MMAA

Chr 4AR

metabolism of cobalamin associated A

Also known as: cblA

The protein encoded by this gene is involved in the translocation of cobalamin into the mitochondrion, where it is used in the final steps of adenosylcobalamin synthesis. Adenosylcobalamin is a coenzyme required for the activity of methylmalonyl-CoA mutase. Defects in this gene are a cause of methylmalonic aciduria. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
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.

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 OE?0.89 (0.621.29)
00.351.4
Missense OE?0.94 (0.841.05)
00.61.4
Synonymous OE?0.98
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

This gene — mechanism propensity

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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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