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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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MMAA
metabolism of cobalamin associated A
Chromosome 4 Β· 4q31.21
NCBI Gene: 166785Ensembl: ENSG00000151611.18HGNC: HGNC:18871UniProt: Q8IVH4
27PubMed Papers
21Diseases
0Drugs
139Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
cobalamin metabolic processGTPase activityprotein bindingGTP bindingmethylmalonic aciduria, cblA typeVitamin B12-responsive methylmalonic acidemia type cblAmethylmalonic acidemiamethylmalonic aciduria (cobalamin deficiency) cblA type
✦AI Summary

MMAA is a GTPase protein essential for intracellular vitamin B12 (cobalamin) metabolism 1. It mediates cobalamin transport into mitochondria and catalyzes the final steps of adenosylcobalamin (AdoCbl) synthesis, functioning as a G-protein chaperone that facilitates AdoCbl cofactor delivery to methylmalonyl-CoA mutase (MMUT) 12. MMAA exhibits dual protective and reactivating roles for MMUT. It acts as a protectase by decreasing the formation of oxidized, inactive hydroxocobalamin (OH2Cbl) during catalysis, and as a reactivase by promoting replacement of damaged cofactor with active AdoCbl through GTP hydrolysis 34. MMAA forms nucleotide-selective complexes with MMUT apoenzyme, with complex formation and cofactor exchange regulated by GTP binding and hydrolysis 1. Mutations in MMAA cause cblA-type methylmalonic aciduria, a rare inborn error of metabolism characterized by accumulation of methylmalonic acid in blood and urine 56. Clinical presentation varies from mild to life-threatening, typically manifesting in early infancy with vomiting, hypotonia, and developmental delay 5. Understanding MMAA's structural and functional properties is crucial for developing therapeutic interventions for affected patients 7.

Sources cited
1
MMAA is a GTPase involved in mitochondrial cobalamin transport and AdoCbl assembly into MMUT; exhibits GTPase activity modulated by MUT interaction
PMID: 20876572
2
MMAA functions as a G-protein chaperone for AdoCbl cofactor delivery to methylmalonyl-CoA mutase
PMID: 28497574
3
MMAA plays dual roles protecting MMUT from inactivation and reactivating it through GTP-dependent cofactor exchange
PMID: 21138732
4
MMAA decreases oxidized cofactor formation rate and removes damaged cofactor through GTP hydrolysis
PMID: 28943303
5
MMAA mutations cause cblA-type methylmalonic aciduria presenting in infancy with vomiting, hypotonia, and developmental delay
PMID: 26101005
6
Mutations in MMAA gene lead to cblA class of methylmalonic aciduria disorder
PMID: 23026888
7
MMAA mutations cause structural instability and impaired GDP binding relevant to methylmalonic acidemia pathogenesis
PMID: 36088076
Disease Associationsβ“˜21
methylmalonic aciduria, cblA typeOpen Targets
0.84Strong
Vitamin B12-responsive methylmalonic acidemia type cblAOpen Targets
0.83Strong
methylmalonic acidemiaOpen Targets
0.67Moderate
methylmalonic aciduria (cobalamin deficiency) cblA typeOpen Targets
0.56Moderate
vitamin B12-responsive methylmalonic acidemiaOpen Targets
0.54Moderate
megaloblastic anemiaOpen Targets
0.39Weak
vitamin B12 deficiencyOpen Targets
0.39Weak
deficiency anemiaOpen Targets
0.38Weak
vitamin B deficiencyOpen Targets
0.38Weak
Methylmalonic aciduriaOpen Targets
0.37Weak
Vitamin B12-responsive methylmalonic acidemia type cblBOpen Targets
0.37Weak
genetic disorderOpen Targets
0.19Weak
jaw diseaseOpen Targets
0.14Weak
cataractOpen Targets
0.12Weak
microcephalyOpen Targets
0.12Weak
Severe global developmental delayOpen Targets
0.12Weak
malariaOpen Targets
0.03Suggestive
dehydrated hereditary stomatocytosisOpen Targets
0.03Suggestive
beta thalassemiaOpen Targets
0.03Suggestive
Beta-thalassemiaOpen Targets
0.03Suggestive
Methylmalonic aciduria, cblA typeUniProt
Pathogenic Variants139
NM_172250.3(MMAA):c.433C>T (p.Arg145Ter)Pathogenic
Methylmalonic aciduria, cblA type|not provided|Methylmalonic acidemia|MMAA-related disorder|See cases
β˜…β˜…β˜†β˜†2026β†’ Residue 145
NM_172250.3(MMAA):c.658G>A (p.Val220Met)Pathogenic
Methylmalonic aciduria, cblA type|Methylmalonic acidemia
β˜…β˜…β˜†β˜†2026β†’ Residue 220
NM_172250.3(MMAA):c.593_596del (p.Thr198fs)Pathogenic
not provided|Methylmalonic aciduria, cblA type|Methylmalonic acidemia|MMAA-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 198
NM_172250.3(MMAA):c.266T>C (p.Leu89Pro)Pathogenic
Methylmalonic aciduria, cblA type
β˜…β˜…β˜†β˜†2026β†’ Residue 89
NM_172250.3(MMAA):c.1075C>T (p.Arg359Ter)Pathogenic
Methylmalonic aciduria, cblA type|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 359
NM_172250.3(MMAA):c.434G>A (p.Arg145Gln)Pathogenic
Methylmalonic aciduria, cblA type|Methylmalonic acidemia
β˜…β˜…β˜†β˜†2025β†’ Residue 145
NM_172250.3(MMAA):c.365T>C (p.Leu122Pro)Pathogenic
Methylmalonic aciduria, cblA type
β˜…β˜…β˜†β˜†2025β†’ Residue 122
NM_172250.3(MMAA):c.64C>T (p.Arg22Ter)Pathogenic
Methylmalonic aciduria, cblA type|not provided|Methylmalonic acidemia
β˜…β˜…β˜†β˜†2025β†’ Residue 22
NM_172250.3(MMAA):c.1196_1197delinsTT (p.Gly399Val)Pathogenic
Methylmalonic aciduria, cblA type
β˜…β˜…β˜†β˜†2025β†’ Residue 399
NM_172250.3(MMAA):c.898C>T (p.Arg300Ter)Pathogenic
Methylmalonic aciduria, cblA type
β˜…β˜…β˜†β˜†2025β†’ Residue 300
NM_172250.3(MMAA):c.963_969+4delPathogenic
Methylmalonic aciduria, cblA type
β˜…β˜…β˜†β˜†2025
NM_172250.3(MMAA):c.820-2A>GLikely pathogenic
Methylmalonic aciduria, cblA type
β˜…β˜…β˜†β˜†2025
NM_172250.3(MMAA):c.388del (p.His130fs)Pathogenic
Methylmalonic aciduria, cblA type
β˜…β˜…β˜†β˜†2025β†’ Residue 130
NM_172250.3(MMAA):c.820-1G>CPathogenic
Methylmalonic aciduria, cblA type
β˜…β˜…β˜†β˜†2025
NM_172250.3(MMAA):c.387C>A (p.Tyr129Ter)Pathogenic
not provided|Methylmalonic aciduria, cblA type|Methylmalonic acidemia|MMAA-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 129
NM_172250.3(MMAA):c.586C>T (p.Arg196Ter)Pathogenic
Methylmalonic aciduria, cblA type|Methylmalonic acidemia|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 196
NM_172250.3(MMAA):c.161G>A (p.Trp54Ter)Pathogenic
Methylmalonic aciduria, cblA type
β˜…β˜…β˜†β˜†2025β†’ Residue 54
NM_172250.3(MMAA):c.820-1G>APathogenic
Methylmalonic aciduria, cblA type
β˜…β˜…β˜†β˜†2025
NM_172250.3(MMAA):c.733+1G>APathogenic
Methylmalonic aciduria, cblA type|not provided
β˜…β˜…β˜†β˜†2025
NM_172250.3(MMAA):c.988C>T (p.Arg330Ter)Pathogenic
not provided|Methylmalonic aciduria, cblA type|Methylmalonic acidemia
β˜…β˜…β˜†β˜†2025β†’ Residue 330
View on ClinVar β†—
Related Genes
CD320Protein interaction100%LMBRD1Protein interaction100%MMADHCProtein interaction97%MMUTProtein interaction95%MCEEProtein interaction95%MMABProtein interaction87%
Tissue Expression6 tissues
Liver
100%
Heart
40%
Brain
27%
Lung
19%
Bone Marrow
18%
Ovary
15%
Gene Interaction Network
Click a node to explore
MMAACD320LMBRD1MMADHCMMUTMCEEMMAB
PROTEIN STRUCTURE
Preparing viewer…
PDB2WWW Β· 2.64 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.16LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.90 [0.70–1.16]
RankingsWhere MMAA stands among ~20K protein-coding genes
  • #12,604of 20,598
    Most Researched27
  • #556of 5,498
    Most Pathogenic Variants139 Β· top quartile
  • #12,066of 17,882
    Most Constrained (LOEUF)1.16
Genes detectedMMAA
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
PMID: 20301409
1.00
2
Structures of the human GTPase MMAA and vitamin B12-dependent methylmalonyl-CoA mutase and insight into their complex formation.
PMID: 20876572
J Biol Chem Β· 2010
0.90
3
Methylmalonic Acidemia.
PMID: 26101005
J Coll Physicians Surg Pak Β· 2015
0.80
4
Human MMAA induces the release of inactive cofactor and restores methylmalonyl-CoA mutase activity through their complex formation.
PMID: 28943303
Biochimie Β· 2017
0.70
5
Protection and reactivation of human methylmalonyl-CoA mutase by MMAA protein.
PMID: 21138732
Biochem Biophys Res Commun Β· 2011
0.60