MCEE

methylmalonyl-CoA epimerase, the group of Glyoxalase domain containing family

Basic information

Region (hg38): 2:71109684-71130239

Links

ENSG00000124370 ∙ NCBI:84693 ∙ OMIM:608419 ∙ HGNC:16732 ∙ Uniprot:Q96PE7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency (Definitive), mode of inheritance: AR
• methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency (Strong), mode of inheritance: AR
• methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Methylmalonyl-CoA epimerase deficiency	AR	Biochemical	Long-term dietary (high-calorie diet low in propiogenic amino acid precursors with carnitine supplementation) and medical management (eg, IM hydroxocobalamin, antibiotics to decrease propionate production) is indicated; Fasting and high-protein consumption should be avoided; In the emergent setting, prompt recognition and appropriate metabolic care may be beneficial to decrease morbidity and mortality; Antioxidants for optic nerve atrophy may be beneficial; Liver/kidney transplant has been described in methylmalonic acidemia	Biochemical; Neurologic; Ophthalmologic	16752391; 17823972; 20301409
No response to vitamin B12 administration was documented in the affected individual

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MCEE gene.

• Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency (3 variants)
• Methylmalonic acidemia (1 variants)
• not provided (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MCEE gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				37		37
missense			30		3	33
nonsense	1					1
start loss			1			1
frameshift	2		1			3
inframe indel						0
splice donor/acceptor (+/-2bp)		2				2
splice region				3		3
non coding		1	2	12	9	24
Total	3	3	34	49	12

Highest pathogenic variant AF is 0.000289

Variants in MCEE

This is a list of pathogenic ClinVar variants found in the MCEE region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-71109708-C-T		Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency	Benign (Nov 15, 2018)
2-71109848-TCA-T		Methylmalonic acidemia	Benign/Likely benign (Nov 16, 2018)
2-71109906-T-G		Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency	Uncertain significance (Apr 27, 2017)
2-71109956-CT-C		not specified	Likely benign (May 04, 2016)
2-71109981-C-G		Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency	Uncertain significance (Jan 09, 2024)
2-71109984-G-A		Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency	Likely benign (Jan 30, 2024)
2-71109994-G-C		Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency	Likely benign (Sep 03, 2023)
2-71110000-A-G		Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency	Likely benign (Jan 20, 2023)
2-71110005-A-T		Inborn genetic diseases	Uncertain significance (Jan 22, 2024)
2-71110018-G-C		Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency	Likely benign (Feb 08, 2023)
2-71110025-A-G		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
2-71110027-C-A		Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency	Likely benign (Aug 11, 2023)
2-71110027-C-T		Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency	Likely benign (Dec 02, 2022)
2-71110032-G-A		Inborn genetic diseases	Uncertain significance (Oct 27, 2023)
2-71110035-T-C		Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency	Uncertain significance (Aug 26, 2021)
2-71110039-A-G		Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency	Likely benign (Nov 05, 2023)
2-71110042-T-G		Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency	Likely benign (Apr 20, 2023)
2-71110061-T-C		Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency	Uncertain significance (Jan 13, 2018)
2-71110073-C-T		not specified • Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency	Benign (Jan 31, 2024)
2-71110074-G-A		Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency • not specified	Conflicting classifications of pathogenicity (Jan 31, 2024)
2-71110076-A-T		Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency	Uncertain significance (Oct 07, 2022)
2-71110081-C-CT		not specified	Uncertain significance (Apr 11, 2022)
2-71110101-C-T		Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency	Uncertain significance (Oct 28, 2022)
2-71110108-A-G		Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency	Likely benign (Mar 20, 2023)
2-71110120-C-G		Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency	Likely benign (Sep 11, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MCEE	protein_coding	protein_coding	ENST00000244217	3	20556

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0269	0.805	125665	0	81	125746	0.000322

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.519	79	93.1	0.849	0.00000434	1127
Missense in Polyphen		21	30.449	0.68969		409
Synonymous	0.855	29	35.5	0.817	0.00000170	371
Loss of Function	1.05	3	5.69	0.527	3.06e-7	69

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000260	0.000260
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000565	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000582	0.000563
Middle Eastern	0.0000565	0.0000544
South Asian	0.0000654	0.0000653
Other	0.000653	0.000652

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Methylmalonyl-CoA epimerase deficiency (MCEED) [MIM:251120]: Autosomal recessive inborn error of amino acid metabolism, involving valine, threonine, isoleucine and methionine. This organic aciduria may present in the neonatal period with life-threatening metabolic acidosis, hyperammonemia, feeding difficulties, pancytopenia and coma. {ECO:0000269|PubMed:16752391}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Propanoate metabolism - Homo sapiens (human);Valine, leucine and isoleucine degradation - Homo sapiens (human);Glyoxylate and dicarboxylate metabolism - Homo sapiens (human);3-Methylglutaconic Aciduria Type I;Valine, Leucine and Isoleucine Degradation;2-Methyl-3-Hydroxybutryl CoA Dehydrogenase Deficiency;Malonyl-coa decarboxylase deficiency;Malonic Aciduria;Isovaleric Aciduria;3-Methylcrotonyl Coa Carboxylase Deficiency Type I;Propionic Acidemia;Maple Syrup Urine Disease;Propanoate Metabolism;3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency;Isobutyryl-coa dehydrogenase deficiency;3-hydroxyisobutyric aciduria;3-hydroxyisobutyric acid dehydrogenase deficiency;Isovaleric acidemia;Methylmalonate Semialdehyde Dehydrogenase Deficiency;Methylmalonic Aciduria;Methylmalonic Aciduria Due to Cobalamin-Related Disorders;3-Methylglutaconic Aciduria Type IV;3-Methylglutaconic Aciduria Type III;Threonine and 2-Oxobutanoate Degradation;Beta-Ketothiolase Deficiency;Vitamin B12 Metabolism;Metabolism of lipids;propionyl-CoA degradation;Propionyl-CoA catabolism;Mitochondrial Fatty Acid Beta-Oxidation;Metabolism;Fatty acid metabolism;Propanoate metabolism;Propanoate metabolism;2-oxobutanoate degradation;superpathway of methionine degradation (Consensus)

Recessive Scores

• pRec: 0.161

Intolerance Scores

• loftool: 0.678
• rvis_EVS: 0.68
• rvis_percentile_EVS: 84.93

Haploinsufficiency Scores

• pHI: 0.0728
• hipred: N
• hipred_score: 0.328
• ghis: 0.398

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.786

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mcee

Gene ontology

• Biological process: short-chain fatty acid catabolic process;L-methylmalonyl-CoA metabolic process
• Cellular component: mitochondrial matrix
• Molecular function: methylmalonyl-CoA epimerase activity;protein binding;metal ion binding