HSD17B2

protein-coding

hydroxysteroid 17-beta dehydrogenase 2, the group of Short chain dehydrogenase/reductase superfamily

Gene summary

Enables estradiol 17-beta-dehydrogenase [NAD(P)+] activity and testosterone dehydrogenase (NAD+) activity. Involved in androgen metabolic process; estrogen biosynthetic process; and response to retinoic acid. Located in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_002153.3

Inheritance

—

ClinVar variants

U:73B:16

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.13

Max pathogenic AF

—

Genomic locus

chr16:82,035,004-82,098,534

External References & Databases

Ensembl (ENSG00000086696)

Transcript & Mutation Effects

hg38 • Region Span ~63.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HSD17B2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 80

not providedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002153.3. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar	4 clinvar	5
missense			73 clinvar	8 clinvar	3 clinvar	84
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	73	9	7	89

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002153.3	RefSeq	NP_002144.1	5	MANE Select
ENST00000199936.9	Ensembl	ENSP00000199936.4	5	MANE Select
ENST00000563491.5	Ensembl	ENSP00000455992.1	2	Standard
ENST00000566213.1	Ensembl	ENSP00000457943.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Steroid hormone biosynthesis - Homo sapiens (human)
Ovarian steroidogenesis - Homo sapiens (human)
Androgen Receptor Network in Prostate Cancer
Vitamin D Receptor Pathway
Steroid Biosynthesis

Biological Process

in utero embryonic development
placenta development
estrogen biosynthetic process
response to retinoic acid
oxidation-reduction process

Molecular Function

estradiol 17-beta-dehydrogenase activity
17-alpha,20-alpha-dihydroxypregn-4-en-3-one dehydrogenase activity
testosterone dehydrogenase (NAD+) activity

Cellular Component

endoplasmic reticulum membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000199936
Coding exons: 5
Length: 63531
Individuals with no LoFs: 125541
Homozygous LoFs: 0
Heterozygous LoFs: 207
Defined: 125748
p: 0.000823

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.57	279	214	1.30	0.0000113	2500
Missense (PolyPhen)		89	69.93	1.2727		815
Synonymous	-2.89	126	90.9	1.39	0.00000534	772
Loss of Function	-0.436	14	12.3	1.13	6.05e-7	148

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.0027	0.0027	notable
European (Non-Finnish)	0.0011	0.0011	notable
South Asian	0.000098	0.000098	rare
Other	0.0011	0.0011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Capable of catalyzing the interconversion of testosterone and androstenedione, as well as estradiol and estrone. Also has 20-alpha-HSD activity. Uses NADH while EDH17B3 uses NADPH.;

Intolerance Scores

LoFtool: 0.326
RVIS EVS: 0.2
RVIS percentile EVS: 67.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.915

Gene Damage Prediction

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