MECR

Chr 1AR

mitochondrial trans-2-enoyl-CoA reductase

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

NCBI Gene: 51102ENSG00000116353UniProt: Q9BV79

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]

Primary Disease Associations & Inheritance

?Optic atrophy 16MIM #620629
AR
Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalitiesMIM #617282
AR
358
ClinVar variants
39
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— MECR
🧬
Gene-Disease Validity (ClinGen)
Leigh syndrome · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
39 Pathogenic / Likely Pathogenic· 101 VUS of 358 total submissions

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.
0.85LOEUF
pLI 0.000
Z-score 2.09
OE 0.51 (0.32–0.85)
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.
0.11Z-score
OE missense 0.98 (0.88–1.10)
214 obs / 218.6 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 (0.32–0.85)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.88–1.10)
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.1.10
0≤1.21.6
LoF obs/exp: 11 / 21.5Missense obs/exp: 214 / 218.6Syn Z: -0.77

ClinVar Variant Classifications

358 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic10
VUS101
Likely Benign191
Benign17
Conflicting10
29
Pathogenic
10
Likely Pathogenic
101
VUS
191
Likely Benign
17
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
1
19
0
29
Likely Pathogenic
7
3
0
0
10
VUS
0
87
14
0
101
Likely Benign
0
12
83
96
191
Benign
0
1
15
1
17
Conflicting
—10
Total1610413197358

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

View in ClinVar →

Protein Context — Lollipop Plot

MECR · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

MECR-related childhood-onset dystonia and optic atrophy

strong
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

?Optic atrophy 16

MIM #620629

Molecular basis of disorder known

Autosomal recessive

Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities

MIM #617282

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — MECR
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Recessive MECR pathogenic variants cause an LHON-like optic neuropathy.
Fiorini C et al.·J Med Genet
2023
Polioencephalopathy in Eurasier dogs.
Rawson F et al.·J Vet Intern Med
2024
An engineered variant of MECR reductase reveals indispensability of long-chain acyl-ACPs for mitochondrial respiration.
Rahman MT et al.·Nat Commun
2023
Engineered bacterial lipoate protein ligase A (lplA) restores lipoylation in cell models of lipoylation deficiency.
Bick NR et al.·J Biol Chem
2024Functional
Ophthalmic manifestations of MEPAN syndrome.
Gupta PR et al.·Ophthalmic Genet
2023
Alternative splicing liberates a cryptic cytoplasmic isoform of mitochondrial MECR that antagonizes influenza virus.
Baker SF et al.·PLoS Biol
2022
Recurrent MECR R258W causes adult-onset optic atrophy: A case report.
Jia N et al.·Eur J Med Genet
2024Case report
Impaired Mitochondrial Fatty Acid Synthesis Leads to Neurodegeneration in Mice.
Nair RR et al.·J Neurosci
2018
Multi-Evidence Clinical Reasoning With Retrieval-Augmented Generation for Emergency Triage: Retrospective Evaluation Study.
Wong HS et al.·JMIR Med Inform
2026
Clinical isolates of Escherichia coli solely resistant to mecillinam: prevalence and epidemiology.
Bousquet A et al.·Int J Antimicrob Agents
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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