MMUT

Chr 6AR

methylmalonyl-CoA mutase

Also known as: MCM, MUT

NCBI Gene: 4594 ENSG00000146085 UniProt: P22033 OMIM: 609058

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes the mitochondrial enzyme methylmalonyl Coenzyme A mutase. In humans, the product of this gene is a vitamin B12-dependent enzyme which catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA, while in other species this enzyme may have different functions. Mutations in this gene may lead to various types of methylmalonic aciduria. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.231 OMIM phenotype

Clinical Summary— MMUT

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Gene-Disease Validity (ClinGen)

methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.23LOEUF

pLI 0.000

Z-score 0.40

OE 0.93 (0.71–1.23)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.23Z-score

OE missense 0.97 (0.89–1.05)

401 obs / 414.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.93 (0.71–1.23)

0≤0.351.4

Missense OE?0.97 (0.89–1.05)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 35 / 37.7Missense obs/exp: 401 / 414.1Syn Z: 0.01

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveMMUT-related methylmalonic aciduriaLOFAR

This gene — mechanism propensity

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

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.