PPARA
peroxisome proliferator activated receptor alpha, the group of Peroxisome proliferator activated receptors
Basic information
Region (hg38): 22:46150521-46243755
Previous symbols: [ "PPAR" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (36 variants)
- not_provided (10 variants)
- PPARA-related_disorder (3 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPARA gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005036.6. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 7 | |||||
| missense | 35 | 39 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 35 | 8 | 3 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PPARA | protein_coding | protein_coding | ENST00000396000 | 6 | 93230 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0302 | 0.968 | 125734 | 0 | 14 | 125748 | 0.0000557 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.81 | 192 | 277 | 0.694 | 0.0000186 | 3094 |
| Missense in Polyphen | 47 | 100.3 | 0.46861 | 1097 | ||
| Synonymous | -0.762 | 130 | 119 | 1.09 | 0.00000979 | 901 |
| Loss of Function | 2.73 | 6 | 18.7 | 0.320 | 0.00000114 | 228 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000578 | 0.0000578 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000791 | 0.0000791 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000653 | 0.0000653 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl- 2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. May be required for the propagation of clock information to metabolic pathways regulated by PER2. {ECO:0000269|PubMed:10195690, ECO:0000269|PubMed:24043310, ECO:0000269|PubMed:7629123, ECO:0000269|PubMed:7684926, ECO:0000269|PubMed:9556573}.;
- Pathway
- Adipocytokine signaling pathway - Homo sapiens (human);Insulin resistance - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);PPAR signaling pathway - Homo sapiens (human);Hepatitis C - Homo sapiens (human);NHR;Energy Metabolism;Nuclear Receptors;SREBF and miR33 in cholesterol and lipid homeostasis;Adipogenesis;Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);PPAR Alpha Pathway;Estrogen Receptor Pathway;Nuclear Receptors Meta-Pathway;Lipid storage and perilipins in skeletal muscle;Nuclear Receptors in Lipid Metabolism and Toxicity;BMAL1-CLOCK,NPAS2 activates circadian gene expression;PPAR signaling pathway;Liver steatosis AOP;Steatosis AOP;Gene expression (Transcription);mechanism of gene regulation by peroxisome proliferators via ppara;Circadian Clock;regulation of pgc-1a;toll-like receptor pathway;Generic Transcription Pathway;Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);Metabolism of lipids;basic mechanism of action of ppara pparb(d) and pparg and effects on gene expression;Nuclear Receptor transcription pathway;RNA Polymerase II Transcription;BMAL1:CLOCK,NPAS2 activates circadian gene expression;Metabolism;-arrestins in gpcr desensitization;RXR and RAR heterodimerization with other nuclear receptor
(Consensus)
Recessive Scores
- pRec
- 0.923
Intolerance Scores
- loftool
- 0.0600
- rvis_EVS
- -0.36
- rvis_percentile_EVS
- 29.31
Haploinsufficiency Scores
- pHI
- 0.321
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.523
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.998
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ppara
- Phenotype
- cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; immune system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); liver/biliary system phenotype;
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;response to hypoxia;transcription initiation from RNA polymerase II promoter;lipid metabolic process;fatty acid metabolic process;multicellular organism development;heart development;epidermis development;hormone-mediated signaling pathway;negative regulation of macrophage derived foam cell differentiation;negative regulation of receptor biosynthetic process;negative regulation of cholesterol storage;negative regulation of sequestering of triglyceride;fatty acid transport;regulation of lipid metabolic process;cell differentiation;intracellular receptor signaling pathway;positive regulation of fatty acid beta-oxidation;negative regulation of protein binding;negative regulation of appetite;response to insulin;circadian regulation of gene expression;response to lipid;behavioral response to nicotine;wound healing;lipoprotein metabolic process;regulation of circadian rhythm;steroid hormone mediated signaling pathway;positive regulation of gluconeogenesis;negative regulation of blood pressure;negative regulation of glycolytic process;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;positive regulation of fatty acid oxidation;negative regulation of inflammatory response;negative regulation of cell growth involved in cardiac muscle cell development;enamel mineralization;regulation of glycolytic process by positive regulation of transcription from RNA polymerase II promoter;regulation of cellular ketone metabolic process by positive regulation of transcription from RNA polymerase II promoter;regulation of lipid transport by positive regulation of transcription from RNA polymerase II promoter;negative regulation of neuron death;negative regulation of pri-miRNA transcription by RNA polymerase II;negative regulation of leukocyte cell-cell adhesion
- Cellular component
- nucleus;nucleoplasm;RNA polymerase II transcription factor complex
- Molecular function
- transcription regulatory region sequence-specific DNA binding;RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II repressing transcription factor binding;transcription coactivator binding;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;steroid hormone receptor activity;nuclear receptor activity;fatty acid binding;protein binding;transcription factor binding;drug binding;zinc ion binding;lipid binding;phosphatase binding;protein domain specific binding;nuclear receptor transcription coactivator activity;ubiquitin conjugating enzyme binding;signaling receptor activity;sequence-specific DNA binding;protein-containing complex binding;NFAT protein binding;MDM2/MDM4 family protein binding