ME1

Chr 6

malic enzyme 1

Also known as: HUMNDME, MES

NCBI Gene: 4199ENSG00000065833UniProt: P48163

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]

87
ClinVar variants
15
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ME1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 Pathogenic / Likely Pathogenic· 68 VUS of 87 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.17LOEUF
pLI 0.000
Z-score 0.86
OE 0.82 (0.59–1.17)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.29Z-score
OE missense 1.05 (0.95–1.15)
312 obs / 298.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.82 (0.59–1.17)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.05 (0.95–1.15)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 23 / 27.9Missense obs/exp: 312 / 298.0Syn Z: -0.21

ClinVar Variant Classifications

87 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
VUS68
Likely Benign3
Benign1
15
Pathogenic
68
VUS
3
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
0
0
0
VUS
0
55
13
0
68
Likely Benign
0
1
2
0
3
Benign
0
0
0
1
1
Total05630187

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ME1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
MALIC ENZYME 1; ME1
MIM #154250 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Glycolysis-related genes predict prognosis and indicate immune microenvironment features in gastric cancer.
Xu L et al.·BMC Cancer
2024
Jumonji histone demethylases as emerging therapeutic targets.
Park SY et al.·Pharmacol Res
2016Review
Comprehensive assessment of cellular senescence in intestinal immunity and biologic therapy response in ulcerative colitis.
Yao B et al.·Sci Rep
2024
Effect of immune infiltration intensity on the efficacy of neoadjuvant immunotherapy for esophageal cancer.
Zhang Y et al.·Front Immunol
2025
SPDYC serves as a prognostic biomarker related to lipid metabolism and the immune microenvironment in breast cancer.
Chen X et al.·Immunol Res
2024
The Story of the Magee Equations: The Ultimate in Applied Immunohistochemistry.
Bhargava R et al.·Appl Immunohistochem Mol Morphol
2023
ME1 promotes basal-like breast cancer progression and associates with poor prognosis.
Liao R et al.·Sci Rep
2018
Expression of Malic Enzymes in Sebaceous Lesions.
Su TF et al.·Am J Dermatopathol
2016
Identification of lipid metabolism-related signature in nonalcoholic fatty liver: evidences from transcriptomics and single cell RNA-sequencing analysis.
Sun Y et al.·Eur J Med Res
2025
Utilization of Industrial Waste for the Production of Bio-Preservative from Bacillus licheniformis Me1 and Its Application in Milk and Milk-Based Food Products.
Nithya V et al.·Probiotics Antimicrob Proteins
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Acinetobacter sp. ME1: a multifunctional bacterium for phytoremediation utilizing melanin production, heavy metal tolerance, and plant growth promotion.
Lee SY et al.·J Zhejiang Univ Sci B
2025Functional
Loss of hepatic ME1 ameliorates MASLD by Suppressing peroxisomal β-Oxidation and Activating Lipophagy/Lipolysis.
Zhang J et al.·J Adv Res
2025
NRF2 maintains redox balance via ME1 and NRF2 inhibitor synergizes with venetoclax in NPM1-mutated acute myeloid leukemia.
Hu J et al.·Cancer Metab
2025🔓 Open Access
The potential of ME1 in guiding immunotherapeutic strategies for ovarian cancer: insights from pan-cancer research.
Wei J et al.·Front Immunol
2025🔓 Open Access
Glabridin protects against paraquat-induced acute lung injury by targeting ME1 to mitigate oxidative stress, mitochondrial dysfunction, and cGAS-STING activation.
Zhao M et al.·Free Radic Biol Med
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools