HSD17B4

Chr 5AR

hydroxysteroid 17-beta dehydrogenase 4

Also known as: DBP, MFE-2, MFP-2, MPF-2, PRLTS1, SDR8C1

The HSD17B4 protein is a bifunctional enzyme that catalyzes hydration and dehydrogenation reactions in the peroxisomal fatty acid beta-oxidation pathway, processing both straight-chain and branched-chain fatty acids. Mutations cause D-bifunctional protein deficiency, a severe peroxisomal disorder typically presenting in infancy with neurodegeneration, and Perrault syndrome 1, characterized by sensorineural hearing loss and ovarian dysgenesis. Both conditions follow autosomal recessive inheritance.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.742 OMIM phenotypes
Clinical SummaryHSD17B4
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Gene-Disease Validity (ClinGen)
d-bifunctional protein deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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GeneReview available — HSD17B4
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.74LOEUF
pLI 0.000
Z-score 2.91
OE 0.53 (0.380.74)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.28Z-score
OE missense 1.04 (0.961.13)
426 obs / 410.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.53 (0.380.74)
00.351.4
Missense OE1.04 (0.961.13)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 23 / 43.8Missense obs/exp: 426 / 410.3Syn Z: -0.98
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveHSD17B4-related D-bifunctional protein deficiencyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.82top 10%
GOF
0.7127th %ile
LOF
0.2385th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

HSD17B4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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