HSD3B1

HSD3B1
Identifiers
Aliases	HSD3B1, 3BETAHSD, HSD3B, HSDB3, HSDB3A, SDR11E1, hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1
External IDs	OMIM: 109715; MGI: 109598; HomoloGene: 133013; GeneCards: HSD3B1; OMA:HSD3B1 - orthologs
Gene location (Human)
Chr.	Chromosome 1 (human)
End	119,515,054 bp
Gene location (Mouse)
Chr.	Chromosome 3 (mouse)
End	98,721,759 bp
RNA expression pattern
	Top expressed in
	placenta; ; decidua; ; skin of thigh; ; vulva; ; right adrenal cortex; ; left adrenal gland; ; left adrenal cortex; ; mucosa of transverse colon; ; mucosa of ileum; ; islet of Langerhans;
	Top expressed in
	adrenal gland; ; genital tubercle; ; placenta; ; adrenal medulla; ; testicle; ; embryo; ; yolk sac; ; tail of embryo; ; secondary oocyte; ; pallidum of neuraxis;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; isomerase activity; catalytic activity; oxidoreductase activity; steroid delta-isomerase activity; 3-beta-hydroxy-delta5-steroid dehydrogenase activity; cholesterol dehydrogenase activity; 3-keto sterol reductase activity; 5alpha-androstane-3beta,17beta-diol dehydrogenase activity;
Cellular component	integral component of membrane; membrane; mitochondrial membranes; mitochondrial intermembrane space; smooth endoplasmic reticulum membrane; endoplasmic reticulum; mitochondrion; mitochondrial inner membrane; endoplasmic reticulum membrane; intracellular membrane-bounded organelle;
Biological process	estrogen biosynthetic process; androgen biosynthetic process; glucocorticoid biosynthetic process; mineralocorticoid biosynthetic process; metabolism; steroid biosynthetic process; C21-steroid hormone metabolic process; hippocampus development; response to corticosterone; lipid metabolism; steroid metabolic process;
	Sources:Amigo / QuickGO
Orthologs
	3283
	15497
	ENSG00000203857
	ENSMUSG00000027869
	P14060
	O35469
	NM_000862; NM_001328615
	NM_013821
	NP_000853; NP_001315544
	NP_038849
	Wikidata
View/Edit Human	View/Edit Mouse

HSD3B1 is a human gene that encodes for a 3beta-hydroxysteroid dehydrogenase/delta(5)-delta(4)isomerase type I or hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1.^[5] While it can carry out the same function as HSD3B2, it localizes primarily to different tissues, such as the placenta and nonsteroidogenic tissues. Its requirement for the production of progesterone by the placenta, which has a vital role in pregnancy, may be one reason why no disease based on mutations in this gene has been identified to date, besides prostate cancer.

Clinical significance

The 1245C allele (HSD3B1 adrenal-permissive homozygous genotype 1245 C/C) encodes for a missense and hyperactive enzyme that increases extragonadal androgen synthesis and is associated with poorer outcomes after androgen deprivation therapy in prostate cancer.^[6]^[7]^[8]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000203857 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000027869 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: HSD3B1 Hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1".
^ Taneja SS (January 2017). "Re: HSD3B1 and Resistance to Androgen-Deprivation Therapy in Prostate Cancer: A Retrospective, Multicohort Study". The Journal of Urology. 197 (1): 150. doi:10.1016/j.juro.2016.10.045. PMID 27979506.
^ Hearn, Jason (October 2016). "HSD3B1 and resistance to androgen-deprivation therapy in prostate cancer: a retrospective, multicohort study". Lancet Oncology. 17 (10): 1435–1444. doi:10.1016/S1470-2045(16)30227-3. PMC 5135009. PMID 27575027.
^ McKay, Rana R.; Nelson, Tyler J.; Pagadala, Meghana S.; Teerlink, Craig C.; Gao, Anthony; Bryant, Alex K.; Agiri, Fatai Y.; Guram, Kripa; Thompson, Reid F.; Pridgen, Kathryn M.; Seibert, Tyler M.; Lee, Kyung Min; Carter, Hannah; Lynch, Julie A.; Hauger, Richard L. (2024-03-20). "Adrenal-Permissive Germline HSD3B1 Allele and Prostate Cancer Outcomes". JAMA Network Open. 7 (3): e242976. doi:10.1001/jamanetworkopen.2024.2976. ISSN 2574-3805.

^[1]

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Lorence MC, Murry BA, Trant JM, Mason JI (May 1990). "Human 3 beta-hydroxysteroid dehydrogenase/delta 5----4isomerase from placenta: expression in nonsteroidogenic cells of a protein that catalyzes the dehydrogenation/isomerization of C21 and C19 steroids". Endocrinology. 126 (5): 2493–8. doi:10.1210/endo-126-5-2493. PMID 2139411.
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Luu The V, Lachance Y, Labrie C, Leblanc G, Thomas JL, Strickler RC, Labrie F (August 1989). "Full length cDNA structure and deduced amino acid sequence of human 3 beta-hydroxy-5-ene steroid dehydrogenase". Molecular Endocrinology. 3 (8): 1310–2. doi:10.1210/mend-3-8-1310. PMID 2779585.
Thomas JL, Frieden C, Nash WE, Strickler RC (September 1995). "An NADH-induced conformational change that mediates the sequential 3 beta-hydroxysteroid dehydrogenase/isomerase activities is supported by affinity labeling and the time-dependent activation of isomerase". The Journal of Biological Chemistry. 270 (36): 21003–8. doi:10.1074/jbc.270.36.21003. PMID 7673125.
Alvarez CI, Genti-Raimondi S, Patrito LC, Flury A (July 1994). "Topography of human placental 3 beta-hydroxysteroid dehydrogenase/delta 5-4 isomerase in microsomal membrane. A study using limited proteolysis and immunoblotting". Biochimica et Biophysica Acta. 1207 (1): 102–8. doi:10.1016/0167-4838(94)90057-4. PMID 8043598.
Cherradi N, Defaye G, Chambaz EM (December 1993). "Dual subcellular localization of the 3 beta-hydroxysteroid dehydrogenase isomerase: characterization of the mitochondrial enzyme in the bovine adrenal cortex". The Journal of Steroid Biochemistry and Molecular Biology. 46 (6): 773–9. doi:10.1016/0960-0760(93)90318-Q. PMID 8274411. S2CID 29330476.
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El-Alfy M, Luu-The V, Huang XF, Berger L, Labrie F, Pelletier G (March 1999). "Localization of type 5 17beta-hydroxysteroid dehydrogenase, 3beta-hydroxysteroid dehydrogenase, and androgen receptor in the human prostate by in situ hybridization and immunocytochemistry". Endocrinology. 140 (3): 1481–91. doi:10.1210/endo.140.3.6585. PMID 10067877.
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