MMAA Gene: Methylmalonic Aciduria (cobalamin deficiency) type A
Essential for vitamin B12 metabolism and mitochondrial function
Gene Information Card
| Symbol | MMAA |
|---|---|
| Full Name | Methylmalonic Aciduria (cobalamin deficiency) type A |
| Gene Type | Protein coding |
| Chromosomal Location | 4q31.21 |
| NCBI Gene ID | 166785 ncbi.nlm.nih.gov/gene/166785 |
| Ensembl ID | ENSG00000151611 |
| UniProt ID | Q8IVH4 |
| OMIM ID | 607481 |
| HGNC ID | 18771 |
| Aliases | cblA, MMA, MAA |
Description
The MMAA gene encodes a mitochondrial protein involved in the metabolism of cobalamin (vitamin B12). It is essential for the conversion of dietary cobalamin into adenosylcobalamin, a cofactor required for the activity of methylmalonyl-CoA mutase. Mutations in MMAA cause methylmalonic aciduria type A (cblA), an autosomal recessive disorder characterized by accumulation of methylmalonic acid and metabolic acidosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Methylmalonic aciduria type A (cblA) | Defective adenosylcobalamin synthesis leads to impaired methylmalonyl-CoA mutase activity, causing accumulation of methylmalonic acid. | ClinVar, OMIM |
| Methylmalonic aciduria with homocystinuria (cblC) | Rarely, MMAA mutations can present with combined deficiency; distinct from cblC. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 10.2 | Medium |
| Heart | 8.1 | Medium |
| Brain | 5.3 | Low |
| Skeletal Muscle | 4.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.3 | Hepatocyte model |
| HEK293 | 9.8 | Embryonic kidney |
| K562 | 6.1 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.433C>T (p.Arg145*) | Nonsense | ~15% of cblA alleles | Premature stop, loss of function |
| c.571C>T (p.Arg191Trp) | Missense | ~10% | Impaired protein stability |
| c.1106G>A (p.Arg369Gln) | Missense | ~8% | Reduced catalytic activity |
Mutation functional classification
Loss of Function (LOF)
Most MMAA mutations are loss-of-function, leading to reduced or absent protein activity and impaired adenosylcobalamin synthesis.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative effects described; disease is recessive.
View complete mutation data：
Gene Ontology (GO)
| • mitochondrion (GO:0005739) | • cobalamin metabolic process (GO:0009235) |
| • cobalamin transporter activity (GO:0015421) | • metal ion binding (GO:0046872) |
Pathways
• Cobalamin (vitamin B12) metabolism
• Propanoate metabolism
Protein Summary
The MMAA protein is a mitochondrial ATPase that facilitates the transport and processing of cobalamin into adenosylcobalamin. It interacts with methylmalonyl-CoA mutase to ensure proper cofactor loading. Deficiency leads to methylmalonic aciduria.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MMAA Knockout HEK293 Cell Line | EDJ-KQ2903 | Human | 166785 | Details Get a Quote |
| MMAA Knockout A-549 Cell Line | EDJ-KQ25361 | Human | 166785 | Details Get a Quote |
| MMAA Knockout HCT 116 Cell Line | EDJ-KQ25362 | Human | 166785 | Details Get a Quote |
| MMAA Knockout HeLa Cell Line | EDJ-KQ25363 | Human | 166785 | Details Get a Quote |
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