RXRA

Summary

RXRA (retinoid X receptor alpha, HGNC:10477) is a protein-coding gene on chromosome 9q34.2, encoding Retinoic acid receptor RXR-alpha (P19793). Receptor for retinoic acid that acts as a transcription factor.

Retinoid X receptors (RXRs) and retinoic acid receptors (RARs) are nuclear receptors that mediate the biological effects of retinoids by their involvement in retinoic acid-mediated gene activation. These receptors function as transcription factors by binding as homodimers or heterodimers to specific sequences in the promoters of target genes. The protein encoded by this gene is a member of the steroid and thyroid hormone receptor superfamily of transcriptional regulators. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 6256 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital heart disease (No Known Disease Relationship, ClinGen)
• GWAS associations: 19
• Clinical variants (ClinVar): 41 total — 1 pathogenic, 1 likely-pathogenic
• Druggable target: yes — 23 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Transcription factor: yes — 119 downstream targets (CollecTRI)
• MANE Select transcript: NM_002957

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10477
Approved symbol	RXRA
Name	retinoid X receptor alpha
Location	9q34.2
Locus type	gene with protein product
Status	Approved
Aliases	NR2B1, RXRalpha, RXR-alpha
Ensembl gene	ENSG00000186350
Ensembl biotype	protein_coding
OMIM	180245
Entrez	6256

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000356384, ENST00000481739, ENST00000484822, ENST00000649020, ENST00000672570

RefSeq mRNA: 3 — MANE Select: NM_002957 NM_001291920, NM_001291921, NM_002957

CCDS: CCDS35172, CCDS94525

Canonical transcript exons

ENST00000481739 — 10 exons

Exon	Start	End
ENSE00001416521	134326455	134326659
ENSE00001843517	134436467	134440585
ENSE00003485717	134431905	134431996
ENSE00003521933	134417158	134417327
ENSE00003534135	134429108	134429240
ENSE00003591922	134401632	134401882
ENSE00003609666	134408149	134408299
ENSE00003615393	134434102	134434207
ENSE00003676511	134408940	134409119
ENSE00003692212	134421676	134421805

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 96.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.6507 / max 451.5550, expressed in 1794 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99315	39.1059	1783
99316	4.5366	1542
99313	4.1810	1230
99317	2.1066	1187
99314	0.9224	639
205657	0.2303	80
99337	0.1819	47
99328	0.1564	50
99345	0.1546	79
99327	0.0750	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of hip	UBERON:0001554	96.61	gold quality
gingival epithelium	UBERON:0001949	96.58	gold quality
pancreatic ductal cell	CL:0002079	96.56	gold quality
gastrocnemius	UBERON:0001388	96.50	gold quality
esophagus squamous epithelium	UBERON:0006920	96.30	gold quality
squamous epithelium	UBERON:0006914	96.27	gold quality
gingiva	UBERON:0001828	96.23	gold quality
right lobe of liver	UBERON:0001114	96.00	gold quality
vastus lateralis	UBERON:0001379	95.98	gold quality
quadriceps femoris	UBERON:0001377	95.93	gold quality
endometrium epithelium	UBERON:0004811	95.90	gold quality
muscle of leg	UBERON:0001383	95.83	gold quality
epithelium of esophagus	UBERON:0001976	95.78	gold quality
muscle organ	UBERON:0001630	95.75	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.75	gold quality
blood	UBERON:0000178	95.73	gold quality
tongue squamous epithelium	UBERON:0006919	95.72	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.60	gold quality
trabecular bone tissue	UBERON:0002483	95.59	gold quality
cervix squamous epithelium	UBERON:0006922	95.53	gold quality
olfactory bulb	UBERON:0002264	95.48	gold quality
hair follicle	UBERON:0002073	95.33	gold quality
lower lobe of lung	UBERON:0008949	95.27	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.24	gold quality
skeletal muscle tissue	UBERON:0001134	95.20	gold quality
liver	UBERON:0002107	95.14	gold quality
triceps brachii	UBERON:0001509	95.13	gold quality
gluteal muscle	UBERON:0002000	95.11	gold quality
monocyte	CL:0000576	95.09	gold quality
upper leg skin	UBERON:0004262	95.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	10.55
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

119 targets.

Target	Regulation
ABCA1	Activation
ABCB1	Unknown
ABCB11	Unknown
ABCC2	Activation
ABCC3	Repression
ACACB	Repression
ACOX1	Activation
ACSL3	Activation
ADAM2
ADRB1
ALDH1A1
APOA1	Unknown
APOA2	Unknown
APOA4
APOC2	Activation
APOC3
APP	Unknown
BCO1	Activation
BGLAP	Unknown
BMAL1
BTG2
CAT
CCNE1	Activation
CEBPE
CGB3	Unknown
CHAT	Activation
CPT1B	Activation
CRABP2
CRYAB
CTNNB1	Repression

JASPAR motifs

Motif	Name	Family
MA0065.1	PPARG::RXRA	Thyroid hormone receptor-related factors (NR1)::RXR-related receptors (NR2)
MA0074.1	RXRA::VDR	RXR-related receptors (NR2)::Thyroid hormone receptor-related factors (NR1)
MA0115.1	NR1H2::RXRA	Thyroid hormone receptor-related factors (NR1)::RXR-related receptors (NR2)
MA0159.1	RARA::RXRA	Thyroid hormone receptor-related factors (NR1)::RXR-related receptors (NR2)
MA1146.1	NR1H4::RXRA	Thyroid hormone receptor-related factors (NR1)::RXR-related receptors (NR2)
MA1146.2	NR1H4::RXRA	Thyroid hormone receptor-related factors (NR1)::RXR-related receptors (NR2)
MA1147.1	NR4A2::RXRA	NGFI-B-related receptors (NR4)::RXR-related receptors (NR2)
MA1147.2	NR4A2::RXRA	NGFI-B-related receptors (NR4)::RXR-related receptors (NR2)
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:11139380, PMID:8674817, PMID:10187832, PMID:17916232, PMID:10744760, PMID:7705655, PMID:8386511

Upstream regulators (CollecTRI, top): MED25, NR1I2, NR3C1, RXRA

miRNA regulators (miRDB)

120 targeting RXRA, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3692-3P	99.98	70.27	2139
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-4645-5P	99.98	65.81	1284
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6739-5P	99.80	67.87	2806

Literature-anchored findings (GeneRIF, showing 40)

