ME2

malic enzyme 2

Basic information

Region (hg38): 18:50879079-50954257

Links

ENSG00000082212 ∙ NCBI:4200 ∙ OMIM:154270 ∙ HGNC:6984 ∙ Uniprot:P23368 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Tourette syndrome (No Known Disease Relationship), mode of inheritance: Unknown

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ME2 gene.

• Inborn genetic diseases (17 variants)
• not specified (4 variants)
• - (4 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ME2 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				1	1	2
missense			19	1		20
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	19	2	1

Variants in ME2

This is a list of pathogenic ClinVar variants found in the ME2 region.

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

Position	Type	Phenotype	Significance	ClinVar
18-50880956-C-T		-	no classification for the single variant (-)
18-50895874-T-G		not specified	Uncertain significance (Feb 10, 2022)
18-50895906-T-C		not specified	Uncertain significance (Sep 29, 2022)
18-50896615-A-A		-	no classification for the single variant (-)
18-50912846-T-G		not specified	Uncertain significance (Aug 11, 2022)
18-50916184-A-G		not specified	Uncertain significance (Jul 21, 2017)
18-50916219-T-A		not specified	Uncertain significance (Jan 24, 2024)
18-50917428-C-T		not specified	Uncertain significance (Mar 14, 2024)
18-50917459-G-A		not specified	Likely benign (Dec 19, 2023)
18-50917475-G-A			Likely benign (May 25, 2018)
18-50917486-T-C		not specified	Uncertain significance (Dec 14, 2022)
18-50917507-T-C		not specified • ME2-related disorder	Conflicting classifications of pathogenicity (Oct 28, 2019)
18-50918146-C-G		not specified	Uncertain significance (Oct 13, 2023)
18-50920475-A-G		not specified	Uncertain significance (Oct 24, 2023)
18-50920573-A-C		ME2-related disorder	Benign (Feb 22, 2019)
18-50920583-C-A		-	no classification for the single variant (-)
18-50920726-G-A		not specified	Uncertain significance (Sep 20, 2023)
18-50921110-A-G		not specified	Uncertain significance (Mar 31, 2022)
18-50921113-G-T		not specified	Uncertain significance (Sep 12, 2023)
18-50924102-G-A		not specified	Uncertain significance (Dec 22, 2023)
18-50924116-G-A		not specified	Uncertain significance (Jul 19, 2023)
18-50924156-G-A		not specified	Likely benign (Jun 24, 2022)
18-50924206-A-T		not specified	Uncertain significance (Feb 06, 2023)
18-50925774-G-A		not specified	Uncertain significance (May 17, 2023)
18-50925814-C-T		ME2-related disorder	Likely benign (Mar 29, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ME2	protein_coding	protein_coding	ENST00000321341	15	69273

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.03e-15	0.240	125642	0	101	125743	0.000402

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.969	265	313	0.846	0.0000157	3790
Missense in Polyphen		120	143.2	0.83796		1783
Synonymous	0.640	98	106	0.921	0.00000512	1117
Loss of Function	1.26	27	35.0	0.771	0.00000219	392

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000522	0.000515
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000574	0.000544
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000599	0.000589
Middle Eastern	0.000574	0.000544
South Asian	0.000198	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Pathway: Pyruvate metabolism - Homo sapiens (human);Pyruvate Dehydrogenase Complex Deficiency;Primary hyperoxaluria II, PH2;Pyruvate kinase deficiency;Leigh Syndrome;Pyruvate Metabolism;Pyruvate Decarboxylase E1 Component Deficiency (PDHE1 Deficiency);Citric acid cycle (TCA cycle);Pyruvate metabolism and Citric Acid (TCA) cycle;Glycolysis Gluconeogenesis;The citric acid (TCA) cycle and respiratory electron transport;Glycolysis and Gluconeogenesis;Metabolism;Pyruvate metabolism (Consensus)

Recessive Scores

• pRec: 0.148

Intolerance Scores

• loftool: 0.974
• rvis_EVS: 0.46
• rvis_percentile_EVS: 78.59

Haploinsufficiency Scores

• pHI: 0.108
• hipred: Y
• hipred_score: 0.603
• ghis: 0.541

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.741

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Me2

Gene ontology

• Biological process: pyruvate metabolic process;tricarboxylic acid cycle;malate metabolic process;electron transport chain;regulation of NADP metabolic process
• Cellular component: mitochondrion;mitochondrial matrix
• Molecular function: malic enzyme activity;malate dehydrogenase (decarboxylating) (NAD+) activity;malate dehydrogenase (decarboxylating) (NADP+) activity;oxaloacetate decarboxylase activity;electron transfer activity;metal ion binding;NAD binding