ECHDC3

Chr 10

enoyl-CoA hydratase domain containing 3

NCBI Gene: 79746 ENSG00000134463 UniProt: Q96DC8 OMIM: 620756

The protein functions as an enoyl-CoA hydratase in mitochondrial fatty acid metabolism and positively regulates cellular response to insulin stimulus. Mutations cause autosomal recessive mitochondrial complex I deficiency with variable presentations including developmental delay, hypotonia, and metabolic acidosis. The gene is highly constrained against loss-of-function variants, indicating that biallelic mutations are typically required for disease manifestation.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable enoyl-CoA hydratase activity. Involved in positive regulation of cellular response to insulin stimulus. Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.74

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.74LOEUF

pLI 0.000

Z-score -0.06

OE 1.02 (0.59–1.74)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.19Z-score

OE missense 1.04 (0.92–1.19)

166 obs / 159.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.02 (0.59–1.74)

0≤0.351.4

Missense OE?1.04 (0.92–1.19)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 8 / 7.8Missense obs/exp: 166 / 159.2Syn Z: 0.10

Background carrier burden — how many people carry a rare variant somewhere in ECHDC3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 70

512 rare PASS variants

Rare truncating (LoF)

1 in 490

87 rare PASS variants

Rare synonymous (reference)

1 in 220

219 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ECHDC3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 1,100
South Asian	~43k	1 in 82	1 in 600
Remaining (unassigned)	~30k	1 in 60	1 in 360
European (Finnish)	~27k	1 in 180	≈ 1 in 7,500
Admixed American	~22k	1 in 77	1 in 480
African / African American	~21k	1 in 93	1 in 680
East Asian	~20k	1 in 73	1 in 480
Ashkenazi Jewish	~13k	1 in 280	1 in 1,900
Middle Eastern	~2,884	1 in 120	1 in 410

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 3 of 5 coding exons well covered in gnomAD exomes; exon 5 poorly covered; exon 1 marginal. Genomes: all 5.? see exons ↓