MLXIPL

Chr 7

MLX interacting protein like

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

This gene encodes a glucose-responsive transcription factor that regulates fatty acid synthesis and glycolysis, serving as a key determinant of systemic insulin sensitivity and glucose homeostasis. MLXIPL is deleted in Williams-Beuren syndrome, a multisystem developmental disorder with autosomal dominant inheritance caused by contiguous gene deletions at chromosome 7q11.23. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.47), suggesting some intolerance to complete loss of function.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.47
Clinical SummaryMLXIPL
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

Moderate LoF intolerance
LoF Constraint
0.47LOEUF
pLI 0.048
Z-score 3.90
OE 0.27 (0.160.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.23Z-score
OE missense 0.84 (0.770.91)
391 obs / 465.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.27 (0.160.47)
00.351.4
Missense OE0.84 (0.770.91)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 9 / 33.2Missense obs/exp: 391 / 465.8Syn Z: 0.89
DN
0.6647th %ile
GOF
0.4480th %ile
LOF
0.4627th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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