EHHADH

Chr 3AD

enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase

Also known as: ECHD, FRTS3, L-PBE, LBFP, MFE1, PBFE

NCBI Gene: 1962 ENSG00000113790 UniProt: Q08426 OMIM: 607037

The protein encoded by this gene is a bifunctional enzyme and is one of the four enzymes of the peroxisomal beta-oxidation pathway. The N-terminal region of the encoded protein contains enoyl-CoA hydratase activity while the C-terminal region contains 3-hydroxyacyl-CoA dehydrogenase activity. Defects in this gene are a cause of peroxisomal disorders such as Zellweger syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

OMIM Research

OMIM ResearchGenerating clinical summary…

DNmechanismADLOEUF 0.971 OMIM phenotype

Clinical Summary— EHHADH

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Gene-Disease Validity (ClinGen)

Fanconi renotubular syndrome 3 · ADLimited

Limited evidence — not for standalone diagnostic reporting

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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

174 VUS of 276 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?

0.97LOEUF

pLI 0.000

Z-score 1.68

OE 0.66 (0.46–0.97)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.03Z-score

OE missense 1.00 (0.92–1.09)

394 obs / 392.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.66 (0.46–0.97)

0≤0.351.4

Missense OE?1.00 (0.92–1.09)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 19 / 28.7Missense obs/exp: 394 / 392.6Syn Z: 0.69

This gene — mechanism propensity

0.7033th %ile

GOF

0.5071th %ile

LOF

0.3067th %ile

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

DNprediction above median · 1 literature citation

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.

Literature Evidence

DNEhhadh knockout mice showed no abnormalities in renal tubular cells, a finding that indicates a dominant negative nature of the mutation rather than haploinsufficiency.1

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

References

1.PMID 24401050 ↗

ClinVar Variant Classifications

276 submitted variants in ClinVar

ClinVar

Classification Summary

VUS174

Likely Benign39

Benign31

Conflicting22

174

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	17	138	3	16	174
Likely Benign	1	12	3	23	39
Benign	0	10	17	4	31
Conflicting	—				22
Total	18	160	23	43	266

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

View in ClinVar →

43 pathogenic / likely-pathogenic (of 47) ClinVar copy-number / structural variants overlap EHHADH — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →