MMAA

Chr 4q31.21

metabolism of cobalamin associated A

Aliases:: cblA
MANE:: ENST00000649156.2

OMIM: 607481 ↗NCBI: 166785 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

MMAA · Q8IVH4

v62025-08-01

Predicted Aligned Error matrix for MMAA — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

78.5/ 100

Confident

418 residues

Confidence breakdown

Very high(≥ 90)57%
Confident(70–90)16%
Low(50–70)8%
Very low(< 50)19%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
BIALLELIC, autosomal or pseudoautosomal
Hyperammonaemia
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism
BIALLELIC, autosomal or pseudoautosomal
Undiagnosed metabolic disorders
BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

methylmalonic aciduria, cblA type
0.84
Vitamin B12-responsive methylmalonic acidemia type cblA
0.83
vitamin B12-responsive methylmalonic acidemia
0.64
methylmalonic acidemia
0.56
methylmalonic aciduria (cobalamin deficiency) cblA type
0.56
vitamin B12 deficiency
0.46
deficiency anemia
0.39
megaloblastic anemia
0.38
Methylmalonic aciduria
0.37
Vitamin B12-responsive methylmalonic acidemia type cblB
0.37

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Methylmalonic aciduria type A protein, mitochondrial

GTPase, binds and hydrolyzes GTP (PubMed:20876572, PubMed:21138732, PubMed:28497574, PubMed:28943303). Involved in intracellular vitamin B12 metabolism, mediates the transport of cobalamin (Cbl) into mitochondria for the final steps of adenosylcobalamin (AdoCbl) synthesis (PubMed:20876572, PubMed:28497574). Functions as a G protein chaperone that assists AdoCbl cofactor delivery from MMAB to the methylmalonyl-CoA mutase (MMUT) (PubMed:20876572, PubMed:28497574). Plays a dual role as both a protectase and a reactivase for MMUT (PubMed:21138732, PubMed:28943303). Protects MMUT from progressive inactivation by oxidation by decreasing the rate of the formation of the oxidized inactive cofactor hydroxocobalamin (OH2Cbl) (PubMed:21138732, PubMed:28943303). Additionally acts a reactivase by promoting the replacement of OH2Cbl by the active cofactor AdoCbl, restoring the activity of MMUT in the presence and hydrolysis of GTP (PubMed:21138732, PubMed:28943303)