ECHS1

Chr 10AR

enoyl-CoA hydratase, short chain 1

Also known as: ECHS1D, SCEH, mECH, mECH1

NCBI Gene: 1892ENSG00000127884UniProt: P30084

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]

Primary Disease Associations & Inheritance

Mitochondrial short-chain enoyl-CoA hydratase 1 deficiencyMIM #616277
AR
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ECHS1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.96LOEUF
pLI 0.001
Z-score 1.69
OE 0.51 (0.29–0.96)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.86Z-score
OE missense 0.81 (0.70–0.94)
131 obs / 161.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.51 (0.29–0.96)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.70–0.94)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07
0≤1.21.6
LoF obs/exp: 7 / 13.8Missense obs/exp: 131 / 161.9Syn Z: -0.42

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

Gene2Phenotype Curations

ECHS1-related mitochondrial short-chain enoyl-CoA hydratase 1 deficiency

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency

MIM #616277

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Leigh Syndrome: A Study of 209 Patients at the Beijing Children's Hospital.
Stenton SL et al.·Ann Neurol
2022Cohort
ECHS1: pathogenic mechanisms, experimental models, and emerging therapeutic strategies.
Fu Q et al.·Orphanet J Rare Dis
2025Review
Understanding the role of OXPHOS dysfunction in the pathogenesis of ECHS1 deficiency.
Burgin HJ et al.·FEBS Lett
2020Review
Pathogenic Biallelic Mutations in ECHS1 in a Case with Short-Chain Enoyl-CoA Hydratase (SCEH) Deficiency-Case Report and Literature Review.
Muntean C et al.·Int J Environ Res Public Health
2022Review
Phenotypic spectrum of short-chain enoyl-Coa hydratase-1 (ECHS1) deficiency.
Masnada S et al.·Eur J Paediatr Neurol
2020Case report
Clinical, biochemical and metabolic characterization of patients with short-chain enoyl-CoA hydratase(ECHS1) deficiency: two case reports and the review of the literature.
Yang H et al.·BMC Pediatr
2020Review
Mendelian etiologies identified with whole exome sequencing in cerebral palsy.
Chopra M et al.·Ann Clin Transl Neurol
2022
Time-resolved mitochondrial screen identifies regulatory components of oxidative metabolism.
Zamora-Dorta M et al.·EMBO Rep
2025
Delineating the neurological phenotype in children with defects in the ECHS1 or HIBCH gene.
Marti-Sanchez L et al.·J Inherit Metab Dis
2021
Clinical, biochemical, and genetic features of four patients with short-chain enoyl-CoA hydratase (ECHS1) deficiency.
Fitzsimons PE et al.·Am J Med Genet A
2018Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
New Neuroimaging Findings in Enoyl-CoA Hydratase Short-Chain 1 (ECHS1) Deficiency.
Tada H et al.·Cureus
2026🔓 Open Access
Downregulated ECHS1 and HADH-mediated fatty acid β-oxidation contributes to mitochondrial dysfunction in salivary glands of Sjögren's syndrome.
Zhou M et al.·J Transl Autoimmun
2026🔓 Open Access
Neurological, metabolic and inflammatory phenotypes in a mouse model of ECHS1 deficiency.
Eller MM et al.·Brain Commun
2025🔓 Open AccessFunctional
Yucan granules alleviate renal injury in diabetic nephropathy by targeting ECH1, DHRS4, ECI2, and ECHS1.
Zhang Y et al.·J Ethnopharmacol
2026
[Clinical characteristics analysis of mitochondrial short-chain enoyl-CoA hydratase 1 deficiency with ECHS1 gene c.489G>A compound heterozygous variants].
Liu Y et al.·Zhonghua Er Ke Za Zhi
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools