ECHS1

Chr 10AR

enoyl-CoA hydratase, short chain 1

Also known as: ECHS1D, SCEH, mECH, mECH1

ECHS1 encodes mitochondrial short-chain enoyl-CoA hydratase, which catalyzes the hydration of 2-trans-enoyl-CoA intermediates to L-3-hydroxyacyl-CoAs in the second step of mitochondrial fatty acid beta-oxidation. Biallelic mutations cause mitochondrial short-chain enoyl-CoA hydratase 1 deficiency, an autosomal recessive disorder resulting from loss of enzyme function. The low pLI score is consistent with the recessive inheritance pattern, where heterozygous carriers are typically unaffected.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.961 OMIM phenotype
Clinical SummaryECHS1
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Gene-Disease Validity (ClinGen)
Leigh syndrome · 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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.96LOEUF
pLI 0.001
Z-score 1.69
OE 0.51 (0.290.96)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.86Z-score
OE missense 0.81 (0.700.94)
131 obs / 161.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.51 (0.290.96)
00.351.4
Missense OE0.81 (0.700.94)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 7 / 13.8Missense obs/exp: 131 / 161.9Syn Z: -0.42
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveECHS1-related mitochondrial short-chain enoyl-CoA hydratase 1 deficiencyLOFAR

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

DN
0.78top 25%
GOF
0.6247th %ile
LOF
0.2776th %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

ECHS1 · 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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