MECR

Chr 1

mitochondrial trans-2-enoyl-CoA reductase

Also known as: CGI-63, DYTOABG, ETR1, FASN2B, NRBF1, OPA16

NCBI Gene: 51102 ENSG00000116353 UniProt: Q9BV79

The protein is a mitochondrial oxidoreductase that catalyzes the final step in mitochondrial fatty acid synthesis. Autosomal recessive mutations cause childhood-onset dystonia with optic atrophy and basal ganglia abnormalities. The pathogenic mechanism involves loss of function, disrupting mitochondrial fatty acid biosynthesis essential for proper neuronal function.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is an oxidoreductase that catalyzes the last step in mitochondrial fatty acid synthesis. Defects in this gene are a cause of childhood-onset dystonia and optic atrophy. [provided by RefSeq, Mar 2017]

GeneReviews ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.85

Clinical Summary— MECR

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Gene-Disease Validity (ClinGen)

Leigh syndrome · ARModerate

Moderate evidence — consider for supplementary testing

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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

34 unique Pathogenic / Likely Pathogenic· 95 VUS of 358 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — MECR

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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?

0.85LOEUF

pLI 0.000

Z-score 2.09

OE 0.51 (0.32–0.85)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.11Z-score

OE missense 0.98 (0.88–1.10)

214 obs / 218.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.51 (0.32–0.85)

0≤0.351.4

Missense OE?0.98 (0.88–1.10)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 11 / 21.5Missense obs/exp: 214 / 218.6Syn Z: -0.77

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongMECR-related childhood-onset dystonia and optic atrophyLOFAR

This gene — mechanism propensity

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

0.80top 25%

GOF

0.6346th %ile

LOF

0.2775th %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

358 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24

Likely Pathogenic10

VUS95

Likely Benign191

Benign17

Conflicting10

Pathogenic

Likely Pathogenic

VUS

191

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	17	2	5	0	24
Likely Pathogenic	7	3	0	0	10
VUS	2	85	8	0	95
Likely Benign	0	12	83	96	191
Benign	0	1	15	1	17
Conflicting	—				10
Total	26	103	111	97	347

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

View in ClinVar →

6 pathogenic / likely-pathogenic (of 12) ClinVar copy-number / structural variants overlap MECR — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →