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NR1H4

gene
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Also known as FXRRIP14HRR1HRR-1

Summary

NR1H4 (nuclear receptor subfamily 1 group H member 4, HGNC:7967) is a protein-coding gene on chromosome 12q23.1, encoding Bile acid receptor (Q96RI1). Ligand-activated transcription factor.

This gene encodes a ligand-activated transcription factor that shares structural features in common with nuclear hormone receptor family members. This protein functions as a receptor for bile acids, and when bound to bile acids, binds to DNA and regulates the expression of genes involved in bile acid synthesis and transport. Alternatively spliced transcript variants encoding different isoforms have been described.

Source: NCBI Gene 9971 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): cholestasis, progressive familial intrahepatic, 5 (Strong, GenCC)
  • GWAS associations: 3
  • Clinical variants (ClinVar): 164 total — 7 pathogenic, 7 likely-pathogenic
  • Phenotypes (HPO): 45
  • Druggable target: yes — 41 molecules with ChEMBL bioactivity
  • Transcription factor: yes — 142 downstream targets (CollecTRI)
  • MANE Select transcript: NM_001206979

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:7967
Approved symbolNR1H4
Namenuclear receptor subfamily 1 group H member 4
Location12q23.1
Locus typegene with protein product
StatusApproved
AliasesFXR, RIP14, HRR1, HRR-1
Ensembl geneENSG00000012504
Ensembl biotypeprotein_coding
OMIM603826
Entrez9971

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 22 protein_coding, 2 nonsense_mediated_decay

ENST00000188403, ENST00000321046, ENST00000392986, ENST00000546380, ENST00000548621, ENST00000548884, ENST00000549996, ENST00000551184, ENST00000551379, ENST00000648861, ENST00000649582, ENST00000909398, ENST00000909399, ENST00000909400, ENST00000909401, ENST00000909402, ENST00000909403, ENST00000909404, ENST00000909405, ENST00000909406, ENST00000909407, ENST00000909408, ENST00000909409, ENST00000909410

RefSeq mRNA: 6 — MANE Select: NM_001206979 NM_001206977, NM_001206978, NM_001206979, NM_001206992, NM_001206993, NM_005123

CCDS: CCDS55873, CCDS55874, CCDS55875, CCDS55876, CCDS9078

Canonical transcript exons

ENST00000392986 — 11 exons

ExonStartEnd
ENSE00000753906100510778100511143
ENSE00000753908100534890100535023
ENSE00000753910100536512100536610
ENSE00000818151100493270100493402
ENSE00001242044100532458100532610
ENSE00001388904100492503100492637
ENSE00002394437100563251100564414
ENSE00003463384100536948100537047
ENSE00003484378100561885100561998
ENSE00003676509100540672100540818
ENSE00003848718100473866100474059

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 96.59.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.5209 / max 324.4416, expressed in 82 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter IDTPM avgSamples expressed
1275730.538749
1275740.516653
1275780.258835
1275760.087324
1275750.057423
1275770.049016
2068590.013011

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
right lobe of liverUBERON:000111496.59gold quality
liverUBERON:000210795.48gold quality
ileal mucosaUBERON:000033194.59gold quality
right adrenal glandUBERON:000123391.34gold quality
right adrenal gland cortexUBERON:003582791.25gold quality
oocyteCL:000002390.74gold quality
adrenal tissueUBERON:001830390.24gold quality
left adrenal glandUBERON:000123490.08gold quality
left adrenal gland cortexUBERON:003582589.62gold quality
adrenal cortexUBERON:000123588.81gold quality
adrenal glandUBERON:000236988.37gold quality
jejunal mucosaUBERON:000039988.08gold quality
duodenumUBERON:000211487.95gold quality
secondary oocyteCL:000065587.53gold quality
small intestine Peyer’s patchUBERON:000345486.31gold quality
mucosa of transverse colonUBERON:000499186.28gold quality
adult mammalian kidneyUBERON:000008285.83gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099184.79gold quality
nephron tubuleUBERON:000123184.61gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047384.32gold quality
small intestineUBERON:000210884.12gold quality
gall bladderUBERON:000211083.74gold quality
kidneyUBERON:000211382.23gold quality
metanephros cortexUBERON:001053382.13gold quality
kidney epitheliumUBERON:000481980.18gold quality
metanephrosUBERON:000008178.25gold quality
left ovaryUBERON:000211977.85gold quality
cortex of kidneyUBERON:000122576.62gold quality
renal glomerulusUBERON:000007475.75gold quality
ovaryUBERON:000099275.72gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

ExperimentMarker?Max mean expression
E-GEOD-125970yes18.03
E-ANND-3yes5.70

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

142 targets.

TargetRegulation
ABCA1Activation
ABCB1
ABCB11Unknown
ABCB4Activation
ABCC2
ABCC3
ABCC4Repression
ABCG5
ACACARepression
ACTG2Repression
ADAM2
ADH4
AGTR2Unknown
AKR1B15
AKR1C2Unknown
ALAS1Activation
APOA1
APOA5Activation
APOC2
APOC3Repression
APOE
APOF
AQP2
ATP5F1A
ATP8B1
C3Activation
CACNA1A
CARM1
CCL2Activation
CCND1Activation

JASPAR motifs

MotifNameFamily
MA1110.1NR1H4Thyroid hormone receptor-related factors (NR1)
MA1146.1NR1H4::RXRAThyroid hormone receptor-related factors (NR1)::RXR-related receptors (NR2)
MA1146.2NR1H4::RXRAThyroid hormone receptor-related factors (NR1)::RXR-related receptors (NR2)

JASPAR matrix evidence (PMIDs): PMID:24498423, PMID:10744760

Upstream regulators (CollecTRI, top): BHLHE40, BHLHE41, EP300, GLI1, HNF1A, HNF4A, IRF6, IRF7, NR0B1, STAT1, YY1

miRNA regulators (miRDB)

31 targeting NR1H4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-3163100.0077.238605
HSA-MIR-4776-3P100.0068.731340
HSA-MIR-137-3P99.8774.742401
HSA-MIR-451799.7669.191867
HSA-MIR-4446-5P99.7269.192544
HSA-MIR-4699-3P99.7170.153142
HSA-MIR-46699.6770.852863
HSA-MIR-80299.6167.701254
HSA-MIR-6832-5P99.5864.821132
HSA-MIR-1252-3P99.5567.712862
HSA-MIR-1212399.5271.792990
HSA-MIR-464399.4967.631791
HSA-MIR-582-5P99.4770.792635
HSA-MIR-6882-5P99.3571.131206
HSA-MIR-499A-3P99.1869.201392
HSA-MIR-499B-3P99.1869.271391
HSA-MIR-5583-3P99.0665.681018
HSA-MIR-10B-3P99.0466.98988
HSA-MIR-42198.9067.041883
HSA-MIR-548AO-5P98.5569.571362
HSA-MIR-548AX98.5569.581362
HSA-MIR-4712-3P98.5265.39822
HSA-MIR-3190-3P97.6166.951406
HSA-MIR-192-3P97.5267.661001
HSA-MIR-6501-5P97.4168.24712
HSA-MIR-526B-5P97.4167.991074
HSA-MIR-1225-5P96.7666.85417
HSA-MIR-313996.6866.77652
HSA-MIR-6861-5P96.2367.19800
HSA-MIR-28-5P96.1666.12579

Literature-anchored findings (GeneRIF, showing 40)

  • Amino acids asparagine 354 and isoleucine 372 of Farnesoid X activated receptor are critical to its function (PMID:12004058)
  • These results provide molecular evidence for a cross-talk between the FXR and PPARalpha pathways in humans. (PMID:12554753)
  • role in regulating syndecan-1 expression (PMID:12660231)
  • FXR regulates bile acid amidation, a critical component of the enterohepatic circulation of bile acids (PMID:12754200)
  • kininogen is a novel and direct target of farnesoid X receptor (PMID:12761213)
  • Farnesoid X receptor (FXR) induces the UGT2B4 enzyme in hepatocytes; this study identifies UGT2B4 as a novel FXR target gene. (PMID:12806625)
  • demonstrated that FGF-19, acting as an FXR-induced signaling molecule, represses expression of the CYP7A1 gene; this signaling cascade defines a novel mechanism for feedback repression of bile acid biosynthesis (PMID:12815072)
  • bile acid and synthetic activators of the nuclear FXR as negative regulators of Apo CIII expression. (PMID:12891557)
  • MDR3 expression is directly up-regulated by FXR in primary human hepatocytes (PMID:14527955)
  • the existence of an auto-regulatory loop in FXR signaling pathways: the binding of each bile acid results in a different FXR conformations, which in turn differentially regulates expression of individual FXR targets (PMID:14684751)
  • Loss of familial intrahepatic cholestasis-1 leads to diminished nuclear translocation of FXR, with subsequent potential for pathologic alterations in intestinal and hepatic bile acid transporter expression. (PMID:14988830)
  • FXR is expressed in a variety of normal and pathological human tissue (PMID:14990788)
  • FXR is activated by DRIP205, which modulates the bile acid response of its target genes (PMID:15187081)
  • PGC-1alpha mediates the ligand-dependent activation of FXR and transcription of SHP gene. (PMID:15202934)
  • Hepatic down-regulation of Farnesoid X receptor contributes to severety of familial intrahepatic cholestasis. (PMID:15317749)
  • FXR has a central role in lipid homeostasis (PMID:15342685)
  • presence of two functional FXR recognition sites located in a 345-bp element within the 5’-flanking region of CYP3A4 (PMID:15454728)
  • studies provide evidence that farnesoid X-receptor(FXR) directly recruits specific chromatin modifying activity of co-activator-associated arginine methyltransferase 1 (CARM1) necessary for full potentiation of bile salt export pump (BSEP) locus in vivo (PMID:15471871)
  • farnesoid X receptor regulates carbohydrate metabolism (PMID:15564327)
  • the coordinate regulation of FXR target genes is lost in cerebrotendinous xanthomatosis (PMID:15576845)
  • complement C3 expression is regulated by the bile acid receptor FXR (PMID:15590640)
  • The FXR isoforms were recently identified that differ either at their N termini and/or by the presence of four amino acids in the hinge region. (PMID:15604525)
  • activation of FXR may suppress glycolysis and enhance oxidation of fatty acids via inactivation of the pyruvate dehydrogenase complex by increasing PDK4 expression (PMID:15721319)
  • FXR-mediated activation of ICAM-1 could be further enhanced by TNF-alpha cotreatment in hepatocytes (PMID:15817812)
  • Induction of alpha A crystallin expression in response to bile acid-activated FXR contributes to cellular defense against bile acid-induced hepatotoxicity (PMID:16012168)
  • FXR agonists may increase gallbladder fluid secretion through transcriptional activation of VPAC1. (PMID:16037943)
  • These results show that the stimulation of ASCT2 expression in response to glutamine in part involves binding of FXR/RXR to the ASCT2 promoter. (PMID:16197915)
  • overexpression of human OSTalpha and OSTbeta facilitated the uptake of conjugated chenodeoxycholate and the activation of FXR target genes (PMID:16251721)
  • OSTalpha/OSTbeta expression is induced by bile acids through ligand-dependent transactivation of both OST genes by the nuclear bile acid receptor/farnesoid X receptor (FXR). (PMID:16269519)
  • These results indicate that expression of Ostalpha and Ostbeta are highly regulated in response to cholestasis and that this response is dependent on the FXR bile acid receptor. (PMID:16423920)
  • FXR is a potential therapeutic target for the treatment and prevention of numerous metabolic and lipid-related diseases (PMID:16460270)
  • The results obtained using truncated PGC-1alpha proteins suggested that two regions are necessary for PGC-1alpha to interact with the DNA-binding complex of RXRalpha/FXR. (PMID:16494845)
  • Taken together, these results suggest that activation of FXR plays a critical role in regulating adipogenesis and insulin signaling. (PMID:16778009)
  • The farnesoid X receptor (FXR) was detected in normal and tumor breast tissue, with a high level of expression in ductal epithelial cells of normal breast and infiltrating ductal carcinoma cells. (PMID:17047076)
  • The bile acid receptor FXR is significantly overexpressed in Barrett’s esophagus compared to normal mucosa, esophagitis and esophageal adenocarcinoma. (PMID:17054793)
  • an SP2/KLF6 repression complex by SHP is required for farnesoid X receptor-induced endothelial cell migration (PMID:17071613)
  • The use of human liver slices in nuclear receptor metabolism research is reported; the farnesoid X receptor system was chosen as a model. (PMID:17241392)
  • FXR is expressed in breast cancer interacts with ER (PMID:17333335)
  • farnesoid X receptor exerts metabolic control beyond bile acid homeostasis, notably effects on HDL, triglyceride and glucose metabolism [review] (PMID:17495603)
  • analysis of the 5’-flanking region of human FXR gene in HepG2 cells (PMID:17507182)

Cross-species orthologs

184 orthologs

OrganismSymbolGene ID
danio_rerionr1h4ENSDARG00000057741
mus_musculusNr1h4ENSMUSG00000047638
rattus_norvegicusNr1h4ENSRNOG00000007197
drosophila_melanogasterHr96FBGN0015240
caenorhabditis_elegansWBGENE00001062
caenorhabditis_elegansWBGENE00003608
caenorhabditis_elegansWBGENE00003611
caenorhabditis_elegansWBGENE00003614
caenorhabditis_elegansWBGENE00003615
caenorhabditis_elegansWBGENE00003617
caenorhabditis_elegansWBGENE00003618
caenorhabditis_elegansWBGENE00003620
caenorhabditis_elegansWBGENE00003624
caenorhabditis_elegansWBGENE00003632
caenorhabditis_elegansWBGENE00003634
caenorhabditis_elegansWBGENE00003638
caenorhabditis_elegansWBGENE00003640
caenorhabditis_elegansWBGENE00003641
caenorhabditis_elegansWBGENE00003642
caenorhabditis_elegansWBGENE00003643
caenorhabditis_elegansWBGENE00003644
caenorhabditis_elegansWBGENE00003645
caenorhabditis_elegansWBGENE00003646
caenorhabditis_elegansWBGENE00003648
caenorhabditis_elegansWBGENE00003649
caenorhabditis_elegansWBGENE00003651
caenorhabditis_elegansWBGENE00003653
caenorhabditis_elegansWBGENE00003655
caenorhabditis_elegansWBGENE00003658
caenorhabditis_elegansWBGENE00003660
caenorhabditis_elegansWBGENE00003662
caenorhabditis_elegansnhr-73WBGENE00003663
caenorhabditis_elegansnhr-77WBGENE00003667
caenorhabditis_elegansWBGENE00003669
caenorhabditis_elegansnhr-81WBGENE00003671
caenorhabditis_elegansnhr-82WBGENE00003672
caenorhabditis_elegansWBGENE00003676
caenorhabditis_elegansWBGENE00003677
caenorhabditis_elegansWBGENE00003680
caenorhabditis_elegansWBGENE00003682
caenorhabditis_elegansWBGENE00003684
caenorhabditis_elegansWBGENE00003685
caenorhabditis_elegansWBGENE00003686
caenorhabditis_elegansWBGENE00003688
caenorhabditis_elegansWBGENE00003689
caenorhabditis_elegansWBGENE00003692
caenorhabditis_elegansWBGENE00003693
caenorhabditis_elegansWBGENE00003694
caenorhabditis_elegansWBGENE00003696
caenorhabditis_elegansWBGENE00003698
caenorhabditis_elegansWBGENE00003699
caenorhabditis_elegansWBGENE00003700
caenorhabditis_elegansWBGENE00003702
caenorhabditis_elegansWBGENE00003704
caenorhabditis_elegansWBGENE00003705
caenorhabditis_elegansWBGENE00003707
caenorhabditis_elegansWBGENE00003708
caenorhabditis_elegansWBGENE00003712
caenorhabditis_elegansWBGENE00003713
caenorhabditis_elegansWBGENE00003714
caenorhabditis_elegansWBGENE00003715
caenorhabditis_elegansWBGENE00003716
caenorhabditis_elegansWBGENE00003717
caenorhabditis_elegansWBGENE00003718
caenorhabditis_elegansWBGENE00003720
caenorhabditis_elegansWBGENE00003721
caenorhabditis_elegansWBGENE00003722
caenorhabditis_elegansWBGENE00003723
caenorhabditis_elegansWBGENE00003724
caenorhabditis_elegansWBGENE00003725
caenorhabditis_elegansWBGENE00003728
caenorhabditis_elegansWBGENE00006471
caenorhabditis_elegansunc-55WBGENE00006790
caenorhabditis_elegansWBGENE00007367
caenorhabditis_elegansWBGENE00008056
caenorhabditis_elegansnhr-165WBGENE00008158
caenorhabditis_elegansWBGENE00008208
caenorhabditis_elegansnhr-169WBGENE00008289
caenorhabditis_elegansWBGENE00008309
caenorhabditis_elegansnhr-174WBGENE00008474
caenorhabditis_elegansWBGENE00008619
caenorhabditis_elegansWBGENE00008630
caenorhabditis_elegansWBGENE00008778
caenorhabditis_elegansWBGENE00008830
caenorhabditis_elegansWBGENE00008884
caenorhabditis_elegansWBGENE00008901
caenorhabditis_elegansnhr-265WBGENE00009608
caenorhabditis_elegansWBGENE00010017
caenorhabditis_elegansWBGENE00010180
caenorhabditis_elegansWBGENE00010186
caenorhabditis_elegansWBGENE00010215
caenorhabditis_elegansWBGENE00010410
caenorhabditis_elegansWBGENE00010600
caenorhabditis_elegansWBGENE00010601
caenorhabditis_elegansWBGENE00010602
caenorhabditis_elegansWBGENE00010603
caenorhabditis_elegansWBGENE00010604
caenorhabditis_elegansWBGENE00011002
caenorhabditis_elegansWBGENE00011150
caenorhabditis_elegansWBGENE00011396
caenorhabditis_elegansWBGENE00011520
caenorhabditis_elegansWBGENE00011565
caenorhabditis_elegansWBGENE00011566
caenorhabditis_elegansWBGENE00011568
caenorhabditis_elegansnhr-217WBGENE00011651
caenorhabditis_elegansWBGENE00011750
caenorhabditis_elegansWBGENE00012050
caenorhabditis_elegansWBGENE00012056
caenorhabditis_elegansWBGENE00012446
caenorhabditis_elegansWBGENE00012449
caenorhabditis_elegansWBGENE00012596
caenorhabditis_elegansWBGENE00012703
caenorhabditis_elegansWBGENE00013067
caenorhabditis_elegansWBGENE00013483
caenorhabditis_elegansnhr-276WBGENE00013512
caenorhabditis_elegansWBGENE00013584
caenorhabditis_elegansWBGENE00013940
caenorhabditis_elegansWBGENE00014068
caenorhabditis_elegansnhr-245WBGENE00014189
caenorhabditis_elegansWBGENE00014193
caenorhabditis_elegansWBGENE00015497
caenorhabditis_elegansWBGENE00015758
caenorhabditis_elegansWBGENE00015897
caenorhabditis_elegansWBGENE00015900
caenorhabditis_elegansWBGENE00015901
caenorhabditis_elegansWBGENE00015902
caenorhabditis_elegansWBGENE00016091
caenorhabditis_elegansWBGENE00016233
caenorhabditis_elegansWBGENE00016364
caenorhabditis_elegansWBGENE00016365
caenorhabditis_elegansWBGENE00016366
caenorhabditis_elegansWBGENE00016367
caenorhabditis_elegansWBGENE00016368
caenorhabditis_elegansWBGENE00016517
caenorhabditis_elegansWBGENE00016772
caenorhabditis_elegansWBGENE00016926
caenorhabditis_elegansWBGENE00016927
caenorhabditis_elegansWBGENE00017503
caenorhabditis_elegansWBGENE00017512
caenorhabditis_elegansWBGENE00017961
caenorhabditis_elegansWBGENE00018189
caenorhabditis_elegansWBGENE00018265
caenorhabditis_elegansWBGENE00018266
caenorhabditis_elegansWBGENE00018404
caenorhabditis_elegansWBGENE00018412
caenorhabditis_elegansWBGENE00018415
caenorhabditis_elegansWBGENE00018539
caenorhabditis_elegansWBGENE00018541
caenorhabditis_elegansWBGENE00018542
caenorhabditis_elegansWBGENE00018544
caenorhabditis_elegansWBGENE00018545
caenorhabditis_elegansWBGENE00018622
caenorhabditis_elegansWBGENE00019115
caenorhabditis_elegansWBGENE00019116
caenorhabditis_elegansWBGENE00019741
caenorhabditis_elegansWBGENE00019742
caenorhabditis_elegansWBGENE00019743
caenorhabditis_elegansWBGENE00020015
caenorhabditis_elegansWBGENE00020062
caenorhabditis_elegansWBGENE00020152
caenorhabditis_elegansWBGENE00020153
caenorhabditis_elegansWBGENE00020385
caenorhabditis_elegansWBGENE00020460
caenorhabditis_elegansWBGENE00020555
caenorhabditis_elegansWBGENE00020750
caenorhabditis_elegansWBGENE00020849
caenorhabditis_elegansWBGENE00020850
caenorhabditis_elegansWBGENE00020851
caenorhabditis_elegansWBGENE00020852
caenorhabditis_elegansWBGENE00021163
caenorhabditis_elegansWBGENE00021522
caenorhabditis_elegansWBGENE00021610
caenorhabditis_elegansWBGENE00021611
caenorhabditis_elegansWBGENE00021617
caenorhabditis_elegansWBGENE00022097
caenorhabditis_elegansWBGENE00022637
caenorhabditis_elegansWBGENE00022639
caenorhabditis_elegansWBGENE00022640
caenorhabditis_elegansWBGENE00022726
caenorhabditis_elegansWBGENE00022756
caenorhabditis_elegansWBGENE00022805
caenorhabditis_elegansWBGENE00044353
caenorhabditis_elegansWBGENE00044699
caenorhabditis_elegansWBGENE00045515

Paralogs (18): 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), PPARA (ENSG00000186951), RORB (ENSG00000198963)

Protein

Protein identifiers

Bile acid receptor — Q96RI1 (reviewed: Q96RI1)

Alternative names: Farnesoid X-activated receptor, Farnesol receptor HRR-1, Nuclear receptor subfamily 1 group H member 4, Retinoid X receptor-interacting protein 14

All UniProt accessions (7): Q96RI1, B6ZGS9, F1DAL1, F8W1M1, F8W656, G8JLB0, H0YHD5

UniProt curated annotations — full annotation on UniProt →

Function. Ligand-activated transcription factor. Receptor for bile acids (BAs) such as chenodeoxycholic acid (CDCA), lithocholic acid, deoxycholic acid (DCA) and allocholic acid (ACA). Plays a essential role in BA homeostasis through the regulation of genes involved in BA synthesis, conjugation and enterohepatic circulation. Also regulates lipid and glucose homeostasis and is involved innate immune response. The FXR-RXR heterodimer binds predominantly to farnesoid X receptor response elements (FXREs) containing two inverted repeats of the consensus sequence 5’-AGGTCA-3’ in which the monomers are spaced by 1 nucleotide (IR-1) but also to tandem repeat DR1 sites with lower affinity, and can be activated by either FXR or RXR-specific ligands. It is proposed that monomeric nuclear receptors such as NR5A2/LRH-1 bound to coregulatory nuclear responsive element (NRE) halfsites located in close proximity to FXREs modulate transcriptional activity. In the liver activates transcription of the corepressor NR0B2 thereby indirectly inhibiting CYP7A1 and CYP8B1 (involved in BA synthesis) implicating at least in part histone demethylase KDM1A resulting in epigenomic repression, and SLC10A1/NTCP (involved in hepatic uptake of conjugated BAs). Activates transcription of the repressor MAFG (involved in regulation of BA synthesis). Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine). Activates transcription of SLC27A5/BACS and BAAT (involved in BA conjugation), ABCB11/BSEP (involved in bile salt export) by directly recruiting histone methyltransferase CARM1, and ABCC2/MRP2 (involved in secretion of conjugated BAs) and ABCB4 (involved in secretion of phosphatidylcholine in the small intestine). In the intestine activates FGF19 expression and secretion leading to hepatic CYP7A1 repression. The function also involves the coordinated induction of hepatic KLB/beta-klotho expression. Regulates transcription of liver UGT2B4 and SULT2A1 involved in BA detoxification; binding to the UGT2B4 promoter seems to imply a monomeric transactivation independent of RXRA. Modulates lipid homeostasis by activating liver NR0B2/SHP-mediated repression of SREBF1 (involved in de novo lipogenesis), expression of PLTP (involved in HDL formation), SCARB1 (involved in HDL hepatic uptake), APOE, APOC1, APOC4, PPARA (involved in beta-oxidation of fatty acids), VLDLR and SDC1 (involved in the hepatic uptake of LDL and IDL remnants), and inhibiting expression of MTTP (involved in VLDL assembly. Increases expression of APOC2 (promoting lipoprotein lipase activity implicated in triglyceride clearance). Transrepresses APOA1 involving a monomeric competition with NR2A1 for binding to a DR1 element. Also reduces triglyceride clearance by inhibiting expression of ANGPTL3 and APOC3 (both involved in inhibition of lipoprotein lipase). Involved in glucose homeostasis by modulating hepatic gluconeogenesis through activation of NR0B2/SHP-mediated repression of respective genes. Modulates glycogen synthesis (inducing phosphorylation of glycogen synthase kinase-3). Modulates glucose-stimulated insulin secretion and is involved in insulin resistance. Involved in intestinal innate immunity. Plays a role in protecting the distal small intestine against bacterial overgrowth and preservation of the epithelial barrier. Down-regulates inflammatory cytokine expression in several types of immune cells including macrophages and mononuclear cells. Mediates trans-repression of TLR4-induced cytokine expression; the function seems to require its sumoylation and prevents N-CoR nuclear receptor corepressor clearance from target genes such as IL1B and NOS2. Involved in the TLR9-mediated protective mechanism in intestinal inflammation. Plays an anti-inflammatory role in liver inflammation; proposed to inhibit pro-inflammatory (but not antiapoptotic) NF-kappa-B signaling). Promotes transcriptional activation of target genes NR0B2/SHP (inducible by unconjugated CDCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; low activity for ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA); not inducible by taurine- and glycine-amidated CDCA. Promotes transcriptional activation of target genes ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA), NR0B2/SHP (inducible by unconjugated CDCA DCA and ACA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; not inducible by taurine- and glycine-amidated CDCA. Promotes transcriptional activation of target genes NR0B2/SHP (inducible by unconjugated CDCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and IBAP; low activity for ABCB11/BSEP (inducible by unconjugated CDCA, DCA and ACA); not inducible by taurine- and glycine-amidated CDCA. Promotes transcriptional activation of target genes ABCB11/BSEP (inducible by unconjugated CDCA, ACA and DCA), NR0B2/SHP (inducible by unconjugated CDCA, ACA and DCA), SLC51B/OSTB (inducible by unconjugated CDCA and DCA) and FABP6/IBAP; most efficient isoform compared to isoforms 1 to 3; not inducible by taurine- and glycine-amidated CDCA.

Subunit / interactions. Heterodimer (via C-terminus) with RXRA (via DBD); the heterodimerization enhances the binding affinity for LXXLL motifs from coactivators. Binds DNA predominantly as a heterodimer with RXRA. After activation by agonist binding interacts with coactivators. Interacts with NCOA1, NCOA2, PPARGC1A, CARM1, SETD7, PRMT1, GPS2, SMARCA4 and MED1. Interacts with EP300 and SMARCD1. Interacts with XRCC5 and XRCC6; decreasing NR1H4/FXR transactivation activity towards ABCB11/BSEP. Interacts with PAGR1 and NCOA6; indicative for an association with an MLL2/MLL3 complex (ASCOM).

Subcellular location. Nucleus Nucleus Nucleus Nucleus Nucleus.

Tissue specificity. Liver and hepatocyte-related cells express mainly FXRalpha1-type isoforms with isoform 3 and isoform 4 in approximately equal proportions. In intestine and kidney mainly FXRalpha2-type isoforms are expressed with isoform 1 and isoform 2 in approximately equal proportions. Expressed in pancreatic beta cells and macrophages.

Post-translational modifications. Acetylated by EP300. Lys-227 as is the major acetylation site for EP300; the dynamicly regulated acetylation inhibits heterodimerization with RXRA and transactivation activity. Deacetylated by SIRT1. Methylation may increase transactivation of target genes. Phosphorylation by PKC/PRKCA increases transactivation activity by promoting association with PPARGC1A. Sumoylated upon ligand binding.

Disease relevance. May be involved in intrahepatic cholestasis of pregnancy. May be involved in cholesterol cholelithiasis. Cholestasis, progressive familial intrahepatic, 5 (PFIC5) [MIM:617049] A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. PFIC5 is an autosomal recessive, severe form characterized by onset of intralobular cholestasis in the neonatal period. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Ursodeoxycholic acid (UDCA), a natural agonist of FXR, is approved to treat primary biliary cirrhosis. However, effects are discussed controversial. UDCA is also used to dissolve (cholesterol) gallstones as alternative to surgery. Produced by alternative promoter usage. Produced by alternative splicing of isoform 1. Produced by alternative promoter usage. Produced by alternative splicing of isoform 3. Produced by alternative splicing of isoform 3.

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

Isoforms (5)

UniProt IDNamesCanonical?
Q96RI1-31, FXRalpha2(+), FXRalpha1, FXRbeta1yes
Q96RI1-42, FXRalpha2(-), FXRalpha4, FXRbeta2
Q96RI1-13, FXRalpha1(+), FXRalpha1
Q96RI1-24, FXRalpha1(-), FXRalpha2
Q96RI1-55

RefSeq proteins (6): NP_001193906, NP_001193907, NP_001193908, NP_001193921, NP_001193922, NP_005114 (=MANE)

Domains & families (InterPro)

IDNameType
IPR000536Nucl_hrmn_rcpt_lig-bdDomain
IPR001628Znf_hrmn_rcptDomain
IPR001723Nuclear_hrmn_rcptFamily
IPR001728ThyrH_rcptFamily
IPR013088Znf_NHR/GATAHomologous_superfamily
IPR035500NHR-like_dom_sfHomologous_superfamily
IPR044114NR_LBD_NR1H4Domain
IPR050234Nuclear_hormone_rcpt_NR1Family

Pfam: PF00104, PF00105

UniProt features (60 total): helix 15, mutagenesis site 13, modified residue 6, strand 6, binding site 4, splice variant 3, turn 3, cross-link 2, zinc finger region 2, sequence conflict 2, chain 1, domain 1, DNA-binding region 1, sequence variant 1

Structure

Experimental structures (PDB)

89 structures, top 30 by resolution.

PDBMethodResolution (Å)
6HL1X-RAY DIFFRACTION1.6
6HL0X-RAY DIFFRACTION1.66
4OIVX-RAY DIFFRACTION1.7
5Q0IX-RAY DIFFRACTION1.7
1OSHX-RAY DIFFRACTION1.8
5Q0KX-RAY DIFFRACTION1.8
5Q0PX-RAY DIFFRACTION1.8
5Q14X-RAY DIFFRACTION1.85
5Q1EX-RAY DIFFRACTION1.85
5Q0VX-RAY DIFFRACTION1.87
5Q1DX-RAY DIFFRACTION1.89
3BEJX-RAY DIFFRACTION1.9
3L1BX-RAY DIFFRACTION1.9
3OLFX-RAY DIFFRACTION1.9
3OMKX-RAY DIFFRACTION1.9
5Q0OX-RAY DIFFRACTION1.9
5Q0UX-RAY DIFFRACTION1.9
5Q0WX-RAY DIFFRACTION1.9
5Q13X-RAY DIFFRACTION1.9
5Q15X-RAY DIFFRACTION1.9
5Q18X-RAY DIFFRACTION1.9
5Q0RX-RAY DIFFRACTION1.91
5Q1IX-RAY DIFFRACTION1.95
5Q19X-RAY DIFFRACTION1.98
3FLIX-RAY DIFFRACTION2
3OKIX-RAY DIFFRACTION2
5Q0JX-RAY DIFFRACTION2
5Q12X-RAY DIFFRACTION2
5Q16X-RAY DIFFRACTION2
5Q1AX-RAY DIFFRACTION2

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q96RI1-F169.160.36

Functional residue map

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

Ligand- & substrate-binding residues (4): 345; 375; 383; 461

Post-translational modifications (8): 164, 167, 220, 227, 456, 132, 289, 145

Mutagenesis-validated functional residues (13):

PositionPhenotype
132abrogates sumo1-mediated inhibition of ligand-induced transcactivation at abcb11/bsep and nr0b2/shp promoters; when asso
132decreases transcriptional activation slc51a/osta, slc51b/ostb and abcb11/bsep, no effect on interaction with rxra and se
145impairs ligand-dependent transactivation activity, impairs interaction with ppargc1a; when associated with a-164.
164impairs ligand-dependent transactivation activity, impairs interaction with ppargc1a; when associated with a-145.
167decreases transcriptional activation of slc51b/ostb, no effect on slc51a/osta and abcb11/bsep, no effect on interaction
220decreases transcriptional activation of slc51b/ostb, no effect on slc51a/osta and abcb11/bsep, impairs interaction with
227decreases transcriptional activation sc51a/osta, slc51b/ostb and abcb11/bsep, impairs interaction with rxra and enhances
289abrogates sumo1-mediated inhibition of ligand-induced transcactivation at abcb11/bsep and nr0b2/shp promoters; when asso
291abrogates sumo1-mediated inhibition of ligand-induced transcactivation at abcb11/bsep and nr0b2/shp promoters; when asso
353decreases transcriptional activation slc51a/osta, slc51b/ostb and abcb11/bsep, no effect on interaction with rxra and se
455as a heterodimer with rxra, impaired transcriptional activity.
456impairs transcriptional activation of abcb11/bsep.
474decreases transcriptional activation slc51a/osta, slc51b/ostb and abcb11/bsep, no effect on interaction with rxra and im

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

IDPathway
R-HSA-159418Recycling of bile acids and salts
R-HSA-192105Synthesis of bile acids and bile salts
R-HSA-193368Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
R-HSA-193807Synthesis of bile acids and bile salts via 27-hydroxycholesterol
R-HSA-1989781PPARA activates gene expression
R-HSA-211976Endogenous sterols
R-HSA-383280Nuclear Receptor transcription pathway
R-HSA-4090294SUMOylation of intracellular receptors

MSigDB gene sets: 453 (showing top): GOBP_ACYLGLYCEROL_HOMEOSTASIS, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_STEROL_HOMEOSTASIS, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_TOLL_LIKE_RECEPTOR_9_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_INSULIN_SECRETION, GOBP_GLUTAMATE_METABOLIC_PROCESS, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION

GO Biological Process (53): negative regulation of transcription by RNA polymerase II (GO:0000122), intracellular glucose homeostasis (GO:0001678), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), inflammatory response (GO:0006954), cell-cell junction assembly (GO:0007043), Notch signaling pathway (GO:0007219), bile acid metabolic process (GO:0008206), negative regulation of tumor necrosis factor-mediated signaling pathway (GO:0010804), negative regulation of very-low-density lipoprotein particle remodeling (GO:0010903), regulation of low-density lipoprotein particle clearance (GO:0010988), bile acid and bile salt transport (GO:0015721), cell differentiation (GO:0030154), intracellular receptor signaling pathway (GO:0030522), negative regulation of type II interferon production (GO:0032689), negative regulation of interleukin-1 production (GO:0032692), negative regulation of interleukin-2 production (GO:0032703), negative regulation of interleukin-6 production (GO:0032715), negative regulation of tumor necrosis factor production (GO:0032720), positive regulation of interleukin-17 production (GO:0032740), toll-like receptor 9 signaling pathway (GO:0034162), obsolete regulation of urea metabolic process (GO:0034255), intracellular triglyceride homeostasis (GO:0035356), positive regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0035774), nuclear receptor-mediated bile acid signaling pathway (GO:0038185), cholesterol homeostasis (GO:0042632), defense response to bacterium (GO:0042742), negative regulation of apoptotic process (GO:0043066), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), innate immune response (GO:0045087), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of insulin receptor signaling pathway (GO:0046628), negative regulation of inflammatory response (GO:0050728), fatty acid homeostasis (GO:0055089), regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0061178), regulation of bile acid biosynthetic process (GO:0070857), cellular response to lipopolysaccharide (GO:0071222), cellular response to fatty acid (GO:0071398)

GO Molecular Function (18): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), transcription coregulator binding (GO:0001221), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), nuclear receptor activity (GO:0004879), zinc ion binding (GO:0008270), nuclear receptor binding (GO:0016922), bile acid binding (GO:0032052), bile acid nuclear receptor activity (GO:0038186), sequence-specific DNA binding (GO:0043565), nuclear retinoid X receptor binding (GO:0046965), chenodeoxycholic acid binding (GO:1902122), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (9): chromatin (GO:0000785), euchromatin (GO:0000791), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), nuclear speck (GO:0016607), signaling receptor complex (GO:0043235), RNA polymerase II transcription regulator complex (GO:0090575), ciliary tip (GO:0097542)

Reactome top-level categories

Rollup of top-6 pathways:

CategoryPathways
Bile acid and bile salt metabolism2
Synthesis of bile acids and bile salts2
Regulation of lipid metabolism by PPARalpha1
Cytochrome P450 - arranged by substrate type1
Generic Transcription Pathway1
SUMO E3 ligases SUMOylate target proteins1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
negative regulation of cytokine production4
cellular anatomical structure4
RNA polymerase II transcription regulatory region sequence-specific DNA binding3
regulation of transcription by RNA polymerase II2
transcription by RNA polymerase II2
DNA-templated transcription2
regulation of DNA-templated transcription2
transcription cis-regulatory region binding2
chromatin2
DNA-binding transcription factor activity, RNA polymerase II-specific2
bile acid binding2
negative regulation of DNA-templated transcription1
glucose homeostasis1
intracellular chemical homeostasis1
regulation of gene expression1
regulation of RNA biosynthetic process1
defense response1
cell junction assembly1
cell-cell junction organization1
cell surface receptor signaling pathway1
steroid metabolic process1
monocarboxylic acid metabolic process1
negative regulation of cytokine-mediated signaling pathway1
regulation of tumor necrosis factor-mediated signaling pathway1
tumor necrosis factor-mediated signaling pathway1
regulation of very-low-density lipoprotein particle remodeling1
very-low-density lipoprotein particle remodeling1
negative regulation of cellular component organization1
negative regulation of multicellular organismal process1
regulation of lipoprotein particle clearance1
low-density lipoprotein particle clearance1
lipid transport1
monocarboxylic acid transport1
organic hydroxy compound transport1
cellular developmental process1
intracellular signal transduction1
type II interferon production1
regulation of type II interferon production1
interleukin-1 production1
regulation of interleukin-1 production1

Protein interactions and networks

STRING

2984 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
NR1H4GPBAR1Q8TDU6992
NR1H4XPR1Q9UBH6990
NR1H4RXRAP19793988
NR1H4NR0B2Q15466981
NR1H4CYP7A1P22680975
NR1H4ABCB11O95342944
NR1H4SLC10A2Q12908903
NR1H4CYP7B1O75881877
NR1H4FABP6P51161866
NR1H4SLC10A1Q14973861
NR1H4ATP8B1O43520846
NR1H4CYP8B1Q9UNU6845
NR1H4ABCG5Q9H222841
NR1H4SREBF1P36956835
NR1H4CYP27A1Q02318830
NR1H4FGFR4P22455830

IntAct

63 interactions, top by confidence:

ABTypeScore
NR1H4SETD7psi-mi:“MI:0213”(methylation reaction)0.630
NR1H4SETD7psi-mi:“MI:0915”(physical association)0.630
NCOA1psi-mi:“MI:0407”(direct interaction)0.620
NCOA1NR1H4psi-mi:“MI:0407”(direct interaction)0.560
NR1H4NCOA1psi-mi:“MI:0407”(direct interaction)0.560
NR1H4FGF19psi-mi:“MI:0914”(association)0.530
RXRApsi-mi:“MI:0915”(physical association)0.520
NR1H4PHF2psi-mi:“MI:0914”(association)0.520
NR1H4PHF2psi-mi:“MI:0407”(direct interaction)0.520
NCOA1psi-mi:“MI:0407”(direct interaction)0.440

BioGRID (47): SUMO1 (Affinity Capture-Western), NR1H4 (Affinity Capture-Western), NR1H4 (Reconstituted Complex), RXRB (Affinity Capture-MS), NR1H4 (Two-hybrid), NCOA1 (Two-hybrid), NR1H4 (Reconstituted Complex), NR1H4 (Affinity Capture-Western), NR1H4 (Reconstituted Complex), NR1H4 (Affinity Capture-MS), RXRG (Two-hybrid), RXRB (Two-hybrid), RXRA (Two-hybrid), NR1H4 (Reconstituted Complex), NR1H4 (Reconstituted Complex)

ESM2 similar proteins: A0JMR6, A1A4L6, A1YG61, A2T737, O70273, O75747, P01105, P10157, P11308, P13474, P14921, P15036, P15037, P15062, P18755, P19102, P26323, P27577, P41156, P41157, P41212, P57782, P81270, P97360, Q08AW4, Q15052, Q32LN0, Q3SZL0, Q3US16, Q58DT0, Q60641, Q6GPJ8, Q6P3D7, Q7ZYI3, Q8BZ05, Q8C7R7, Q8HWS3, Q8N8B7, Q8NDB2, Q8VDK3

Diamond homologs: A0JNE3, A2T928, A4IIG7, G5ECR9, G5EDJ0, O02151, O45666, O76202, O97716, P10276, P10588, P10826, P10827, P10828, P11416, P12813, P13056, P13631, P16376, P18117, P18514, P18515, P18516, P18911, P20153, P22448, P22449, P22605, P22736, P22829, P28699, P31396, P33242, P33244, P41828, P41830, P43354, P45447, P49116, P49117

SIGNOR signaling

4 interactions.

AEffectBMechanism
PRKCZup-regulatesNR1H4phosphorylation
PRKCAup-regulatesNR1H4phosphorylation
NR1H4“up-regulates quantity by expression”ABCB4“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 24 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:

PathwayPartnersFoldFDR
Regulation of IFNA/IFNB signaling591.5×5e-07
TRAF6 mediated IRF7 activation579.3×5e-07
Evasion by RSV of host interferon responses568.0×6e-07
Interferon alpha/beta signaling531.7×2e-05
SARS-CoV-2 activates/modulates innate and adaptive immune responses726.0×6e-07
Factors involved in megakaryocyte development and platelet production513.8×8e-04

GO biological processes:

GO termPartnersFoldFDR
B cell activation involved in immune response5219.4×3e-09
natural killer cell activation involved in immune response5206.5×3e-09
T cell activation involved in immune response5146.3×1e-08
response to exogenous dsRNA5109.7×5e-08
type I interferon-mediated signaling pathway571.7×4e-07
humoral immune response558.5×8e-07
cellular response to virus541.8×4e-06
adaptive immune response724.6×4e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic7
Likely pathogenic7
Uncertain significance84
Likely benign32
Benign20

Top pathogenic / likely-pathogenic (14)

Variant IDHGVSClassification
219162NM_001206979.2(NR1H4):c.419_420insAAA (p.Tyr139_Asn140insLys)Pathogenic
219163NG_029843.1:g.23704_55438delPathogenic
219164NM_001206979.2(NR1H4):c.526C>T (p.Arg176Ter)Pathogenic
2687827NM_001206979.2(NR1H4):c.1280del (p.Gln427fs)Pathogenic
2830660NM_001206979.2(NR1H4):c.565G>T (p.Glu189Ter)Pathogenic
3237163NM_001206979.2(NR1H4):c.79G>T (p.Gly27Cys)Pathogenic
498806NM_001206979.2(NR1H4):c.547C>T (p.Arg183Ter)Pathogenic
1339549NM_001206979.2(NR1H4):c.887C>T (p.Thr296Ile)Likely pathogenic
1683627NM_001206979.2(NR1H4):c.831+1G>TLikely pathogenic
1691436NM_001206979.2(NR1H4):c.91G>T (p.Glu31Ter)Likely pathogenic
2687828NM_001206979.2(NR1H4):c.976G>C (p.Gly326Arg)Likely pathogenic
593285NM_001206979.2(NR1H4):c.733-2A>GLikely pathogenic
598396NM_001206979.2(NR1H4):c.923dup (p.Leu309fs)Likely pathogenic
804467NM_001206979.2(NR1H4):c.1034del (p.Pro345fs)Likely pathogenic

SpliceAI

1557 predictions. Top by Δscore:

VariantEffectΔscore
12:100492638:G:GGdonor_gain1.0000
12:100532567:G:GTdonor_gain1.0000
12:100535022:GG:Gdonor_gain1.0000
12:100535023:GG:Gdonor_gain1.0000
12:100536593:G:GTdonor_gain1.0000
12:100536594:A:Tdonor_gain1.0000
12:100536608:ATT:Adonor_gain1.0000
12:100536611:G:GGdonor_gain1.0000
12:100536946:A:AGacceptor_gain1.0000
12:100536947:G:GGacceptor_gain1.0000
12:100540670:A:AGacceptor_gain1.0000
12:100540670:AG:Aacceptor_gain1.0000
12:100540671:G:GCacceptor_gain1.0000
12:100540671:GG:Gacceptor_gain1.0000
12:100540671:GGA:Gacceptor_gain1.0000
12:100540814:TAGTG:Tdonor_gain1.0000
12:100540816:GTG:Gdonor_gain1.0000
12:100540819:G:GGdonor_gain1.0000
12:100540819:G:Tdonor_loss1.0000
12:100540820:T:Gdonor_loss1.0000
12:100561994:TCCAG:Tdonor_loss1.0000
12:100561995:CCAG:Cdonor_loss1.0000
12:100561996:CAG:Cdonor_loss1.0000
12:100561997:AG:Adonor_loss1.0000
12:100561998:GGTAA:Gdonor_loss1.0000
12:100561999:G:Tdonor_loss1.0000
12:100562000:T:Adonor_loss1.0000
12:100563237:A:AGacceptor_gain1.0000
12:100474056:CCAA:Cdonor_gain0.9900
12:100474056:CCAAG:Cdonor_loss0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000001043 (12:100481478 T>C), RS1000049463 (12:100517310 A>G), RS1000115634 (12:100559806 C>T), RS1000126156 (12:100517455 C>T), RS1000136771 (12:100475201 G>A), RS1000167027 (12:100522063 C>T), RS1000206653 (12:100479265 A>G), RS1000210904 (12:100475754 G>A,T), RS1000228738 (12:100503248 C>G), RS1000316381 (12:100553919 G>T), RS1000338135 (12:100509800 A>T), RS1000378501 (12:100504881 A>T), RS1000387223 (12:100516236 C>G), RS1000397085 (12:100524142 C>A), RS1000409524 (12:100505286 T>C)

Disease associations

OMIM: gene MIM:603826 | disease phenotypes: MIM:617049, MIM:211600

GenCC curated gene-disease

DiseaseClassificationInheritance
cholestasis, progressive familial intrahepatic, 5StrongAutosomal recessive

Mondo (2): cholestasis, progressive familial intrahepatic, 5 (MONDO:0014884), progressive familial intrahepatic cholestasis type 1 (MONDO:0008892)

Orphanet (2): Progressive familial intrahepatic cholestasis type 5 (Orphanet:480476), Progressive familial intrahepatic cholestasis type 1 (Orphanet:79306)

HPO phenotypes

45 total (30 of 45 shown, HPO-id order):

HPOTerm
HP:0000007Autosomal recessive inheritance
HP:0000716Depression
HP:0000821Hypothyroidism
HP:0000952Jaundice
HP:0000988Skin rash
HP:0000989Pruritus
HP:0001082Cholecystitis
HP:0001337Tremor
HP:0001394Cirrhosis
HP:0001399Hepatic failure
HP:0001508Failure to thrive
HP:0001518Small for gestational age
HP:0001522Death in infancy
HP:0001541Ascites
HP:0001622Premature birth
HP:0001732Abnormality of the pancreas
HP:0001790Nonimmune hydrops fetalis
HP:0001943Hypoglycemia
HP:0001987Hyperammonemia
HP:0002027Abdominal pain
HP:0002202Pleural effusion
HP:0002643Neonatal respiratory distress
HP:0002904Hyperbilirubinemia
HP:0002908Conjugated hyperbilirubinemia
HP:0002910Elevated circulating hepatic transaminase concentration
HP:0002960Autoimmunity
HP:0003155Elevated circulating alkaline phosphatase concentration
HP:0003577Congenital onset
HP:0003593Infantile onset
HP:0003623Neonatal onset

GWAS associations

3 associations (top):

StudyTraitp-value
GCST001827_1Squamous cell carcinoma1.000000e-10
GCST006004_3Low density lipoprotein cholesterol levels5.000000e-08
GCST90013407_73Liver enzyme levels (gamma-glutamyl transferase)5.000000e-12

EFO canonical traits (2, from GWAS)

EFO IDTrait name
EFO:0004611low density lipoprotein cholesterol measurement
EFO:0004532serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2047 (SINGLE PROTEIN), CHEMBL6195566 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

41 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,181,197 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL104CLOTRIMAZOLE456,325
CHEMBL1064SIMVASTATIN4123,163
CHEMBL111RIMONABANT415,726
CHEMBL112ACETAMINOPHEN4157,242
CHEMBL1221SULCONAZOLE412,121
CHEMBL1272REPAGLINIDE433,453
CHEMBL1292CLOFAZIMINE415,481
CHEMBL1358FULVESTRANT456,655
CHEMBL139DICLOFENAC4125,009
CHEMBL1428NIMODIPINE432,587
CHEMBL1480FELODIPINE430,761
CHEMBL1487ATORVASTATIN468,788
CHEMBL157101KETOCONAZOLE475,361
CHEMBL160CYCLOSPORINE4168,247
CHEMBL1624LEVOTHYROXINE481,643
CHEMBL1946170REGORAFENIB412,678
CHEMBL205596CHOLIC ACID476,195
CHEMBL2107430FLUTRIMAZOLE42,604
CHEMBL21333PRANLUKAST412,755
CHEMBL240597CHENODIOL424,403
CHEMBL272427TAURURSODIOL4
CHEMBL388590BENZBROMARONE4
CHEMBL406393DEOXYCHOLIC ACID4
CHEMBL408TROGLITAZONE4
CHEMBL4297588ODEVIXIBAT4
CHEMBL535SUNITINIB4
CHEMBL56337EPALRESTAT4
CHEMBL566315OBETICHOLIC ACID4
CHEMBL603ZAFIRLUKAST4
CHEMBL6067487IVERMECTIN4

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

PharmGKB variants

1 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs4764980NR1H40.000

GtoPdb / IUPHAR curated pharmacology

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

Target class: nhr — 1H. Liver X receptor-like receptors

Most potent curated ligand interactions (19 total), top 19:

LigandActionAffinityParameter
tropifexorAgonist9.7pEC50
nidufexorPartial agonist9.3pEC50
HPG1860Agonist8.3pEC50
DY268Antagonist8.12pIC50
GW4064Agonist7.8pEC50
cilofexorAgonist7.6pEC50
INT-767Agonist7.52pEC50
BMS-986339Agonist7.47pEC50
BMS-986318Agonist7.28pEC50
obeticholic acidAgonist7.0pEC50
fexaramineAgonist6.6pEC50
compound 3f [Festa et al., 2019]Antagonist6.24pIC50
compound 25 [PMID: 32687365]Agonist6.03pEC50
guggulsteroneAntagonist6.0pIC50
22R-hydroxycholesterolAgonist5.5pEC50
chenodeoxycholic acidAgonist5.3pEC50
lithocholic acidAgonist5.3pEC50
cholic acidAgonist5.0pEC50
deoxycholic acidAgonist4.0pEC50

Binding affinities (BindingDB)

443 measured of 662 human assays (662 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
(2S,3R)-2-[[(2R)-2-[[2-[(3,3-dibutyl-7-methylsulfanyl-1,1-dioxo-5-phenyl-2,4-dihydro-1lambda6,2,5-benzothiadiazepin-8-yl)oxy]acetyl]amino]-2-(4-hydroxyphenyl)acetyl]amino]-3-hydroxybutanoic acidIC500.11 nMUS-9694018: IBAT inhibitors for the treatment of liver disease
(2S)-2-[[(2R)-2-[[2-[(3,3-dibutyl-7-methylsulfanyl-1,1-dioxo-5-phenyl-2,4-dihydro-1lambda6,2,5-benzothiadiazepin-8-yl)oxy]acetyl]amino]-2-(4-hydroxyphenyl)acetyl]amino]-3-methylbutanoic acidIC500.13 nMUS-9694018: IBAT inhibitors for the treatment of liver disease
(2S)-2-[[(2R)-2-[[2-[(3-butyl-7-methylsulfanyl-1,1-dioxo-5-phenyl-3-propyl-2,4-dihydro-1lambda6,5-benzothiazepin-8-yl)oxy]acetyl]amino]-2-(4-hydroxyphenyl)acetyl]amino]butanoic acidIC500.15 nMUS-9694018: IBAT inhibitors for the treatment of liver disease
OdevixibatIC500.16 nMUS-9694018: IBAT inhibitors for the treatment of liver disease
(2S)-2-[[(2R)-2-[[2-[(3,3-dibutyl-7-methylsulfanyl-1,1-dioxo-5-phenyl-2,4-dihydro-1lambda6,2,5-benzothiadiazepin-8-yl)oxy]acetyl]amino]-2-phenylacetyl]amino]butanoic acidIC500.18 nMUS-9694018: IBAT inhibitors for the treatment of liver disease
(2S)-2-[[(2R)-2-[[2-[(3,3-dibutyl-7-methylsulfanyl-1,1-dioxo-5-phenyl-2,4-dihydro-1lambda6,2,5-benzothiadiazepin-8-yl)oxy]acetyl]amino]-2-phenylacetyl]amino]propanoic acidIC500.2 nMUS-9694018: IBAT inhibitors for the treatment of liver disease
FXR_55IC500.3 nM
(2S)-2-[[(2R)-2-[[2-[(3,3-dibutyl-7-methylsulfanyl-1,1-dioxo-5-phenyl-2,4-dihydro-1lambda6,2,5-benzothiadiazepin-8-yl)oxy]acetyl]amino]-2-(4-hydroxyphenyl)acetyl]amino]propanoic acidIC500.3 nMUS-9694018: IBAT inhibitors for the treatment of liver disease
(2R)-2-[[(2R)-2-[[2-[(3,3-dibutyl-7-methylsulfanyl-1,1-dioxo-5-phenyl-2,4-dihydro-1lambda6,2,5-benzothiadiazepin-8-yl)oxy]acetyl]amino]-2-phenylacetyl]amino]-3-methylsulfanylpropanoic acidIC500.35 nMUS-9694018: IBAT inhibitors for the treatment of liver disease
(2S)-2-[[(2R)-2-[[2-[(3,3-dibutyl-7-methylsulfanyl-1,1-dioxo-5-phenyl-2,4-dihydro-1lambda6,2,5-benzothiadiazepin-8-yl)oxy]acetyl]amino]-2-phenylacetyl]amino]-3-methylbutanoic acidIC500.36 nMUS-9694018: IBAT inhibitors for the treatment of liver disease
(2S)-2-[[(2R)-2-[[2-[(3,3-dibutyl-7-methylsulfanyl-1,1-dioxo-5-phenyl-2,4-dihydro-1lambda6,5-benzothiazepin-8-yl)oxy]acetyl]amino]-2-phenylacetyl]amino]propanoic acidIC500.39 nMUS-9694018: IBAT inhibitors for the treatment of liver disease
2-[[(2R)-2-[[2-[(3,3-dibutyl-7-methylsulfanyl-1,1-dioxo-5-phenyl-2,4-dihydro-1lambda6,2,5-benzothiadiazepin-8-yl)oxy]acetyl]amino]-2-phenylacetyl]amino]acetic acidIC500.45 nMUS-9694018: IBAT inhibitors for the treatment of liver disease
CHEMBL4061776EC500.46 nM
CHEMBL4076774EC500.57 nM
CHEMBL4084716EC500.69 nM
CHEMBL4083548EC500.8 nM
CHEMBL4103787EC500.82 nM
2-[[(2R)-2-[[2-[(3,3-dibutyl-7-methylsulfanyl-1,1-dioxo-5-phenyl-2,4-dihydro-1lambda6,5-benzothiazepin-8-yl)oxy]acetyl]amino]-2-phenylacetyl]amino]acetic acidIC501.2 nMUS-9694018: IBAT inhibitors for the treatment of liver disease
6-[3-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]phenyl]-3-hydroxyazetidin-1-yl]pyridine-3-carboxylic acidEC502.6 nMUS-10329286: FXR (NR1H4) modulating compounds
6-[3-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]phenyl]-3-hydroxyazetidin-1-yl]-2-(trifluoromethyl)pyridine-3-carboxylic acidEC503.1 nMUS-10329286: FXR (NR1H4) modulating compounds
6-[3-[2-chloro-4-[[5-cyclopropyl-3-(3,5-dichloro-4-pyridinyl)-1,2-oxazol-4-yl]methoxy]phenyl]-3-hydroxyazetidin-1-yl]-5-fluoropyridine-3-carboxylic acidEC503.4 nMUS-10329286: FXR (NR1H4) modulating compounds
6-[3-[2-chloro-4-[[4-cyclopropyl-1-(2,6-dichlorophenyl)pyrazol-5-yl]methoxy]phenyl]-3-hydroxyazetidin-1-yl]-5-fluoropyridine-3-carboxylic acidEC503.8 nMUS-10329286: FXR (NR1H4) modulating compounds
6-[3-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]phenyl]-3-hydroxyazetidin-1-yl]-5-methylpyridine-3-carboxylic acidEC503.9 nMUS-10329286: FXR (NR1H4) modulating compounds
propan-2-yl 3-[(3,4-difluorophenyl)carbonyl]-1,1-dimethyl-1H,2H,3H,6H-azepino[4,5-b]indole-5-carboxylateEC504 nM
6-[3-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]phenyl]-3-hydroxyazetidin-1-yl]-2-methylpyridine-3-carboxylic acidEC504.4 nMUS-10329286: FXR (NR1H4) modulating compounds
6-[3-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]phenyl]-3-hydroxyazetidin-1-yl]-5-fluoropyridine-3-carboxylic acidEC504.8 nMUS-10329286: FXR (NR1H4) modulating compounds
[(1R,5S)-8-[4-(propylsulfonylcarbamoyl)phenyl]-8-azabicyclo[3.2.1]octan-3-yl] 5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carboxylateEC505.01 nMUS-11091482: Isoxazolyl-carbonyloxy azabicyclo[3.2.1]octanyl compounds as FXR activators
3-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]-N-methylsulfonyl-5,6-dihydro-[1]benzoxepino[3,2-b]pyridine-9-carboxamideEC506 nMUS-10183917: Tricyclic compounds and uses thereof in medicine
3-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]-5,5-dioxo-6H-benzo[b][1,5]benzoxathiepine-9-carboxylic acidEC506 nMUS-10183917: Tricyclic compounds and uses thereof in medicine
6-[3-[2-chloro-4-[[5-cyclopropyl-3-(3,5-dichloro-4-pyridinyl)-1,2-oxazol-4-yl]methoxy]phenyl]-3-hydroxyazetidin-1-yl]pyridine-3-carboxylic acidEC506.1 nMUS-10329286: FXR (NR1H4) modulating compounds
2-[(1R,5S)-3-[3-(2,6-dichlorophenyl)-5-(1-fluorocyclopropyl)-1,2-oxazole-4-carbonyl]oxy-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acidEC506.31 nMUS-11091482: Isoxazolyl-carbonyloxy azabicyclo[3.2.1]octanyl compounds as FXR activators
[(1R,5S)-8-[4-(pentylsulfonylcarbamoyl)phenyl]-8-azabicyclo[3.2.1]octan-3-yl] 5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carboxylateEC506.31 nMUS-11091482: Isoxazolyl-carbonyloxy azabicyclo[3.2.1]octanyl compounds as FXR activators
[(1S,5R)-8-[4-(cyclopropylsulfonylcarbamoyl)phenyl]-8-azabicyclo[3.2.1]octan-3-yl] 5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carboxylateEC506.31 nMUS-11091482: Isoxazolyl-carbonyloxy azabicyclo[3.2.1]octanyl compounds as FXR activators
FXR_34IC507.9 nM
propan-2-yl 3-[(4-fluorophenyl)carbonyl]-1,1-dimethyl-1H,2H,3H,6H-azepino[4,5-b]indole-5-carboxylateEC508 nM
FXR_31IC508.4 nM
6-[3-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]phenyl]-3-hydroxyazetidin-1-yl]-4-methylpyridine-3-carboxylic acidEC508.5 nMUS-10329286: FXR (NR1H4) modulating compounds
(S)-3-chloro-4-(2-(2-(4-chlorophenyl)-5,6-difluoro-1H-benzo[d]imidazol-1-yl)-2-cyclohexylacetamido)benzoic acidIC508.7 nM
FXR_22IC508.9 nM
FXR_57IC509.1 nM
FXR_14IC509.6 nM
2-[(1R,5S)-3-[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carbonyl]oxy-8-azabicyclo[3.2.1]octan-8-yl]-4-methoxy-1,3-benzothiazole-6-carboxylic acidEC5010 nMUS-11091482: Isoxazolyl-carbonyloxy azabicyclo[3.2.1]octanyl compounds as FXR activators
3-[(1S,5R)-3-[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carbonyl]oxy-8-azabicyclo[3.2.1]octan-8-yl]-5-fluorobenzoic acidEC5010 nMUS-11091482: Isoxazolyl-carbonyloxy azabicyclo[3.2.1]octanyl compounds as FXR activators
[(1R,5S)-8-[4-(cyclopropylmethylsulfonylcarbamoyl)phenyl]-8-azabicyclo[3.2.1]octan-3-yl] 5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carboxylateEC5010 nMUS-11091482: Isoxazolyl-carbonyloxy azabicyclo[3.2.1]octanyl compounds as FXR activators
3-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]-N-ethyl-5,6-dihydro-[1]benzoxepino[3,2-b]pyridine-9-carboxamideEC5011 nMUS-10183917: Tricyclic compounds and uses thereof in medicine
13-[[3-(2,6-dichlorophenyl)-5-propan-2-yltriazol-4-yl]methoxy]-2-oxotricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaene-5-carboxylic acidEC5012 nMUS-10183917: Tricyclic compounds and uses thereof in medicine
2-[(1R,5S)-3-[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carbonyl]oxy-8-azabicyclo[3.2.1]octan-8-yl]-4-(trifluoromethoxy)-1,3-benzothiazole-6-carboxylic acidEC5012.6 nMUS-11091482: Isoxazolyl-carbonyloxy azabicyclo[3.2.1]octanyl compounds as FXR activators
2-[(1R,5S)-3-[5-cyclobutyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carbonyl]oxy-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acidEC5012.6 nMUS-11091482: Isoxazolyl-carbonyloxy azabicyclo[3.2.1]octanyl compounds as FXR activators
[(1R,5S)-8-[4-(methylsulfonylcarbamoyl)phenyl]-8-azabicyclo[3.2.1]octan-3-yl] 5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole-4-carboxylateEC5012.6 nMUS-11091482: Isoxazolyl-carbonyloxy azabicyclo[3.2.1]octanyl compounds as FXR activators
FXR_20IC5013.5 nM

ChEMBL bioactivities

3945 potent at pChembl≥5 of 4187 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
10.30IC500.05nMCHEMBL4169596
10.30IC500.05nMCHEMBL4453417
10.30IC500.05nMCHEMBL4783205
10.22IC500.06nMCHEMBL4162312
10.22IC500.06nMCHEMBL4749439
10.05IC500.09nMCHEMBL4783777
10.05EC500.09nMCHEMBL5269567
10.00EC500.1nMCHEMBL5559957
10.00EC500.1nMCHEMBL5559067
10.00EC500.1nMCHEMBL6022184
9.96IC500.11nMCHEMBL4785930
9.96IC500.11nMCHEMBL5778792
9.90EC500.126nMCHEMBL5794992
9.89IC500.13nMCHEMBL5980362
9.82IC500.15nMCHEMBL5890939
9.80IC500.16nMODEVIXIBAT
9.80EC500.158nMCHEMBL6055223
9.74IC500.18nMCHEMBL5868054
9.70EC500.2nMCHEMBL4062567
9.70IC500.2nMCHEMBL4159402
9.70IC500.2nMCHEMBL5776872
9.70EC500.2nMCHEMBL5969888
9.70EC500.2nMCHEMBL6049423
9.70EC500.2nMCHEMBL5942305
9.70EC500.2nMCHEMBL6133358
9.60EC500.251nMCHEMBL5912129
9.60EC500.251nMCHEMBL5876378
9.60EC500.251nMCHEMBL5893870
9.59EC500.26nMCHEMBL4062567
9.57EC500.27nMCHEMBL4083548
9.52EC500.3nMCHEMBL4077016
9.52EC500.3nMCHEMBL5271104
9.52EC500.3nMTROPIFEXOR
9.52IC500.3nMCHEMBL5808613
9.52EC500.3nMCHEMBL6145182
9.50EC500.316nMCHEMBL5965579
9.46IC500.35nMCHEMBL6016158
9.44IC500.36nMCHEMBL6045294
9.41IC500.39nMCHEMBL6002118
9.40EC500.4nMCHEMBL4074393
9.40EC500.4nMCHEMBL4751757
9.40IC500.4nMCHEMBL5270123
9.40EC500.398nMCHEMBL6016337
9.40EC500.398nMCHEMBL5911663
9.40EC500.398nMCHEMBL5889337
9.40EC500.398nMCHEMBL5843614
9.40EC500.398nMCHEMBL6048214
9.40EC500.398nMCHEMBL6045396
9.40EC500.398nMCHEMBL6042489
9.40EC500.398nMCHEMBL5912676

PubChem BioAssay actives

2065 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.

CompoundAssayTypeValueUnit
3-[(1S)-1-(1-methylbenzimidazol-2-yl)-2-[1-(2-methylpropanoyl)piperidin-4-yl]ethyl]-1-(4-phenoxyphenyl)imidazolidine-2,4-dione1350160: Antagonist activity at human FXR expressed in Hep3B cells assessed as inhibition of CDCA-induced FXR response element driven luciferase activity after 24 hrsic50<0.0001uM
3-[(1S)-1-(1,6-dimethylbenzimidazol-2-yl)-2-[1-(2-methylpropanoyl)piperidin-4-yl]ethyl]-1-(4-phenoxyphenyl)imidazolidine-2,4-dione1350160: Antagonist activity at human FXR expressed in Hep3B cells assessed as inhibition of CDCA-induced FXR response element driven luciferase activity after 24 hrsic50<0.0001uM
3-[(1S)-2-(1-acetylpiperidin-4-yl)-1-(1-methylbenzimidazol-2-yl)ethyl]-1-(4-phenoxyphenyl)imidazolidine-2,4-dione1350160: Antagonist activity at human FXR expressed in Hep3B cells assessed as inhibition of CDCA-induced FXR response element driven luciferase activity after 24 hrsic50<0.0001uM
3-[(1S)-2-[1-(cyclopentanecarbonyl)piperidin-4-yl]-1-(1,6-dimethylbenzimidazol-2-yl)ethyl]-1-(4-phenoxyphenyl)imidazolidine-2,4-dione1350160: Antagonist activity at human FXR expressed in Hep3B cells assessed as inhibition of CDCA-induced FXR response element driven luciferase activity after 24 hrsic50<0.0001uM
3-[(1S)-1-(1,6-dimethylbenzimidazol-2-yl)-2-[1-(2-methylpropanoyl)piperidin-4-yl]ethyl]-1-[4-(4-methoxyphenoxy)phenyl]imidazolidine-2,4-dione1544570: Antagonist activity at human FXR expressed in Huh7 cells assessed as inhibition of CDCA-induced FXR response element driven luciferase activity after 24 hrsic50<0.0001uM
3-[(1S)-1-(1,5-dimethylbenzimidazol-2-yl)-2-[1-(2-methylpropanoyl)piperidin-4-yl]ethyl]-1-(4-phenoxyphenyl)imidazolidine-2,4-dione1544570: Antagonist activity at human FXR expressed in Huh7 cells assessed as inhibition of CDCA-induced FXR response element driven luciferase activity after 24 hrsic50<0.0001uM
3-[(1S)-1-(6-fluoro-1-methylbenzimidazol-2-yl)-2-[1-(2-methylpropanoyl)piperidin-4-yl]ethyl]-1-[4-(4-methoxyphenoxy)phenyl]imidazolidine-2,4-dione1694728: Antagonist activity against recombinant human FXR transfected in human HuH-7 cells co-transfected with FRE-luciferase assessed as reduction in CDCA-induced luciferase expression incubated for 24 hrs by luciferase reporter gene assayic50<0.0001uM
3-[(1S)-1-(6-chloro-1-methylbenzimidazol-2-yl)-2-[1-(2-methylpropanoyl)piperidin-4-yl]ethyl]-1-(4-phenoxyphenyl)imidazolidine-2,4-dione1350160: Antagonist activity at human FXR expressed in Hep3B cells assessed as inhibition of CDCA-induced FXR response element driven luciferase activity after 24 hrsic500.0001uM
3-[(1S)-1-(5-fluoro-1-methylbenzimidazol-2-yl)-2-[1-(2-methylpropanoyl)piperidin-4-yl]ethyl]-1-(4-phenoxyphenyl)imidazolidine-2,4-dione1350160: Antagonist activity at human FXR expressed in Hep3B cells assessed as inhibition of CDCA-induced FXR response element driven luciferase activity after 24 hrsic500.0001uM
3-[(1S)-1-(1,6-dimethylbenzimidazol-2-yl)-2-[1-(2-methylpropanoyl)piperidin-4-yl]ethyl]-1-[4-(4-fluorophenoxy)phenyl]imidazolidine-2,4-dione1544570: Antagonist activity at human FXR expressed in Huh7 cells assessed as inhibition of CDCA-induced FXR response element driven luciferase activity after 24 hrsic500.0001uM
3-[(1S)-1-(1-cyclopropyl-6-methylbenzimidazol-2-yl)-2-[1-(2-methylpropanoyl)piperidin-4-yl]ethyl]-1-[4-(4-fluorophenoxy)phenyl]imidazolidine-2,4-dione1694728: Antagonist activity against recombinant human FXR transfected in human HuH-7 cells co-transfected with FRE-luciferase assessed as reduction in CDCA-induced luciferase expression incubated for 24 hrs by luciferase reporter gene assayic500.0001uM
3-[(1S)-1-(1-cyclopropyl-6-fluorobenzimidazol-2-yl)-2-[1-(2-methylpropanoyl)piperidin-4-yl]ethyl]-1-[4-(4-fluorophenoxy)phenyl]imidazolidine-2,4-dione1694728: Antagonist activity against recombinant human FXR transfected in human HuH-7 cells co-transfected with FRE-luciferase assessed as reduction in CDCA-induced luciferase expression incubated for 24 hrs by luciferase reporter gene assayic500.0001uM
3-[(1S)-1-(6-fluoro-1-methylbenzimidazol-2-yl)-2-[1-(2-methylpropanoyl)piperidin-4-yl]ethyl]-1-[4-(4-fluorophenoxy)phenyl]imidazolidine-2,4-dione1694728: Antagonist activity against recombinant human FXR transfected in human HuH-7 cells co-transfected with FRE-luciferase assessed as reduction in CDCA-induced luciferase expression incubated for 24 hrs by luciferase reporter gene assayic500.0001uM
3-[(1S)-1-(1-cyclopropyl-6-methylbenzimidazol-2-yl)-2-[1-(2-methylpropanoyl)piperidin-4-yl]ethyl]-1-[4-(4-methoxyphenoxy)phenyl]imidazolidine-2,4-dione1694728: Antagonist activity against recombinant human FXR transfected in human HuH-7 cells co-transfected with FRE-luciferase assessed as reduction in CDCA-induced luciferase expression incubated for 24 hrs by luciferase reporter gene assayic500.0001uM
6-[2-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxymethyl]-7-azaspiro[3.5]nonan-7-yl]-1-ethylindole-3-carboxylic acid2082867: Agonist activity at GST-tagged human FXR LBD expressed in HEK293T cotransfected with FXRE-luciferase reporter plasmid by luciferase reporter gene assayec500.0001uM
6-[2-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxymethyl]-7-azaspiro[3.5]nonan-7-yl]-1-ethylindole-3-carboxylic acid2082867: Agonist activity at GST-tagged human FXR LBD expressed in HEK293T cotransfected with FXRE-luciferase reporter plasmid by luciferase reporter gene assayec500.0001uM
3-[(4-tert-butylbenzoyl)amino]benzoic acid1932916: Agonist activity at FXR in human HeLa cells by Dual-Glo luciferase assayec500.0001uM
3-[(1S)-2-(1-acetylpiperidin-4-yl)-1-(1,6-dimethylbenzimidazol-2-yl)ethyl]-1-(4-phenoxyphenyl)imidazolidine-2,4-dione1350160: Antagonist activity at human FXR expressed in Hep3B cells assessed as inhibition of CDCA-induced FXR response element driven luciferase activity after 24 hrsic500.0002uM
2-[3-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acid1477476: Agonist activity at recombinant human GST-tagged FXR ligand binding domain (193 to 472 residues) expressed in baculovirus infected insect cells assessed as induction of interaction with biotin labelled SRC-1 after 1 hr by HTRF assayec500.0002uM
6-chloro-2-(4-chloro-2-pyridinyl)-N-[(4-methoxyphenyl)methyl]imidazo[1,2-a]pyridin-3-amine1458342: Transactivation of human FXR expressed in human HeLa cells co-expressing BSEP after 24 hrs by dual-glo luciferase reporter gene assayec500.0003uM
3-[[4-(dimethylamino)benzoyl]amino]benzoic acid1932916: Agonist activity at FXR in human HeLa cells by Dual-Glo luciferase assayec500.0003uM
2-[3-[[5-cyclopropyl-3-[2-(difluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acid1477476: Agonist activity at recombinant human GST-tagged FXR ligand binding domain (193 to 472 residues) expressed in baculovirus infected insect cells assessed as induction of interaction with biotin labelled SRC-1 after 1 hr by HTRF assayec500.0003uM
4-tert-butyl-N-[[4-(trifluoromethylsulfanyl)phenyl]methyl]benzamide1451491: Transactivation of human FXR expressed in human HeLa cells co-expressing BSEP after 24 hrs by dual-glo luciferase reporter gene assayec500.0004uM
6-[3-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxymethyl]-3-fluoro-8-azabicyclo[3.2.1]octan-8-yl]-1-methylindole-3-carboxylic acid1698077: Agonist activity at human FXR expressed in HEK293 cells measured after 18 hrs by steady-glo luciferase reporter gene assayec500.0004uM
N-[5-chloro-2-[1-(cyclohexylmethyl)-5,6-difluorobenzimidazol-2-yl]phenyl]-2-fluoro-4-(2H-tetrazol-5-yl)benzamide1944046: Agonist activity at FXR (unknown origin)ic500.0004uM
2-[3-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]-8-azabicyclo[3.2.1]octan-8-yl]-4-methoxy-1,3-benzothiazole-6-carboxylic acid1477478: Agonist activity at human FXR expressed in HEK293T cells assessed as BSEP promoter driven cellular transcriptional activity after 24 hrs by luciferase reporter gene assayec500.0004uM
2-[(1R,5S)-3-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acid1604910: Agonist activity at GST-tagged human FXR-LBD (193 to 472 residues) using biotinylated SRC-1 peptide as substrate incubated for 1 hrs by HTRF assayec500.0005uM
3-(cyclohexylmethyl)-2-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]phenyl]benzimidazole-5-carboxylic acid1664089: Agonist activity at human FXR expressed in human HuH7 cells by luciferase reporter gene assayec500.0005uM
6-[3-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxymethyl]-3-fluoro-8-azabicyclo[3.2.1]octan-8-yl]-1-ethylindole-3-carboxylic acid1698077: Agonist activity at human FXR expressed in HEK293 cells measured after 18 hrs by steady-glo luciferase reporter gene assayec500.0005uM
2-[3-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]-8-azabicyclo[3.2.1]octan-8-yl]-1,3-benzothiazole-6-carboxylic acid1477476: Agonist activity at recombinant human GST-tagged FXR ligand binding domain (193 to 472 residues) expressed in baculovirus infected insect cells assessed as induction of interaction with biotin labelled SRC-1 after 1 hr by HTRF assayec500.0005uM
2-[3-[[5-cyclopropyl-3-[2-(trifluoromethyl)phenyl]-1,2-oxazol-4-yl]methoxy]-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acid1477476: Agonist activity at recombinant human GST-tagged FXR ligand binding domain (193 to 472 residues) expressed in baculovirus infected insect cells assessed as induction of interaction with biotin labelled SRC-1 after 1 hr by HTRF assayec500.0005uM
2-[3-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]-8-azabicyclo[3.2.1]octan-8-yl]-4-methyl-1,3-benzothiazole-6-carboxylic acid1477476: Agonist activity at recombinant human GST-tagged FXR ligand binding domain (193 to 472 residues) expressed in baculovirus infected insect cells assessed as induction of interaction with biotin labelled SRC-1 after 1 hr by HTRF assayec500.0005uM
6-[3-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxymethyl]-3-fluoro-8-azabicyclo[3.2.1]octan-8-yl]-1-benzothiophene-3-carboxylic acid1698077: Agonist activity at human FXR expressed in HEK293 cells measured after 18 hrs by steady-glo luciferase reporter gene assayec500.0007uM
3-[(1S)-2-(1-acetylpiperidin-4-yl)-1-(6-chloro-1-methylbenzimidazol-2-yl)ethyl]-1-(4-phenoxyphenyl)imidazolidine-2,4-dione1350160: Antagonist activity at human FXR expressed in Hep3B cells assessed as inhibition of CDCA-induced FXR response element driven luciferase activity after 24 hrsic500.0008uM
2-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]phenyl]-3-pentan-3-ylbenzimidazole-5-carboxylic acid1664089: Agonist activity at human FXR expressed in human HuH7 cells by luciferase reporter gene assayec500.0008uM
[(2S)-2-[(3R,5S,6R,7R,8S,9S,10S,13R,14S,17R)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]propyl] N-(4-propan-2-yloxyphenyl)sulfonylcarbamate1932912: Agonist activity at human FXR in expressed in CHO cells by luciferase reporter assayec500.0010uM
3-[(1S)-2-(1-acetylpiperidin-4-yl)-1-(5-fluoro-1-methylbenzimidazol-2-yl)ethyl]-1-(4-phenoxyphenyl)imidazolidine-2,4-dione1350160: Antagonist activity at human FXR expressed in Hep3B cells assessed as inhibition of CDCA-induced FXR response element driven luciferase activity after 24 hrsic500.0010uM
6-[4-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxymethyl]-4-fluoropiperidin-1-yl]-1-benzothiophene-3-carboxylic acid1698077: Agonist activity at human FXR expressed in HEK293 cells measured after 18 hrs by steady-glo luciferase reporter gene assayec500.0010uM
4-[4-[[6-[[1-tert-butyl-5-(4-fluorophenyl)pyrazole-4-carbonyl]amino]indazol-1-yl]methyl]piperidin-1-yl]benzoic acid1442211: Antagonist activity at human FXR expressed in COS1 cells assessed as inhibition of CDCA-induced receptor activation after 2 days by luciferase reporter gene assayic500.0010uM
6-[3-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]-8-azabicyclo[3.2.1]octan-8-yl]naphthalene-2-carboxylic acid1944053: Agonist activity at human GST-tagged FXR LBD (193 to 472 residues) by FRET assayec500.0010uM
1-[4-[[(2S)-2-[2-(4-chlorophenyl)-5,6-difluorobenzimidazol-1-yl]-2-cyclohexylacetyl]amino]-3-fluorophenoxy]cyclopropane-1-carboxylic acid568244: Displacement of radioligand from human FXR by scintillation proximity assayic500.0010uM
2-[4-[(4-tert-butyl-2-methoxybenzoyl)amino]phenyl]acetic acid1397541: Antagonist activity at full length human FXR expressed in HeLa cells co-expressing BSEP-pGL3/pSG5-hRXR after 24 hrs by luciferase reporter gene assayic500.0013uM
2-[4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]-2-fluorophenyl]-3-pentan-3-ylbenzimidazole-5-carboxylic acid1664089: Agonist activity at human FXR expressed in human HuH7 cells by luciferase reporter gene assayec500.0013uM
6-[4-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxymethyl]-4-fluoropiperidin-1-yl]-1-methylindole-3-carboxylic acid1698077: Agonist activity at human FXR expressed in HEK293 cells measured after 18 hrs by steady-glo luciferase reporter gene assayec500.0013uM
6-[5-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-1-methylindole-3-carboxylic acid2082867: Agonist activity at GST-tagged human FXR LBD expressed in HEK293T cotransfected with FXRE-luciferase reporter plasmid by luciferase reporter gene assayec500.0013uM
3-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]spiro[6H-[1]benzoxepino[3,2-b]pyridine-5,1’-cyclopropane]-9-carboxylic acid1900734: Agonist activity at FXR-LBD (unknown origin) assessed as induction of coactivator SRC-1 peptide recruitment measured by TR-FRET assayec500.0014uM
N-benzyl-2-(4-chloro-2-pyridinyl)-6-methylimidazo[1,2-a]pyridin-3-amine1458342: Transactivation of human FXR expressed in human HeLa cells co-expressing BSEP after 24 hrs by dual-glo luciferase reporter gene assayec500.0015uM
6-[4-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxymethyl]-4-fluoropiperidin-1-yl]-1-ethylindole-3-carboxylic acid1698077: Agonist activity at human FXR expressed in HEK293 cells measured after 18 hrs by steady-glo luciferase reporter gene assayec500.0015uM
2-[2-chloro-4-[[3-(2,6-dichlorophenyl)-5-propan-2-yl-1,2-oxazol-4-yl]methoxy]phenyl]-3-pentan-3-ylbenzimidazole-5-carboxylic acid1664089: Agonist activity at human FXR expressed in human HuH7 cells by luciferase reporter gene assayec500.0016uM
2-[[6-[3-[[5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]-1-oxa-8-azaspiro[4.5]decan-8-yl]pyridine-3-carbonyl]amino]acetic acid1932906: Agonist activity at FXR (unknown origin) incubated for 180 mins by TR-FRET assayec500.0017uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Chenodeoxycholic Aciddecreases expression, affects activity, affects reaction, decreases reaction, increases activity (+6 more)38
GW 4064affects binding, decreases expression, increases reaction, increases export, increases phosphorylation (+4 more)25
Lithocholic Acidincreases reaction, affects binding, increases activity, decreases expression, increases expression (+2 more)12
Deoxycholic Acidaffects cotreatment, decreases expression, affects binding, increases activity, decreases reaction (+1 more)9
pregna-4,17-diene-3,16-dionedecreases activity, decreases reaction, increases expression, increases activity, increases abundance (+3 more)7
obeticholic acidaffects binding, increases activity, increases reaction7
Acetaminophendecreases expression, affects cotreatment, decreases reaction7
Benzo(a)pyreneaffects methylation, decreases expression, increases methylation7
Ursodeoxycholic Acidaffects binding, decreases reaction, increases activity, decreases activity, decreases expression (+1 more)6
alisol B 23-acetateaffects binding, increases activity, increases expression, decreases reaction5
Cyclosporineaffects cotreatment, decreases expression, affects expression5
Aflatoxin B1affects expression, decreases expression, decreases methylation5
Taurocholic Acidincreases reaction, affects binding, increases activity, increases expression, decreases reaction (+1 more)4
Tetrachlorodibenzodioxindecreases expression4
Cholic Acidaffects binding, increases activity, increases expression4
sodium arsenitedecreases expression, increases expression3
Ethanoldecreases expression, decreases reaction, increases expression, increases activity, increases reaction (+1 more)3
Glycocholic Acidaffects cotreatment, decreases expression, increases activity3
Glycodeoxycholic Acidincreases activity, affects cotreatment, decreases expression3
Triclosanincreases expression, decreases activity, affects cotreatment, decreases expression, decreases reaction3
Oleic Acidaffects cotreatment, decreases expression, increases expression, affects expression3
Palmitic Aciddecreases reaction, affects expression, affects cotreatment, increases expression3
moxidectinincreases activity, decreases activity, affects binding, decreases reaction, increases reaction2
lacidipineaffects binding, decreases reaction, increases reaction, increases activity, decreases activity2
benidipinedecreases reaction, increases reaction, decreases activity, increases activity, affects binding2
cilnidipineaffects binding, decreases reaction, increases reaction, increases activity, decreases activity2
doramectinincreases activity, decreases activity, affects binding, decreases reaction, increases reaction2
selamectinaffects binding, decreases reaction, increases reaction, increases activity, decreases activity2
ST 1481decreases reaction, increases activity, decreases activity2
emamectindecreases reaction, increases reaction, increases activity, decreases activity, affects binding2

ChEMBL screening assays

1034 unique, capped per target: 873 binding, 154 functional, 6 admet, 1 unclassified

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1015272BindingIncrease in transcriptional activity of FXR ligand binding domain expressed in human Hep G2 cells co-transfected with Gal4-DBD by luciferase reporter gene assayCrystal structure of the peroxisome proliferator-activated receptor gamma (PPARgamma) ligand binding domain complexed with a novel partial agonist: a new region of the hydrophobic pocket could be exploited for drug design. — J Med Chem
CHEMBL1027008FunctionalAgonist activity at human FXR transfected in human HuH7 cells co-transfected with human BSEP promoter reporter plasmid at 10 uM after 30 hrs by dual-luciferase reporter assay relative to controlEffect of guggulsterone and cembranoids of Commiphora mukul on pancreatic phospholipase A(2): role in hypocholesterolemia. — J Nat Prod
CHEMBL1738629UnclassifiedPUBCHEM_BIOASSAY: Late stage results from the probe development effort to identify novel modulators of the Retinoic acid receptor-related Orphan Receptors (ROR). (Class of assay: screening) [Related pubchem assays (depositor defined):AID213PubChem BioAssay data set

Cellosaurus cell lines

11 cell lines: 6 cancer cell line, 3 embryonic stem cell, 1 spontaneously immortalized cell line, 1 transformed cell line

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

CellosaurusNameCategorySex
CVCL_A4T6SEES3-1V human NR1H4, clone1Embryonic stem cellMale
CVCL_A4T7SEES3-1V human NR1H4, clone2Embryonic stem cellMale
CVCL_A4T8SEES3-1V human NR1H4, clone3Embryonic stem cellMale
CVCL_B6ACHepaRG FXR KOCancer cell lineFemale
CVCL_B7YLAbcam Raji NR1H4 KOCancer cell lineMale
CVCL_B9ZBAbcam THP-1 NR1H4 KOCancer cell lineMale
CVCL_C7B0Abcam PC-3 NR1H4 KOCancer cell lineMale
CVCL_D9W6Ubigene Hep 3B2.1-7 NR1H4 KOCancer cell lineMale
CVCL_E0VUUbigene Huh-7 NR1H4 KOCancer cell lineMale
CVCL_KX08PathHunter CHO-K1 FXR Protein InteractionSpontaneously immortalized cell lineFemale

Clinical trials (associated diseases)

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

TrialPhaseStatusTitle
NCT03353454PHASE3WITHDRAWNA Placebo-controlled Study of Maralixibat (SHP625) in Pediatric Subjects With Progressive Familial Intrahepatic Cholestasis (PFIC)
NCT03566238PHASE3COMPLETEDThis Study Will Investigate the Efficacy and Safety of A4250 in Children With PFIC Types 1 or 2
NCT03659916PHASE3COMPLETEDLong Term Safety & Efficacy Study Evaluating The Effect of A4250 in Children With PFIC
NCT03905330PHASE3COMPLETEDA Study to Evaluate the Efficacy and Safety of Maralixibat in Subjects With Progressive Familial Intrahepatic Cholestasis (MARCH-PFIC)
NCT04185363PHASE3COMPLETEDAn Extension Study of Maralixibat in Patients With Progressive Familial Intrahepatic Cholestasis (PFIC)
NCT05543187PHASE3COMPLETEDA Study of TAK-625 for the Treatment of Progressive Familial Intrahepatic Cholestasis (PFIC)
NCT02057718PHASE2COMPLETEDOpen Label Study to Evaluate Efficacy and Long Term Safety of LUM001 (Maralixibat) in the Treatment of Cholestatic Liver Disease in Patients With Progressive Familial Intrahepatic Cholestasis
NCT04729751PHASE2COMPLETEDA Study to Evaluate the Safety and Tolerability of Maralixibat in Infant Participants With Cholestatic Liver Diseases Including Progressive Familial Intrahepatic Cholestasis (PFIC) and Alagille Syndrome (ALGS).
NCT02963077PHASE1COMPLETEDA Safety and Pharmakokinetic Study of A4250 Alone or in Combination With A3384
NCT03082937PHASE1COMPLETEDAn Open Label, Single-dose, Single Period ADME Study of A4250 in Healthy Subjects
NCT01784718Not specifiedNO_LONGER_AVAILABLEBuphenyl Therapy for Byler’s Disease
NCT01949766Not specifiedNO_LONGER_AVAILABLETransition From Buphenyl to RAVICTI for the Therapy of Byler Disease
NCT02094222Not specifiedNO_LONGER_AVAILABLEExpanded Access Protocol for an Intermediate Size Population - RAVICTI for Byler Disease
NCT02131623Not specifiedCOMPLETEDValidation of the Itch Reported Outcome (ItchRO) Diaries in Pediatric Cholestatic Liver Disease
NCT03930810Not specifiedENROLLING_BY_INVITATIONNAtural Course and Prognosis of PFIC and Effect of Biliary Diversion
NCT04071197Not specifiedUNKNOWNGastrostomy-Biliary Diversion: Innovative Management for Bile Canalicular Transport Disorders
NCT04483531Not specifiedAPPROVED_FOR_MARKETINGOdevixibat for the Treatment of Progressive Familial Intrahepatic Cholestasis
NCT05687474Not specifiedCOMPLETEDBaby Detect : Genomic Newborn Screening
NCT05704517Not specifiedUNKNOWNProgressive Familial Intrahepatic Cholestasis in Indian Children - Establishing an Indian PFIC Registry
NCT06193928Not specifiedRECRUITINGLong-Term SafEty and Clinical Outcomes of LivmArli in Patients in the United States (LEAP-US)
NCT06777914Not specifiedRECRUITINGFamilial Intrahepatic Cholestasis-related Genes Associated with Disease Susceptibility in Hepato-biliary Cancers
NCT06778174Not specifiedRECRUITINGProspective Analysis of the Treatment of Progressive Familial Intrahepatic Cholestasis (TreatFIC)
NCT06781242Not specifiedRECRUITINGGenotype-phenotype Relationship Between Cryptogenic Cholestasis and Familial Intrahepatic Cholestasis
NCT07185919Not specifiedRECRUITINGA Study of the Effectiveness, Safety and the Long-term Outcomes of Participants With Progressive Familial Intrahepatic Cholestasis (PFIC) Who Take Odevixibat (Bylvay) in South Korea
NCT07293897Not specifiedRECRUITINGA Database Study of Maralixibat (TAK-625) in Participants With Alagille Syndrome (ALGS) and Progressive Familial Intrahepatic Cholestasis (PFIC)
NCT07317193Not specifiedRECRUITINGDEFINING THE GENETIC DRIVERS OF ADULT-ONSET CHOLESTATIC LIVER DISEASE
NCT07588880Not specifiedRECRUITINGA Study of the Effectiveness, Safety and the Long-term Outcomes of Participants With Progressive Familial Intrahepatic Cholestasis (PFIC) Who Take Odevixibat (Bylvay) in China

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

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This page pulls from 81 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot