PPARA

Chr 22

peroxisome proliferator activated receptor alpha

Also known as: NR1C1, PPAR, PPAR-alpha, PPARalpha, hPPAR

NCBI Gene: 5465ENSG00000186951UniProt: Q07869

Peroxisome proliferators include hypolipidemic drugs, herbicides, leukotriene antagonists, and plasticizers; this term arises because they induce an increase in the size and number of peroxisomes. Peroxisomes are subcellular organelles found in plants and animals that contain enzymes for respiration and for cholesterol and lipid metabolism. The action of peroxisome proliferators is thought to be mediated via specific receptors, called PPARs, which belong to the steroid hormone receptor superfamily. PPARs affect the expression of target genes involved in cell proliferation, cell differentiation and in immune and inflammation responses. Three closely related subtypes (alpha, beta/delta, and gamma) have been identified. This gene encodes the subtype PPAR-alpha, which is a nuclear transcription factor. Multiple alternatively spliced transcript variants have been described for this gene, although the full-length nature of only two has been determined. [provided by RefSeq, Jul 2008]

151
ClinVar variants
82
Pathogenic / LP
0.03
pLI score
5
Active trials
Clinical Summary— PPARA
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.
📋
ClinVar Variants
82 Pathogenic / Likely Pathogenic· 45 VUS of 151 total submissions
💊
Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available

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.
0.63LOEUF
pLI 0.030
Z-score 2.73
OE 0.32 (0.17–0.63)
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.
1.81Z-score
OE missense 0.69 (0.62–0.78)
192 obs / 276.8 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.0.32 (0.17–0.63)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.69 (0.62–0.78)
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.1.09
0≤1.21.6
LoF obs/exp: 6 / 18.7Missense obs/exp: 192 / 276.8Syn Z: -0.76

ClinVar Variant Classifications

151 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic79
Likely Pathogenic3
VUS45
Likely Benign8
Benign5
Conflicting1
79
Pathogenic
3
Likely Pathogenic
45
VUS
8
Likely Benign
5
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
79
0
79
Likely Pathogenic
0
0
3
0
3
VUS
0
38
7
0
45
Likely Benign
0
2
1
5
8
Benign
0
2
1
2
5
Conflicting
—1
Total042917141

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PPARA · 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
Hepatocyte-specific Mas activation enhances lipophagy and fatty acid oxidation to protect against acetaminophen-induced hepatotoxicity in mice.
Chen S et al.·J Hepatol
2023
Autophagy deficiency abolishes liver mitochondrial DNA segregation.
Tostes K et al.·Autophagy
2022
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
Genetic evidence for high-altitude adaptation in Tibet.
Simonson TS et al.·Science
2010
Obesity-associated exosomal miRNAs modulate glucose and lipid metabolism in mice.
Castaño C et al.·Proc Natl Acad Sci U S A
2018
Phytochemical gallic acid alleviates nonalcoholic fatty liver disease via AMPK-ACC-PPARa axis through dual regulation of lipid metabolism and mitochondrial function.
Zhang J et al.·Phytomedicine
2023
Intestinal PPARα Protects Against Colon Carcinogenesis via Regulation of Methyltransferases DNMT1 and PRMT6.
Luo Y et al.·Gastroenterology
2019
Exposure to environmental contaminants is associated with altered hepatic lipid metabolism in non-alcoholic fatty liver disease.
Sen P et al.·J Hepatol
2022
Ganoderic acid A inhibits ox-LDL-induced THP-1-derived macrophage inflammation and lipid deposition via Notch1/PPARγ/CD36 signaling.
Wang T et al.·Adv Clin Exp Med
2021
Metabolic effects of RUBCN/Rubicon deficiency in kidney proximal tubular epithelial cells.
Matsuda J et al.·Autophagy
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
SARS-CoV-2 E protein reduces PPARA activity in colonic and pulmonary epithelial cells, driving diarrhea and pneumonia in COVID-19.
Wu Q et al.·Int Immunopharmacol
2026
HPV11 targeting PPARA regulates the autophagy to inhibit the occurrence and development of nasal inverted papilloma.
Zhu G et al.·Front Oncol
2025🔓 Open Access
Unveiling the Potential Mechanism of Asymmetric Fat Infiltration in Paraspinal Muscles of Adult Degenerative Scoliosis: The Role of the Hsa_circ_0006156/miR-122-5p/PPARA Regulatory Network.
Yang X et al.·JOR Spine
2025🔓 Open AccessFunctional
High-throughput screening reveals paeoniflorin's efficacy against Apoc2-deficient hypertriglyceridemia via HNF4A/PPARA/LDLR.
Li Q et al.·Biochem Pharmacol
2025
Capsaicin Alleviates Autophagy-Lysosomal Dysfunction via PPARA-Mediated V-ATPase Subunit ATP6V0E1 Signaling in 3xTg-AD Mice.
Yu H et al.·Adv Sci (Weinh)
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
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
Nonalcoholic SteatohepatitisLiver Fibrosis

Thyroid Hormone for Treatment of Nonalcoholic Steatohepatitis in Veterans

RECRUITING
NCT05526144Phase PHASE2VA Office of Research and DevelopmentStarted 2023-04-01
SynthroidPlacebo
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
Obesity Type I and IIObesity and Overweight

Metabolic Investigation, Physical Performance, Physical Training At Different Times of the Day in Obese Women

ACTIVE NOT RECRUITING
NCT06601660Phase NAState University of Minas GeraisStarted 2024-09-16
Morning Physical TrainingNight Physical TrainingNo intervention
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

External Resources

Links to major genomics databases and tools