PPARA

Summary

PPARA (peroxisome proliferator activated receptor alpha, HGNC:9232) is a protein-coding gene on chromosome 22q13.31, encoding Peroxisome proliferator-activated receptor alpha (Q07869). Ligand-activated transcription factor.

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.

Source: NCBI Gene 5465 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cholesterol metabolism disease (Limited, GenCC)
• GWAS associations: 13
• Clinical variants (ClinVar): 61 total
• Druggable target: yes — 39 molecules with ChEMBL bioactivity
• Transcription factor: yes — 287 downstream targets (CollecTRI)
• MANE Select transcript: NM_005036

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9232
Approved symbol	PPARA
Name	peroxisome proliferator activated receptor alpha
Location	22q13.31
Locus type	gene with protein product
Status	Approved
Aliases	hPPAR, NR1C1
Ensembl gene	ENSG00000186951
Ensembl biotype	protein_coding
OMIM	170998
Entrez	5465

Gene structure

Transcript identifiers

Ensembl transcripts: 51 — 45 protein_coding, 4 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000402126, ENST00000407236, ENST00000415785, ENST00000420804, ENST00000440343, ENST00000460086, ENST00000481567, ENST00000484619, ENST00000493286, ENST00000496865, ENST00000624793, ENST00000873468, ENST00000873469, ENST00000873470, ENST00000873471, ENST00000873472, ENST00000873473, ENST00000873474, ENST00000873475, ENST00000873476, ENST00000873477, ENST00000873478, ENST00000873479, ENST00000873480, ENST00000873481, ENST00000873482, ENST00000873483, ENST00000873484, ENST00000873485, ENST00000873486, ENST00000873487, ENST00000873488, ENST00000873489, ENST00000873490, ENST00000873491, ENST00000873492, ENST00000873493, ENST00000873494, ENST00000873495, ENST00000873496, ENST00000873497, ENST00000873498, ENST00000873499, ENST00000873500, ENST00000942788, ENST00000942789, ENST00000942790, ENST00000942791, ENST00000942792, ENST00000942793, ENST00000942794

RefSeq mRNA: 12 — MANE Select: NM_005036 NM_001001928, NM_001001929, NM_001362872, NM_001362873, NM_001393941, NM_001393942, NM_001393943, NM_001393944, NM_001393945, NM_001393946, NM_001393947, NM_005036

CCDS: CCDS33669

Canonical transcript exons

ENST00000407236 — 9 exons

Exon	Start	End
ENSE00001046654	46151888	46151970
ENSE00001411734	46150526	46150652
ENSE00001559128	46235133	46243755
ENSE00001561793	46176753	46176836
ENSE00002517229	46219812	46220014
ENSE00002712432	46198342	46198591
ENSE00003486069	46218263	46218401
ENSE00003567892	46215173	46215333
ENSE00003586693	46231792	46232239

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 95.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.0814 / max 54.2742, expressed in 1425 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192792	1.5350	980
192793	1.3464	724
192791	0.1388	44
192794	0.0611	24

Top tissues by expression

296 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
renal medulla	UBERON:0000362	95.47	gold quality
jejunal mucosa	UBERON:0000399	92.97	gold quality
biceps brachii	UBERON:0001507	92.41	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.36	gold quality
right lobe of liver	UBERON:0001114	92.09	gold quality
jejunum	UBERON:0002115	91.67	gold quality
pigmented layer of retina	UBERON:0001782	91.64	gold quality
retina	UBERON:0000966	91.62	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.35	gold quality
heart right ventricle	UBERON:0002080	91.06	gold quality
body of tongue	UBERON:0011876	90.63	gold quality
liver	UBERON:0002107	90.48	gold quality
adrenal tissue	UBERON:0018303	88.41	gold quality
mucosa of sigmoid colon	UBERON:0004993	88.36	gold quality
colonic mucosa	UBERON:0000317	88.34	gold quality
duodenum	UBERON:0002114	88.31	gold quality
muscle of leg	UBERON:0001383	87.72	gold quality
gastrocnemius	UBERON:0001388	87.65	gold quality
cardiac ventricle	UBERON:0002082	86.61	gold quality
nipple	UBERON:0002030	86.50	gold quality
heart left ventricle	UBERON:0002084	86.44	gold quality
mammalian vulva	UBERON:0000997	86.01	gold quality
apex of heart	UBERON:0002098	85.94	gold quality
adult mammalian kidney	UBERON:0000082	85.68	gold quality
sural nerve	UBERON:0015488	85.66	gold quality
tongue	UBERON:0001723	85.53	gold quality
tibia	UBERON:0000979	85.42	gold quality
skeletal muscle organ	UBERON:0014892	85.42	gold quality
muscle organ	UBERON:0001630	85.41	gold quality
upper leg skin	UBERON:0004262	85.40	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.20
E-CURD-10	no	187.39
E-MTAB-7606	no	34.74

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

287 targets.

Target	Regulation
ABCA1	Activation
ABCA12	Unknown
ABCB1	Repression
ABCB4	Activation
ABCB5
ABCC1	Repression
ABCD2	Activation
ABCG2	Unknown
ACADL	Unknown
ACADM	Activation
ACE	Unknown
ACMSD	Repression
ACOT13	Activation
ACOT2	Unknown
ACOX1	Unknown
ACOX2	Unknown
ACSL1	Repression
ADAM2
ADIPOQ	Unknown
ADSS2	Repression
AGT	Unknown
AGTR1	Unknown
AHR
ALAD	Activation
ALAS1	Activation
ALDH2	Unknown
ALDH3A2	Activation
ANG	Unknown
ANGPTL4	Activation
AP1	Repression

JASPAR motifs

Motif	Name	Family
MA1148.1	PPARA::RXRA	Thyroid hormone receptor-related factors (NR1)::RXR-related receptors (NR2)
MA1148.2	PPARA::RXRA	Thyroid hormone receptor-related factors (NR1)::RXR-related receptors (NR2)

JASPAR matrix evidence (PMIDs): PMID:8386511

Upstream regulators (CollecTRI, top): BMAL1, CLOCK, CREBBP, ESR1, ESRRA, GLI2, HIF1A, HNF4A, ISL1, JUN, KDM3B, MEF2C, MLXIPL, NCOA2, NCOA3, NFKB1, NFKB, NR1H3, NR1H4, NR2C2, NR2F2, NRIP1, PPARA, PPARD, PPARG, RELA, SP1, STAT1, STAT3, STAT6, TP63, USF2

miRNA regulators (miRDB)

267 targeting PPARA, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790

Literature-anchored findings (GeneRIF, showing 40)

• polymorphism is unrelated to schizophrenia or alcoholism. (PMID:11840500)
• crystal structure of a ternary complex containing the peroxisome proliferator-activated receptor-alpha ligand-binding domain bound to the antagonist GW6471 and a SMRT co-repressor motif (PMID:11845213)
• Peroxisome proliferator-activated receptor (PPARalpha and PPARgamma) agonists decrease lipoprotein lipase secretion and glycated LDL uptake by human macrophages. (PMID:11852057)
• Variation in the PPAR gene influences human left ventricular growth in response to exercise and hypertension (PMID:11864924)
• cPLA(2) plays a critical role in PPAR-mediated gene transcription in HepG2 cells (PMID:11897617)
• A Val227Ala polymorphism in the peroxisome proliferator activated receptor alpha (PPARalpha) gene is associated with variations in serum lipid levels. (PMID:11897821)
• activation of PPARalpha in human CD4-positive T cells limits the expression of proinflammatory cytokines, such as IFNgamma (PMID:11934839)
• The results suggest that homocysteine may enhance vascular constrictive remodeling by inactivating PPAR-alpha and -gamma in ECs and PPAR-gamma in SMCs. (PMID:11940516)
• differential regulation of vascular endothelial growth factor expression in bladder cancer cells (peroxisome proliferative activated receptor, beta) (PMID:11980898)
• the organization of the 5’-flanking and untranslated region of the hPPARalpha gene was characterized and the hPPARalpha promoter region has been identified (PMID:11981036)
• PPARA L162V polymorphism is associated with increase in plasma LDL cholesterol levels. (PMID:12006394)
• PPARalpha binds to apolipoprotein a enhancers and influences estrogen-mediated transcription (PMID:12023905)
• regulation of human ASBT gene by PPARalpha (PMID:12055195)
• turnover is predicted by the ubiquitin-proteasome system which controls the ligand-induced expression level of its target genes (PMID:12118000)
• redundancy in the functions of PPARs alpha and delta as transcriptional regulators of fatty acid homeostasis and suggest that in skeletal muscle high levels of the delta-subtype can compensate for deficiency of PPAR alpha (PMID:12118038)
• PPARalpha is regulated by fatty acids in human cells (PMID:12161442)
• PPARalpha binding characteristics by FRET. (PMID:12163133)
• Our results established the presence of PPARalpha in human breast cancer cell lines and showed for the first time that activation of PPARalpha in human breast cancer cells promoted proliferation. (PMID:12203367)
• 5’-flanking region of this gene is transcriptionally active and binds PPARalpha, we characterized the peroxisome proliferator-responsive element in the proximal promoter of the CPT II gene, which appears to be a novel PPRE. (PMID:12408750)
• PPARA gene is a modifier of the familial combined hyperlipidemia phenotype (PMID:12468272)
• These results provide molecular evidence for a cross-talk between the FXR and PPARalpha pathways in humans. (PMID:12554753)
• The PPAR alpha subtype localizes to the nuclear and perinuclear regions of human airway smooth muscle cells. (PMID:12594295)
• Expression of peroxisome proliferator-activated receptors (PPARs) in human urinary bladder carcinoma and growth inhibition by its agonists. (PMID:12594814)
• TR2 and TR4 can have distinct functions. Existence of differential and bi-directional regulation between PPAR alpha and TR2/TR4. Possible roles in PPAR alpha signaling pathway in human keratinocytes. (PMID:12615366)
• decrease in cardiac PPARalpha transcription factor gene expression observed in the failing human heart could play an important role in a reduction in fatty acid utilisation by the adult heart during cardiac hypertrophy (PMID:12655356)
• PPARalpha regulates the human apolipoprotein AV gene (PMID:12709436)
• Molecular characterisation of six alternatively spliced variants and a novel promoter in peroxisome proliferator-activated receptor alpha. (PMID:12745064)
• PPARA has a role as an important modulator of the metabolism of endobiotics and xenobiotics in human hepatocytes (PMID:12810707)
• There seems to be an association between the polymorphism of the PPARA gene and decreased fasting serum triglyceride levels in glucose tolerant subjects. (PMID:12835617)
• These results identify hepatic activation of peroxisome proliferator-activated receptor-alpha as a mechanism underlying glucocorticoid-induced insulin resistance. (PMID:12847522)
• peroxisome proliferator-activated receptor alpha V162 allele is associated with reduced adiposity (PMID:12855749)
• ARA70, a coactivator of the androgen receptor and PPARgamma, was identified as a ligand-enhanced coactivator of peroxisome proliferator-activated receptor alpha in a prostate cancer cell line. (PMID:12897377)
• PPARalpha/RXRalpha complex was counteracted by the expression of ERRalpha in HeLa cells. (PMID:12914524)
• agonists of PPAR alpha increased basal and insulin-stimulated PAI-1 antigen release with a mechanism involving gene transcription and requiring signaling through the ERK1/2 signaling pathway (PMID:14515181)
• In humans skeletal muscle PPARalpha expression and genes regulating lipid metabolism are tightly linked, but there was no association between both insulin sensitivity and BMI with PPARalpha expression in skeletal muscle. (PMID:14519597)
• PPARalpha transcription factor as a major factor governing hepatic CoA levels by specific modulation of PANK1alpha gene expression (PMID:14523052)
• Increases in PGC-1 and PPAR-alpha levels may play an important role in changes in muscle mitochondria content, oxidative phenotype, and sensitivity to insulin induced by endurance training. (PMID:14633846)
• In type 2 diabetes there is a significant gene to gene interaction between the Ala55Val polymorphism in the uncoupling protein 2 gene ( UCP2) and the 161C>T polymorphism in the exon 6 of ppargamma. (PMID:14730379)
• chronic treatment with the PPARalpha agonist fully prevents the acute phase response gene expression in wild-type but not in PPARalpha-deficient mice (PMID:14764586)
• PPARalpha protects EC from glucose-mediated monocyte adhesion, in part through regulation of IL-6 production. (PMID:15001458)

