ECHS1

Chr 10AR

enoyl-CoA hydratase, short chain 1

Also known as: ECHS1D, SCEH, mECH, mECH1

NCBI Gene: 1892 ENSG00000127884 UniProt: P30084 OMIM: 602292

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene functions in the second step of the mitochondrial fatty acid beta-oxidation pathway. It catalyzes the hydration of 2-trans-enoyl-coenzyme A (CoA) intermediates to L-3-hydroxyacyl-CoAs. The gene product is a member of the hydratase/isomerase superfamily. It localizes to the mitochondrial matrix. Transcript variants utilizing alternative transcription initiation sites have been described in the literature. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.961 OMIM phenotype

Clinical Summary— ECHS1

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Gene-Disease Validity (ClinGen)

Leigh syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

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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

65 unique Pathogenic / Likely Pathogenic· 111 VUS of 410 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — ECHS1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.96LOEUF

pLI 0.001

Z-score 1.69

OE 0.51 (0.29–0.96)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.86Z-score

OE missense 0.81 (0.70–0.94)

131 obs / 161.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.51 (0.29–0.96)

0≤0.351.4

Missense OE?0.81 (0.70–0.94)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

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

This gene — mechanism propensity

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

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

410 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27

Likely Pathogenic38

VUS111

Likely Benign153

Benign41

Conflicting29

Pathogenic

Likely Pathogenic

111

VUS

153

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	10	13	4	0	27
Likely Pathogenic	7	29	1	1	38
VUS	3	93	13	2	111
Likely Benign	0	3	76	74	153
Benign	0	2	36	3	41
Conflicting	—				29
Total	20	140	130	80	399

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

View in ClinVar →

97 pathogenic / likely-pathogenic (of 119) ClinVar copy-number / structural variants overlap ECHS1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →