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MCEE
methylmalonyl-CoA epimerase
The MCEE gene encodes the methylmalonyl-CoA epimerase enzyme, crucial for converting methylmalonyl-CoA during the metabolic breakdown of certain amino acids, fats, and cholesterol. The MCEE gene provides instructions for creating methylmalonyl-CoA epimerase, an enzyme vital for normal metabolic function.
MCEE is located on the short (p) arm of chromosome 2, at band 2p13.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The MCEE gene, or methylmalonyl-CoA epimerase, is essential for metabolic processes within the body. It plays a key role in the breakdown pathways for specific amino acids, fats, and cholesterol. Understanding the function of MCEE is important for comprehending conditions related to its disruption.
What the gene does
The MCEE gene provides the blueprint for an enzyme called methylmalonyl-CoA epimerase. This enzyme's primary function is to catalyse the conversion of D-methylmalonyl-CoA to L-methylmalonyl-CoA. This specific chemical transformation is an integral part of a broader metabolic pathway that converts propionyl-CoA into succinyl-CoA. This pathway is crucial for the efficient breakdown of various building blocks, including certain amino acids, specific types of fats, and cholesterol. Without a functional MCEE enzyme, this conversion cannot occur effectively, potentially leading to a build-up of metabolic intermediates.
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Chromosome location
The MCEE gene is situated on chromosome 2, specifically at position 2p13.3. This location denotes its precise physical address within the human genome.
Protein structure
The MCEE protein consists of 176 amino acids. A key functional region has been identified as the VOC (Domain), which spans amino acids 47-176. This domain is integral to the enzyme's catalytic activity.
Key variants
Genetic changes, known as variants, in the MCEE gene can affect the function of the methylmalonyl-CoA epimerase enzyme. These alterations can range from single nucleotide changes to larger deletions or insertions, potentially leading to a non-functional or less efficient enzyme. The impact of such variants can vary depending on their specific nature and location within the gene.
Sample of pathogenic variants
6 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.139C>T | p.Arg47Ter | Pathogenic | ★★☆☆ | Inborn genetic diseases |
g.(?_71109950)_(71130239_?)del | - | Pathogenic | ★☆☆☆ | Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency |
c.102_105dup | p.Asp36fs | Pathogenic | ★☆☆☆ | Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency |
c.19dup | p.Ala7fs | Pathogenic | ★☆☆☆ | Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency |
c.208_209insCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCAGGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAGAATATTCTGG | p.Gly70delinsAlaGlyArgGlyGlySerArgLeuTer | Pathogenic | ★☆☆☆ | Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency |
c.49dup | p.Ser17fs | Pathogenic | ★☆☆☆ | Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in the MCEE gene are associated with methylmalonic acidaemia. This condition is characterised by difficulties with feeding, developmental delays, and potentially long-term health complications. Individuals with methylmalonic acidaemia due to MCEE gene variants typically have an enzyme with little or no activity.
No disease links recorded for this gene in our reference set.
UK clinical status
The MCEE gene is included in several expert-curated panels within the NHS Genomic Medicine Service's PanelApp. It is designated as 'green' for conditions such as DDG2P, Ketotic hypoglycaemia, Likely inborn error of metabolism, and Undiagnosed metabolic disorders, indicating strong evidence for its association with these conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the MCEE gene?
The MCEE gene provides instructions for the methylmalonyl-CoA epimerase enzyme, which converts D-methylmalonyl-CoA to L-methylmalonyl-CoA. This conversion is crucial for the metabolic breakdown of specific amino acids, fats, and cholesterol.
What health condition is associated with variants in the MCEE gene?
Variants in the MCEE gene are associated with methylmalonic acidaemia. This condition can lead to feeding difficulties, developmental delays, and other long-term health issues.
Where is the MCEE gene located in the human genome?
The MCEE gene is located on chromosome 2, specifically at band 2p13.3.
References
- Gradinger AB, Bélair C, Worgan LC. Atypical methylmalonic aciduria: frequency of mutations in the methylmalonyl CoA epimerase gene (MCEE). Human mutation. 2007. PMID: 17823972
- Dobson CM, Gradinger A, Longo N. Homozygous nonsense mutation in the MCEE gene and siRNA suppression of methylmalonyl-CoA epimerase expression: a novel cause of mild methylmalonic aciduria. Molecular genetics and metabolism. 2006. PMID: 16697227
- Bikker H, Bakker HD, Abeling NG. A homozygous nonsense mutation in the methylmalonyl-CoA epimerase gene (MCEE) results in mild methylmalonic aciduria. Human mutation. 2006. PMID: 16752391