MLXIPL

Chr 7

MLX interacting protein like

Also known as: CHREBP, MIO, MONDOB, WBSCR14, WS-bHLH, bHLHd14

NCBI Gene: 51085ENSG00000009950UniProt: Q9NP71

This gene encodes a basic helix-loop-helix leucine zipper transcription factor of the Myc/Max/Mad superfamily. This protein forms a heterodimeric complex and binds and activates, in a glucose-dependent manner, carbohydrate response element (ChoRE) motifs in the promoters of triglyceride synthesis genes. The gene is deleted in Williams-Beuren syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at chromosome 7q11.23. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

0
ClinVar variants
0
Pathogenic / LP
0.05
pLI score
0
Active trials
Clinical Summary— MLXIPL
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.47LOEUF
pLI 0.048
Z-score 3.90
OE 0.27 (0.16–0.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.23Z-score
OE missense 0.84 (0.77–0.91)
391 obs / 465.8 exp
Tolerant

Mild missense constraint

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.0.27 (0.16–0.47)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.77–0.91)
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.0.92
0≤1.21.6
LoF obs/exp: 9 / 33.2Missense obs/exp: 391 / 465.8Syn Z: 0.89

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

MLXIPL · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Williams syndrome.
Kozel BA et al.·Nat Rev Dis Primers
2021Review
Benefits of the Mediterranean Diet: Insights From the PREDIMED Study.
Martínez-González MA et al.·Prog Cardiovasc Dis
2015Review
Genetic susceptibility to caffeine intake and metabolism: a systematic review.
Low JJ et al.·J Transl Med
2024Review
A genome-first approach to variants in MLXIPL and their association with hepatic steatosis and plasma lipids.
Hehl L et al.·Hepatol Commun
2024
Association of the ESR1 polymorphism with menopause and MLXIPL genetic variant influence serum uric acid levels in Slovak midlife women.
Vorobeľová L et al.·Menopause
2019
Association between the rs3812316 Single Nucleotide Variant of the MLXIPL Gene and Alpha-Linolenic Acid Intake with Triglycerides in Mexican Mestizo Women.
Maldonado-González M et al.·Nutrients
2022
Triglyceride level modifying functional variants of GALTN2 and MLXIPL in patients with ischaemic stroke.
Polgár N et al.·Eur J Neurol
2010Cohort
Spatial transcriptomics and scRNA-seq: decoding tumor complexity and constructing prognostic models in colorectal cancer.
Song W et al.·Hum Genomics
2025Functional
Metabolic abnormalities in Williams-Beuren syndrome.
Palacios-Verdú MG et al.·J Med Genet
2015
High prevalence of an anti-hypertriglyceridemic variant of the MLXIPL gene in Central Asia.
Nakayama K et al.·J Hum Genet
2011
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools