PPARG: Peroxisome Proliferator-Activated Receptor Gamma
A key regulator of adipogenesis, glucose metabolism, and insulin sensitivity; implicated in metabolic disorders and cancer.
Gene Information Card
| Symbol | PPARG |
|---|---|
| Full Name | Peroxisome Proliferator-Activated Receptor Gamma |
| Gene Type | protein-coding |
| Chromosomal Location | 3p25.2 |
| NCBI Gene ID | 5468 ncbi.nlm.nih.gov/gene/5468 |
| Ensembl ID | ENSG00000132170 |
| UniProt ID | P37231 |
| OMIM ID | 601487 |
| HGNC ID | 9236 |
| Aliases | PPARG1, PPARG2, NR1C3, GLM1, CIMT1 |
Description
PPARG (Peroxisome Proliferator-Activated Receptor Gamma) is a nuclear receptor that functions as a transcription factor. It is a master regulator of adipogenesis, promoting the differentiation of preadipocytes into mature adipocytes. PPARG also plays critical roles in glucose homeostasis, lipid metabolism, and insulin sensitivity. It is the molecular target of thiazolidinedione (TZD) drugs used to treat type 2 diabetes. Mutations in PPARG are associated with familial partial lipodystrophy, severe insulin resistance, and increased risk of obesity and type 2 diabetes. Additionally, PPARG is implicated in various cancers, including glioblastoma and colon cancer, where it can act as a tumor suppressor or promoter depending on the context.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial partial lipodystrophy type 3 (FPLD3) | Loss-of-function mutations in PPARG impair adipocyte differentiation, leading to abnormal fat distribution and severe insulin resistance. | OMIM #604367; PMID: 10587585 |
| Type 2 diabetes | PPARG variants (e.g., Pro12Ala) modulate insulin sensitivity; TZD agonists improve glycemic control by activating PPARG. | OMIM #125853; PMID: 10802651 |
| Obesity | PPARG polymorphisms are associated with body mass index and fat mass; PPARG activation promotes adipogenesis. | OMIM #601665; PMID: 10949030 |
| Glioblastoma | PPARG is overexpressed in glioblastoma; its activation can inhibit tumor growth via cell cycle arrest and apoptosis. | PMID: 19137023; COSMIC analysis |
| Colon cancer | PPARG mutations and altered expression are found in colorectal tumors; PPARG ligands can modulate tumor progression. | PMID: 15601839; COSMIC analysis |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | High | High |
| Colon | Medium | Medium |
| Small intestine | Medium | Medium |
| Liver | Low | Low |
| Skeletal muscle | Low | Low |
| Kidney | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| 3T3-L1 (preadipocyte) | High | Differentiation-dependent expression |
| HepG2 (hepatocellular carcinoma) | Low | Low basal expression |
| HT-29 (colon adenocarcinoma) | Medium | Moderate expression |
| U87MG (glioblastoma) | High | Overexpressed in glioblastoma cell lines |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Pro12Ala (rs1801282) | SNP | Common (allele frequency ~12% in Europeans) | Reduced PPARG transcriptional activity; associated with decreased risk of type 2 diabetes but increased risk of obesity. |
| Val290Met | Missense | Rare | Loss of function; causes familial partial lipodystrophy type 3. |
| Arg425Cys | Missense | Rare | Dominant-negative effect; associated with severe insulin resistance and lipodystrophy. |
| c.484C>T (p.Arg162Trp) | Missense | Rare | Loss of function; linked to lipodystrophy and metabolic syndrome. |
Mutation functional classification
Loss of Function (LOF)
Mutations such as Val290Met and Arg162Trp impair PPARG's ability to bind DNA or coactivators, reducing transcriptional activity and leading to lipodystrophy and insulin resistance.
Gain of Function (GOF)
Gain-of-function mutations are rare; some somatic mutations in cancer may enhance PPARG activity, promoting cell survival.
Dominant Negative (DN)
Mutations like Arg425Cys produce a protein that interferes with wild-type PPARG function, causing severe metabolic phenotypes.
View complete mutation data：
Gene Ontology (GO)
| • GO:0003707 (nuclear receptor activity) | • GO:0004879 (nuclear receptor transcription coactivator activity) |
| • GO:0005515 (protein binding) | • GO:0008134 (transcription factor binding) |
| • GO:0042803 (protein homodimerization activity) | • GO:0000978 (RNA polymerase II cis-regulatory region sequence-specific DNA binding) |
| • GO:0001228 (DNA-binding transcription activator activity | • RNA polymerase II-specific) |
| • GO:0005737 (cytoplasm) | • GO:0005634 (nucleus) |
| • GO:0005654 (nucleoplasm) | • GO:0005829 (cytosol) |
| • GO:0005886 (plasma membrane) | • GO:0006357 (regulation of transcription by RNA polymerase II) |
| • GO:0006355 (regulation of transcription | • DNA-templated) |
| • GO:0006629 (lipid metabolic process) | • GO:0006631 (fatty acid metabolic process) |
| • GO:0007165 (signal transduction) | • GO:0008284 (positive regulation of cell population proliferation) |
| • GO:0008285 (negative regulation of cell population proliferation) | • GO:0010863 (positive regulation of phospholipase C activity) |
| • GO:0019216 (regulation of lipid metabolic process) | • GO:0030154 (cell differentiation) |
| • GO:0032868 (response to insulin) | • GO:0043066 (negative regulation of apoptotic process) |
| • GO:0045444 (fat cell differentiation) | • GO:0045595 (regulation of cell differentiation) |
| • GO:0045944 (positive regulation of transcription by RNA polymerase II) | • GO:0050796 (regulation of insulin secretion) |
| • GO:0055088 (lipid homeostasis) | • GO:0071392 (cellular response to estradiol stimulus) |
| • GO:0071407 (cellular response to organic cyclic compound) | • GO:0090090 (negative regulation of canonical Wnt signaling pathway) |
| • GO:1902895 (positive regulation of pri-miRNA transcription by RNA polymerase II) |
Pathways
• PPAR signaling pathway (KEGG: hsa03320)
• Adipogenesis (Reactome: R-HSA-381340)
• Regulation of lipid metabolism by PPARalpha (Reactome: R-HSA-400206)
• Transcriptional regulation of white adipocyte differentiation (Reactome: R-HSA-381340)
• Insulin resistance (KEGG: hsa04931)
• Type II diabetes mellitus (KEGG: hsa04930)
• Non-alcoholic fatty liver disease (KEGG: hsa04932)
Protein Summary
PPARG (Peroxisome Proliferator-Activated Receptor Gamma) is a 505-amino acid nuclear receptor protein (UniProt P37231). It contains a DNA-binding domain (DBD) with two zinc fingers and a ligand-binding domain (LBD). PPARG forms heterodimers with retinoid X receptor (RXR) and binds to PPAR response elements (PPREs) in target gene promoters. It is activated by natural ligands such as fatty acids and prostaglandins, as well as synthetic TZD drugs. PPARG regulates genes involved in adipogenesis, lipid storage, glucose metabolism, and inflammation. Alternative splicing produces two isoforms: PPARG1 (ubiquitous) and PPARG2 (adipose-specific with an additional 28 N-terminal amino acids). Post-translational modifications include phosphorylation, sumoylation, and ubiquitination, which modulate its activity and stability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PPARG Knockout HEK293 Cell Line | EDJ-KQ1115 | Human | 5468 | Details Get a Quote |
| PPARGC1A Knockout HEK293 Cell Line | EDJ-KQ1452 | Human | 10891 | Details Get a Quote |
| PPARGC1B Knockout HEK293 Cell Line | EDJ-KQ9316 | Human | 133522 | Details Get a Quote |
| PPARGC1A Knockout HeLa Cell Line | EDJ-KQ21008 | Human | 10891 | Details Get a Quote |
| PPARGC1B Knockout HCT 116 Cell Line | EDJ-KQ35941 | Human | 133522 | Details Get a Quote |
| PPARG Knockout A-549 Cell Line | EDJ-KQ20301 | Human | 5468 | Details Get a Quote |
| PPARG（PPARγ） Knockout HCT 116 Cell Line | EDC09847 | Human | 5468 | Details Get a Quote |
| PPARG Knockout HeLa Cell Line | EDJ-KQ20303 | Human | 5468 | Details Get a Quote |
| PPARGC1B Knockout HeLa Cell Line | EDJ-KQ34698 | Human | 133522 | Details Get a Quote |
| PPARGC1A Knockout A-549 Cell Line | EDJ-KQ64008 | Human | 10891 | Details Get a Quote |
| PPARGC1B Knockout A-549 Cell Line | EDJ-KQ66816 | Human | 133522 | Details Get a Quote |
| PPARGC1A Knockout HCT 116 Cell Line | EDJ-KQ72459 | Human | 10891 | Details Get a Quote |
| PPARG Knockout BEAS-2B Cell Line | EDC90244 | Human | 5468 | Details Get a Quote |
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