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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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MLXIPL
MLX interacting protein like
Chromosome 7 · 7q11.23
NCBI Gene: 51085Ensembl: ENSG00000009950.17HGNC: HGNC:12744UniProt: Q9NP71
143PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
negative regulation of signal transduction by p53 class mediatornucleoplasmprotein homodimerization activitypositive regulation of cell population proliferationgoutfamilial hyperlipidemiafamilial lipoprotein lipase deficiencydiabetes mellitus
✦AI Summary

MLXIPL (MLX interacting protein like), also known as ChR7 (carbohydrate-responsive element binding protein), is a glucose-responsive transcription factor that serves as a key regulator of hepatic carbohydrate and lipid metabolism. MLXIPL functions primarily as a transcriptional activator that senses intracellular glucose and carbohydrate levels, controlling the expression of de novo lipogenesis (DNL) genes including fatty acid synthase, acetyl-CoA carboxylase, and ATP citrate lyase 1. The protein binds to E-box DNA sequences and can be activated by reductive stress (elevated NADH/NAD+ ratios), with this activation representing a critical mechanism linking glucose sensing to lipogenic gene expression 2. MLXIPL plays a central role in systemic metabolic homeostasis. Its dysregulation contributes to nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes development through excessive conversion of carbohydrates to triglycerides 1. In response to high carbohydrate or sugar diets, MLXIPL activation increases hepatic lipogenesis and influences branched-chain amino acid metabolism 3. Genetic variants in MLXIPL are associated with differential responses to Mediterranean diet interventions and modifications of cardiometabolic risk factors including insulin sensitivity and glucose homeostasis 4. Additionally, MLXIPL deletion is implicated in Williams syndrome pathophysiology, though its specific clinical contributions require further investigation 5. MLXIPL represents a promising therapeutic target for metabolic disease prevention and treatment.

Sources cited
1
MLXIPL/ChREBP senses intracellular carbohydrates and activates de novo lipogenesis genes; dysregulation contributes to NAFLD and T2DM
PMID: 37055547
2
ChREBP is activated by reductive stress and mediates GCKR-associated metabolic traits including hepatic fat accumulation and circulating metabolite changes
PMID: 38101397
3
ChREBP transcription factor is induced by high-carbohydrate diets and regulates lipogenic enzymes and branched-chain amino acid metabolism
PMID: 34044180
4
MLXIPL genetic variants interact with Mediterranean diet interventions to influence intermediate and final metabolic phenotypes including insulin sensitivity
PMID: 25940230
5
MLXIPL deletion in Williams syndrome is associated with phenotypic consequences, though mechanisms require further investigation
PMID: 34140529
Disease Associationsⓘ20
goutOpen Targets
0.49Moderate
familial hyperlipidemiaOpen Targets
0.48Moderate
familial lipoprotein lipase deficiencyOpen Targets
0.44Moderate
diabetes mellitusOpen Targets
0.43Moderate
HypercholesterolemiaOpen Targets
0.43Moderate
metabolic diseaseOpen Targets
0.38Weak
Abnormal urine sodium concentrationOpen Targets
0.37Weak
alcohol drinkingOpen Targets
0.35Weak
type 2 diabetes mellitusOpen Targets
0.34Weak
migraine disorderOpen Targets
0.28Weak
response to statinOpen Targets
0.27Weak
cervical carcinomaOpen Targets
0.27Weak
Alzheimer diseaseOpen Targets
0.26Weak
squamous cell carcinomaOpen Targets
0.25Weak
Intrahepatic cholestasis of pregnancyOpen Targets
0.25Weak
endometrial cancerOpen Targets
0.25Weak
breast cancerOpen Targets
0.23Weak
hyperlipidemiaOpen Targets
0.23Weak
metabolic syndromeOpen Targets
0.22Weak
cholelithiasisOpen Targets
0.21Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
OGTProtein interaction99%MLXIPProtein interaction99%BCL7BProtein interaction94%TBL2Protein interaction94%YWHABProtein interaction92%FASNProtein interaction90%
Tissue Expression6 tissues
Liver
100%
Ovary
1%
Lung
0%
Brain
0%
Heart
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
MLXIPLOGTMLXIPBCL7BTBL2YWHABFASN
PROTEIN STRUCTURE
Preparing viewer…
PDB8BTQ · 1.60 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.88LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.70 [0.55–0.88]
RankingsWhere MLXIPL stands among ~20K protein-coding genes
  • #3,199of 20,598
    Most Researched143 · top quartile
  • #7,876of 17,882
    Most Constrained (LOEUF)0.88
Genes detectedMLXIPL
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Williams syndrome.
PMID: 34140529
Nat Rev Dis Primers · 2021
1.00
2
Benefits of the Mediterranean Diet: Insights From the PREDIMED Study.
PMID: 25940230
Prog Cardiovasc Dis · 2015
0.90
3
The ménage à trois of autophagy, lipid droplets and liver disease.
PMID: 33794741
Autophagy · 2022
0.80
4
The role of ChREBP in carbohydrate sensing and NAFLD development.
PMID: 37055547
Nat Rev Endocrinol · 2023
0.70
5
Insulin action, type 2 diabetes, and branched-chain amino acids: A two-way street.
PMID: 34044180
Mol Metab · 2021
0.60