PPARG
Chr 3ADARMultiperoxisome proliferator activated receptor gamma
Also known as: CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2, PPARG5, PPARgamma
The protein is a ligand-activated transcription factor that regulates adipocyte differentiation, lipid metabolism, and glucose homeostasis by forming heterodimers with retinoid X receptors and binding to specific DNA response elements. Mutations cause familial partial lipodystrophy type 3, severe insulin resistance, type 2 diabetes, and severe obesity, affecting metabolic regulation throughout life. Inheritance patterns include autosomal dominant, autosomal recessive, and multifactorial depending on the specific condition.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
297 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 7 | 3 | 25 | 0 | 35 |
Likely Pathogenic | 8 | 13 | 1 | 0 | 22 |
VUS | 2 | 113 | 4 | 2 | 121 |
Likely Benign | 0 | 8 | 22 | 51 | 81 |
Benign | 0 | 0 | 11 | 4 | 15 |
Conflicting | — | 11 | |||
| Total | 17 | 137 | 63 | 57 | 285 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PPARG · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
A Phase 2b/3 Clinical Study Evaluating T3D-959 in Mild-to-Moderate Alzheimer's Disease Subjects
NOT YET RECRUITINGObesity, Insulin Resistance, and PASC: Persistent SARS-CoV-2
RECRUITINGThe LD Lync Study - Natural History Study of Lipodystrophy Syndromes
RECRUITINGDORAvirine Versus DOlutegravir Based Antiretroviral Regimens in Treatment-naïve People Living With HIV-1 Infection
RECRUITINGOnco Move - Improvement of Psychophysical Fitness in Adult Cancer Survivors
NOT YET RECRUITINGPrecision Nutrition Technologies for Obesity Management
NOT YET RECRUITINGSafety and Efficacy of PMT Therapy of hPAP
RECRUITINGIntegrating Tumor Genomics and Urinary Exosomal Proteomics to Establish a Multi-Layer Biomarker Framework for Early Risk Stratification and Post-Treatment Surveillance in Fresh Thyroid Cancer Patients
NOT YET RECRUITINGThyroid Hormone for Treatment of Nonalcoholic Steatohepatitis in Veterans
RECRUITINGEpithelial Dysmetabolism and Renal Fibrosis in ANCA Vasculitis
NOT YET RECRUITINGThe Developmental Origins of Obesity
RECRUITINGExercise to Fight Obesity
RECRUITINGExternal Resources
Links to major genomics databases and tools