HSD17B2

Chr 16

hydroxysteroid 17-beta dehydrogenase 2

Also known as: EDH17B2, HSD17, SDR9C2

NCBI Gene: 3294 ENSG00000086696 UniProt: P37059 OMIM: 109685

The protein catalyzes NAD-dependent oxidation of highly active 17β-hydroxysteroids including estradiol, testosterone, and dihydrotestosterone to their less active forms, thereby regulating steroid hormone biological potency. Mutations cause disease through a dominant-negative mechanism, though specific pediatric phenotypes associated with HSD17B2 mutations are not established in the provided data. The gene shows tolerance to loss-of-function variants based on constraint metrics.

OMIM ResearchSummary from RefSeq, UniProt, Mechanism

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]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.73

Clinical Summary— HSD17B2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

73 VUS of 90 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.73LOEUF

pLI 0.000

Z-score -0.44

OE 1.13 (0.75–1.73)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.57Z-score

OE missense 1.30 (1.18–1.44)

279 obs / 214.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.13 (0.75–1.73)

0≤0.351.4

Missense OE?1.30 (1.18–1.44)

0≤0.61.4

Synonymous OE?1.39

0≤1.21.6

LoF obs/exp: 14 / 12.3Missense obs/exp: 279 / 214.4Syn Z: -2.89

This gene — mechanism propensity

0.77top 25%

GOF

0.5955th %ile

LOF

0.2679th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

90 submitted variants in ClinVar

ClinVar

Classification Summary

VUS73

Likely Benign9

Benign7

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	73	0	73
Likely Benign	8	1	9
Benign	3	4	7
Total	84	5	89

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

38 pathogenic / likely-pathogenic (of 61) ClinVar copy-number / structural variants overlap HSD17B2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →