MMAB Gene: Methylmalonic Aciduria (Cobalamin Deficiency) cblB Type
Comprehensive genomic and functional analysis of the MMAB gene encoding ATP:cobalamin adenosyltransferase
Gene Information Card
| Symbol | MMAB |
|---|---|
| Full Name | Methylmalonic Aciduria (Cobalamin Deficiency) cblB Type |
| Gene Type | Protein coding |
| Chromosomal Location | 12q24.11 |
| NCBI Gene ID | 326625 ncbi.nlm.nih.gov/gene/326625 |
| Ensembl ID | ENSG00000139410 |
| UniProt ID | Q96EY8 |
| OMIM ID | 607568 |
| HGNC ID | 4931 |
| Aliases | cblB, ATP:cobalamin adenosyltransferase, ATTR, MGC22960 |
Description
The MMAB gene encodes ATP:cobalamin adenosyltransferase, a mitochondrial enzyme that catalyzes the final step in the conversion of vitamin B12 (cobalamin) to adenosylcobalamin (AdoCbl), a cofactor required for the activity of methylmalonyl-CoA mutase. Mutations in MMAB cause methylmalonic aciduria type cblB (MMA cblB), an autosomal recessive disorder characterized by accumulation of methylmalonic acid and metabolic acidosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Methylmalonic Aciduria cblB Type | Loss-of-function mutations in MMAB impair adenosylcobalamin synthesis, reducing methylmalonyl-CoA mutase activity and causing methylmalonic acid accumulation. | ClinVar, OMIM |
| Methylmalonic Aciduria with Homocystinuria (cblC/D/F/J) | Secondary involvement; MMAB defects are specific to cblB type, not associated with homocystinuria. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 8.3 | Medium |
| Heart | 6.1 | Low |
| Brain | 4.2 | Low |
| Testis | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line |
| HEK293 | 9.7 | Embryonic kidney cells |
| K562 | 5.4 | Chronic myelogenous leukemia |
| HeLa | 4.1 | Cervical adenocarcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.394C>T (p.Arg132Ter) | Nonsense | ~30% of cblB alleles | Loss of function; premature truncation |
| c.557A>G (p.Asp186Gly) | Missense | ~15% | Reduced enzyme activity |
| c.1A>G (p.Met1Val) | Missense (start loss) | ~5% | Loss of translation initiation |
| c.700C>T (p.Arg234Cys) | Missense | ~10% | Impaired substrate binding |
Mutation functional classification
Loss of Function (LOF)
Most MMAB mutations are loss-of-function, leading to reduced or absent adenosylcobalamin synthesis and subsequent methylmalonic aciduria.
Gain of Function (GOF)
No gain-of-function mutations reported in MMAB.
Dominant Negative (DN)
No dominant-negative effects described; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding (GO:0005524) | • cobalamin adenosyltransferase activity (GO:0008817) |
| • mitochondrion (GO:0005739) | • cobalamin metabolic process (GO:0009235) |
| • transferase activity (GO:0016740) |
Pathways
• Vitamin B12 metabolism (Reactome: R-HSA-196741)
• Propionate metabolism (KEGG: hsa00640)
• Methylmalonyl-CoA mutase pathway
Protein Summary
ATP:cobalamin adenosyltransferase (ATR) is a 250-amino acid mitochondrial enzyme that catalyzes the ATP-dependent adenosylation of cobalamin to form adenosylcobalamin. The enzyme functions as a homotrimer and is essential for the activity of methylmalonyl-CoA mutase. Defects in this protein lead to methylmalonic aciduria type cblB.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MMAB Knockout HEK293 Cell Line | EDJ-KQ12051 | Human | 326625 | Details Get a Quote |
| MMAB Knockout A-549 Cell Line | EDJ-KQ40688 | Human | 326625 | Details Get a Quote |
| MMAB Knockout HCT 116 Cell Line | EDJ-KQ40689 | Human | 326625 | Details Get a Quote |
| MMAB Knockout HeLa Cell Line | EDJ-KQ40690 | Human | 326625 | Details Get a Quote |
| MMAB (p.M239K) Point Mutation in HAP1 Cell Line | EDC03546 | Human | 326625 | Details Get a Quote |
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