HSD17B3 (hydroxysteroid 17-beta dehydrogenase 3)

Gene

• Entrez ID: 3293
• Gene name: Hydroxysteroid 17-beta dehydrogenase 3
• Gene symbol: HSD17B3
• Synonyms (NCBI Gene): EDH17B3, SDR12C2
• Chromosome: 9
• Chromosome location: 9q22.32
• Summary: 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 w

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28939085	G>A	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs119481074	T>C	Pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs119481075	C>T	Likely-pathogenic, pathogenic	Non coding transcript variant, 5 prime UTR variant, intron variant, coding sequence variant, missense variant
rs119481076	G>A,T	Pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs119481077	G>A	Likely-pathogenic, pathogenic	Non coding transcript variant, 5 prime UTR variant, intron variant, coding sequence variant, missense variant
rs119481078	C>T	Pathogenic	Coding sequence variant, non coding transcript variant, 5 prime UTR variant, missense variant
rs119481079	T>C	Pathogenic	Coding sequence variant, non coding transcript variant, 5 prime UTR variant, missense variant
rs119481080	C>T	Pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs144809928	G>A,C	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs149607031	C>G	Likely-pathogenic, pathogenic	Intron variant, splice acceptor variant
rs201115371	T>A	Pathogenic	Intron variant
rs372027264	A>T	Pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs730880305	C>T	Pathogenic	Splice acceptor variant
rs747329682	G>A	Likely-pathogenic	5 prime UTR variant, missense variant, non coding transcript variant, synonymous variant, coding sequence variant
rs747724352	C>T	Pathogenic	Non coding transcript variant, missense variant, 5 prime UTR variant, coding sequence variant
rs767765046	A>C,G	Likely-pathogenic	Intron variant, coding sequence variant, non coding transcript variant, stop gained, 5 prime UTR variant, missense variant
rs780178733	T>C,G	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant, 5 prime UTR variant, intron variant
rs1378603446	C>T	Pathogenic	Intron variant, splice acceptor variant
rs1554694678	AAG>-	Likely-pathogenic	5 prime UTR variant, non coding transcript variant, coding sequence variant, inframe deletion
rs1554705693	TT>-	Pathogenic	5 prime UTR variant, non coding transcript variant, coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT018186	hsa-miR-335-5p	Microarray	18185580
MIRT025169	hsa-miR-181a-5p	Microarray	17612493
MIRT1055421	hsa-miR-3157-5p	CLIP-seq
MIRT1055422	hsa-miR-338-3p	CLIP-seq
MIRT1055423	hsa-miR-3663-5p	CLIP-seq
MIRT1055424	hsa-miR-3909	CLIP-seq
MIRT1055425	hsa-miR-4691-3p	CLIP-seq
MIRT1055421	hsa-miR-3157-5p	CLIP-seq
MIRT2451410	hsa-miR-3199	CLIP-seq
MIRT1055422	hsa-miR-338-3p	CLIP-seq
MIRT2451411	hsa-miR-4299	CLIP-seq
MIRT2451412	hsa-miR-4515	CLIP-seq
MIRT1055425	hsa-miR-4691-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004303	Function	Estradiol 17-beta-dehydrogenase [NAD(P)+] activity	IEA
GO:0005515	Function	Protein binding	IPI	28514442, 33961781
GO:0005783	Component	Endoplasmic reticulum	IBA
GO:0005783	Component	Endoplasmic reticulum	IDA	26545797
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0006629	Process	Lipid metabolic process	IEA
GO:0006694	Process	Steroid biosynthetic process	IBA
GO:0006694	Process	Steroid biosynthetic process	IEA
GO:0006702	Process	Androgen biosynthetic process	IEA
GO:0006702	Process	Androgen biosynthetic process	TAS
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0030539	Process	Male genitalia development	TAS	8075637
GO:0043231	Component	Intracellular membrane-bounded organelle	TAS	8075637
GO:0047045	Function	Testosterone dehydrogenase (NADP+) activity	IBA
GO:0047045	Function	Testosterone dehydrogenase (NADP+) activity	IDA	26545797
GO:0047045	Function	Testosterone dehydrogenase (NADP+) activity	IEA
GO:0061370	Process	Testosterone biosynthetic process	IEA
GO:0072582	Function	17-beta-hydroxysteroid dehydrogenase (NADP+) activity	IEA

Other IDs

• MIM: 605573
• HGNC: 5212
• e!Ensembl: ENSG00000130948

Protein

• UniProt ID: P37058
• Protein name: 17-beta-hydroxysteroid dehydrogenase type 3 (17-beta-HSD 3) (Estradiol 17-beta-dehydrogenase 2) (EC 1.1.1.62) (Short chain dehydrogenase/reductase family 12C member 2) (Testicular 17-beta-hydroxysteroid dehydrogenase) (Testosterone 17-beta-dehydrogenase 3
• Protein function: Catalyzes the conversion of 17-oxosteroids to 17beta-hydroxysteroids (PubMed:16216911, PubMed:26545797, PubMed:27927697, PubMed:8075637). Favors the reduction of androstenedione to testosterone (PubMed:16216911, PubMed:26545797, PubMed:27927697)
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00106	adh_short	49 → 243	short chain dehydrogenase	Domain

• Tissue specificity: TISSUE SPECIFICITY: Testis. {ECO:0000269|PubMed:8075637}.
• Sequence:

  MGDVLEQFFILTGLLVCLACLAKCVRFSRCVLLNYWKVLPKSFLRSMGQWAVITGAGDGI
  GKAYSFELAKRGLNVVLISRTLEKLEAIATEIERTTGRSVKIIQADFTKDDIYEHIKEKL
  AGLEIGILVNNVGMLPNLLPSHFLNAPDEIQSLIHCNITSVVKMTQLILKHMESRQKGLI
  LNISSGIALFPWPLYSMYSASKAFVCAFSKALQEEYKAKEVIIQVLTPYAVSTAMTKYLN
  TNVITKTADEFVKESLNYVTIGGETCGCLAHEILAGFLSLIPAWAFYSGAFQRLLLTHYV
  AYLKLNTKVR

• Sequence length: 310

Pathways

KEGG:

Steroid hormone biosynthesis
Metabolic pathways

Reactome:

Androgen biosynthesis
Synthesis of very long-chain fatty acyl-CoAs

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Differences in sex development	Pathogenic; Likely pathogenic	rs119481075, rs746001525, rs149607031	RCV005865157 RCV005865643 RCV005865354	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Disorder of sexual differentiation	Pathogenic; Likely pathogenic	rs1318050831, rs2130805147	RCV001568325 RCV002273837	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Familial cancer of breast	Pathogenic	rs119481076	RCV005887298	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
HSD17B3-related disorder	Pathogenic	rs201115371	RCV003917727	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Malignant tumor of esophagus	Pathogenic	rs201115371	RCV005892219	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ovarian cancer	Pathogenic	rs201115371	RCV005892220	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Pseudohermaphroditism	Pathogenic; Likely pathogenic	rs119481075, rs119481076, rs119481077, rs201115371, rs144809928, rs372027264, rs773720185, rs1554694264, rs1554694678, rs747724352, rs149607031, rs1554705693	RCV000581347 RCV000584321 RCV000584139 RCV000582593 RCV000583165 RCV000582417 RCV000583085 RCV000581820 RCV000583898 RCV000583122 RCV000584223 RCV000582835	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Testosterone 17-beta-dehydrogenase deficiency	Likely pathogenic; Pathogenic	rs191153391, rs777697545, rs28939085, rs119481074, rs119481075, rs119481076, rs119481077, rs730880305, rs119481078, rs119481079, rs119481080, rs201115371, rs747329682, rs115063639, rs2490210569, rs144809928, rs753360928, rs1354232643, rs746001525, rs2490090743, rs1440711824, rs768355659, rs2490090849, rs767259718, rs2490210441, rs780178733, rs1378603446, rs372027264, rs149607031, rs370264627	RCV004526221 RCV003459769 RCV000005148 RCV000005149 RCV000005150 RCV000005151 RCV000005153 RCV000005154 RCV000005155 RCV000005156 RCV000005157 RCV000190594 RCV004555548 RCV003146073 RCV003146083 RCV004701359 RCV003324315 RCV003459907 RCV003459908 RCV003459910 RCV003459911 RCV003459913 RCV003486323 RCV004701734 RCV003985997 RCV001796081 RCV003459416 RCV004767420 RCV001783086 RCV001167098	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Thyroid cancer, nonmedullary, 1	Pathogenic	rs149607031	RCV005898584	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
17-BETA HYDROXYSTEROID DEHYDROGENASE III DEFICIENCY	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
17-HYDROXYSTEROID DEHYDROGENASE DEFICIENCY	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
46,XY DISORDER OF SEX DEVELOPMENT DUE TO 17-BETA-HYDROXYSTEROID DEHYDROGENASE 3 DEFICIENCY	—	GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DISORDERS OF SEX DEVELOPMENT	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
JUVENILE MYOCLONIC EPILEPSY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATIC NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
17-Hydroxysteroid Dehydrogenase Deficiency	17-hydroxysteroid dehydrogenase deficiency	CLINVAR_DG	10599740, 17509588, 19498320, 21214500, 22212252, 23295294, 24025597, 8550739, 9758445		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
17-Hydroxysteroid Dehydrogenase Deficiency	17-hydroxysteroid dehydrogenase deficiency	UNIPROT_DG	11158067, 26545797, 8075637, 8550739, 9709959, 9758445		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
17-Hydroxysteroid Dehydrogenase Deficiency	17-hydroxysteroid dehydrogenase deficiency	BEFREE	15745934, 18296911, 22445608, 25064799, 25536660, 26956191, 27073926, 28739554, 28774765		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
17-Hydroxysteroid Dehydrogenase Deficiency	17-hydroxysteroid dehydrogenase deficiency	CTD_human_DG	25526675		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
17-Hydroxysteroid Dehydrogenase Deficiency	17-hydroxysteroid dehydrogenase deficiency	ORPHANET_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
17-Hydroxysteroid Dehydrogenase Deficiency	17-hydroxysteroid dehydrogenase deficiency	GENOMICS_ENGLAND_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
3 beta-Hydroxysteroid dehydrogenase deficiency	3 beta-hydroxysteroid dehydrogenase deficiency	BEFREE	7989489, 8126127		★☆☆☆☆ Found in Text Mining only
46, XY Disorders of Sex Development	46, XY disorder of sex development	BEFREE	21214500, 22594312, 25064799, 25740850, 26545797, 26956191, 27073926, 28774765, 28847746, 28859874		★☆☆☆☆ Found in Text Mining only
46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency	46, XY disorder of sex development	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
5-Alpha Reductase Deficiency	5-alpha reductase deficiency	BEFREE	25740850, 31004515		★☆☆☆☆ Found in Text Mining only
Acne	Acne	BEFREE	24157973		★☆☆☆☆ Found in Text Mining only
Acne Vulgaris	Acne	BEFREE	24157973		★☆☆☆☆ Found in Text Mining only
Adrenal Hyperplasia Congenital	Congenital adrenal hyperplasia	Pubtator	34616364	Associate	★☆☆☆☆ Found in Text Mining only
Ambiguous Genitalia	Ambiguous Genitalia	CTD_human_DG	17071532		★☆☆☆☆ Found in Text Mining only
Ambiguous Genitalia	Ambiguous Genitalia	BEFREE	25536660, 31476086		★☆☆☆☆ Found in Text Mining only
Ambiguous Genitalia	Ambiguous Genitalia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Amenorrhea	Amenorrhea	Pubtator	36617173	Associate	★☆☆☆☆ Found in Text Mining only
Benign Prostatic Hyperplasia	Benign Prostatic Hyperplasia	BEFREE	23132791		★☆☆☆☆ Found in Text Mining only
Colitis Ulcerative	Ulcerative colitis	Pubtator	36445533	Associate	★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Disorder of Sex Development 46 XY	46, xy disorder of sex development	Pubtator	17509588, 21214500, 33389920, 33984517, 34946839, 36563763, 36617173	Associate	★☆☆☆☆ Found in Text Mining only
Disorders of Sex Development	Disorders of sex development	Pubtator	29176693, 34946839, 35432193, 35689291	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Endometriosis	Endometriosis	BEFREE	23139742		★☆☆☆☆ Found in Text Mining only
Endometriosis	Endometriosis	Pubtator	23139742	Inhibit	★☆☆☆☆ Found in Text Mining only
Endometriosis	Endometriosis	Pubtator	23139742	Associate	★☆☆☆☆ Found in Text Mining only
Gynecomastia	Gynecomastia	BEFREE	22212252, 9467575		★☆☆☆☆ Found in Text Mining only
Gynecomastia	Gynecomastia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hermaphroditism	Hermaphroditism	CTD_human_DG	17071532		★☆☆☆☆ Found in Text Mining only
Hypertrophy of clitoris	Hypertrophy Of Clitoris	BEFREE	31476086		★☆☆☆☆ Found in Text Mining only
Hypogonadotropic hypogonadism	Hypogonadotropic Hypogonadism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypospadias	Hypospadias	BEFREE	20059664, 28663096, 28739554		★☆☆☆☆ Found in Text Mining only
Hypospadias	Hypospadias	Pubtator	20059664, 24281767, 28739554	Associate	★☆☆☆☆ Found in Text Mining only
Hypothyroidism	Hypothyroidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intersex Conditions	Disorder of sex development	CTD_human_DG	17071532		★☆☆☆☆ Found in Text Mining only
Male Pseudohermaphroditism	Male Pseudohermaphroditism	BEFREE	8626842, 9467575, 9709959, 9758445		★☆☆☆☆ Found in Text Mining only
Male Pseudohermaphroditism	Male Pseudohermaphroditism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	12210481, 19505920, 22209174, 28182747, 28267564, 29201087, 31268309		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	CTD_human_DG	12210481		★☆☆☆☆ Found in Text Mining only
Micropenis	Micropenis	BEFREE	28739554		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	23132791, 28182747		★☆☆☆☆ Found in Text Mining only
Penile hypospadias	Penile Hypospadias	BEFREE	20059664, 28663096, 28739554		★☆☆☆☆ Found in Text Mining only
Penis agenesis	Penis Agenesis	BEFREE	28739554		★☆☆☆☆ Found in Text Mining only
Primary physiologic amenorrhea	Physiologic Amenorrhea	BEFREE	23796702		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	12210481, 19505920, 22209174, 28182747, 28267564, 29201087, 31268309		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic Neoplasms	CTD_human_DG	12210481		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	21900597, 22542949	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pseudohermaphroditism	Pseudohermaphroditism	CTD_human_DG	17071532		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Pseudohermaphroditism	Pseudohermaphroditism	BEFREE	8626842		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Pseudohermaphroditism	Pseudohermaphroditism	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Pseudovaginal Perineoscrotal Hypospadias	5-alpha reductase deficiency	BEFREE	25740850, 31004515		★☆☆☆☆ Found in Text Mining only
Sertoli-Leydig cell tumor of ovary	Sertoli-Leydig Cell Tumor	BEFREE	9314929		★☆☆☆☆ Found in Text Mining only
Sex Differentiation Disorders	Sex Differentiation Disorders	CTD_human_DG	17071532		★☆☆☆☆ Found in Text Mining only
Sex Differentiation Disorders	Sex Differentiation Disorders	BEFREE	20689261, 22212252, 25064799, 25740850, 27163392		★☆☆☆☆ Found in Text Mining only
Testicular Feminization	Testicular Feminization	BEFREE	23375913, 31283987		★☆☆☆☆ Found in Text Mining only