Cross-species orthologs

189 orthologs

Organism	Symbol	Gene ID
danio_rerio	pparaa	ENSDARG00000031777
danio_rerio	pparab	ENSDARG00000054323
mus_musculus	Ppara	ENSMUSG00000022383
rattus_norvegicus	Ppara	ENSRNOG00000021463
drosophila_melanogaster	EcR	FBGN0000546
drosophila_melanogaster	Hr96	FBGN0015240
caenorhabditis_elegans		WBGENE00001062
caenorhabditis_elegans	nhr-2	WBGENE00003601
caenorhabditis_elegans		WBGENE00003608
caenorhabditis_elegans		WBGENE00003611
caenorhabditis_elegans		WBGENE00003614
caenorhabditis_elegans		WBGENE00003615
caenorhabditis_elegans		WBGENE00003617
caenorhabditis_elegans		WBGENE00003618
caenorhabditis_elegans		WBGENE00003620
caenorhabditis_elegans	nhr-23	WBGENE00003622
caenorhabditis_elegans		WBGENE00003624
caenorhabditis_elegans		WBGENE00003632
caenorhabditis_elegans		WBGENE00003634
caenorhabditis_elegans		WBGENE00003638
caenorhabditis_elegans		WBGENE00003640
caenorhabditis_elegans		WBGENE00003641
caenorhabditis_elegans		WBGENE00003642
caenorhabditis_elegans		WBGENE00003643
caenorhabditis_elegans		WBGENE00003644
caenorhabditis_elegans		WBGENE00003645
caenorhabditis_elegans		WBGENE00003646
caenorhabditis_elegans		WBGENE00003648
caenorhabditis_elegans		WBGENE00003649
caenorhabditis_elegans		WBGENE00003651
caenorhabditis_elegans		WBGENE00003653
caenorhabditis_elegans		WBGENE00003655
caenorhabditis_elegans		WBGENE00003658
caenorhabditis_elegans		WBGENE00003660
caenorhabditis_elegans		WBGENE00003662
caenorhabditis_elegans	nhr-73	WBGENE00003663
caenorhabditis_elegans	nhr-77	WBGENE00003667
caenorhabditis_elegans		WBGENE00003669
caenorhabditis_elegans	nhr-81	WBGENE00003671
caenorhabditis_elegans	nhr-82	WBGENE00003672
caenorhabditis_elegans		WBGENE00003676
caenorhabditis_elegans		WBGENE00003677
caenorhabditis_elegans		WBGENE00003680
caenorhabditis_elegans		WBGENE00003682
caenorhabditis_elegans		WBGENE00003684
caenorhabditis_elegans		WBGENE00003685
caenorhabditis_elegans		WBGENE00003686
caenorhabditis_elegans		WBGENE00003688
caenorhabditis_elegans		WBGENE00003689
caenorhabditis_elegans		WBGENE00003692
caenorhabditis_elegans		WBGENE00003693
caenorhabditis_elegans		WBGENE00003694
caenorhabditis_elegans		WBGENE00003696
caenorhabditis_elegans		WBGENE00003698
caenorhabditis_elegans		WBGENE00003699
caenorhabditis_elegans		WBGENE00003700
caenorhabditis_elegans		WBGENE00003702
caenorhabditis_elegans		WBGENE00003704
caenorhabditis_elegans		WBGENE00003705
caenorhabditis_elegans		WBGENE00003707
caenorhabditis_elegans		WBGENE00003708
caenorhabditis_elegans		WBGENE00003712
caenorhabditis_elegans		WBGENE00003713
caenorhabditis_elegans		WBGENE00003714
caenorhabditis_elegans		WBGENE00003715
caenorhabditis_elegans		WBGENE00003716
caenorhabditis_elegans		WBGENE00003717
caenorhabditis_elegans		WBGENE00003718
caenorhabditis_elegans		WBGENE00003720
caenorhabditis_elegans		WBGENE00003721
caenorhabditis_elegans		WBGENE00003722
caenorhabditis_elegans		WBGENE00003723
caenorhabditis_elegans		WBGENE00003724
caenorhabditis_elegans		WBGENE00003725
caenorhabditis_elegans		WBGENE00003728
caenorhabditis_elegans		WBGENE00004786
caenorhabditis_elegans		WBGENE00006471
caenorhabditis_elegans	unc-55	WBGENE00006790
caenorhabditis_elegans		WBGENE00007367
caenorhabditis_elegans		WBGENE00008056
caenorhabditis_elegans	nhr-165	WBGENE00008158
caenorhabditis_elegans		WBGENE00008208
caenorhabditis_elegans	nhr-169	WBGENE00008289
caenorhabditis_elegans		WBGENE00008309
caenorhabditis_elegans	nhr-174	WBGENE00008474
caenorhabditis_elegans		WBGENE00008619
caenorhabditis_elegans		WBGENE00008630
caenorhabditis_elegans		WBGENE00008778
caenorhabditis_elegans		WBGENE00008830
caenorhabditis_elegans		WBGENE00008884
caenorhabditis_elegans		WBGENE00008901
caenorhabditis_elegans	nhr-265	WBGENE00009608
caenorhabditis_elegans		WBGENE00010017
caenorhabditis_elegans		WBGENE00010180
caenorhabditis_elegans		WBGENE00010186
caenorhabditis_elegans		WBGENE00010215
caenorhabditis_elegans		WBGENE00010410
caenorhabditis_elegans		WBGENE00010600
caenorhabditis_elegans		WBGENE00010601
caenorhabditis_elegans		WBGENE00010602
caenorhabditis_elegans		WBGENE00010603
caenorhabditis_elegans		WBGENE00010604
caenorhabditis_elegans		WBGENE00011002
caenorhabditis_elegans		WBGENE00011150
caenorhabditis_elegans		WBGENE00011396
caenorhabditis_elegans		WBGENE00011520
caenorhabditis_elegans		WBGENE00011565
caenorhabditis_elegans		WBGENE00011566
caenorhabditis_elegans		WBGENE00011568
caenorhabditis_elegans	nhr-217	WBGENE00011651
caenorhabditis_elegans		WBGENE00011750
caenorhabditis_elegans		WBGENE00012050
caenorhabditis_elegans		WBGENE00012056
caenorhabditis_elegans		WBGENE00012446
caenorhabditis_elegans		WBGENE00012449
caenorhabditis_elegans		WBGENE00012596
caenorhabditis_elegans		WBGENE00012703
caenorhabditis_elegans		WBGENE00013067
caenorhabditis_elegans		WBGENE00013483
caenorhabditis_elegans	nhr-276	WBGENE00013512
caenorhabditis_elegans		WBGENE00013584
caenorhabditis_elegans		WBGENE00013940
caenorhabditis_elegans		WBGENE00014068
caenorhabditis_elegans	nhr-245	WBGENE00014189
caenorhabditis_elegans		WBGENE00014193
caenorhabditis_elegans		WBGENE00015497
caenorhabditis_elegans		WBGENE00015758
caenorhabditis_elegans		WBGENE00015897
caenorhabditis_elegans		WBGENE00015900
caenorhabditis_elegans		WBGENE00015901
caenorhabditis_elegans		WBGENE00015902
caenorhabditis_elegans		WBGENE00016091
caenorhabditis_elegans		WBGENE00016233
caenorhabditis_elegans		WBGENE00016364
caenorhabditis_elegans		WBGENE00016365
caenorhabditis_elegans		WBGENE00016366
caenorhabditis_elegans		WBGENE00016367
caenorhabditis_elegans		WBGENE00016368
caenorhabditis_elegans		WBGENE00016517
caenorhabditis_elegans		WBGENE00016772
caenorhabditis_elegans		WBGENE00016926
caenorhabditis_elegans		WBGENE00016927
caenorhabditis_elegans		WBGENE00017503
caenorhabditis_elegans		WBGENE00017512
caenorhabditis_elegans		WBGENE00017961
caenorhabditis_elegans		WBGENE00018189
caenorhabditis_elegans		WBGENE00018265
caenorhabditis_elegans		WBGENE00018266
caenorhabditis_elegans		WBGENE00018404
caenorhabditis_elegans		WBGENE00018412
caenorhabditis_elegans		WBGENE00018415
caenorhabditis_elegans		WBGENE00018539
caenorhabditis_elegans		WBGENE00018541
caenorhabditis_elegans		WBGENE00018542
caenorhabditis_elegans		WBGENE00018544
caenorhabditis_elegans		WBGENE00018545
caenorhabditis_elegans		WBGENE00018622
caenorhabditis_elegans		WBGENE00019115
caenorhabditis_elegans		WBGENE00019116
caenorhabditis_elegans		WBGENE00019741
caenorhabditis_elegans		WBGENE00019742
caenorhabditis_elegans		WBGENE00019743
caenorhabditis_elegans		WBGENE00020015
caenorhabditis_elegans		WBGENE00020062
caenorhabditis_elegans		WBGENE00020152
caenorhabditis_elegans		WBGENE00020153
caenorhabditis_elegans		WBGENE00020385
caenorhabditis_elegans		WBGENE00020460
caenorhabditis_elegans		WBGENE00020555
caenorhabditis_elegans		WBGENE00020750
caenorhabditis_elegans		WBGENE00020849
caenorhabditis_elegans		WBGENE00020850
caenorhabditis_elegans		WBGENE00020851
caenorhabditis_elegans		WBGENE00020852
caenorhabditis_elegans		WBGENE00021163
caenorhabditis_elegans		WBGENE00021522
caenorhabditis_elegans		WBGENE00021610
caenorhabditis_elegans		WBGENE00021611
caenorhabditis_elegans		WBGENE00021617
caenorhabditis_elegans		WBGENE00022097
caenorhabditis_elegans		WBGENE00022637
caenorhabditis_elegans		WBGENE00022639
caenorhabditis_elegans		WBGENE00022640
caenorhabditis_elegans		WBGENE00022726
caenorhabditis_elegans		WBGENE00022756
caenorhabditis_elegans		WBGENE00022805
caenorhabditis_elegans		WBGENE00044353
caenorhabditis_elegans		WBGENE00044699
caenorhabditis_elegans		WBGENE00045515

Paralogs (18): NR1H4 (ENSG00000012504), NR1H3 (ENSG00000025434), RORA (ENSG00000069667), RARB (ENSG00000077092), VDR (ENSG00000111424), PPARD (ENSG00000112033), THRA (ENSG00000126351), NR1D1 (ENSG00000126368), NR1H2 (ENSG00000131408), RARA (ENSG00000131759), PPARG (ENSG00000132170), NR1I3 (ENSG00000143257), RORC (ENSG00000143365), NR1I2 (ENSG00000144852), THRB (ENSG00000151090), RARG (ENSG00000172819), NR1D2 (ENSG00000174738), RORB (ENSG00000198963)

Protein

Protein identifiers

Peroxisome proliferator-activated receptor alpha — Q07869 (reviewed: Q07869)

Alternative names: Nuclear receptor subfamily 1 group C member 1

All UniProt accessions (5): Q07869, B0QYX1, B0QYX2, F1D8S4, Q86SF0

UniProt curated annotations — full annotation on UniProt →

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 a 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.

Subunit / interactions. Heterodimer; with RXRA. This heterodimerization is required for DNA binding and transactivation activity. Interacts with NCOA3 coactivator. Interacts with CITED2; the interaction stimulates its transcriptional activity. Also interacts with PPARBP in vitro. Interacts with AKAP13, LPIN1, PRDM16 and coactivator NCOA6. Interacts with ASXL1 and ASXL2. Interacts with PER2. Interacts with SIRT1; the interaction seems to be modulated by NAD(+) levels. Interacts with CRY1 and CRY2. In hepatocytes, interacts with PAQR3 and HUWE1; the interactions promote PPARA poylubiquitination and HUWE1-mediated degradation.

Subcellular location. Nucleus.

Tissue specificity. Skeletal muscle, liver, heart and kidney. Expressed in monocytes.

Post-translational modifications. Ubiquitinated by E3 ubiquitin-protein ligase HUWE1; leading to proteasomal degradation. Phosphorylated.

Induction. Down-regulated by aging.

Similarity. Belongs to the nuclear hormone receptor family. NR1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q07869-1	1	yes
Q07869-2	2

RefSeq proteins (12): NP_001001928, NP_001001929, NP_001349801, NP_001349802, NP_001380870, NP_001380871, NP_001380872, NP_001380873, NP_001380874, NP_001380875, NP_001380876, NP_005027* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000536	Nucl_hrmn_rcpt_lig-bd	Domain
IPR001628	Znf_hrmn_rcpt	Domain
IPR001723	Nuclear_hrmn_rcpt	Family
IPR003074	1Cnucl_rcpt	Family
IPR003076	PPAR-alpha	Family
IPR013088	Znf_NHR/GATA	Homologous_superfamily
IPR035500	NHR-like_dom_sf	Homologous_superfamily
IPR050234	Nuclear_hormone_rcpt_NR1	Family

Pfam: PF00104, PF00105

UniProt features (56 total): helix 16, sequence variant 7, mutagenesis site 7, strand 6, sequence conflict 4, turn 4, binding site 3, splice variant 2, zinc finger region 2, chain 1, domain 1, DNA-binding region 1, region of interest 1, site 1

Structure

Experimental structures (PDB)

79 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6KAX	X-RAY DIFFRACTION	1.23
6LXA	X-RAY DIFFRACTION	1.23
6KB1	X-RAY DIFFRACTION	1.25
6LX6	X-RAY DIFFRACTION	1.3
6KB0	X-RAY DIFFRACTION	1.35
9IWM	X-RAY DIFFRACTION	1.39
6LX9	X-RAY DIFFRACTION	1.4
6LX7	X-RAY DIFFRACTION	1.41
6KB4	X-RAY DIFFRACTION	1.42
6KB6	X-RAY DIFFRACTION	1.43
6KB3	X-RAY DIFFRACTION	1.45
9VZS	X-RAY DIFFRACTION	1.46
6KB8	X-RAY DIFFRACTION	1.47
9VZT	X-RAY DIFFRACTION	1.48
6KAZ	X-RAY DIFFRACTION	1.48
9IWO	X-RAY DIFFRACTION	1.49
7BQ2	X-RAY DIFFRACTION	1.52
7BQ1	X-RAY DIFFRACTION	1.52
6LX8	X-RAY DIFFRACTION	1.54
6KB9	X-RAY DIFFRACTION	1.55
7E5I	X-RAY DIFFRACTION	1.58
8YT9	X-RAY DIFFRACTION	1.59
9IWN	X-RAY DIFFRACTION	1.59
7BQ4	X-RAY DIFFRACTION	1.62
8HUQ	X-RAY DIFFRACTION	1.65
7E5G	X-RAY DIFFRACTION	1.66
7E5H	X-RAY DIFFRACTION	1.66
6KAY	X-RAY DIFFRACTION	1.74
9T5S	X-RAY DIFFRACTION	1.74
3VI8	X-RAY DIFFRACTION	1.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q07869-F1	81.18	0.66

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 433 (essential for heterodimerization with rxra)

Ligand- & substrate-binding residues (3): 280; 314; 464

Mutagenesis-validated functional residues (7):

Position	Phenotype
122	prevents dna binding but no effect on heterodimerization with rxra.
304	reduced heterodimerization with rxra. reduced dna binding.
370	abolishes heterodimerization with rxra. no dna binding.
391	abolishes heterodimerization with rxra. no dna binding.
422	no effect on heterodimerization with rxra nor on dna binding and transactivation activity.
431	no effect on heterodimerization with rxra nor on dna binding.
433	abolishes heterodimerization with rxra, dna binding and transactivation activity.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-1368108	BMAL1:CLOCK,NPAS2 activates circadian expression
R-HSA-1989781	PPARA activates gene expression
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis
R-HSA-2426168	Activation of gene expression by SREBF (SREBP)
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation
R-HSA-383280	Nuclear Receptor transcription pathway
R-HSA-400206	Regulation of lipid metabolism by PPARalpha
R-HSA-4090294	SUMOylation of intracellular receptors
R-HSA-9707564	Cytoprotection by HMOX1
R-HSA-9707616	Heme signaling
R-HSA-9844594	Transcriptional regulation of brown and beige adipocyte differentiation by EBF2
R-HSA-9931509	Expression of BMAL (ARNTL), CLOCK, and NPAS2
R-HSA-9933387	RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression

MSigDB gene sets: 512 (showing top): GOBP_CIRCADIAN_RHYTHM, REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, GOBP_LIPID_MODIFICATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOBP_FATTY_ACID_CATABOLIC_PROCESS, GOBP_REGULATION_OF_LIPID_STORAGE, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_REGULATION_OF_EPITHELIAL_CELL_APOPTOTIC_PROCESS, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_BEHAVIOR, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS

GO Biological Process (57): negative regulation of transcription by RNA polymerase II (GO:0000122), response to hypoxia (GO:0001666), gluconeogenesis (GO:0006094), fatty acid metabolic process (GO:0006631), heart development (GO:0007507), response to nutrient (GO:0007584), lactation (GO:0007595), epidermis development (GO:0008544), cellular response to starvation (GO:0009267), hormone-mediated signaling pathway (GO:0009755), gene expression (GO:0010467), regulation of ketone metabolic process (GO:0010565), negative regulation of macrophage derived foam cell differentiation (GO:0010745), negative regulation of cholesterol storage (GO:0010887), protein ubiquitination (GO:0016567), regulation of fatty acid metabolic process (GO:0019217), cell differentiation (GO:0030154), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), intracellular receptor signaling pathway (GO:0030522), positive regulation of fatty acid beta-oxidation (GO:0032000), negative regulation of appetite (GO:0032099), response to insulin (GO:0032868), circadian regulation of gene expression (GO:0032922), behavioral response to nicotine (GO:0035095), peroxisome proliferator activated receptor signaling pathway (GO:0035357), wound healing (GO:0042060), lipoprotein metabolic process (GO:0042157), regulation of circadian rhythm (GO:0042752), response to ethanol (GO:0045471), positive regulation of gluconeogenesis (GO:0045722), negative regulation of blood pressure (GO:0045776), negative regulation of glycolytic process (GO:0045820), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of fatty acid metabolic process (GO:0045923), positive regulation of transcription by RNA polymerase II (GO:0045944), nitric oxide metabolic process (GO:0046209), positive regulation of fatty acid oxidation (GO:0046321), positive regulation of lipid biosynthetic process (GO:0046889), negative regulation of inflammatory response (GO:0050728), defense response to virus (GO:0051607)

GO Molecular Function (25): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity (GO:0001216), transcription coactivator binding (GO:0001223), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), nuclear steroid receptor activity (GO:0003707), nuclear receptor activity (GO:0004879), zinc ion binding (GO:0008270), lipid binding (GO:0008289), phosphatase binding (GO:0019902), protein domain specific binding (GO:0019904), mitogen-activated protein kinase kinase kinase binding (GO:0031435), ubiquitin conjugating enzyme binding (GO:0031624), sequence-specific DNA binding (GO:0043565), protein-containing complex binding (GO:0044877), NFAT protein binding (GO:0051525), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), MDM2/MDM4 family protein binding (GO:0097371), protein binding (GO:0005515), signaling receptor activity (GO:0038023), metal ion binding (GO:0046872), DNA-binding transcription factor binding (GO:0140297)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Circadian clock	3
Regulation of lipid metabolism by PPARalpha	1
Mitochondrial biogenesis	1
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1
Adipogenesis	1
Generic Transcription Pathway	1
Metabolism of lipids	1
SUMO E3 ligases SUMOylate target proteins	1
Cellular response to chemical stress	1
Cellular responses to stress	1
Transcriptional regulation of brown and beige adipocyte differentiation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	4
DNA-binding transcription factor activity, RNA polymerase II-specific	3
regulation of transcription by RNA polymerase II	2
DNA-binding transcription factor activity	2
transcription cis-regulatory region binding	2
binding	2
cellular anatomical structure	2
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
response to stress	1
response to decreased oxygen levels	1
glucose metabolic process	1
hexose biosynthetic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
animal organ development	1
circulatory system development	1
response to nutrient levels	1
response to chemical	1
body fluid secretion	1
mammary gland development	1
milk ejection reflex	1
tissue development	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
signal transduction	1
cellular response to hormone stimulus	1
macromolecule biosynthetic process	1
regulation of metabolic process	1
ketone metabolic process	1
macrophage derived foam cell differentiation	1
regulation of macrophage derived foam cell differentiation	1
negative regulation of cell differentiation	1
cholesterol storage	1
regulation of cholesterol storage	1
negative regulation of lipid storage	1
protein modification by small protein conjugation	1
fatty acid metabolic process	1
regulation of ketone metabolic process	1

Protein interactions and networks

STRING

4570 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPARA	PPARGC1A	Q9UBK2	999
PPARA	PER2	O15055	989
PPARA	RXRA	P19793	986
PPARA	JUN	P05412	979
PPARA	XPR1	Q9UBH6	970
PPARA	LPIN1	Q14693	964
PPARA	UCP1	P25874	914
PPARA	FABP1	P07148	913
PPARA	ADIPOQ	Q15848	912
PPARA	SCARB2	Q14108	908
PPARA	NCOR1	O75376	907
PPARA	CD36	P16671	905
PPARA	INS	P01308	899
PPARA	ADIPOR2	Q86V24	897
PPARA	SCARB1	Q8WTV0	893

IntAct

113 interactions, top by confidence:

A	B	Type	Score
PPARA	VCP	psi-mi:“MI:0915”(physical association)	0.670
PPARA	NCOR1	psi-mi:“MI:0407”(direct interaction)	0.660
PPARA	NCOR1	psi-mi:“MI:0915”(physical association)	0.660
NCOR1	PPARA	psi-mi:“MI:0915”(physical association)	0.660
NCOR2	PPARA	psi-mi:“MI:0915”(physical association)	0.650
PPARA	NCOR2	psi-mi:“MI:0407”(direct interaction)	0.650
PPARA	NCOR2	psi-mi:“MI:0915”(physical association)	0.650
PPARA	NR1H3	psi-mi:“MI:0407”(direct interaction)	0.610
PPARA	NR1H3	psi-mi:“MI:0915”(physical association)	0.610
GRB2	PPARA	psi-mi:“MI:0915”(physical association)	0.570
PPARA	GRB2	psi-mi:“MI:0915”(physical association)	0.570
ALB	PPARA	psi-mi:“MI:0915”(physical association)	0.560
CASP6	PPARA	psi-mi:“MI:0915”(physical association)	0.560
PPARA	CCK	psi-mi:“MI:0915”(physical association)	0.560
PPARA	DMWD	psi-mi:“MI:0915”(physical association)	0.560
PPARA		psi-mi:“MI:0915”(physical association)	0.560
PPARA	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	PPARA	psi-mi:“MI:0915”(physical association)	0.560
PPARA	GSN	psi-mi:“MI:0915”(physical association)	0.560
PPARA	LAMP2	psi-mi:“MI:0915”(physical association)	0.560
PPARA	PMP22	psi-mi:“MI:0915”(physical association)	0.560
PPARA	RAD23A	psi-mi:“MI:0915”(physical association)	0.560
RAN	PPARA	psi-mi:“MI:0915”(physical association)	0.560
PPARA	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (120): PPARA (Reconstituted Complex), PPARA (Reconstituted Complex), RXRA (Affinity Capture-Western), RXRB (Affinity Capture-Western), RXRG (Affinity Capture-Western), RXRA (Reconstituted Complex), NCOA1 (Reconstituted Complex), NCOA2 (Reconstituted Complex), NCOA3 (Reconstituted Complex), PPARA (Reconstituted Complex), PPARA (Biochemical Activity), STAC3 (Two-hybrid), PPARA (Two-hybrid), NCOA1 (FRET), PPARA (Two-hybrid)

ESM2 similar proteins: A8XNK6, G5ED47, G5EEM0, O01930, O01931, O02151, O02279, O16391, O16425, O17611, O17898, O17933, O18141, O44960, O45436, O45460, O62389, P23204, P37230, P37232, P37233, P41235, P41999, P49700, P54779, P57797, P79926, P91829, Q07869, Q09528, Q09565, Q09587, Q14541, Q17905, Q18192, Q18299, Q21701, Q21878, Q22127, Q23294

Diamond homologs: A0JNE3, A0P8Z4, A2T928, A4IIG7, F1QJF4, F1QLY4, O01639, O09018, O18924, O18971, O35507, O62807, O77245, O88275, P10276, P10589, P10826, P11416, P13055, P13056, P13631, P16375, P16376, P17671, P18514, P18515, P18516, P18911, P22448, P22605, P24468, P28699, P31396, P33244, P35398, P37231, P37233, P37238, P41828, P41829

SIGNOR signaling

35 interactions.

A	Effect	B	Mechanism
RXRA	up-regulates	PPARA	binding
RXRB	up-regulates	PPARA	binding
NR0B2	up-regulates	PPARA	binding
MAPK1	“up-regulates activity”	PPARA	phosphorylation
MAPK3	“up-regulates activity”	PPARA	phosphorylation
STAT6	“up-regulates quantity by expression”	PPARA	“transcriptional regulation”
PPARA	“up-regulates activity”	LPL
PPARA	“up-regulates quantity by expression”	ACSL1	“transcriptional regulation”
PPARA	“up-regulates quantity by expression”	AQP3	“transcriptional regulation”
PPARA	“up-regulates quantity by expression”	PLIN2	“transcriptional regulation”
PPARA	“up-regulates quantity by expression”	CPT1A	“transcriptional regulation”
gemfibrozil	“up-regulates activity”	PPARA	“chemical activation”
PPARA	up-regulates	Fatty_acid_oxidation
“mono(2-ethylhexyl) phthalate”	“up-regulates activity”	PPARA	“chemical activation”
Monobutylphthalate	“up-regulates activity”	PPARA	“chemical activation”
“perfluorooctanoic acid”	“up-regulates activity”	PPARA	“chemical activation”
Gbeta	“up-regulates activity”	PPARA	phosphorylation
ERK1/2	“up-regulates activity”	PPARA	phosphorylation
GSK3A	“up-regulates activity”	PPARA	phosphorylation
HUWE1	“down-regulates quantity by destabilization”	PPARA	ubiquitination
PPARA	“up-regulates quantity by expression”	SLC25A20	“transcriptional regulation”
KDM3B	“up-regulates quantity by expression”	PPARA	“transcriptional regulation”
PPARA	“up-regulates quantity by expression”	ARNTL	“transcriptional regulation”
ARNTL	“up-regulates quantity by expression”	PPARA	“transcriptional regulation”
“perfluorooctane-1-sulfonic acid”	“up-regulates activity”	PPARA	“chemical activation”
“dibutyl phthalate”	“up-regulates activity”	PPARA	“chemical activation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 51 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression	7	63.4×	4e-09
BMAL1:CLOCK,NPAS2 activates circadian expression	5	47.0×	2e-06
Expression of BMAL (ARNTL), CLOCK, and NPAS2	7	45.5×	2e-08
Regulation of cholesterol biosynthesis by SREBP (SREBF)	6	42.3×	3e-07
R-HSA-400253	5	38.5×	5e-06
Activation of gene expression by SREBF (SREBP)	6	34.6×	7e-07
Heme signaling	7	33.5×	1e-07
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	7	33.5×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	5	25.8×	8e-04
positive regulation of ERK1 and ERK2 cascade	5	8.9×	9e-03
positive regulation of gene expression	9	7.3×	8e-04
DNA damage response	6	6.7×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

61 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2929 predictions. Top by Δscore:

Variant	Effect	Δscore
22:46198340:A:AG	acceptor_gain	1.0000
22:46198341:G:GA	acceptor_gain	1.0000
22:46198341:GT:G	acceptor_gain	1.0000
22:46198341:GTA:G	acceptor_gain	1.0000
22:46198341:GTAGC:G	acceptor_gain	1.0000
22:46198343:A:AG	acceptor_gain	1.0000
22:46198344:G:GA	acceptor_gain	1.0000
22:46198589:CGGG:C	donor_loss	1.0000
22:46198590:GG:G	donor_gain	1.0000
22:46198591:GG:G	donor_gain	1.0000
22:46198591:GGTA:G	donor_loss	1.0000
22:46198592:G:GG	donor_gain	1.0000
22:46198592:GT:G	donor_loss	1.0000
22:46198593:T:A	donor_loss	1.0000
22:46218258:CACA:C	acceptor_loss	1.0000
22:46218260:CAGGG:C	acceptor_loss	1.0000
22:46218261:A:AG	acceptor_gain	1.0000
22:46218261:A:T	acceptor_loss	1.0000
22:46218261:AG:A	acceptor_gain	1.0000
22:46218262:G:GG	acceptor_gain	1.0000
22:46218262:GG:G	acceptor_gain	1.0000
22:46218399:ACGGT:A	donor_loss	1.0000
22:46218400:CGGT:C	donor_loss	1.0000
22:46218402:G:GG	donor_loss	1.0000
22:46218402:GTAG:G	donor_gain	1.0000
22:46218403:T:A	donor_loss	1.0000
22:46219804:A:G	acceptor_gain	1.0000
22:46219995:G:GT	donor_gain	1.0000
22:46219996:A:T	donor_gain	1.0000
22:46220015:G:GG	donor_gain	1.0000

AlphaMissense

3101 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:46215268:T:A	C102S	1.000
22:46215268:T:C	C102R	1.000
22:46215269:G:A	C102Y	1.000
22:46215269:G:C	C102S	1.000
22:46215270:T:G	C102W	1.000
22:46215277:T:A	C105S	1.000
22:46215277:T:C	C105R	1.000
22:46215278:G:A	C105Y	1.000
22:46215278:G:C	C105S	1.000
22:46215278:G:T	C105F	1.000
22:46215279:C:G	C105W	1.000
22:46215290:C:A	A109D	1.000
22:46215295:G:C	G111R	1.000
22:46215296:G:A	G111D	1.000
22:46215301:C:A	H113N	1.000
22:46215301:C:G	H113D	1.000
22:46215302:A:G	H113R	1.000
22:46215303:T:A	H113Q	1.000
22:46215303:T:G	H113Q	1.000
22:46215304:T:A	Y114N	1.000
22:46215304:T:C	Y114H	1.000
22:46215305:A:G	Y114C	1.000
22:46215307:G:A	G115R	1.000
22:46215307:G:C	G115R	1.000
22:46215308:G:A	G115E	1.000
22:46215308:G:T	G115V	1.000
22:46215311:T:A	V116D	1.000
22:46215317:C:A	A118E	1.000
22:46215319:T:A	C119S	1.000
22:46215319:T:C	C119R	1.000

dbSNP variants (sampled 300 via entrez): RS1000013265 (22:46233264 C>T), RS1000018141 (22:46166749 G>A), RS1000070599 (22:46188365 C>T), RS1000082007 (22:46202712 C>T), RS1000129697 (22:46195196 C>A,T), RS1000130952 (22:46225847 GCACA>G,GCA,GCACACA), RS1000142133 (22:46153292 C>T), RS1000167257 (22:46239584 A>C,G,T), RS1000215169 (22:46188330 T>C), RS1000219557 (22:46157112 G>C), RS1000246650 (22:46182100 C>A), RS1000289041 (22:46162430 C>A), RS1000303434 (22:46199659 G>A), RS1000382145 (22:46220368 G>A), RS1000395613 (22:46151574 T>A)

Disease associations

OMIM: gene MIM:170998 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
cholesterol metabolism disease	Limited	Autosomal dominant

Mondo (1): cholesterol metabolism disease (MONDO:0045008)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST002221_31	Cholesterol, total	1.000000e-08
GCST002222_8	LDL cholesterol	3.000000e-08
GCST002690_20	Very long-chain saturated fatty acid levels (fatty acid 20:0)	1.000000e-06
GCST004420_2	CTACK levels	2.000000e-12
GCST006138_45	Resting-state electroencephalogram vigilance	2.000000e-06
GCST007628_5	Impulsivity (motor)	5.000000e-08
GCST008114_20	Type 2 diabetes	4.000000e-06
GCST010002_84	Refractive error	1.000000e-26
GCST010244_131	Triglyceride levels	2.000000e-13
GCST90002381_450	Eosinophil count	2.000000e-16
GCST90002382_514	Eosinophil percentage of white cells	3.000000e-21
GCST90013406_63	Liver enzyme levels (alkaline phosphatase)	7.000000e-12
GCST90020028_1549	Hip circumference adjusted for BMI	7.000000e-10

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0006796	very long-chain saturated fatty acid measurement
EFO:0008082	chemokine (C-C motif) ligand 27 measurement
EFO:0004357	electroencephalogram measurement
EFO:0006946	behavioural disinhibition measurement
EFO:0004530	triglyceride measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004533	alkaline phosphatase measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2111325 (SELECTIVITY GROUP), CHEMBL239 (SINGLE PROTEIN), CHEMBL3559683 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

39 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 544,103 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL121	ROSIGLITAZONE	4	58,849
CHEMBL160	CYCLOSPORINE	4	168,247
CHEMBL2103772	RACECADOTRIL	4	1,787
CHEMBL230158	SELADELPAR	4	854
CHEMBL247951	PEMAFIBRATE	4	604
CHEMBL295124	BERBERINE	4	26,682
CHEMBL3707395	ELAFIBRANOR	4	1,948
CHEMBL457	GEMFIBROZIL	4	35,238
CHEMBL557555	CIPROFIBRATE	4	11,386
CHEMBL565	CLOFIBRATE	4	39,543
CHEMBL595	PIOGLITAZONE	4	57,130
CHEMBL672	FENOFIBRATE	4	42,568
CHEMBL981	FENOFIBRIC ACID	4	6,353
CHEMBL186179	MURAGLITAZAR	3	1,191
CHEMBL264374	BEZAFIBRATE	3	21,822
CHEMBL282686	TESAGLITAZAR	3	7,488
CHEMBL3585580	LOBEGLITAZONE	3	1,212
CHEMBL3780740	LOBEGLITAZONE SULFATE	3	29
CHEMBL4091374	LANIFIBRANOR	3	992
CHEMBL460026	ICOSAPENT	3	60,180
CHEMBL464982	GAMOLENIC ACID	3
CHEMBL519504	ALEGLITAZAR	3
CHEMBL592054	IMIGLITAZAR	3
CHEMBL107367	FARGLITAZAR	2
CHEMBL1232583	INDEGLITAZAR	2
CHEMBL169	URSOLIC ACID	2
CHEMBL181954	NAVEGLITAZAR	2
CHEMBL219586	GW590735	2
CHEMBL24038	RAGAGLITAZAR	2
CHEMBL267476	LINOLEIC ACID	2

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

11 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs135543	Efficacy	3	fenofibrate
rs135550	Efficacy	3	fenofibrate
rs149711321	Efficacy,Metabolism/PK	3	metformin	Diabetes Mellitus
rs4253728	Efficacy	3	simvastatin
rs4253728	Dosage	3	phenprocoumon
rs4253728	Toxicity	3	tacrolimus	Kidney Transplantation
rs4253778	Efficacy	3	Beta Blocking Agents	Coronary Disease
rs4253778	Efficacy	3	fenofibrate	Diabetes Mellitus
rs4823613	Efficacy	3	simvastatin
rs4823613	Other	3	tacrolimus	Organ Transplantation
rs9626730	Efficacy	3	fenofibrate

PharmGKB variants

13 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs135543	PPARA	3	2.50	1	fenofibrate
rs135550	PPARA	3	2.50	1	fenofibrate
rs135561	PPARA		0.00	0
rs1800206	PPARA		0.00	0
rs4253728	PPARA	3	2.00	3	simvastatin;tacrolimus;phenprocoumon
rs4253778	PPARA	3	2.50	2	Beta Blocking Agents;fenofibrate
rs4823613	PPARA	3	1.50	2	simvastatin;tacrolimus
rs9626730	PPARA	3	2.50	1	fenofibrate
rs149711321	PPARA	3	2.75	1	metformin
rs1800234	PPARA		0.00	0
rs4253730	PPARA		0.00	0
rs9626736	PPARA		0.00	0
rs881740	PPARA		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: nhr — 1C. Peroxisome proliferator-activated receptors

Most potent curated ligand interactions (38 total), top 25:

Ligand	Action	Affinity	Parameter
saroglitazar	Agonist	13.19	pEC50
GW409544	Agonist	8.7	pIC50
elafibranor	Agonist	8.22	pEC50
GW7647	Agonist	8.2	pEC50
MK-0767	Agonist	7.64	pKd
LY-518674	Agonist	7.6	pIC50
TZD18	Agonist	7.6	pIC50
LY-510929	Agonist	7.55	pIC50
GW9578	Agonist	7.3	pEC50
CP-775146	Agonist	7.3	pEC50
imiglitazar	Agonist	7.17	pEC50
AZD4619	Agonist	7.1	pEC50
LTB4	Agonist	7.0	pIC50
8S-HETE	Agonist	7.0	pKd
N-oleoylethanolamide	Agonist	6.92	pIC50
LY-465608	Agonist	6.8	pIC50
GW2331	Agonist	6.8	pKd
NS-220	Agonist	6.73	pEC50
eicosatetranoic acid	Agonist	6.7	pIC50
GW6471	Antagonist	6.6	pIC50
(R)-16 [PMID: 32267688]	Agonist	6.37	pEC50
farglitazar	Agonist	6.35	pEC50
ciprofibrate	Agonist	6.05	pEC50
seladelpar	Agonist	6.0	pEC50
MK-886	Antagonist	6.0	pIC50

Binding affinities (BindingDB)

234 measured of 286 human assays (287 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-[2-ethyl-4-[2-[5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]ethoxy]phenyl]propanoic acid	EC50	4 nM	US-9346770: Compounds having activating effect on subtypes of peroxisome proliferator-activated receptors and its preparation method and uses
2-methyl-2-{4-[({4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}formamido)methyl]phenoxy}propanoic acid	EC50	4 nM
2-methyl-2-{4-[({4-methyl-2-[4-(trifluoromethoxy)phenyl]-1,3-thiazol-5-yl}formamido)methyl]phenoxy}propanoic acid	EC50	4 nM
2-methyl-2-{4-[({4-methyl-2-[3-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}formamido)methyl]phenoxy}propanoic acid	EC50	4 nM
2-methyl-2-[4-({[4-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]formamido}methyl)phenoxy]propanoic acid	EC50	4 nM
2-{(5-{[2-(4-chlorophenyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-2-fluorophenyl)methylamino}acetic acid	EC50	4 nM
2-[4-({[2-(4-tert-butylphenyl)-4-methyl-1,3-thiazol-5-yl]formamido}methyl)phenoxy]-2-methylpropanoic acid	EC50	5 nM
(+/-)-2-{5-[(4-Adamantan-1-yl-benzoylamino)-methyl]-4-ethoxy-2-fluoro-benzyl}-butyric acid	EC50	7.1 nM
(+/-)-2-{5-[(4-Adamantan-1-yl-2-fluoro-benzoylamino)-methyl]-4-ethoxy-2-fluoro-benzyl}-butyric acid	EC50	7.5 nM
2-[4-({[2-(4-chlorophenyl)-4-methyl-1,3-thiazol-5-yl]formamido}methyl)phenoxy]-2-methylpropanoic acid	EC50	10 nM
2-[4-({[2-(4-methoxyphenyl)-4-methyl-1,3-thiazol-5-yl]formamido}methyl)phenoxy]-2-methylpropanoic acid	EC50	10 nM
2-{(3-{[2-(4-chlorophenyl)-5-methyl-1,3-oxazol-4-yl]methoxy}phenyl)methylamino}acetic acid	EC50	10 nM
2-[2-(4-fluorophenyl)ethylsulfanyl]-3-[4-[[2-phenyl-5-(trifluoromethyl)-1,3-oxazole-4-carbonyl]oxymethyl]phenyl]propanoic acid	EC50	12 nM	US-9181181: 2-substituted-3-phenylpropionic acid derivatives and their use in the treatment of inflammatory bowel disease
(S)-2-{5-[(4-Adamantan-1-yl-2-fluoro-benzoylamino)-methyl]-2-fluoro-4-propoxy-benzyl}-butyric acid	EC50	12 nM
(+/-)-2-{5-[(4-Adamantan-1-yl-benzoylamino)-methyl]-2-fluoro-4-methoxy-benzyl}-butyric acid	EC50	13 nM
(+/-)-2-{5-[(4-Adamantan-1-yl-2-fluoro-benzoylamino)-methyl]-2-fluoro-4-propoxy-benzyl}-butyric acid	EC50	13 nM
(+/-)-2-{5-[(4-Adamantan-1-yl-benzoylamino)-methyl]-2-fluoro-4-propoxy-benzyl}-butyric acid	EC50	17 nM
racemic	IC50	24 nM
CHEMBL270664	EC50	28 nM
2-[[4-[[2-[4-(trifluoromethyl)phenyl]acetyl]oxymethyl]phenyl]sulfanylmethyl]benzoic acid	EC50	29 nM	US-9181181: 2-substituted-3-phenylpropionic acid derivatives and their use in the treatment of inflammatory bowel disease
3-[2-ethyl-4-[2-[2-(4-fluorophenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy]phenyl]propanoic acid	EC50	29 nM	US-9346770: Compounds having activating effect on subtypes of peroxisome proliferator-activated receptors and its preparation method and uses
2-methyl-2-[4-({[4-methyl-2-(4-nitrophenyl)-1,3-thiazol-5-yl]formamido}methyl)phenoxy]propanoic acid	EC50	30 nM
2-methyl-2-{2-methyl-4-[({3-[4-(trifluoromethoxy)phenyl]-1,2,4-thiadiazol-5-yl}methyl)sulfanyl]phenoxy}propanoic acid	EC50	33 nM
phenylpropanoic acid derivative, 17j	IC50	34 nM
2-[4-({[2-(4-fluorophenyl)-4-methyl-1,3-thiazol-5-yl]formamido}methyl)phenoxy]-2-methylpropanoic acid	EC50	40 nM
CHEMBL270665	EC50	41 nM
2-[(1S)-5-{3-[2-propyl-4-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)phenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl]acetic acid	EC50	43 nM
2-[(1S)-5-{3-[2-methoxy-4-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)phenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl]acetic acid	EC50	44 nM
2-[(1S)-5-(3-{4-[4-(propan-2-yloxy)-1,3-thiazol-2-yl]-2-propylphenoxy}propoxy)-2,3-dihydro-1H-inden-1-yl]acetic acid	EC50	47 nM
2-[(1S)-5-[3-(4-{4H,5H,6H-cyclopenta[d][1,3]thiazol-2-yl}-2-methoxyphenoxy)propoxy]-2,3-dihydro-1H-inden-1-yl]acetic acid	EC50	53 nM
rac-2-{3-[(4-adamantan-1-yl-benzoylamino)-methyl]-4-methoxy-benzyl}-butyric acid	EC50	53 nM
2-[2-(4-fluorophenyl)ethylsulfanyl]-3-[4-[2-oxo-2-[[4-(trifluoromethyl)phenyl]methoxy]ethyl]phenyl]propanoic acid	EC50	56 nM	US-9181181: 2-substituted-3-phenylpropionic acid derivatives and their use in the treatment of inflammatory bowel disease
(2S)-2-(4-propoxy-3-{[({4-[(3S,5S,7S)-tricyclo[3.3.1.13,7]dec-1-yl]phenyl}carbonyl)amino]methyl}benzyl)butanoic acid	EC50	58 nM
(+/-)-2-{3-[(4-Adamantan-1-yl-2-fluoro-benzoylamino)-methyl]-4-methoxy-benzyl}-butyric acid	EC50	60 nM
2-[(1S)-5-{3-[4-(4-ethoxy-5-methyl-1,3-thiazol-2-yl)-2-propylphenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl]acetic acid	EC50	61 nM
2-[4-({[3-(4-tert-butylphenyl)-1,2,4-thiadiazol-5-yl]methyl}sulfanyl)-2-methylphenoxy]-2-methylpropanoic acid	EC50	64 nM
2-methyl-2-(4-{[({4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)amino]methyl}phenoxy)propanoic acid	EC50	70 nM
2-methyl-2-{2-methyl-4-[({3-[4-(trifluoromethyl)phenyl]-1,2,4-thiadiazol-5-yl}methyl)sulfanyl]phenoxy}propanoic acid	EC50	79 nM
2-[(1S)-5-{3-[4-(4,5-dimethyl-1,3-thiazol-2-yl)-2-methoxyphenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl]acetic acid	EC50	83 nM
2-[(1S)-5-{3-[4-(4-tert-butyl-1,3-thiazol-2-yl)-2-propylphenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl]acetic acid	EC50	87 nM
2-methyl-2-[2-methyl-4-({3-[4-(trifluoromethyl)phenyl]-1,2,4-thiadiazol-5-yl}methoxy)phenoxy]propanoic acid	EC50	94 nM
2-methyl-2-[2-methyl-4-({3-[4-(trifluoromethoxy)phenyl]-1,2,4-thiadiazol-5-yl}methoxy)phenoxy]propanoic acid	EC50	94 nM
2-[(1S)-5-{3-[4-(4-ethoxy-1,3-thiazol-2-yl)phenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl]acetic acid	EC50	100 nM
2-[(1S)-5-[3-(2-propyl-4-{5H,6H,7H-pyrano[2,3-d][1,3]thiazol-2-yl}phenoxy)propoxy]-2,3-dihydro-1H-inden-1-yl]acetic acid	EC50	101 nM
2-[(1S)-5-{3-[4-(4-ethoxy-1,3-thiazol-2-yl)-2-propylphenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl]acetic acid	EC50	105 nM
2-methyl-2-{4-[2-({4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}formamido)ethyl]phenoxy}propanoic acid	EC50	110 nM
2-[(1S)-5-{3-[2-propyl-4-(1,3-thiazol-2-yl)phenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl]acetic acid	EC50	111 nM
2-[(1S)-5-[3-(4-{4H,5H,6H-cyclopenta[d][1,3]thiazol-2-yl}phenoxy)propoxy]-2,3-dihydro-1H-inden-1-yl]acetic acid	EC50	112 nM
2-methyl-2-(4-{[(4-methyl-2-phenyl-1,3-thiazol-5-yl)formamido]methyl}phenoxy)propanoic acid	EC50	120 nM
2-[2-(4-fluorophenyl)ethylsulfanyl]-3-[4-[[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)acetyl]oxymethyl]phenyl]propanoic acid	EC50	130 nM	US-9181181: 2-substituted-3-phenylpropionic acid derivatives and their use in the treatment of inflammatory bowel disease

ChEMBL bioactivities

3910 potent at pChembl≥5 of 4276 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.89	EC50	0.01288	nM	CHEMBL315048
10.83	EC50	0.01479	nM	CHEMBL86657
10.76	EC50	0.01738	nM	CHEMBL314483
10.59	EC50	0.026	nM	CHEMBL1813003
10.52	EC50	0.03	nM	CHEMBL468160
10.35	EC50	0.04467	nM	CHEMBL327481
10.27	Ki	0.0541	nM	GW7647
10.14	EC50	0.072	nM	CHEMBL481551
10.05	EC50	0.089	nM	CHEMBL513145
10.00	EC50	0.1	nM	CHEMBL1813008
9.80	EC50	0.16	nM	CHEMBL3354987
9.56	EC50	0.272	nM	CHEMBL467349
9.55	IC50	0.28	nM	CHEMBL2088421
9.52	EC50	0.3	nM	CHEMBL253310
9.34	IC50	0.46	nM	GW7647
9.23	IC50	0.59	nM	CHEMBL2088422
9.22	EC50	0.6	nM	GW7647
9.22	EC50	0.6	nM	CHEMBL5409347
9.22	EC50	0.6	nM	CHEMBL468159
9.21	EC50	0.615	nM	CHEMBL318351
9.15	EC50	0.7	nM	CHEMBL5417169
9.12	Kd	0.75	nM	CHEMBL4092600
9.10	EC50	0.8	nM	CHEMBL5433219
9.07	Kd	0.86	nM	CHEMBL4073499
9.07	EC50	0.85	nM	CHEMBL4866115
9.06	EC50	0.87	nM	CHEMBL4861761
9.05	EC50	0.89	nM	GW7647
9.05	EC50	0.9	nM	CHEMBL5400319
9.02	EC50	0.95	nM	CHEMBL4879102
9.00	EC50	1	nM	CHEMBL2237300
9.00	Kd	1	nM	GW7647
9.00	EC50	1	nM	PEMAFIBRATE
9.00	EC50	1	nM	CHEMBL3398443
9.00	EC50	1	nM	CHEMBL424685
9.00	EC50	1	nM	CHEMBL264385
9.00	EC50	1	nM	CHEMBL246281
9.00	EC50	1	nM	CHEMBL427701
9.00	EC50	1	nM	CHEMBL246070
9.00	EC50	1	nM	CHEMBL245866
9.00	EC50	1	nM	CHEMBL4855604
9.00	EC50	1	nM	CHEMBL4847453
9.00	EC50	1	nM	GW7647
9.00	EC50	1	nM	CHEMBL481550
9.00	EC50	1	nM	CHEMBL5402111
9.00	EC50	1	nM	CHEMBL5406894
9.00	EC50	1	nM	CHEMBL456912
9.00	EC50	1	nM	CHEMBL21706
8.96	EC50	1.1	nM	CHEMBL1494365
8.96	EC50	1.09	nM	CHEMBL512084
8.92	Ki	1.2	nM	GW7647

