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

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Differences in sex development	Pathogenic; Likely pathogenic	rs119481075, rs746001525, rs149607031	RCV005865157 RCV005865643 RCV005865354
Disorder of sexual differentiation	Pathogenic; Likely pathogenic	rs1318050831, rs2130805147	RCV001568325 RCV002273837
Familial cancer of breast	Pathogenic	rs119481076	RCV005887298
HSD17B3-related disorder	Pathogenic	rs201115371	RCV003917727
Malignant tumor of esophagus	Pathogenic	rs201115371	RCV005892219
Ovarian cancer	Pathogenic	rs201115371	RCV005892220
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
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
Thyroid cancer, nonmedullary, 1	Pathogenic	rs149607031	RCV005898584

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Gastric cancer	Benign	rs113256345	RCV005924439
Ovarian serous cystadenocarcinoma	Benign	rs113256345	RCV005924440
See cases	Conflicting classifications of pathogenicity	rs139084702	RCV003128420
Uterine corpus endometrial carcinoma	Benign	rs113256345	RCV005924441

Associations from Text Mining
Disease Name	Relationship Type	References
17 Hydroxysteroid Dehydrogenase Deficiency	Associate	21214500, 26831562, 28739554, 33389920
17 Hydroxysteroid Dehydrogenase Deficiency	Stimulate	26831562
17 Hydroxysteroid Dehydrogenase Deficiency	Inhibit	35689291
46 XX Testicular Disorders of Sex Development	Associate	17071532
46 XY female	Associate	26831562
Adrenal hyperplasia 2	Associate	21214500
Adrenal Hyperplasia Congenital	Associate	34616364
Adrenal Rest Tumor	Associate	34616364, 36047744
Amenorrhea	Associate	36617173
Colitis Ulcerative	Associate	36445533
Disorder of Sex Development 46 XY	Associate	17509588, 21214500, 33389920, 33984517, 34946839, 36563763, 36617173
Disorders of Sex Development	Associate	29176693, 34946839, 35432193, 35689291
Endometriosis	Inhibit	23139742
Endometriosis	Associate	23139742
Genetic Diseases Inborn	Associate	35689291
Hypospadias	Associate	20059664, 24281767, 28739554
Immunologic Deficiency Syndromes	Inhibit	34946839
Immunologic Deficiency Syndromes	Associate	34946839
Mental Retardation X Linked Syndromic 10	Associate	17509588, 33984517, 36563763
Mental Retardation X Linked Syndromic 10	Inhibit	36563763
Neoplasm Metastasis	Associate	18519708
Penis agenesis	Associate	28739554
Prostatic Neoplasms	Associate	21900597, 22542949
Prostatic Neoplasms Castration Resistant	Associate	18519708
Prostatic Neoplasms Castration Resistant	Stimulate	21365123