GeneBe

HSD3B2

protein-coding

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

Gene summary

The protein encoded by this gene is a bifunctional enzyme that catalyzes the oxidative conversion of delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. It plays a crucial role in the biosynthesis of all classes of hormonal steroids. This gene is predominantly expressed in the adrenals and the gonads. Mutations in this gene are associated with 3-beta-hydroxysteroid dehydrogenase, type II, deficiency. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2009]

MANE transcript

NM_000198.4

Inheritance

AR

ClinVar variants

P:89U:102B:203

Top phenotype

Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency

gnomAD constraint

pLI —, LoF o/e 0.99

Max pathogenic AF

—

Genomic locus

chr1:119,414,931-119,423,035

External References & Databases

Ensembl (ENSG00000203859)NCBI Gene (3284)OMIM (613890)HGNC:5218GenCCUniProt (P26439)AlphaFoldClinVar (HSD3B2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~8.1 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008727

Submitter: Orphanet

congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008727

Submitter: Labcorp Genetics (formerly Invitae)

congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008727

Submitter: PanelApp Australia

congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiencyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008727

Submitter: Natera

Clinical Genomic Database (CGD)

Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiencyAR

Manifestation: Endocrine; Genitourinary

Intervention: Endocrine

Rationale: Adrenal replacement can be effective, though individuals may nevertheless demonstrate severe manifestations

Refs: 13968789; 295036; 3088022; 2826919; 1309452; 1363812; 14764797; 18252794; 24553428Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HSD3B2 variants in ClinVar

10 Conditions Cataloged
not providedTotal: 301
3 beta-Hydroxysteroid dehydrogenase deficiencyTotal: 160
Inborn genetic diseasesTotal: 37
not specifiedTotal: 22
HSD3B2-related disorderTotal: 20
Congenital adrenal hyperplasiaTotal: 17
HSD3B2-related disordersTotal: 10
Differences in sex developmentTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000198.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
6
clinvar
190
clinvar
 196
missense
7
clinvar
19
clinvar
96
clinvar
13
clinvar
 135
nonsense
10
clinvar
19
clinvar
 29
start loss
1
clinvar
1
clinvar
 2
frameshift
14
clinvar
14
clinvar
 28
splice donor/acceptor (+/-2bp)
1
clinvar
3
clinvar
 4
Total33561022030394

Highest pathogenic variant AF is 0.000083028586

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000198.4RefSeqNP_000189.13MANE Select
ENST00000369416.4EnsemblENSP00000358424.33MANE Select
NM_001166120.2RefSeqNP_001159592.13Standard
ENST00000433745.5EnsemblENSP00000388292.13Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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)

Biological Process

  • steroid biosynthetic process
  • androgen biosynthetic process
  • glucocorticoid biosynthetic process
  • mineralocorticoid biosynthetic process
  • C21-steroid hormone metabolic process

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

Cellular Component

  • mitochondrial inner membrane
  • mitochondrial intermembrane space
  • endoplasmic reticulum
  • endoplasmic reticulum membrane
  • integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000543831
Coding exons
3
Length
8105
Individuals with no LoFs
125699
Homozygous LoFs
0
Heterozygous LoFs
45
Defined
125744
p
0.000179
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.6561671930.8670.00001102413
Missense (PolyPhen)5564.7140.8499879
Synonymous-2.3511082.81.330.00000511750
Loss of Function0.01941111.10.9945.74e-7153

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000310.00031rare
Latino/Admixed American0.000120.00012rare
Ashkenazi Jewish00.0absent
East Asian0.000160.00016rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.000190.00019rare
South Asian0.000330.00033rare
Other00.0absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec
0.273

Intolerance Scores

LoFtool
0.129
RVIS EVS
0.09
RVIS percentile EVS
60.47

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.636

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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