MCCC2 Gene: Beta-Methylcrotonyl-CoA Carboxylase Subunit 2
MCCC2: A key enzyme in leucine catabolism and its role in methylcrotonylglycinuria
Gene Information Card
| Symbol | MCCC2 |
|---|---|
| Full Name | Methylcrotonoyl-CoA carboxylase subunit 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q13.2 |
| NCBI Gene ID | 64087 ncbi.nlm.nih.gov/gene/64087 |
| Ensembl ID | ENSG00000113580 |
| UniProt ID | Q9HCC0 |
| OMIM ID | 609014 |
| HGNC ID | 6937 |
| Aliases | MCCC-beta, MCCB, 3-methylcrotonyl-CoA carboxylase 2 |
Description
The MCCC2 gene encodes the beta subunit of the mitochondrial enzyme 3-methylcrotonyl-CoA carboxylase (MCC), a biotin-dependent carboxylase that catalyzes the carboxylation of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA, a critical step in the leucine catabolic pathway. Mutations in MCCC2 cause 3-methylcrotonyl-CoA carboxylase deficiency (MCC deficiency), an autosomal recessive disorder of leucine metabolism, often presenting with metabolic acidosis, ketosis, and developmental delay. The gene is located on chromosome 5q13.2 and is expressed in multiple tissues, with highest levels in liver and kidney.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| 3-Methylcrotonyl-CoA carboxylase deficiency (MCC deficiency) | Loss-of-function mutations in MCCC2 impair the carboxylation of 3-methylcrotonyl-CoA, leading to accumulation of toxic metabolites such as 3-methylcrotonylglycine and 3-hydroxyisovaleric acid, causing metabolic acidosis and neurological symptoms. | ClinVar, OMIM |
| Methylcrotonylglycinuria | Deficiency of MCC due to MCCC2 mutations results in increased urinary excretion of 3-methylcrotonylglycine and 3-hydroxyisovalerate, characteristic of this organic aciduria. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 10.2 | High |
| Heart | 6.8 | Medium |
| Skeletal Muscle | 5.1 | Medium |
| Brain | 3.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.3 | Hepatocellular carcinoma cell line |
| HEK293 | 8.7 | Embryonic kidney cells |
| K562 | 4.2 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1205G>A (p.Arg402Gln) | Missense | Common in European populations | Reduced enzyme activity; associated with MCC deficiency |
| c.838C>T (p.Arg280Ter) | Nonsense | Rare | Premature stop codon; loss of function |
| c.1522C>T (p.Arg508Trp) | Missense | Reported in multiple families | Impaired biotin binding; decreased catalytic activity |
Mutation functional classification
Loss of Function (LOF)
Most MCCC2 mutations are loss-of-function, leading to reduced or absent MCC enzyme activity, causing 3-methylcrotonyl-CoA carboxylase deficiency.
Gain of Function (GOF)
No gain-of-function mutations have been reported for MCCC2.
Dominant Negative (DN)
No dominant-negative effects have been described; the disorder is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • methylcrotonoyl-CoA carboxylase activity (GO:0004485) | • isoleucine catabolic process (GO:0006549) |
| • leucine catabolic process (GO:0006552) | • mitochondrion (GO:0005739) |
| • biotin binding (GO:0009374) | • ligase activity (GO:0016874) |
Pathways
• Leucine degradation (Reactome: R-HSA-70895)
• Biotin metabolism (Reactome: R-HSA-196849)
• Valine
• leucine and isoleucine degradation (KEGG: hsa00280)
Protein Summary
The MCCC2 protein (UniProt Q9HCC0) is the beta subunit of the heterodimeric 3-methylcrotonyl-CoA carboxylase (MCC) complex. It contains a biotin carboxylase domain and a biotin-binding domain, and is essential for the carboxylation of 3-methylcrotonyl-CoA. The protein localizes to the mitochondrial matrix and is expressed in tissues with high metabolic activity. Defects in MCCC2 lead to accumulation of leucine catabolites and cause metabolic disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MCCC2 Knockout HEK293 Cell Line | EDJ-KQ14216 | Human | 64087 | Details Get a Quote |
| MCCC2 Knockout HeLa Cell Line | EDJ-KQ42962 | Human | 64087 | Details Get a Quote |
| MCCC2 Knockout A-549 Cell Line | EDJ-KQ44176 | Human | 64087 | Details Get a Quote |
| MCCC2 Knockout HCT 116 Cell Line | EDJ-KQ44177 | Human | 64087 | Details Get a Quote |
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