ECI1

Chr 16

enoyl-CoA delta isomerase 1

Also known as: DCI

NCBI Gene: 1632 ENSG00000167969 UniProt: P42126 OMIM: 600305

The protein is a key mitochondrial enzyme that catalyzes the isomerization of 3-cis and 3-trans-enoyl-CoA esters to 2-trans-enoyl-CoA intermediates during beta-oxidation of unsaturated fatty acids. Mutations cause autosomal recessive defects in fatty acid oxidation leading to metabolic dysfunction. The gene shows very low constraint against loss-of-function variants (extremely low pLI score), consistent with recessive inheritance patterns.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the hydratase/isomerase superfamily. The protein encoded is a key mitochondrial enzyme involved in beta-oxidation of unsaturated fatty acids. It catalyzes the transformation of 3-cis and 3-trans-enoyl-CoA esters arising during the stepwise degradation of cis-, mono-, and polyunsaturated fatty acids to the 2-trans-enoyl-CoA intermediates. Alternatively spliced transcript variants have been described. [provided by RefSeq, May 2010]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.84

Clinical Summary— ECI1

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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

73 VUS of 98 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.84LOEUF

pLI 0.000

Z-score -0.95

OE 1.29 (0.87–1.84)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.42Z-score

OE missense 1.09 (0.97–1.23)

192 obs / 176.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.29 (0.87–1.84)

0≤0.351.4

Missense OE?1.09 (0.97–1.23)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 16 / 12.4Missense obs/exp: 192 / 176.2Syn Z: -0.57

This gene — mechanism propensity

0.6746th %ile

GOF

0.5562th %ile

LOF

0.3745th %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

98 submitted variants in ClinVar

ClinVar

Classification Summary

VUS73

Likely Benign5

Benign3

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	72	0	0	73
Likely Benign	0	3	0	2	5
Benign	0	1	1	1	3
Total	1	76	1	3	81

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

View in ClinVar →

29 pathogenic / likely-pathogenic (of 45) ClinVar copy-number / structural variants overlap ECI1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →