MMAA

Chr 4AR

metabolism of cobalamin associated A

Also known as: cblA

The encoded protein translocates cobalamin into mitochondria for adenosylcobalamin synthesis, which serves as a coenzyme for methylmalonyl-CoA mutase. Mutations cause vitamin B12-responsive methylmalonic aciduria (cblA type) through an autosomal recessive inheritance pattern. The pathogenic mechanism involves dominant-negative effects that disrupt normal cobalamin transport and metabolism.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 1.291 OMIM phenotype
Clinical SummaryMMAA
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Gene-Disease Validity (ClinGen)
methylmalonic aciduria, cblA type · 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.
📖
GeneReview available — MMAA
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
1.29LOEUF
pLI 0.000
Z-score 0.49
OE 0.89 (0.621.29)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.33Z-score
OE missense 0.94 (0.841.05)
209 obs / 222.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.89 (0.621.29)
00.351.4
Missense OE0.94 (0.841.05)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 20 / 22.5Missense obs/exp: 209 / 222.9Syn Z: 0.13
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveMMAA-related methylmalonic aciduriaLOFAR

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

DN
0.7229th %ile
GOF
0.5563th %ile
LOF
0.4039th %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

MMAA · 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.

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Clinical Literature
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