PubChem BioAssay actives

2689 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-methyl-5-[[4-[[5-methyl-2-(4-methylphenyl)-1,3-oxazol-4-yl]methoxy]phenyl]methyl]-1,3-dioxane-2-carboxylic acid	365528: Agonist activity at PPARalpha expressed in human HepG2 cells assessed as induction of receptor transactivation by reporter gene assay relative to control	ec50	0.0001	uM
2-[4-[2-[4-cyclohexylbutyl(cyclohexylcarbamoyl)amino]ethyl]phenyl]sulfanyl-2-methylpropanoic acid	1451039: Displacement of Fluormone-Pan-PPAR Green from human GST-tagged PPARalpha LBD by TR-FRET assay	ki	0.0001	uM
3-[5-[(E)-[3-[2-(4-fluoroanilino)-2-oxoethyl]-2,4-dioxo-1,3-thiazolidin-5-ylidene]methyl]furan-2-yl]-2-methylbenzoic acid	1175818: Agonist activity at GAL4-tagged PPARalpha ligand-binding domain (unknown origin) expressed in HEK293T cells incubated for 16 to 19 hrs by beta-lactamase reporter gene assay	ec50	0.0002	uM
2-[4-[[2,5-dioxo-3-[4-(trifluoromethoxy)phenyl]imidazolidin-1-yl]methyl]-2,6-dimethylphenoxy]-2-methylpropanoic acid	1990529: Agonist activity at human PPARalpha transfected in african green monkey COS7 cells assessed transactivation incubated for 16 hrs by luciferase assay	ec50	0.0006	uM
2-[4-[[2,5-dioxo-3-[4-(trifluoromethyl)phenyl]imidazolidin-1-yl]methyl]-2,6-dimethylphenoxy]-2-methylpropanoic acid	1990529: Agonist activity at human PPARalpha transfected in african green monkey COS7 cells assessed transactivation incubated for 16 hrs by luciferase assay	ec50	0.0007	uM
2-[4-[3-[1,4-bis[(4-methylphenyl)methyl]-5-oxo-1,2,4-triazol-3-yl]propyl]phenoxy]-2-methylpropanoic acid	1754399: Agonist activity at Gal4-fused human PPARalpha co-expressed with RXRalpha in monkey CV1 cells assessed as PPRE transcriptional activation incubated for 45 hrs by luciferase reporter gene assay	ec50	0.0008	uM
(2S)-2-[4-[[4-[(2-phenyl-1,3-oxazol-4-yl)methoxy]phenyl]methyl]phenoxy]propanoic acid	1440531: Binding affinity to PPARalpha (unknown origin) assessed as thermodynamic dissociation constant by SPR assay	kd	0.0008	uM
2-[4-[[2,5-dioxo-3-(4-propan-2-ylphenyl)imidazolidin-1-yl]methyl]-2,6-dimethylphenoxy]-2-methylpropanoic acid	1990529: Agonist activity at human PPARalpha transfected in african green monkey COS7 cells assessed transactivation incubated for 16 hrs by luciferase assay	ec50	0.0008	uM
2-[4-[3-[4-[(4-fluorophenyl)methyl]-1-[(4-methylphenyl)methyl]-5-oxo-1,2,4-triazol-3-yl]propyl]phenoxy]-2-methylpropanoic acid	1754399: Agonist activity at Gal4-fused human PPARalpha co-expressed with RXRalpha in monkey CV1 cells assessed as PPRE transcriptional activation incubated for 45 hrs by luciferase reporter gene assay	ec50	0.0009	uM
2-[4-[3-[4-[(4-methoxyphenyl)methyl]-1-[(4-methylphenyl)methyl]-5-oxo-1,2,4-triazol-3-yl]propyl]phenoxy]-2-methylpropanoic acid	1754399: Agonist activity at Gal4-fused human PPARalpha co-expressed with RXRalpha in monkey CV1 cells assessed as PPRE transcriptional activation incubated for 45 hrs by luciferase reporter gene assay	ec50	0.0009	uM
(2R)-2-[4-[[4-[(2-phenyl-1,3-oxazol-4-yl)methoxy]phenyl]methyl]phenoxy]propanoic acid	1440531: Binding affinity to PPARalpha (unknown origin) assessed as thermodynamic dissociation constant by SPR assay	kd	0.0009	uM
2-[4-[[2,5-dioxo-3-(4-phenylphenyl)imidazolidin-1-yl]methyl]-2,6-dimethylphenoxy]-2-methylpropanoic acid	1990529: Agonist activity at human PPARalpha transfected in african green monkey COS7 cells assessed transactivation incubated for 16 hrs by luciferase assay	ec50	0.0009	uM
(3R,4S)-4-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-1-phenoxycarbonylpyrrolidine-3-carboxylic acid	1192048: Agonist activity at GAL4 tagged human PPARalpha ligand binding domain expressed in HEK293 cells by luciferase reporter gene assay	ec50	0.0010	uM
(2S)-3-[4-[2-(2-cyclohexyl-5-methyl-1,3-oxazol-4-yl)ethoxy]phenyl]-2-methyl-2-phenoxypropanoic acid	156129: Transcriptional activation of reporter assay by human Peroxisome proliferator activated receptor alpha in CV-1 cells	ec50	0.0010	uM
2-[3-[[1,3-benzoxazol-2-yl-[3-(4-methoxyphenoxy)propyl]amino]methyl]phenoxy]butanoic acid	308331: Agonist activity at human recombinant PPARalpha by GAL4 transactivation assay	ec50	0.0010	uM
(2R)-2-[3-[[1,3-benzoxazol-2-yl-[3-(4-methoxyphenoxy)propyl]amino]methyl]phenoxy]butanoic acid	1175818: Agonist activity at GAL4-tagged PPARalpha ligand-binding domain (unknown origin) expressed in HEK293T cells incubated for 16 to 19 hrs by beta-lactamase reporter gene assay	ec50	0.0010	uM
2-[4-[3-[4-[(3-methoxyphenyl)methyl]-1-[(4-methylphenyl)methyl]-5-oxo-1,2,4-triazol-3-yl]propyl]phenoxy]-2-methylpropanoic acid	1754399: Agonist activity at Gal4-fused human PPARalpha co-expressed with RXRalpha in monkey CV1 cells assessed as PPRE transcriptional activation incubated for 45 hrs by luciferase reporter gene assay	ec50	0.0010	uM
2-[4-[3-[4-[(4-chlorophenyl)methyl]-1-[(4-methylphenyl)methyl]-5-oxo-1,2,4-triazol-3-yl]propyl]phenoxy]-2-methylpropanoic acid	1754399: Agonist activity at Gal4-fused human PPARalpha co-expressed with RXRalpha in monkey CV1 cells assessed as PPRE transcriptional activation incubated for 45 hrs by luciferase reporter gene assay	ec50	0.0010	uM
2-[4-[[3-[3-chloro-4-(trifluoromethyl)phenyl]-2,5-dioxoimidazolidin-1-yl]methyl]-2,6-dimethylphenoxy]-2-methylpropanoic acid	1990529: Agonist activity at human PPARalpha transfected in african green monkey COS7 cells assessed transactivation incubated for 16 hrs by luciferase assay	ec50	0.0010	uM
2-[4-[[3-(4-ethylphenyl)-2,5-dioxoimidazolidin-1-yl]methyl]-2,6-dimethylphenoxy]-2-methylpropanoic acid	1990529: Agonist activity at human PPARalpha transfected in african green monkey COS7 cells assessed transactivation incubated for 16 hrs by luciferase assay	ec50	0.0010	uM
methyl 7-[2-[5-methyl-2-(4-methylphenyl)-1,3-oxazol-4-yl]ethoxy]-2-oxochromene-3-carboxylate	396052: Agonist activity at human PPARalpha in U2OS cells by transactivation assay	ec50	0.0010	uM
2-[4-[2-[4-cyclohexylbutyl-[(3,5-dichlorophenyl)carbamoyl]amino]ethyl]phenyl]sulfanyl-2-methylpropanoic acid	156137: In vitro transcriptional activation in CV-1 cells expressing human Gal4-PPAR alpha ligand binding domain	ec50	0.0010	uM
(2S)-2-[[4-[3-(2-chloro-4-cyclohexylphenoxy)propoxy]phenyl]methyl]-2-methylbutanoic acid	261946: Transactivation by human PPAR alpha in COS1 cells	ec50	0.0010	uM
(2S)-2-[[4-[3-[2-chloro-4-(2,2,2-trifluoroethyl)phenoxy]propoxy]phenyl]methyl]-2-methylbutanoic acid	261943: Binding affinity to human PPAR alpha	ic50	0.0010	uM
2-[[3-[(4-pentoxycarbonylphenyl)carbamoyl]phenyl]carbamoyl]benzoic acid	1175818: Agonist activity at GAL4-tagged PPARalpha ligand-binding domain (unknown origin) expressed in HEK293T cells incubated for 16 to 19 hrs by beta-lactamase reporter gene assay	ec50	0.0011	uM
(3E)-3-butoxyimino-2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]butanoic acid	289934: Agonist activity at human PPARalpha in HepG2 cells by PPAR-GAL4 transactivation assay	ec50	0.0013	uM
2-[2,6-dimethyl-4-[[3-[3-methyl-4-(trifluoromethoxy)phenyl]-2,5-dioxoimidazolidin-1-yl]methyl]phenoxy]-2-methylpropanoic acid	1990529: Agonist activity at human PPARalpha transfected in african green monkey COS7 cells assessed transactivation incubated for 16 hrs by luciferase assay	ec50	0.0014	uM
2-[4-[3-[4-benzyl-1-[(4-methylphenyl)methyl]-5-oxo-1,2,4-triazol-3-yl]propyl]phenoxy]-2-methylpropanoic acid	1754399: Agonist activity at Gal4-fused human PPARalpha co-expressed with RXRalpha in monkey CV1 cells assessed as PPRE transcriptional activation incubated for 45 hrs by luciferase reporter gene assay	ec50	0.0015	uM
2-[4-[[3-(4-tert-butylphenyl)-2,5-dioxoimidazolidin-1-yl]methyl]-2,6-dimethylphenoxy]-2-methylpropanoic acid	1990529: Agonist activity at human PPARalpha transfected in african green monkey COS7 cells assessed transactivation incubated for 16 hrs by luciferase assay	ec50	0.0015	uM
2-[4-[2-[4-cyclohexylbutyl-[(2-methoxyphenyl)carbamoyl]amino]ethyl]phenyl]sulfanyl-2-methylpropanoic acid	683294: Agonist activity at PPARalpha-LBD expressed in HEK293 cells co-expressing GAL4-DBD after 16 to 19 hrs by beta lactamase reporter gene assay	ic50	0.0019	uM
2-[4-[3-[1-[(4-tert-butylphenyl)methyl]-4-methyl-5-oxo-1,2,4-triazol-3-yl]propyl]phenoxy]-2-methylpropanoic acid	156131: Cotransfection activity against human Peroxisome proliferator activated receptor alpha	ec50	0.0020	uM
(2R)-7-[3-(2-chloro-4-cyclohexylphenoxy)propoxy]-2-methyl-3,4-dihydrochromene-2-carboxylic acid	246052: Agonist activity against human PPARalpha in COS-1 cell Gal4 assay	ec50	0.0020	uM
(2S)-5-[3-[2-chloro-4-(trifluoromethoxy)phenoxy]propoxy]-2-ethyl-3H-1-benzofuran-2-carboxylic acid	246706: Effective concentration against human PPAR-alpha in Gal4 transactivation assay	ec50	0.0020	uM
2-methyl-2-[2-methyl-4-[[[1-methyl-5-[4-(2-methylpropyl)phenyl]pyrazole-3-carbonyl]amino]methyl]phenoxy]propanoic acid	410081: Agonist activity at human PPARalpha receptor by cell based transient transfection assay	ec50	0.0020	uM
(2R)-5-[3-[2-chloro-4-(trifluoromethoxy)phenoxy]propoxy]-2-propan-2-yl-3H-1-benzofuran-2-carboxylic acid	246706: Effective concentration against human PPAR-alpha in Gal4 transactivation assay	ec50	0.0020	uM
2-tert-butyl-5-[3-[2-chloro-4-(2,2,2-trifluoroethyl)phenoxy]propoxy]-3H-1-benzofuran-2-carboxylic acid	246706: Effective concentration against human PPAR-alpha in Gal4 transactivation assay	ec50	0.0020	uM
2-[4-[3-[(3-phenyl-7-propyl-1,2-benzoxazol-6-yl)oxy]propoxy]indol-1-yl]acetic acid	256777: Functional activity at human PPAR alpha in Huh7 cells by transactivation assay	ec50	0.0020	uM
(2S)-3-[4-[(E)-3-[3,5-bis(2,2,2-trifluoroethoxy)phenyl]prop-2-enoxy]phenyl]-2-ethoxypropanoic acid	307130: Agonist activity at human PPARalpha by transactivation assay	ec50	0.0020	uM
(2R)-2-[3-[[3-(4-chlorobenzoyl)-2-methyl-6-(trifluoromethoxy)indol-1-yl]methyl]phenoxy]-3-methylbutanoic acid	421050: Agonist activity at human PPARalpha receptor expressed in african green monkey COS1 cells co-transfected with fused yeast Gal4-DBD by transactivation assay	ec50	0.0020	uM
2-methyl-2-[4-[4-[(3-phenyl-7-propyl-1,2-benzoxazol-6-yl)oxy]butoxy]phenyl]propanoic acid	155988: Agonistic activity was determined in COS1 cells transfected with GAL 4-PPAR alpha receptor	ec50	0.0020	uM
2-methyl-2-[4-[4-[(3-phenyl-7-propyl-1,2-benzoxazol-6-yl)oxy]butoxy]phenoxy]propanoic acid	155988: Agonistic activity was determined in COS1 cells transfected with GAL 4-PPAR alpha receptor	ec50	0.0020	uM
2-[4-[3-[(3-phenyl-7-propyl-1,2-benzoxazol-6-yl)oxy]propoxy]phenoxy]propanoic acid	155988: Agonistic activity was determined in COS1 cells transfected with GAL 4-PPAR alpha receptor	ec50	0.0020	uM
2-[4-[[3-[3-fluoro-4-(trifluoromethyl)phenyl]-2,5-dioxoimidazolidin-1-yl]methyl]-2,6-dimethylphenoxy]-2-methylpropanoic acid	1990529: Agonist activity at human PPARalpha transfected in african green monkey COS7 cells assessed transactivation incubated for 16 hrs by luciferase assay	ec50	0.0021	uM
(2S)-2-[[4-[3-[2-chloro-4-(trifluoromethoxy)phenoxy]propoxy]phenyl]methyl]-2-methylbutanoic acid	261946: Transactivation by human PPAR alpha in COS1 cells	ec50	0.0021	uM
2-[2,6-dibromo-4-[[2,5-dioxo-3-[4-(trifluoromethyl)phenyl]imidazolidin-1-yl]methyl]phenoxy]-2-methylpropanoic acid	1990529: Agonist activity at human PPARalpha transfected in african green monkey COS7 cells assessed transactivation incubated for 16 hrs by luciferase assay	ec50	0.0022	uM
(3E)-2-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-3-(2-methylpropoxyimino)butanoic acid	289934: Agonist activity at human PPARalpha in HepG2 cells by PPAR-GAL4 transactivation assay	ec50	0.0022	uM
2-[[5-[[2-(4-chlorophenyl)-5-methyl-1,3-oxazol-4-yl]methoxy]-2-fluorophenyl]methyl-(2-methylpropoxycarbonyl)amino]acetic acid	1313442: Agonist activity at Gal4-tagged human PPAR-alpha expressed in HEK cells by transactivation assay	ec50	0.0023	uM
2-[[4-[3-[2-chloro-4-(4-fluorophenoxy)phenoxy]propoxy]phenyl]methyl]-2-methylbutanoic acid	261946: Transactivation by human PPAR alpha in COS1 cells	ec50	0.0025	uM
2-[[5-[[2-(4-tert-butylphenyl)-5-methyl-1,3-oxazol-4-yl]methoxy]-2-fluorophenyl]methyl-methoxycarbonylamino]acetic acid	1313442: Agonist activity at Gal4-tagged human PPAR-alpha expressed in HEK cells by transactivation assay	ec50	0.0027	uM
2-[2,6-dimethyl-4-[[3-(4-methylsulfanylphenyl)-2,5-dioxoimidazolidin-1-yl]methyl]phenoxy]-2-methylpropanoic acid	1990529: Agonist activity at human PPARalpha transfected in african green monkey COS7 cells assessed transactivation incubated for 16 hrs by luciferase assay	ec50	0.0027	uM

CTD chemical–gene interactions

344 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
pirinixic acid	increases expression, increases reaction, affects reaction, increases transport, decreases expression (+6 more)	44
Bezafibrate	affects localization, affects binding, affects reaction, increases activity, increases reaction (+7 more)	18
perfluorooctanoic acid	increases activity, decreases expression, decreases response to substance, affects response to substance, affects cotreatment (+6 more)	17
Oleic Acid	affects cotreatment, increases activity, increases localization, increases reaction, affects expression (+5 more)	14
Fenofibrate	increases reaction, increases response to substance, affects binding, decreases reaction, affects cotreatment (+4 more)	13
GW 7647	affects binding, decreases reaction, increases activity	12
Diethylhexyl Phthalate	decreases reaction, increases activity, increases localization, decreases expression, affects response to substance (+6 more)	11
Valproic Acid	increases methylation, affects cotreatment, increases expression, affects expression, affects binding (+1 more)	11
mono-(2-ethylhexyl)phthalate	affects binding, increases reaction, decreases expression, increases expression, affects reaction (+2 more)	10
Palmitic Acid	affects cotreatment, decreases expression, decreases reaction, increases reaction, increases expression (+4 more)	10
Linoleic Acid	increases expression, affects binding, increases activity, increases oxidation, affects reaction (+1 more)	9
MK-886	affects binding, decreases activity, decreases response to substance, increases reaction, decreases expression (+3 more)	8
bisphenol A	affects expression, affects binding, increases expression, decreases expression, decreases methylation	7
Ethanol	decreases expression, decreases reaction, affects cotreatment, affects reaction, increases activity (+1 more)	7
Benzo(a)pyrene	affects methylation, affects cotreatment, decreases expression, decreases reaction, decreases methylation (+1 more)	7
Clofibrate	affects reaction, affects binding, increases activity, increases expression	7
perfluorooctane sulfonic acid	increases expression, decreases reaction, increases activity, decreases expression	6
Pioglitazone	affects binding, increases activity, affects reaction, increases expression	6
Glucose	affects binding, decreases abundance, increases activity, increases reaction, affects reaction (+3 more)	6
fenofibric acid	affects binding, increases expression, increases activity, affects reaction, decreases reaction	5
Plant Extracts	increases activity, affects binding, decreases expression, increases expression, decreases reaction	5
Gemfibrozil	decreases reaction, increases expression, affects reaction, affects binding, increases activity (+2 more)	5
perfluorooctanesulfonamide	increases expression, decreases activity, decreases expression, increases activity	4
5-((2,4-dioxo-5-thiazolidinyl)methyl)-2-methoxy-N-((4-(trifluoromethyl)phenyl)methyl)benzamide	affects binding, increases activity	4
perfluorohexanoic acid	affects binding, increases activity, increases expression	4
dorsomorphin	decreases expression, affects cotreatment, increases reaction, increases expression, decreases reaction (+1 more)	4
Resveratrol	decreases reaction, increases expression, affects binding, increases activity, increases chemical synthesis (+1 more)	4
Aspirin	increases expression, affects activity, decreases activity, decreases expression	4
Docosahexaenoic Acids	increases reaction, affects binding, increases activity, affects reaction, decreases reaction (+1 more)	4
Aflatoxin B1	affects expression, decreases expression	4

ChEMBL screening assays

1232 unique, capped per target: 928 binding, 263 functional, 41 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3077605	Binding	Transactivation of GAL4-fused Homo sapiens (human) PPARalpha/PPARgamma DNA binding domain expressed in African green monkey CV1 cells by luciferase reporter gene assay	3D-QSAR study of tyrosine and propanoic acid derivatives as PPAR/ dual agonists using CoMSIA — Med Chem Res
CHEMBL4184538	ADMET	Modulatory activity at PPARalpha/PPARgamma in human primary muscle cells assessed as effect on AKR1B1 gene expression at EC50 measured after 24 hrs	Highly selective peroxisome proliferator-activated receptor δ (PPARδ) modulator demonstrates improved safety profile compared to GW501516. — Bioorg Med Chem Lett
CHEMBL1000234	Functional	Agonist activity at PPARalpha receptor	An innovative method to study target protein-drug interactions by mass spectrometry. — J Med Chem

Cellosaurus cell lines

13 cell lines: 7 cancer cell line, 3 embryonic stem cell, 2 transformed cell line, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A5N4	SEES3-1V human PPARA, clone1	Embryonic stem cell	Male
CVCL_A5N5	SEES3-1V human PPARA, clone2	Embryonic stem cell	Male
CVCL_A5N6	SEES3-1V human PPARA, clone3	Embryonic stem cell	Male
CVCL_B8MV	Abcam HCT 116 PPARA KO	Cancer cell line	Male
CVCL_B9Q4	Abcam A-549 PPARA KO	Cancer cell line	Male
CVCL_D2H0	Abcam MCF-7 PPARA KO	Cancer cell line	Female
CVCL_D7Y2	Ubigene A-549 PPARA KO	Cancer cell line	Male
CVCL_D8TI	Ubigene HCT 116 PPARA KO	Cancer cell line	Male
CVCL_D9P1	Ubigene HEK293 PPARA KO	Transformed cell line	Female
CVCL_E0LD	Ubigene HeLa PPARA KO	Cancer cell line	Female

Clinical trials (associated diseases)

2 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01603758	PHASE1	COMPLETED	Physiological Study of Human Cholesterol Metabolism and Excretion
NCT02854475	Not specified	COMPLETED	Confocal Raman Spectroscopy: in Vivo Measurement of Physiological Skin Parameters