184	Not specified	UNKNOWN	COPENHAGEN Minipuberty Study
NCT03102554	Not specified	ENROLLING_BY_INVITATION	Genetics of Differences of Sex Development and Hypospadias
NCT03283852	Not specified	RECRUITING	Identifying New Genetic Causes to Development Disorders
NCT04195490	Not specified	UNKNOWN	Evaluation of Outcomes of Feminizing Genitoplasty in Children With Disorders of Sex Development
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT04717349	Not specified	RECRUITING	Data Collection Study of Pediatric and Adolescent Gynecology Conditions
NCT05058781	Not specified	RECRUITING	Minipuberty in Infants Born With Potential Hypogonadism Hypogonadotrope
NCT06692049	Not specified	RECRUITING	Gonadal Tissue Cryopreservation for Fertility Preservation in Children with a Disorder of Sex Development
NCT06989593	Not specified	RECRUITING	Breaking Silence Through Story: A Narrative Medicine Intervention for Parents of Children With Urogenital Conditions
NCT00172510	Not specified	UNKNOWN	Mutation Analysis of 17α-Hydroxylase
NCT00173654	Not specified	UNKNOWN	Mutation Analysis of 17βhydroxysteroid Dehydrogenase 3 Deficiency