PPARG

Chr 3

peroxisome proliferator activated receptor gamma

Also known as: CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2, PPARG5, PPARgamma

NCBI Gene: 5468ENSG00000132170UniProt: P37231

This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) subfamily of nuclear receptors. PPARs form heterodimers with retinoid X receptors (RXRs) and these heterodimers regulate transcription of various genes. Three subtypes of PPARs are known: PPAR-alpha, PPAR-delta, and PPAR-gamma. The protein encoded by this gene is PPAR-gamma and is a regulator of adipocyte differentiation. Additionally, PPAR-gamma has been implicated in the pathology of numerous diseases including obesity, diabetes, atherosclerosis and cancer. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

UniProtObesity
UniProtLipodystrophy, familial partial, 3
UniProtGlioma 1
301
ClinVar variants
69
Pathogenic / LP
0.03
pLI score
11
Active trials
Clinical Summary— PPARG
🧬
Gene-Disease Validity (ClinGen)
lipodystrophy · SDDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.
📋
ClinVar Variants
69 Pathogenic / Likely Pathogenic· 123 VUS of 301 total submissions
💊
Clinical Trials
11 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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.
0.64LOEUF
pLI 0.029
Z-score 2.71
OE 0.32 (0.17–0.64)
Tolerant

Typical tolerance to LoF variation

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.
2.12Z-score
OE missense 0.65 (0.57–0.73)
183 obs / 283.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.32 (0.17–0.64)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.65 (0.57–0.73)
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.1.01
0≤1.21.6
LoF obs/exp: 6 / 18.6Missense obs/exp: 183 / 283.4Syn Z: -0.06

ClinVar Variant Classifications

301 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic45
Likely Pathogenic24
VUS123
Likely Benign82
Benign16
Conflicting11
45
Pathogenic
24
Likely Pathogenic
123
VUS
82
Likely Benign
16
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
8
30
0
45
Likely Pathogenic
6
15
3
0
24
VUS
2
113
6
2
123
Likely Benign
0
8
22
52
82
Benign
0
1
11
4
16
Conflicting
—11
Total151457258301

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.

Gene2Phenotype Curations

PPARG-related lipodystrophy, familial partial

definitive
ADDominant NegativeAltered Gene Product Structure
Skin
G2P ↗

PPARG-related acanthosis nigricans with insulin resistance syndrome and hypertension

definitive
ADDominant NegativeAltered Gene Product Structure
Skin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Exploring antidiabetic drug targets as potential disease-modifying agents in osteoarthritis.
Fu K et al.·EBioMedicine
2024
Single-cell RNA-sequencing atlas reveals an FABP1-dependent immunosuppressive environment in hepatocellular carcinoma.
Tang W et al.·J Immunother Cancer
2023
Uncovering the mechanism of resveratrol in the treatment of diabetic kidney disease based on network pharmacology, molecular docking, and experimental validation.
Chen S et al.·J Transl Med
2023Functional
S100a8/a9 Signaling Causes Mitochondrial Dysfunction and Cardiomyocyte Death in Response to Ischemic/Reperfusion Injury.
Li Y et al.·Circulation
2019
Dissecting intratumoral myeloid cell plasticity by single cell RNA-seq.
Song Q et al.·Cancer Med
2019
Heterogeneity in NECTIN4 Expression Across Molecular Subtypes of Urothelial Cancer Mediates Sensitivity to Enfortumab Vedotin.
Chu CE et al.·Clin Cancer Res
2021
CARM1 drives mitophagy and autophagy flux during fasting-induced skeletal muscle atrophy.
Stouth DW et al.·Autophagy
2024
Integrated bioinformatics and network pharmacology to explore the therapeutic target and molecular mechanisms of Bailing capsule on polycystic ovary syndrome.
Guan HR et al.·BMC Complement Med Ther
2023Functional
Decoding the anti-hypertensive mechanism of α-mangostin based on network pharmacology, molecular docking and experimental validation.
Xue QQ et al.·Mol Med
2024Functional
Single-cell RNA sequencing revealed PPARG promoted osteosarcoma progression: based on osteoclast proliferation.
Sun L et al.·Front Immunol
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Schisandrin B enhances autophagy and random flaps survival through the PPARG-mediated PI3K/AKT/mTOR signaling pathway.
Li Y et al.·Free Radic Biol Med
2026
A Novel PPARG R212W Variant Causes Familial Partial Lipodystrophy Type 3: Clinical Presentation and Functional Characterization.
Gao Y et al.·Int J Mol Sci
2026Functional
Soufeng Sanjie formula and its active ingredient formononetin alleviate osteoarthritis via PPARG-AKT-ERK1/2 promoted cartilage extracellular matrix anabolism.
Liu Q et al.·J Ethnopharmacol
2026
Exploring the mechanism of Rhodiola kirilowii (Regel) Maxim regulating PPARG/PTGS2 to alleviate LPS-induced acute lung injury in mice based on UPLC-Q-TOF-MSE combined with system pharmacology.
Cui S et al.·Nat Prod Res
2026Functional
Effects of dexamethasone on luteal steroidogenesis, cell apoptosis and PKA/CREB/PPARG pathway in rats.
Zhao J et al.·Reprod Toxicol
2026
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Maternal ObesityObesity

