HSD17B4

Chr 5AR

hydroxysteroid 17-beta dehydrogenase 4

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

The protein encoded by this gene is a bifunctional enzyme that is involved in the peroxisomal beta-oxidation pathway for fatty acids. It also acts as a catalyst for the formation of 3-ketoacyl-CoA intermediates from both straight-chain and 2-methyl-branched-chain fatty acids. Defects in this gene that affect the peroxisomal fatty acid beta-oxidation activity are a cause of D-bifunctional protein deficiency (DBPD). An apparent pseudogene of this gene is present on chromosome 8. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 0.742 OMIM phenotypes
Clinical SummaryHSD17B4
🧬
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.
📋
ClinVar Variants
156 unique Pathogenic / Likely Pathogenic· 163 VUS of 739 total submissions
📖
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 OE?0.53 (0.380.74)
00.351.4
Missense OE?1.04 (0.961.13)
00.61.4
Synonymous OE?1.11
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

This gene — mechanism propensity

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

739 submitted variants in ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic114
VUS163
Likely Benign309
Benign25
Conflicting60
42
Pathogenic
114
Likely Pathogenic
163
VUS
309
Likely Benign
25
Benign
60
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
37
4
1
0
42
Likely Pathogenic
86
27
1
0
114
VUS
5
140
15
3
163
Likely Benign
2
12
145
150
309
Benign
0
7
15
3
25
Conflicting
60
Total130190177156713

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap HSD17B4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

HSD17B4 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →