MMUT

Chr 6AR

methylmalonyl-CoA mutase

Also known as: MCM, MUT

The MMUT gene encodes methylmalonyl-CoA mutase, a vitamin B12-dependent mitochondrial enzyme that catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA in the tricarboxylic acid cycle. Mutations cause methylmalonic aciduria (mut0 type), an autosomal recessive disorder typically presenting in the neonatal period with metabolic acidosis, hyperammonemia, and failure to thrive. The gene shows tolerance to loss-of-function variants (LOEUF 1.232), consistent with recessive inheritance where heterozygous carriers are unaffected.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.231 OMIM phenotype
Clinical SummaryMMUT
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Gene-Disease Validity (ClinGen)
methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — MMUT
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
1.23LOEUF
pLI 0.000
Z-score 0.40
OE 0.93 (0.711.23)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.23Z-score
OE missense 0.97 (0.891.05)
401 obs / 414.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.93 (0.711.23)
00.351.4
Missense OE0.97 (0.891.05)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 35 / 37.7Missense obs/exp: 401 / 414.1Syn Z: 0.01
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveMMUT-related methylmalonic aciduriaLOFAR

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

DN
0.6841th %ile
GOF
0.6345th %ile
LOF
0.3551th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MMUT · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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