• The role of retinoid X receptor messenger RNA expression in curatively resected non-small cell lung cancer (PMID:11839661)
• Retinoid signaling is attenuated by retinoic acid-induced proteasome-mediated degradation of RXRA in human keratocytes. (PMID:11855864)
• the effect of STAT5b-RARalpha on the activity of myeloid transcription factors including RARalpha/retinoid X receptor (RXR) alpha (PMID:11929748)
• Interactions that determine the assembly of a retinoid X receptor/corepressor complex (PMID:11972046)
• retinoid x receptor alpha structural results support the idea that docosa hexaenoic acid and related fatty acids could be natural agonists of RXRs (PMID:11981034)
• RXR alpha responsive element-dependent expression and RXR alpha-dependent transcriptional activation is regulated in T lymphocytes by cellular Ser/Thr phosphatases PP1 and PP2A. (PMID:12097375)
• regulates vitamin D receptor functions in part by regulating subcellular localization (PMID:12145331)
• Results demonstrate that human papilloma virus 16 E6 oncoprotein inhibits the RXR(alpha)-mediated transactivation of target genes, implying that perturbation of RXR-mediated transactivation by E6 could contribute to HPV oncogenesis. (PMID:12235159)
• in response to retinoic acid and in a manner requiring the activity of RXRalpha, secretes trophic factors which drive fetal cardiomyocyte proliferation and promote ventricular chamber morphogenesis (PMID:12297106)
• IL-3-induced enhancement of retinoic acid receptor activity is mediated through Stat5, which physically associates with recombinant human retinoic acid receptors in an IL-3-dependent manner. (PMID:12393611)
• With PPAR-gamma, forms heterodimers in the regulation of human trophoblast invasion (PMID:12485829)
• RXRalpha and RXRgamma immunodetected in all normal, nodular, and basal cell hyperplasia, as well as carcinomatous prostates. In atrophic glands, the expression of both receptors was found in 22.5% of samples. (PMID:12514092)
• results suggest that oxidized phospholipids inhibit transcription of the thrombomodulin gene in vascular endothelium by inhibiting the binding of retinoic acid receptor beta-retinoid x receptor alpha heterodimer and Sp1 and Sp3 to thrombomodulin promoter (PMID:12576329)
• RXR and its agonists have roles in the regulation of beta-catenin turnover and related biological events (PMID:12771132)
• Transcriptionlal activation driven by the PPARalpha/RXRalpha complex was counteracted by the expression of ERRalpha in HeLa cells. (PMID:12914524)
• RXRalpha up-regulation was associated with the early stages of laryngeal carcinogenesis (PMID:12969790)
• Expression of adipophilin is enhanced during trophoblast differentiation and is up-regulated by ligand-activated PPARgamma/retinoid X receptor. May contribute to fatty acid uptake by placenta. (PMID:14671211)
• depletion of vitamin A and retinoid receptors by UV irradiation, together with unchanged or even increased c-Jun levels, might seriously interfere with retinoid signaling and thus promote future tumor development, especially in keratinocytes. (PMID:14705796)
• Retinoid x receptor alpha (RXRalpha) may be actively involved in cell proliferation and cell cycle regulation in human hepatocyte cell line Hep3B cells. (PMID:14738865)
• results suggest a novel function of RNF8 as a regulator of RXR alpha-mediated transcriptional activity through interaction between their respective N-terminal regions (PMID:14981089)
• Decrease of RXRalpha in prostate basal cells may serve as a marker for prostate carcinoma-associated field change, which may represent an early event in the prostate carcinogenic process. (PMID:15006913)
• RXR could function as a fatty acid receptor in vivo. (PMID:15073272)
• Data suggest that altered localization of retinoid X receptor alpha to the splicing factor compartment may be an important factor for the loss of retinoid responsiveness in MDA-MB-231 breast cancer cells. (PMID:15082790)
• Casein kinase 1alpha interacts with retinoid X receptor and interferes with agonist-induced apoptosis (PMID:15131121)
• Results show an increased DNA binding of the retinoic acid receptor alpha/retinoid X receptor alpha heterodimer and the stability of nuclear localization of this heterodimer, which facilitates signal transduction. (PMID:15171703)
• Increase in expression of RXRalpha is associated with esophageal squamous cell carcinomas (PMID:15255287)
• study indicated that the subcellular intratumoral distribution pattern of RXR-alpha could independently predict the survival of RCC patients (PMID:15285879)
• novel aspect of RXRalpha function: it acts as a carrier for nucleocytoplasmic translocation of orphan receptors (PMID:15494375)
• nongenotropic function of RXRalpha and its involvement in the regulation of the Nur77-dependent apoptotic pathway (PMID:15509776)
• results suggest specific physiological roles of two novel human RXR alpha splice variants (PMID:15544927)
• The receptor, alpha shows abundant expression in the variety of tissues. (PMID:15608692)
• 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)
• These results indicate that the RXRalpha gene is transcribed at stable levels, similar to most housekeeping genes, and its transcription is regulated by ATRA. (PMID:16517099)
• Results suggest that the binding of PPARbeta-specific ligand enhances the affinity between RXRalpha and activated PPARbeta and thus may regulate angptl3 gene expression through a DR4 element by competing with LXRalpha for RXRalpha. (PMID:16806672)
• SUSP1 plays an important role in the control of the transcriptional activity of RXRalpha and thus in the RXRalpha-mediated cellular processes (PMID:16912044)
• metabolism of a parent compound, beta-carotene, may alternatively activate (9-cisRA) or inhibit (beta-apo-14’-carotenal) specific RXR and PPAR responses (PMID:17008383)
• Down-regulation of RXRalpha is critically required for neutrophil development since ectopic RXRalpha inhibited granulopoiesis by impairing proliferation and differentiation (PMID:17018855)
• in addition to the induction of coactivator peptide binding, all well-known RXRalpha agonists also induce binding of corepressor peptides to RXRalpha (PMID:17038419)
• Accumulation of full-length retinoid X receptor alpha (RXRalpha) in leiomyomas that is not associated with a modification of its gene expression. (PMID:17170071)
• our results indicate that activator Sp1 and repressor RXRalpha:RARalpha act in concert to regulate MRP3 expression. (PMID:17272513)

