MCEE

Chr 2AR

methylmalonyl-CoA epimerase

Also known as: GLOD2, MCE, MMCE

The protein catalyzes the interconversion of D- and L-methylmalonyl-CoA during the degradation of branched chain amino acids and odd chain-length fatty acids. Mutations cause methylmalonyl-CoA epimerase deficiency, which presents as mild to moderate methylmalonic aciduria with autosomal recessive inheritance. This gene shows relatively low constraint to loss-of-function variation compared to other genes associated with metabolic disorders.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.341 OMIM phenotype
Clinical SummaryMCEE
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Gene-Disease Validity (ClinGen)
methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
20 unique Pathogenic / Likely Pathogenic· 47 VUS of 156 total submissions
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GeneReview available — MCEE
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.34LOEUF
pLI 0.027
Z-score 1.05
OE 0.53 (0.241.34)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.52Z-score
OE missense 0.85 (0.711.02)
79 obs / 93.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.53 (0.241.34)
00.351.4
Missense OE0.85 (0.711.02)
00.61.4
Synonymous OE0.82
01.21.6
LoF obs/exp: 3 / 5.7Missense obs/exp: 79 / 93.1Syn Z: 0.86
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveMCEE-related methylmalonyl-CoA epimerase deficiencyLOFAR

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

DN
0.79top 25%
GOF
0.5071th %ile
LOF
0.3453th %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

156 submitted variants in ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic7
VUS47
Likely Benign60
Benign19
Conflicting6
13
Pathogenic
7
Likely Pathogenic
47
VUS
60
Likely Benign
19
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
0
8
0
13
Likely Pathogenic
3
0
4
0
7
VUS
2
38
7
0
47
Likely Benign
1
1
16
42
60
Benign
0
3
16
0
19
Conflicting
6
Total11425142152

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

View in ClinVar →

Protein Context — Lollipop Plot

MCEE · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC