MMACHC Gene: Methylmalonic Aciduria and Homocystinuria Type C Protein
Key regulator of vitamin B12 metabolism and cobalamin trafficking
Gene Information Card
| Symbol | MMACHC |
|---|---|
| Full Name | Methylmalonic Aciduria and Homocystinuria Type C Protein |
| Gene Type | Protein coding |
| Chromosomal Location | 1p34.1 |
| NCBI Gene ID | 25974 ncbi.nlm.nih.gov/gene/25974 |
| Ensembl ID | ENSG00000132763 |
| UniProt ID | Q9Y4U1 |
| OMIM ID | 609831 |
| HGNC ID | 24525 |
| Aliases | cblC, FLJ10540, MGC138216 |
Description
The MMACHC gene encodes a cytoplasmic protein involved in the intracellular processing of cobalamin (vitamin B12). It catalyzes the decyanation of cyanocobalamin and the dealkylation of alkylcobalamins, facilitating the conversion of dietary cobalamin into active cofactors for methionine synthase and methylmalonyl-CoA mutase. Mutations in MMACHC cause combined methylmalonic aciduria and homocystinuria type C (cblC disease), an autosomal recessive disorder of cobalamin metabolism.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Methylmalonic aciduria and homocystinuria type C (cblC) | Loss-of-function mutations impair cobalamin processing, leading to deficient adenosylcobalamin and methylcobalamin synthesis | OMIM #277400; ClinVar; multiple case reports |
| Methylmalonic aciduria | Secondary to impaired adenosylcobalamin production, causing accumulation of methylmalonic acid | OMIM; NCBI Gene |
| Homocystinuria | Secondary to impaired methylcobalamin production, causing elevated homocysteine and decreased methionine | OMIM; NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 14.2 | High |
| Kidney | 11.5 | High |
| Heart | 8.3 | Medium |
| Brain | 6.1 | Medium |
| Lung | 5.4 | Medium |
| Skeletal muscle | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 12.1 | Hepatocellular carcinoma cell line |
| HEK293 | 9.7 | Embryonic kidney cells |
| K562 | 7.4 | Leukemia cell line |
| HeLa | 6.2 | Cervical adenocarcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.271dupA (p.Arg91Lysfs*14) | Frameshift | Common (founder mutation in European populations) | Loss of function; truncated protein |
| c.394C>T (p.Arg132*) | Nonsense | Recurrent | Loss of function; premature stop codon |
| c.482G>A (p.Arg161Gln) | Missense | Rare | Impaired cobalamin binding and processing |
| c.609G>A (p.Trp203*) | Nonsense | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most MMACHC mutations are loss-of-function, leading to reduced or absent cobalamin processing activity, causing cblC disease.
Gain of Function (GOF)
No gain-of-function mutations have been reported for MMACHC.
Dominant Negative (DN)
No dominant-negative mutations have been described; the disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • GO:0009235 - cobalamin metabolic process | • GO:0031418 - L-ascorbic acid binding |
| • GO:0046872 - metal ion binding | • GO:0050897 - cobalt ion binding |
| • GO:1904047 - S-adenosylmethionine binding |
Pathways
• Vitamin B12 metabolism (Reactome: R-HSA-196741)
• Cobalamin (B12) transport and metabolism (KEGG: hsa00860)
Protein Summary
The MMACHC protein (UniProt Q9Y4U1) is a 282-amino acid cytoplasmic enzyme that binds and processes cobalamin. It catalyzes the removal of upper axial ligands (e.g., cyano, methyl, or adenosyl groups) from cobalamin, enabling its conversion to active cofactors. The protein contains a cobalamin-binding domain and a flavin mononucleotide (FMN)-binding site. Defects in this protein disrupt both adenosylcobalamin and methylcobalamin synthesis, leading to combined methylmalonic aciduria and homocystinuria.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MMACHC Knockout HEK293 Cell Line | EDC07667 | Human | 25974 | Details Get a Quote |
| MMACHC Knockout A-549 Cell Line | EDJ-KQ24227 | Human | 25974 | Details Get a Quote |
| MMACHC Knockout HCT 116 Cell Line | EDJ-KQ24228 | Human | 25974 | Details Get a Quote |
| MMACHC Knockout HeLa Cell Line | EDJ-KQ24229 | Human | 25974 | Details Get a Quote |
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