The Developmental Origins of Obesity

RECRUITING
NCT06981676Phase NAPontificia Universidad Catolica de ChileStarted 2023-07-25
DHA and EPA
Morbid ObesityBariatric SurgeryTelerehabilitation

Exercise to Fight Obesity

RECRUITING
NCT06934681Phase NAInstituto de Investigacion Sanitaria La FeStarted 2025-05-19
Usual Care GroupControlled exercise with telerehabilitation
Hereditary Pulmonary Alveolar Proteinosis

Safety and Efficacy of PMT Therapy of hPAP

RECRUITING
NCT05761899Phase PHASE1, PHASE2Children's Hospital Medical Center, CincinnatiStarted 2023-06-26
Gene-Corrected Macrophages administered by bronchoscopic instillation
ANCA Associated VasculitisExtramembranous GlomerulopathyNephrotic Syndrome, Minimal Change

Epithelial Dysmetabolism and Renal Fibrosis in ANCA Vasculitis

NOT YET RECRUITING
NCT07010250Assistance Publique - Hôpitaux de ParisStarted 2025-06-02
Alzheimer's Disease

A Phase 2b/3 Clinical Study Evaluating T3D-959 in Mild-to-Moderate Alzheimer's Disease Subjects

NOT YET RECRUITING
NCT06964230Phase PHASE2, PHASE3T3D Therapeutics, Inc.Started 2026-10-26
T3D-959Placebo Comparator
HIV-1-infection

DORAvirine Versus DOlutegravir Based Antiretroviral Regimens in Treatment-naïve People Living With HIV-1 Infection

RECRUITING
NCT06203132Phase PHASE3ANRS, Emerging Infectious DiseasesStarted 2025-01-27
Doravirine + tenofovir DF + lamivudineDolutegravir + tenofovir DF + lamivudine or emtricitabine
Nonalcoholic SteatohepatitisLiver Fibrosis

Thyroid Hormone for Treatment of Nonalcoholic Steatohepatitis in Veterans

RECRUITING
NCT05526144Phase PHASE2VA Office of Research and DevelopmentStarted 2023-04-01
SynthroidPlacebo
Lipodystrophy (Genetic or Acquired, Non HIV)

The LD Lync Study - Natural History Study of Lipodystrophy Syndromes

RECRUITING
NCT03087253University of MichiganStarted 2018-02-27
Cancer

Onco Move - Improvement of Psychophysical Fitness in Adult Cancer Survivors

NOT YET RECRUITING
NCT07087652Phase NAGdansk University of Physical Education and SportStarted 2025-09-01
Onco Move multicomponent face-to-face training program
Long COVIDInsulin ResistanceInsulin Sensitivity

Obesity, Insulin Resistance, and PASC: Persistent SARS-CoV-2

RECRUITING
NCT05833217Phase NAStanford UniversityStarted 2023-06-06
Adipose Tissue BiopsySteady State Plasma Glucose (SSPG) Test
Obesity and Obesity-related Medical Conditions

Precision Nutrition Technologies for Obesity Management

NOT YET RECRUITING
NCT07101133Phase NAYuan HeStarted 2025-07-27
Control group: Energy-limited balanced diet group

External Resources

Links to major genomics databases and tools