PPARA
protein-codingperoxisome proliferator activated receptor alpha, the group of Peroxisome proliferator activated receptors
Gene summary
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]
- PPAR
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~93.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0045008
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PPARA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005036.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | 2 | 7 | |||
| missense | 42 | 3 | 1 | 46 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 43 | 8 | 3 | 54 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005027.2 | 6 | MANE Select | |
| Ensembl | ENSP00000385523.1 | 6 | MANE Select | |
| RefSeq | NP_001001928.1 | 6 | Standard | |
| RefSeq | NP_001001929.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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)
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
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
Cellular Component
- nucleus
- nucleoplasm
- RNA polymerase II transcription factor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000396000
- Coding exons
- 6
- Length
- 93230
- Individuals with no LoFs
- 125734
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 14
- Defined
- 125748
- p
- 0.0000557
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.81 | 192 | 277 | 0.694 | 0.0000186 | 3094 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000079 | 0.000079 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
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}.;
Recessive Scores
- pRec
- 0.923
Intolerance Scores
- LoFtool
- 0.0600
- RVIS EVS
- -0.36
- RVIS percentile EVS
- 29.31
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.998
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |