HSD3B2

hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2, the group of Short chain dehydrogenase/reductase superfamily

Basic information

Region (hg38): 1:119414930-119423035

Links

ENSG00000203859 ∙ NCBI:3284 ∙ OMIM:613890 ∙ HGNC:5218 ∙ Uniprot:P26439 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency (Strong), mode of inheritance: AR
• congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency	AR	Endocrine	Adrenal replacement can be effective, though individuals may nevertheless demonstrate severe manifestations	Endocrine; Genitourinary	13968789; 295036; 3088022; 2826919; 1309452; 1363812; 14764797; 18252794; 24553428

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HSD3B2 gene.

• not provided (241 variants)
• 3 beta-Hydroxysteroid dehydrogenase deficiency (78 variants)
• Congenital adrenal hyperplasia (12 variants)
• Inborn genetic diseases (9 variants)
• not specified (8 variants)
• HSD3B2-related condition (2 variants)
• - (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HSD3B2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				142	1	143
missense	7	6	34	4		51
nonsense	15	8				23
start loss	1					1
frameshift	13	2				15
inframe indel						0
splice donor/acceptor (+/-2bp)	1	2				3
splice region				5	1	6
non coding			7	9	6	22
Total	37	18	41	155	7

Highest pathogenic variant AF is 0.000210

Variants in HSD3B2

This is a list of pathogenic ClinVar variants found in the HSD3B2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-119415147-G-A		Congenital adrenal hyperplasia	Conflicting classifications of pathogenicity (May 21, 2021)
1-119415186-T-C		3 beta-Hydroxysteroid dehydrogenase deficiency	Uncertain significance (Apr 27, 2017)
1-119415420-A-T			Pathogenic (Jul 29, 2023)
1-119415424-G-T		HSD3B2-related disorder	Likely benign (Jan 31, 2024)
1-119415425-C-T			Likely benign (May 20, 2023)
1-119415428-G-A		3 beta-Hydroxysteroid dehydrogenase deficiency	Pathogenic (Jul 22, 2021)
1-119415431-C-T			Likely benign (Oct 04, 2023)
1-119415432-T-A		3 beta-Hydroxysteroid dehydrogenase deficiency	Conflicting classifications of pathogenicity (Jan 31, 2024)
1-119415434-C-A		3 beta-Hydroxysteroid dehydrogenase deficiency	Pathogenic (Jan 18, 2024)
1-119415434-C-T			Likely benign (Feb 11, 2023)
1-119415441-A-G		Inborn genetic diseases	Uncertain significance (Feb 14, 2024)
1-119415446-A-G			Likely benign (Aug 14, 2021)
1-119415448-C-A		3 beta-Hydroxysteroid dehydrogenase deficiency	Likely pathogenic (May 14, 2022)
1-119415452-A-G			Likely benign (Jan 13, 2024)
1-119415454-G-A			Likely pathogenic (Jun 19, 2022)
1-119415455-G-A			Likely benign (Aug 19, 2023)
1-119415458-T-A			Likely benign (Aug 07, 2021)
1-119415460-T-C		Inborn genetic diseases	Uncertain significance (Dec 12, 2023)
1-119415467-G-A			Likely benign (Feb 25, 2019)
1-119415470-G-A		3 beta-Hydroxysteroid dehydrogenase deficiency • HSD3B2-related disorder	Likely benign (Jan 25, 2024)
1-119415473-C-T			Likely benign (Sep 13, 2023)
1-119415476-C-T			Likely benign (Feb 02, 2022)
1-119415479-C-G			Likely benign (Apr 14, 2022)
1-119415479-C-T			Likely benign (Mar 01, 2023)
1-119415482-G-GT		3 beta-Hydroxysteroid dehydrogenase deficiency	Pathogenic (Nov 20, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HSD3B2	protein_coding	protein_coding	ENST00000543831	3	8105

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.18e-8	0.154	125699	0	45	125744	0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.656	167	193	0.867	0.0000110	2413
Missense in Polyphen		55	64.714	0.8499		879
Synonymous	-2.35	110	82.8	1.33	0.00000511	750
Loss of Function	0.0194	11	11.1	0.994	5.74e-7	153

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000423	0.000423
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000194	0.000193
Middle Eastern	0.000163	0.000163
South Asian	0.000327	0.000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 3-beta-HSD is a bifunctional enzyme, that catalyzes the oxidative conversion of Delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids.
• Disease: DISEASE: Note=Mild HSD3B2 deficiency in hyperandrogenic females is associated with characteristic traits of polycystic ovary syndrome, such as insulin resistance and luteinizing hormone hypersecretion. {ECO:0000269|PubMed:14764797}.
• Pathway: Cortisol synthesis and secretion - Homo sapiens (human);Aldosterone synthesis and secretion - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Steroid hormone biosynthesis - Homo sapiens (human);Ovarian steroidogenesis - Homo sapiens (human);Steroidogenesis;Apparent mineralocorticoid excess syndrome;3-Beta-Hydroxysteroid Dehydrogenase Deficiency;21-hydroxylase deficiency (CYP21);Corticosterone methyl oxidase I deficiency (CMO I);Corticosterone methyl oxidase II deficiency - CMO II;Adrenal Hyperplasia Type 5 or Congenital Adrenal Hyperplasia due to 17 Alpha-hydroxylase Deficiency;Adrenal Hyperplasia Type 3 or Congenital Adrenal Hyperplasia due to 21-hydroxylase Deficiency;Congenital Lipoid Adrenal Hyperplasia (CLAH) or Lipoid CAH;17-alpha-hydroxylase deficiency (CYP17);11-beta-hydroxylase deficiency (CYP11B1);Androgen Receptor Network in Prostate Cancer;Corticotropin-releasing hormone signaling pathway;Glucocorticoid and Mineralcorticoid Metabolism;Steroid Biosynthesis;Metabolism of lipids;Androgen and estrogen biosynthesis and metabolism;Metabolism;Mineralocorticoid biosynthesis;Androgen biosynthesis;Metabolism of steroid hormones;Metabolism of steroids;Bile acid biosynthesis;C21-steroid hormone biosynthesis and metabolism;Glucocorticoid biosynthesis;androgen biosynthesis;progesterone biosynthesis;superpathway of steroid hormone biosynthesis;Steroid hormones (Consensus)

Recessive Scores

• pRec: 0.273

Intolerance Scores

• loftool: 0.129
• rvis_EVS: 0.09
• rvis_percentile_EVS: 60.47

Haploinsufficiency Scores

• pHI: 0.133
• hipred: N
• hipred_score: 0.112

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.636

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hsd3b6

Gene ontology

• Biological process: steroid biosynthetic process;androgen biosynthetic process;glucocorticoid biosynthetic process;mineralocorticoid biosynthetic process;C21-steroid hormone metabolic process;hippocampus development;response to corticosterone;oxidation-reduction process
• Cellular component: mitochondrial inner membrane;mitochondrial intermembrane space;endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane;smooth endoplasmic reticulum membrane;mitochondrial membrane;intracellular membrane-bounded organelle
• Molecular function: 3-beta-hydroxy-delta5-steroid dehydrogenase activity;steroid delta-isomerase activity;oxidoreductase activity;oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor;cholesterol dehydrogenase activity