ECHDC2

Chr 1

enoyl-CoA hydratase domain containing 2

NCBI Gene: 55268 ENSG00000121310 UniProt: Q86YB7

The protein is predicted to function as a lyase in mitochondrial fatty acid beta-oxidation. Mutations cause autosomal recessive disorders affecting metabolism and development. The gene shows minimal constraint against loss-of-function variants, consistent with recessive inheritance patterns.

ResearchSummary from RefSeq

Predicted to enable lyase activity. Predicted to be involved in fatty acid beta-oxidation. Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.25

Clinical Summary— ECHDC2

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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

55 VUS of 72 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.25LOEUF

pLI 0.000

Z-score 0.69

OE 0.84 (0.57–1.25)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.09Z-score

OE missense 0.98 (0.87–1.11)

185 obs / 188.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.84 (0.57–1.25)

0≤0.351.4

Missense OE?0.98 (0.87–1.11)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 17 / 20.3Missense obs/exp: 185 / 188.6Syn Z: -0.14

This gene — mechanism propensity

0.75top 25%

GOF

0.6149th %ile

LOF

0.3066th %ile

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

DNprediction above median

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.

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

ClinVar Variant Classifications

72 submitted variants in ClinVar

ClinVar

Classification Summary

VUS55

Likely Benign3

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	55	0	55
Likely Benign	2	1	3
Benign	0	0	0
Total	57	1	58

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap ECHDC2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →