ME1

protein-coding

malic enzyme 1

Gene summary

This gene encodes a cytosolic, NADP-dependent enzyme that generates NADPH for fatty acid biosynthesis. The activity of this enzyme, the reversible oxidative decarboxylation of malate, links the glycolytic and citric acid cycles. The regulation of expression for this gene is complex. Increased expression can result from elevated levels of thyroid hormones or by higher proportions of carbohydrates in the diet. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002395.6

Inheritance

—

ClinVar variants

U:65B:2

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.82

Max pathogenic AF

—

Genomic locus

chr6:83,210,402-83,431,051

External References & Databases

Ensembl (ENSG00000065833)

Transcript & Mutation Effects

hg38 • Region Span ~220.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ME1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 57

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002395.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar		1 clinvar	3
missense			60 clinvar	1 clinvar		61
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	65	1	1	67

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002395.6	RefSeq	NP_002386.1	14	MANE Select
ENST00000369705.4	Ensembl	ENSP00000358719.3	14	MANE Select
ENST00000901909.1	Ensembl	ENSP00000571968.1	13	Standard
ENST00000901909.2	Ensembl	ENSP00000571968.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pyruvate metabolism - Homo sapiens (human)
PPAR signaling pathway - Homo sapiens (human)
Pyruvate Dehydrogenase Complex Deficiency
Transfer of Acetyl Groups into Mitochondria
Primary hyperoxaluria II, PH2

Biological Process

carbohydrate metabolic process
pyruvate metabolic process
malate metabolic process
NADP biosynthetic process
response to hormone

Molecular Function

malic enzyme activity
malate dehydrogenase (decarboxylating) (NAD+) activity
malate dehydrogenase (decarboxylating) (NADP+) activity
oxaloacetate decarboxylase activity
electron transfer activity

Cellular Component

mitochondrion
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369705
Coding exons: 14
Length: 220690
Individuals with no LoFs: 124543
Homozygous LoFs: 4
Heterozygous LoFs: 1200
Defined: 125747
p: 0.00480

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.287	312	298	1.05	0.0000150	3709
Missense (PolyPhen)		111	117.99	0.94073		1408
Synonymous	-0.212	106	103	1.03	0.00000505	1096
Loss of Function	0.857	23	27.9	0.825	0.00000137	363

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0018	0.0016	notable
Latino/Admixed American	0.0022	0.0017	notable
Ashkenazi Jewish	0.00022	0.00020	rare
East Asian	0.00068	0.00065	rare
Finnish	0.0061	0.0059	notable
European (Non-Finnish)	0.0087	0.0078	notable
South Asian	0.0030	0.0024	notable
Other	0.0031	0.0026	notable

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.198

Intolerance Scores

LoFtool: 0.930
RVIS EVS: -0.27
RVIS percentile EVS: 34.82

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.780

Gene Damage Prediction

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