ME3
protein-codingmalic enzyme 3
Gene summary
Malic enzyme catalyzes the oxidative decarboxylation of malate to pyruvate using either NAD+ or NADP+ as a cofactor. Mammalian tissues contain 3 distinct isoforms of malic enzyme: a cytosolic NADP(+)-dependent isoform, a mitochondrial NADP(+)-dependent isoform, and a mitochondrial NAD(+)-dependent isoform. This gene encodes a mitochondrial NADP(+)-dependent isoform. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~231.5 kbGenCC 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 ME3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001161586.3. 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 | 1 | 2 | 1 | 4 | ||
| missense | 74 | 74 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 77 | 2 | 1 | 80 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001155058.1 | 14 | MANE Select | |
| Ensembl | ENSP00000440246.1 | 14 | MANE Select | |
| RefSeq | NP_001014811.1 | 14 | Standard | |
| RefSeq | NP_001338863.1 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Pyruvate metabolism - Homo sapiens (human)
- Citric acid cycle (TCA cycle)
- Pyruvate metabolism and Citric Acid (TCA) cycle
- Glycolysis Gluconeogenesis
- The citric acid (TCA) cycle and respiratory electron transport
Biological Process
- pyruvate metabolic process
- tricarboxylic acid cycle
- malate metabolic process
- aerobic respiration
- oxidation-reduction process
Molecular Function
- malic enzyme activity
- malate dehydrogenase (decarboxylating) (NAD+) activity
- malate dehydrogenase (decarboxylating) (NADP+) activity
- oxaloacetate decarboxylase activity
- metal ion binding
Cellular Component
- mitochondrion
- mitochondrial matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000543262
- Coding exons
- 14
- Length
- 231529
- Individuals with no LoFs
- 125687
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 61
- Defined
- 125748
- p
- 0.000243
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.33 | 291 | 362 | 0.803 | 0.0000212 | 3923 |
| Missense (PolyPhen) | 114 | 151.97 | 0.75014 | 1551 | ||
| Synonymous | -0.829 | 164 | 151 | 1.09 | 0.00000984 | 1225 |
| Loss of Function | 1.24 | 24 | 31.5 | 0.762 | 0.00000177 | 329 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00045 | 0.00043 | rare |
| Latino/Admixed American | 0.00023 | 0.00023 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00025 | 0.00025 | rare |
| South Asian | 0.00029 | 0.00029 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.184
Intolerance Scores
- LoFtool
- 0.799
- RVIS EVS
- -0.82
- RVIS percentile EVS
- 11.88
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Indispensability pred.
- N
- Indispensability score
- 0.130
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |