HSD17B7

Chr 1

hydroxysteroid 17-beta dehydrogenase 7

Also known as: PRAP, SDR37C1

NCBI Gene: 51478 ENSG00000132196 UniProt: P56937 OMIM: 606756

This enzyme functions as both a 17-beta-hydroxysteroid dehydrogenase in sex steroid metabolism and a 3-ketosteroid reductase in cholesterol biosynthesis, catalyzing NADP(H)-dependent reduction reactions that regulate steroid hormone potency. Mutations cause Perrault syndrome, an autosomal recessive disorder characterized by sensorineural hearing loss in both sexes and ovarian dysgenesis in females. The gene shows high tolerance to loss-of-function variants (pLI near 0), consistent with the recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

HSD17B7 encodes an enzyme that functions both as a 17-beta-hydroxysteroid dehydrogenase (EC 1.1.1.62) in the biosynthesis of sex steroids and as a 3-ketosteroid reductase (EC 1.1.1.270) in the biosynthesis of cholesterol (Marijanovic et al., 2003 [PubMed 12829805]).[supplied by OMIM, May 2010]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.16

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.16LOEUF

pLI 0.000

Z-score 1.12

OE 0.68 (0.42–1.16)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.59Z-score

OE missense 0.88 (0.77–1.00)

159 obs / 181.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.68 (0.42–1.16)

0≤0.351.4

Missense OE?0.88 (0.77–1.00)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 10 / 14.6Missense obs/exp: 159 / 181.3Syn Z: -0.35

Background carrier burden — how many people carry a rare variant somewhere in HSD17B7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

326 rare PASS variants

Rare truncating (LoF)

1 in 5,300

30 rare PASS variants

Rare synonymous (reference)

1 in 270

133 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for HSD17B7. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 220	1 in 7,400
South Asian	~43k	1 in 170	1 in 4,300
Remaining (unassigned)	~30k	1 in 190	≈ 1 in 15,000
European (Finnish)	~27k	1 in 550	1 in 5,300
Admixed American	~22k	1 in 180	≈ 1 in 5,500
African / African American	~21k	1 in 170	none seen
East Asian	~20k	1 in 190	1 in 580
Ashkenazi Jewish	~13k	1 in 570	1 in 1,700
Middle Eastern	~2,884	1 in 190	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 8 of 9 coding exons well covered in gnomAD exomes; exon 7 marginal. Genomes: 8 of 9 (exon 1 below).? see exons ↓