PPARA

peroxisome proliferator activated receptor alpha, the group of Peroxisome proliferator activated receptors

Basic information

Region (hg38): 22:46150520-46243755

Previous symbols: [ "PPAR" ]

Links

ENSG00000186951 ∙ NCBI:5465 ∙ OMIM:170998 ∙ HGNC:9232 ∙ Uniprot:Q07869 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PPARA gene.

• Inborn genetic diseases (12 variants)
• not provided (10 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4	2	6
missense			11	1	1	13
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	11	5	3

Variants in PPARA

This is a list of pathogenic ClinVar variants found in the PPARA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
22-46198422-A-G		PPARA-related disorder	Likely benign (Mar 07, 2019)
22-46198426-G-C		not specified	Uncertain significance (Aug 30, 2022)
22-46198568-G-T		not specified	Uncertain significance (Apr 06, 2023)
22-46198580-C-T		not specified	Uncertain significance (Nov 07, 2023)
22-46215209-C-T			Likely benign (Mar 29, 2018)
22-46215279-C-T			Likely benign (Mar 29, 2018)
22-46218315-G-A		not specified	Uncertain significance (Aug 17, 2021)
22-46218333-A-G		not specified	Uncertain significance (Feb 15, 2023)
22-46218336-A-G		not specified	Uncertain significance (Jan 08, 2024)
22-46218377-C-G		Hyperapobetalipoproteinemia, susceptibility to	Benign (Jan 01, 2004)
22-46219853-C-T			Benign (Jun 12, 2018)
22-46219860-C-T		not specified	Uncertain significance (Feb 16, 2023)
22-46219904-G-A		not specified	Uncertain significance (Nov 01, 2022)
22-46219931-A-C		not specified	Uncertain significance (Mar 20, 2023)
22-46219937-G-A		not specified	Conflicting classifications of pathogenicity (Sep 01, 2021)
22-46219959-A-G		not specified	Uncertain significance (Feb 03, 2022)
22-46219983-T-C		PPARA-related disorder	Benign (Jan 27, 2020)
22-46220008-C-T			Benign (Dec 31, 2019)
22-46231883-C-T		PPARA-related disorder	Likely benign (Aug 01, 2019)
22-46231951-G-A		not specified	Uncertain significance (Feb 23, 2023)
22-46232064-C-T			Likely benign (Jul 20, 2018)
22-46232073-G-A			Likely benign (Feb 26, 2018)
22-46235130-T-C			Likely benign (May 30, 2018)
22-46235180-G-A		not specified	Uncertain significance (Feb 14, 2023)
22-46235322-C-T		not specified	Uncertain significance (Jun 21, 2021)

GnomAD

Source: gnomAD

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: dbNSFP

• 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
• 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