Cross-species orthologs

31 orthologs

Organism	Symbol	Gene ID
danio_rerio	rxrab	ENSDARG00000035127
danio_rerio	rxraa	ENSDARG00000057737
mus_musculus	Rxra	ENSMUSG00000015846
rattus_norvegicus	Rxra	ENSRNOG00000009446
drosophila_melanogaster	usp	FBGN0003964
drosophila_melanogaster	Hr78	FBGN0015239
drosophila_melanogaster	Hr83	FBGN0037436
caenorhabditis_elegans		WBGENE00003626
caenorhabditis_elegans		WBGENE00003650
caenorhabditis_elegans	nhr-69	WBGENE00003659
caenorhabditis_elegans		WBGENE00003683
caenorhabditis_elegans		WBGENE00003706
caenorhabditis_elegans		WBGENE00003719
caenorhabditis_elegans		WBGENE00003726
caenorhabditis_elegans		WBGENE00007547
caenorhabditis_elegans		WBGENE00008221
caenorhabditis_elegans		WBGENE00011097
caenorhabditis_elegans		WBGENE00011098
caenorhabditis_elegans		WBGENE00011099
caenorhabditis_elegans		WBGENE00011100
caenorhabditis_elegans		WBGENE00015395
caenorhabditis_elegans		WBGENE00015396
caenorhabditis_elegans		WBGENE00015397
caenorhabditis_elegans		WBGENE00015705
caenorhabditis_elegans		WBGENE00016975
caenorhabditis_elegans		WBGENE00017198
caenorhabditis_elegans		WBGENE00017787
caenorhabditis_elegans		WBGENE00020748
caenorhabditis_elegans		WBGENE00021848
caenorhabditis_elegans		WBGENE00022423
caenorhabditis_elegans		WBGENE00044354

Paralogs (11): HNF4A (ENSG00000101076), NR2E1 (ENSG00000112333), NR2C1 (ENSG00000120798), RXRG (ENSG00000143171), NR2F6 (ENSG00000160113), HNF4G (ENSG00000164749), NR2F1 (ENSG00000175745), NR2C2 (ENSG00000177463), NR2F2 (ENSG00000185551), RXRB (ENSG00000204231), NR2E3 (ENSG00000278570)

Protein

Protein identifiers

Retinoic acid receptor RXR-alpha — P19793 (reviewed: P19793)

Alternative names: Nuclear receptor subfamily 2 group B member 1, Retinoid X receptor alpha

All UniProt accessions (4): P19793, A0A3B3IS44, A0A5F9ZHH6, F1D8Q5

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for retinoic acid that acts as a transcription factor. Forms homo- or heterodimers with retinoic acid receptors (RARs) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5’-AGGTCA-3’ sites known as DR1-DR5 to regulate transcription. The high affinity ligand for retinoid X receptors (RXRs) is 9-cis retinoic acid. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone deacetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and coactivators are recruited leading to transcriptional activation. Serves as a common heterodimeric partner for a number of nuclear receptors, such as RARA, RARB and PPARA. The RXRA/RARB heterodimer can act as a transcriptional repressor or transcriptional activator, depending on the RARE DNA element context. The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes. Together with RARA, positively regulates microRNA-10a expression, thereby inhibiting the GATA6/VCAM1 signaling response to pulsatile shear stress in vascular endothelial cells. Acts as an enhancer of RARA binding to RARE DNA element. May facilitate the nuclear import of heterodimerization partners such as VDR and NR4A1. Promotes myelin debris phagocytosis and remyelination by macrophages. Plays a role in the attenuation of the innate immune system in response to viral infections, possibly by negatively regulating the transcription of antiviral genes such as type I IFN genes. Involved in the regulation of calcium signaling by repressing ITPR2 gene expression, thereby controlling cellular senescence.

Subunit / interactions. Homodimer. Heterodimer (via C-terminus) with RARA; required for ligand-dependent retinoic acid receptor transcriptional activity; association with RARA is enhanced by pulsatile shear stress. Heterodimer with PPARA (via the leucine-like zipper in the LBD); the interaction is required for PPARA transcriptional activity. Heterodimerizes with PPARG. Heterodimerizes (via NR LBD) with RARB. Heterodimerizes with NR1H4; the heterodimerization enhances the binding affinity for LXXLL motifs from coactivators. Interacts with NCOA3 and NCOA6 coactivators. Interacts with coactivator FAM120B. Interacts with coactivator PELP1, SENP6, SFPQ, DNTTIP2 and RNF8. Interacts with PRMT2. Interacts with ASXL1. Interacts with BHLHE40/DEC1, BHLHE41/DEC2, NCOR1 and NCOR2. Interacts in a ligand-dependent fashion with MED1 and NCOA1. Interacts with VDR. Interacts with EP300; the interaction is decreased by 9-cis retinoic acid. Heterodimer (via C-terminus) with NR4A1 (via DNA-binding domain); DNA-binding of the heterodimer is enhanced by 9-cis retinoic acid. NR4A1 competes with EP300 for interaction with RXRA and thereby attenuates EP300 mediated acetylation of RXRA. In the absence of hormonal ligand, interacts with TACC1. Interacts ith IGFBP3. (Microbial infection) Interacts (via the DNA binding domain) with HCV core protein; the interaction enhances the transcriptional activities of the RXRA/RARA and the RXRA/PPARA heterodimers.

Subcellular location. Nucleus. Cytoplasm. Mitochondrion.

Tissue specificity. Expressed in lung fibroblasts (at protein level). Expressed in monocytes. Highly expressed in liver, also found in kidney and brain.

Post-translational modifications. Acetylated by EP300; acetylation enhances DNA binding and transcriptional activity. Phosphorylated on serine and threonine residues mainly in the N-terminal modulating domain. Constitutively phosphorylated on Ser-21 in the presence or absence of ligand. Under stress conditions, hyperphosphorylated by activated JNK on Ser-56, Ser-70, Thr-82 and Ser-260. Phosphorylated on Ser-27, in vitro, by PKA. This phosphorylation is required for repression of cAMP-mediated transcriptional activity of RARA. Ubiquitinated by UBR5, leading to its degradation: UBR5 specifically recognizes and binds ligand-bound RXRA when it is not associated with coactivators (NCOAs). In presence of NCOAs, the UBR5-degron is not accessible, preventing its ubiquitination and degradation. Sumoylation negatively regulates transcriptional activity. Desumoylated specifically by SENP6.

Domain organisation. Composed of three domains: a modulating N-terminal domain (AF1 domain), a DNA-binding domain and a C-terminal ligand-binding domain (AF2 domain).

Induction. Down-regulated by aging. Induced by pulsatile shear stress.

Similarity. Belongs to the nuclear hormone receptor family. NR2 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P19793-1	1	yes
P19793-2	2

RefSeq proteins (3): NP_001278849, NP_001278850, NP_002948* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000003	Retinoid-X_rcpt/HNF4	Family
IPR000536	Nucl_hrmn_rcpt_lig-bd	Domain
IPR001628	Znf_hrmn_rcpt	Domain
IPR001723	Nuclear_hrmn_rcpt	Family
IPR013088	Znf_NHR/GATA	Homologous_superfamily
IPR021780	Nuc_recep-AF1	Domain
IPR035500	NHR-like_dom_sf	Homologous_superfamily
IPR050274	Nuclear_hormone_rcpt_NR2	Family

Pfam: PF00104, PF00105, PF11825

UniProt features (87 total): helix 19, binding site 12, mutagenesis site 12, modified residue 9, strand 9, region of interest 6, compositionally biased region 4, sequence variant 4, turn 4, zinc finger region 2, cross-link 2, chain 1, domain 1, DNA-binding region 1, splice variant 1

Structure

Experimental structures (PDB)

110 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9QX6	X-RAY DIFFRACTION	1.46
6LB4	X-RAY DIFFRACTION	1.5
7A77	X-RAY DIFFRACTION	1.5
6FBQ	X-RAY DIFFRACTION	1.6
9RMR	X-RAY DIFFRACTION	1.65
1DSZ	X-RAY DIFFRACTION	1.7
5MKU	X-RAY DIFFRACTION	1.78
2P1T	X-RAY DIFFRACTION	1.8
4ZSH	X-RAY DIFFRACTION	1.8
6L6K	X-RAY DIFFRACTION	1.8
7UW2	X-RAY DIFFRACTION	1.88
6STI	X-RAY DIFFRACTION	1.89
1MV9	X-RAY DIFFRACTION	1.9
1MVC	X-RAY DIFFRACTION	1.9
1MZN	X-RAY DIFFRACTION	1.9
2NLL	X-RAY DIFFRACTION	1.9
3E94	X-RAY DIFFRACTION	1.9
4RMD	X-RAY DIFFRACTION	1.9
5MJ5	X-RAY DIFFRACTION	1.9
8PP0	X-RAY DIFFRACTION	1.9
9S70	X-RAY DIFFRACTION	1.95
5JI0	X-RAY DIFFRACTION	1.98
1G5Y	X-RAY DIFFRACTION	2
3FUG	X-RAY DIFFRACTION	2
3PCU	X-RAY DIFFRACTION	2
4CN5	X-RAY DIFFRACTION	2
4K4J	X-RAY DIFFRACTION	2
4POJ	X-RAY DIFFRACTION	2
4PP3	X-RAY DIFFRACTION	2
4PP5	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P19793-F1	76.67	0.56

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 (12): 135; 138; 152; 155; 171; 177; 187; 190; 316; 316; 327; 327

Post-translational modifications (11): 21, 27, 56, 70, 82, 129, 145, 259, 260, 4, 108

Mutagenesis-validated functional residues (12):

Position	Phenotype
27	abolishes phosphorylation. no change in increase of rara-mediated transcriptional activity.
27	increase in rara-mediated transcriptional activity.
133–156	abolishes acetylation by ep300.
145	abolishes acetylation by ep300, dna binding and transcriptional activity. impairs interaction with ep300.
158–159	abolishes nuclear export.
160–165	abolishes nuclear localization and transcriptional activity.
206–216	no impact on acetylation by ep300.
280	abolished ubiquitination and degradation by ubr5.
352–462	no impact on acetylation by ep300.
357–360	abolishes nuclear export.
418–430	abolishes nuclear localization.
434	as a heterodimer with nr1h4, impairs interaction with coactivator ncoa1. impairs transcriptional activity.

Function

Pathways and Gene Ontology

Reactome pathways

66 pathways

ID	Pathway
R-HSA-1368108	BMAL1:CLOCK,NPAS2 activates circadian expression
R-HSA-159418	Recycling of bile acids and salts
R-HSA-192105	Synthesis of bile acids and bile salts
R-HSA-193368	Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
R-HSA-193807	Synthesis of bile acids and bile salts via 27-hydroxycholesterol
R-HSA-1989781	PPARA activates gene expression
R-HSA-200425	Carnitine shuttle
R-HSA-211976	Endogenous sterols
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-5362517	Signaling by Retinoic Acid
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-9029558	NR1H2 & NR1H3 regulate gene expression linked to lipogenesis
R-HSA-9029569	NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux
R-HSA-9031525	NR1H2 & NR1H3 regulate gene expression to limit cholesterol uptake
R-HSA-9031528	NR1H2 & NR1H3 regulate gene expression linked to triglyceride lipolysis in adipose
R-HSA-9616222	Transcriptional regulation of granulopoiesis
R-HSA-9623433	NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis
R-HSA-9632974	NR1H2 & NR1H3 regulate gene expression linked to gluconeogenesis
R-HSA-9707564	Cytoprotection by HMOX1
R-HSA-9707616	Heme signaling
R-HSA-9839394	TGFBR3 expression
R-HSA-9841922	MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis
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: 0 (showing top):

GO Biological Process (22): negative regulation of transcription by RNA polymerase II (GO:0000122), positive regulation of thyroid hormone receptor signaling pathway (GO:0002157), nervous system development (GO:0007399), hormone-mediated signaling pathway (GO:0009755), positive regulation of cholesterol efflux (GO:0010875), cell differentiation (GO:0030154), monocyte differentiation (GO:0030224), positive regulation of bone mineralization (GO:0030501), response to retinoic acid (GO:0032526), peroxisome proliferator activated receptor signaling pathway (GO:0035357), mRNA transcription by RNA polymerase II (GO:0042789), positive regulation of lipid metabolic process (GO:0045834), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), retinoic acid receptor signaling pathway (GO:0048384), cell maturation (GO:0048469), positive regulation of vitamin D receptor signaling pathway (GO:0070564), cellular response to low-density lipoprotein particle stimulus (GO:0071404), positive regulation of lipoprotein transport (GO:0140077), regulation of DNA-templated transcription (GO:0006355), nuclear receptor-mediated steroid hormone signaling pathway (GO:0030518), nuclear protein quality control by the ubiquitin-proteasome system (GO:0071630)

GO Molecular Function (24): 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), retinoic acid binding (GO:0001972), double-stranded DNA binding (GO:0003690), DNA-binding transcription factor activity (GO:0003700), nuclear steroid receptor activity (GO:0003707), nuclear receptor activity (GO:0004879), zinc ion binding (GO:0008270), enzyme binding (GO:0019899), peptide binding (GO:0042277), identical protein binding (GO:0042802), nuclear vitamin D receptor binding (GO:0042809), sequence-specific DNA binding (GO:0043565), retinoic acid-responsive element binding (GO:0044323), DNA binding domain binding (GO:0050692), LBD domain binding (GO:0050693), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872), vitamin D response element binding (GO:0070644)

GO Cellular Component (9): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), mitochondrion (GO:0005739), cytosol (GO:0005829), signaling receptor complex (GO:0043235), RNA polymerase II transcription regulator complex (GO:0090575), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
NR1H2 and NR1H3-mediated signaling	4
Bile acid and bile salt metabolism	2
Synthesis of bile acids and bile salts	2
Circadian clock	1
Regulation of lipid metabolism by PPARalpha	1
Fatty acid metabolism	1
Cytochrome P450 - arranged by substrate type	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
Signaling by Nuclear Receptors	1
Activation of HOX genes during differentiation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
positive regulation of intracellular signal transduction	2
cellular developmental process	2
nuclear receptor-mediated signaling pathway	2
DNA-templated transcription	2
regulation of DNA-templated transcription	2
transcription cis-regulatory region binding	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
DNA binding	2
protein binding	2
protein domain specific binding	2
intracellular membrane-bounded organelle	2
protein-containing complex	2
cytoplasm	2
negative regulation of DNA-templated transcription	1
thyroid hormone receptor signaling pathway	1
regulation of thyroid hormone receptor signaling pathway	1
system development	1
signal transduction	1
cellular response to hormone stimulus	1
regulation of cholesterol efflux	1
positive regulation of cholesterol transport	1
cholesterol efflux	1
myeloid leukocyte differentiation	1
mononuclear cell differentiation	1
bone mineralization	1
regulation of bone mineralization	1
positive regulation of ossification	1
positive regulation of biomineral tissue development	1
response to lipid	1
response to oxygen-containing compound	1
mRNA transcription	1
lipid metabolic process	1
positive regulation of metabolic process	1
regulation of lipid metabolic process	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
hormone-mediated signaling pathway	1

Protein interactions and networks

STRING

2808 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RXRA	NR1H4	Q96RI1	988
RXRA	PPARG	P37231	987
RXRA	PPARA	Q07869	986
RXRA	RARA	P10276	983
RXRA	NR1I2	O75469	982
RXRA	IGFBP3	P17936	907
RXRA	THRA	P10827	867
RXRA	TXNRD2	Q9NNW7	864
RXRA	XPR1	Q9UBH6	840
RXRA	PPARD	Q03181	839
RXRA	NR1H2	P55055	827
RXRA	RARS1	P54136	825
RXRA	NR1H3	Q13133	813
RXRA	NR1I3	Q14994	806
RXRA	NCOA1	Q15788	802

IntAct

222 interactions, top by confidence:

A	B	Type	Score
RARA	RXRA	psi-mi:“MI:0407”(direct interaction)	0.950
RARA	RXRA	psi-mi:“MI:0915”(physical association)	0.950
RXRA	RARA	psi-mi:“MI:0915”(physical association)	0.950
RXRA	RARA	psi-mi:“MI:2364”(proximity)	0.950
RXRA	RARA	psi-mi:“MI:0407”(direct interaction)	0.950
NCOA1	RARA	psi-mi:“MI:0915”(physical association)	0.870
RXRA	NCOA1	psi-mi:“MI:0407”(direct interaction)	0.860
NCOA1	RXRA	psi-mi:“MI:0407”(direct interaction)	0.860
MED1	RARA	psi-mi:“MI:0915”(physical association)	0.820
RARA	NCOR1	psi-mi:“MI:0914”(association)	0.800
RXRA	VDR	psi-mi:“MI:0407”(direct interaction)	0.790
RXRA	VDR	psi-mi:“MI:0915”(physical association)	0.790
VDR	RXRA	psi-mi:“MI:0407”(direct interaction)	0.790
RXRA	NCOA2	psi-mi:“MI:0407”(direct interaction)	0.780
NCOA2	RXRA	psi-mi:“MI:0915”(physical association)	0.780

BioGRID (391): RXRA (Two-hybrid), RXRA (Reconstituted Complex), PPARA (Reconstituted Complex), PPARG (Reconstituted Complex), RXRA (Co-localization), RXRA (Reconstituted Complex), RXRA (Reconstituted Complex), RXRA (Reconstituted Complex), NCOR1 (Reconstituted Complex), RXRA (Reconstituted Complex), RXRA (Reconstituted Complex), RXRA (Co-crystal Structure), RXRA (Affinity Capture-Western), RXRA (Affinity Capture-Western), RXRA (Affinity Capture-Western)

ESM2 similar proteins: A0A1L8GWK2, A0JMA8, A2BGA0, A4IIG7, B5DF21, E7F187, O00482, O15178, P16375, P19793, P24781, P28700, P28701, P28705, P43354, P45448, P48443, P51128, P51129, P70302, P83093, P84903, Q05343, Q06219, Q07917, Q08E53, Q09555, Q0GFF6, Q0IHW3, Q0VC20, Q13586, Q26622, Q33E94, Q5BJR8, Q5FWP2, Q5R5Y4, Q5REL6, Q6DHP9, Q7SYN5, Q7TNK1

Diamond homologs: A2T928, A2T929, A4IIG7, O35507, O42295, O42450, O57606, O77245, O97716, P03373, P04625, P10276, P10826, P10827, P10828, P11416, P12813, P13631, P15204, P17671, P18113, P18115, P18117, P18119, P18514, P18515, P18516, P18911, P19793, P22448, P22605, P22736, P22829, P28699, P28700, P28701, P28702, P28704, P28705, P37242

SIGNOR signaling

45 interactions.

A	Effect	B	Mechanism
RXRA	down-regulates	CTNNB1	binding
NR1I3	up-regulates	RXRA	binding
PRKACA	down-regulates	RXRA	phosphorylation
RXRA	up-regulates	PPARA	binding
RXRA	up-regulates	PPARD	binding
RXRA	up-regulates	PPARG	binding
NR1I2	up-regulates	RXRA	binding
NCOA2	up-regulates	RXRA	binding
RXRA	up-regulates	NR1H2	binding
MAPK8	“down-regulates activity”	RXRA	phosphorylation
MAPK9	“down-regulates activity”	RXRA	phosphorylation
RARA	up-regulates	RXRA	binding
RARB	up-regulates	RXRA	binding
RARG	up-regulates	RXRA	binding
RXRA	up-regulates	RARA	binding
RXRA	up-regulates	RARB	binding
RXRA	up-regulates	RARG	binding
ERK1/2	“down-regulates activity”	RXRA	phosphorylation
ASXL1	“up-regulates activity”	RXRA	binding
sulindac	“down-regulates activity”	RXRA	“chemical inhibition”
“[5-fluoro-1-(4-isopropylbenzylidene)-2-methylinden-3-yl]acetic acid”	“down-regulates activity”	RXRA	“chemical inhibition”
bexarotene	“up-regulates activity”	RXRA	“chemical activation”
“9-cis-retinoic acid”	“up-regulates activity”	RXRA	“chemical activation”
MAPK1	“down-regulates activity”	RXRA	phosphorylation
MAPK3	“down-regulates activity”	RXRA	phosphorylation
RXRA	“up-regulates activity”	THR	binding
RXRA	up-regulates	RAR	binding
RXRA	up-regulates	THR	binding
RAR	up-regulates	RXRA	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 68 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
Nuclear Receptor transcription pathway	14	49.2×	4e-18
SUMOylation of intracellular receptors	8	47.1×	5e-10
RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression	6	42.9×	2e-07
BMAL1:CLOCK,NPAS2 activates circadian expression	5	37.1×	6e-06
R-HSA-400253	6	36.4×	4e-07
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	5	33.4×	8e-06
Downregulation of SMAD2/3:SMAD4 transcriptional activity	5	32.3×	1e-05
Expression of BMAL (ARNTL), CLOCK, and NPAS2	6	30.8×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
intracellular receptor signaling pathway	5	79.9×	4e-07
retinoic acid receptor signaling pathway	7	73.2×	7e-10
negative regulation of miRNA transcription	5	50.3×	4e-06
mRNA transcription by RNA polymerase II	9	48.0×	4e-11
positive regulation of miRNA transcription	7	32.8×	2e-07
hormone-mediated signaling pathway	5	32.4×	3e-05
regulation of circadian rhythm	6	25.1×	1e-05
response to estradiol	5	16.0×	6e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — BLCA.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	25
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
563671	GRCh37/hg19 9q34.13-34.3(chr9:135105971-141020389)x3	Pathogenic
800311	NM_002957.6(RXRA):c.671G>A (p.Ser224Asn)	Likely pathogenic

SpliceAI

4093 predictions. Top by Δscore:

Variant	Effect	Δscore
9:134326655:GCTCG:G	donor_gain	1.0000
9:134326658:CGG:C	donor_loss	1.0000
9:134326659:GGT:G	donor_loss	1.0000
9:134326660:G:GG	donor_gain	1.0000
9:134326660:GTGA:G	donor_loss	1.0000
9:134326661:T:A	donor_loss	1.0000
9:134401880:CAGG:C	donor_loss	1.0000
9:134401881:AGGT:A	donor_loss	1.0000
9:134401883:G:GA	donor_loss	1.0000
9:134401884:T:G	donor_loss	1.0000
9:134408147:A:AG	acceptor_gain	1.0000
9:134408148:G:GG	acceptor_gain	1.0000
9:134408148:GCTCA:G	acceptor_gain	1.0000
9:134408297:CAGGT:C	donor_loss	1.0000
9:134408298:AGG:A	donor_loss	1.0000
9:134408300:GT:G	donor_loss	1.0000
9:134408301:T:A	donor_loss	1.0000
9:134408935:CGCA:C	acceptor_loss	1.0000
9:134408937:CAGG:C	acceptor_loss	1.0000
9:134408938:A:AG	acceptor_gain	1.0000
9:134408938:AG:A	acceptor_gain	1.0000
9:134408938:AGGC:A	acceptor_loss	1.0000
9:134408939:G:A	acceptor_loss	1.0000
9:134408939:G:GG	acceptor_gain	1.0000
9:134408939:GG:G	acceptor_gain	1.0000
9:134408939:GGC:G	acceptor_gain	1.0000
9:134408939:GGCA:G	acceptor_gain	1.0000
9:134408939:GGCAA:G	acceptor_gain	1.0000
9:134409069:GCC:G	donor_gain	1.0000
9:134409088:G:GT	donor_gain	1.0000

AlphaMissense

3033 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:134408272:T:A	C135S	1.000
9:134408272:T:C	C135R	1.000
9:134408272:T:G	C135G	1.000
9:134408273:G:A	C135Y	1.000
9:134408273:G:C	C135S	1.000
9:134408273:G:T	C135F	1.000
9:134408274:C:G	C135W	1.000
9:134408278:A:T	I137F	1.000
9:134408279:T:A	I137N	1.000
9:134408279:T:C	I137T	1.000
9:134408279:T:G	I137S	1.000
9:134408281:T:A	C138S	1.000
9:134408281:T:C	C138R	1.000
9:134408281:T:G	C138G	1.000
9:134408282:G:A	C138Y	1.000
9:134408282:G:C	C138S	1.000
9:134408282:G:T	C138F	1.000
9:134408283:C:G	C138W	1.000
9:134408287:G:C	D140H	1.000
9:134408288:A:C	D140A	1.000
9:134408288:A:G	D140G	1.000
9:134408288:A:T	D140V	1.000
9:134408294:C:T	S142F	1.000
9:134408297:C:T	S143L	1.000
9:134408299:G:A	G144S	1.000
9:134408299:G:C	G144R	1.000
9:134408299:G:T	G144C	1.000
9:134408940:G:A	G144D	1.000
9:134408940:G:C	G144A	1.000
9:134408940:G:T	G144V	1.000

dbSNP variants (sampled 300 via entrez): RS1000061318 (9:134404998 C>T), RS1000065519 (9:134440794 C>T), RS1000101731 (9:134380565 C>T), RS1000103777 (9:134439308 C>T), RS1000109480 (9:134415532 G>A), RS1000139611 (9:134439182 G>A), RS1000227175 (9:134366763 T>C), RS1000295976 (9:134406453 C>T), RS1000308760 (9:134401052 G>A), RS1000333268 (9:134440948 C>T), RS1000345878 (9:134354384 G>A), RS1000349662 (9:134340939 C>T), RS1000373850 (9:134390165 G>A), RS1000386448 (9:134388765 C>G), RS1000389835 (9:134419324 C>A,T)

Disease associations

OMIM: gene MIM:180245 | disease phenotypes: MIM:254500

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital heart disease	No Known Disease Relationship	Unknown

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
congenital heart disease	No Known Disease Relationship	UD

Mondo (2): plasma cell myeloma (MONDO:0009693), congenital heart disease (MONDO:0005453)

Orphanet (2): Multiple myeloma (Orphanet:29073), AL amyloidosis (Orphanet:85443)

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST001428_20	Intelligence	8.000000e-08
GCST001614_2	Central corneal thickness	3.000000e-10
GCST001806_12	Corneal structure	3.000000e-22
GCST001903_1	Central corneal thickness	6.000000e-08
GCST001903_2	Central corneal thickness	8.000000e-10
GCST002006_1	Adverse response to chemotherapy (neutropenia/leucopenia) (paclitaxel + carboplatin)	7.000000e-07
GCST002017_1	Crohn’s disease (need for surgery)	6.000000e-06
GCST002497_24	Blood pressure	8.000000e-07
GCST003856_1	Central corneal thickness	9.000000e-11
GCST003856_4	Central corneal thickness	2.000000e-08
GCST005580_227	Intraocular pressure	1.000000e-18
GCST005580_230	Intraocular pressure	1.000000e-17
GCST005959_5	Waist-to-hip ratio adjusted for BMI x sex interaction	2.000000e-06
GCST006366_6	Central corneal thickness	1.000000e-13
GCST008317_7	Central corneal thickness	6.000000e-09
GCST009414_22	Central corneal thickness	1.000000e-14
GCST010002_281	Refractive error	5.000000e-12
GCST011743_49	HDL cholesterol levels in HIV infection	5.000000e-06
GCST90013442_13	Keratoconus	2.000000e-28

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004731	eye measurement
EFO:0004345	corneal topography
EFO:0006340	mean arterial pressure
EFO:0005213	central corneal thickness
EFO:0004695	intraocular pressure measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008343	sex interaction measurement
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D009101	Multiple Myeloma	C04.557.595.500; C14.907.454.460; C15.378.147.780.650; C15.378.463.515.460; C20.683.515.845; C20.683.780.650

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (11): CHEMBL2061 (SINGLE PROTEIN), CHEMBL2111394 (PROTEIN COMPLEX), CHEMBL2363070 (PROTEIN FAMILY), CHEMBL2363071 (PROTEIN FAMILY), CHEMBL3430878 (PROTEIN COMPLEX), CHEMBL3430879 (PROTEIN COMPLEX), CHEMBL3430883 (PROTEIN COMPLEX), CHEMBL3885613 (PROTEIN COMPLEX), CHEMBL3885631 (PROTEIN COMPLEX), CHEMBL3885632 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

23 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 842,572 (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
CHEMBL1023	BEXAROTENE	4	40,951
CHEMBL1071	OXAPROZIN	4	51,044
CHEMBL1237061	PITAVASTATIN CALCIUM	4	1,118
CHEMBL15770	SULINDAC	4	80,712
CHEMBL1624	LEVOTHYROXINE	4	81,643
CHEMBL219916	DOMPERIDONE	4	18,305
CHEMBL2220442	FLUVASTATIN	4	53,699
CHEMBL38	TRETINOIN	4	194,008
CHEMBL705	ALITRETINOIN	4	39,246
CHEMBL843	ROSIGLITAZONE MALEATE	4	22,589
CHEMBL1715	PIOGLITAZONE HYDROCHLORIDE	4	10,091
CHEMBL509	MECLOFENAMIC ACID	4	45,809
CHEMBL846	CALCITRIOL	4	29,522
CHEMBL367149	DOCONEXENT	3	63,817
CHEMBL41632	TIRATRICOL	3	46,632
CHEMBL460026	ICOSAPENT	3	60,180
CHEMBL295416	PIRINIXIC ACID	2	830
CHEMBL75133	IRX-4204	2	452
CHEMBL12089	BERBERINE CHLORIDE	1	1,860
CHEMBL3098771	UAB-30	1	64
CHEMBL3360975	BMS-779788	1
CHEMBL3945199	BMS-852927	1
CHEMBL456237	LXR-623	1

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

PharmGKB clinical annotations

5 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11185647	Toxicity	3	docetaxel	Anemia;Nasopharyngeal Neoplasms;Neutropenia
rs1536475	Toxicity	3	docetaxel	Nasopharyngeal Neoplasms
rs2234753	Toxicity	3	docetaxel	Anemia;Nasopharyngeal Neoplasms
rs62576288	Toxicity	3	docetaxel	Nasopharyngeal Neoplasms
rs6413517	Toxicity	3	docetaxel	Anemia;Nasopharyngeal Neoplasms

PharmGKB variants

7 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1536475	RXRA	3	1.50	1	docetaxel
rs2234753	RXRA	3	1.50	1	docetaxel
rs3132291	RXRA		0.00	0
rs6413517	RXRA	3	1.50	1	docetaxel
rs11185647	RXRA	3	2.00	1	docetaxel
rs62576288	RXRA	3	1.50	1	docetaxel
rs1805343	RXRA		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: nhr — 2B. Retinoid X receptors

Most potent curated ligand interactions (15 total), top 15:

Ligand	Action	Affinity	Parameter
AGN194204	Agonist	9.4	pIC50
LG100268	Agonist	8.5	pIC50
CD3254	Agonist	8.5	pIC50
LG100754	Antagonist	8.5	pIC50
alitretinoin	Agonist	8.2	pIC50
[3H]9-cis-retinoic acid	Full agonist	7.8	pKd
SR11237	Agonist	7.5	pEC50
bexarotene	Agonist	7.4	pIC50
fluorobexarotene	Agonist	7.37	pEC50
PA452	Antagonist	7.11	pA2
compound 28 [Heitel et al., 2019]	Agonist	6.55	pEC50
HX 531	Antagonist	6.05	pIC50
methoprene acid	Agonist	5.7	pIC50
K-80003	Antagonist	5.62	pIC50
sulindac	Antagonist	4.1	pIC50

Binding affinities (BindingDB)

33 measured of 33 human assays (33 total across all organisms); most potent 33 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl]benzoic acid	KD	18 nM
3-[5-[(4-chlorophenyl)methyl]-7-fluoro-4-oxo-1H-quinolin-2-yl]-4-methylsulfonylbenzonitrile	EC50	55 nM	US-20250186425: PPARG INVERSE AGONISTS AND USES THEREOF
USRE46024, 16	EC50	66 nM	US-RE46024
USRE46024, 13	EC50	92 nM	US-RE46024
USRE46024, 9	EC50	115 nM	US-RE46024
USRE46024, 7	EC50	117 nM	US-RE46024
USRE46024, 12	EC50	133 nM	US-RE46024
USRE46024, 22	EC50	136 nM	US-RE46024
USRE46024, 8	EC50	192 nM	US-RE46024
Retinoic Acid	EC50	316 nM	US-10188615: Alkoxy compounds for disease treatment
USRE46024, 3	EC50	519 nM	US-RE46024
3-[5-(4-chlorophenoxy)-7-fluoro-4-oxo-1H-quinolin-2-yl]-4-methylsulfonylbenzonitrile	EC50	550 nM	US-20250186425: PPARG INVERSE AGONISTS AND USES THEREOF
4-chloro-3-[5-(4-chlorophenoxy)-7-fluoro-4-oxo-1H-quinolin-2-yl]benzonitrile	EC50	550 nM	US-20250186425: PPARG INVERSE AGONISTS AND USES THEREOF
3-[7-chloro-5-(1-methylpyrazol-4-yl)oxy-4-oxo-1H-quinolin-2-yl]-4-methylsulfonylbenzonitrile	EC50	550 nM	US-20250186425: PPARG INVERSE AGONISTS AND USES THEREOF
4-chloro-3-[5-[(4-chlorophenyl)methoxy]-7-fluoro-4-oxo-1H-quinolin-2-yl]benzonitrile	EC50	550 nM	US-20250186425: PPARG INVERSE AGONISTS AND USES THEREOF
USRE46024, 15	EC50	601 nM	US-RE46024
USRE46024, 6	EC50	666 nM	US-RE46024
USRE46024, 5	EC50	699 nM	US-RE46024
USRE46024, 10	EC50	767 nM	US-RE46024
USRE46024, 11	EC50	1200 nM	US-RE46024
USRE46024, 17	EC50	2040 nM	US-RE46024
USRE46024, 4	EC50	2330 nM	US-RE46024
4-{2-[(adamantane-1-carbonyl)-amino]-5,7,7,10,10-pentamethyl-7,8,9,10-tetrahydro-5H-5,13-diaza-benzo[4,5]cyclohepta[1,2-b]naphthalen-12-yl}-benzoic acid	IC50	2900 nM
USRE46024, 14	EC50	2990 nM	US-RE46024
USRE46024, 21	EC50	3210 nM	US-RE46024
3-[7-fluoro-5-(1-methylpyrazol-4-yl)oxy-4-oxo-1H-quinolin-2-yl]-4-methylsulfonylbenzonitrile	EC50	5500 nM	US-20250186425: PPARG INVERSE AGONISTS AND USES THEREOF
USRE46024, 19	EC50	6980 nM	US-RE46024
USRE46024, 20	EC50	7040 nM	US-RE46024
USRE46024, 2	EC50	7310 nM	US-RE46024
USRE46024, 1	EC50	7740 nM	US-RE46024
USRE46024, 18	EC50	9180 nM	US-RE46024
9-cis-retinoic acid (9cRA)	IC50	27100 nM

ChEMBL bioactivities

2065 potent at pChembl≥5 of 2166 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.80	EC50	0.016	nM	CHEMBL4764328
10.46	EC50	0.035	nM	CHEMBL4756418
10.28	EC50	0.052	nM	CHEMBL4764838
10.17	EC50	0.067	nM	CHEMBL4747448
10.10	EC50	0.08	nM	CHEMBL4764328
10.08	EC50	0.083	nM	CHEMBL4745005
10.06	EC50	0.088	nM	CHEMBL4797369
10.04	EC50	0.092	nM	CHEMBL4757761
10.02	EC50	0.095	nM	CHEMBL4760781
10.01	EC50	0.098	nM	T091317
9.99	EC50	0.103	nM	CHEMBL4749385
9.97	EC50	0.108	nM	T091317
9.89	EC50	0.13	nM	CHEMBL2325917
9.85	EC50	0.14	nM	CHEMBL2321917
9.84	EC50	0.145	nM	CHEMBL4756418
9.79	EC50	0.161	nM	CHEMBL4745005
9.76	EC50	0.174	nM	CHEMBL4764838
9.76	EC50	0.174	nM	CHEMBL4755317
9.70	EC50	0.2	nM	IRX-4204
9.67	EC50	0.214	nM	CHEMBL4747448
9.67	EC50	0.212	nM	LXR-623
9.64	EC50	0.228	nM	CHEMBL59030
9.60	EC50	0.251	nM	CHEMBL4749385
9.57	Ki	0.27	nM	CHEMBL3814574
9.57	EC50	0.27	nM	CHEMBL4797369
9.57	EC50	0.27	nM	CHEMBL4762546
9.56	EC50	0.277	nM	CHEMBL4760781
9.56	EC50	0.274	nM	CHEMBL4757761
9.55	EC50	0.281	nM	CHEMBL4762546
9.47	EC50	0.341	nM	CHEMBL4757158
9.43	EC50	0.372	nM	CHEMBL4755317
9.43	EC50	0.369	nM	CHEMBL4764539
9.40	Kd	0.4	nM	IRX-4204
9.40	EC50	0.401	nM	CHEMBL59030
9.40	Ki	0.4	nM	TRETINOIN
9.37	EC50	0.431	nM	LXR-623
9.37	EC50	0.43	nM	CHEMBL4777240
9.35	EC50	0.445	nM	CHEMBL4781683
9.32	EC50	0.474	nM	CHEMBL4748480
9.24	EC50	0.58	nM	CHEMBL5289973
9.20	EC50	0.632	nM	CHEMBL4791199
9.17	EC50	0.68	nM	CHEMBL4780872
9.15	EC50	0.708	nM	CHEMBL4757158
9.15	EC50	0.7	nM	CHEMBL5404648
9.10	EC50	0.7943	nM	CHEMBL5266566
9.10	Ki	0.8	nM	CHEMBL133915
9.10	Ki	0.8	nM	CHEMBL130374
9.07	EC50	0.843	nM	CHEMBL4791199
9.05	EC50	0.9	nM	CHEMBL248415
9.04	EC50	0.905	nM	CHEMBL4762542

PubChem BioAssay actives

1298 with measured affinity, of 3614 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
tert-butyl (2’R,3R)-2’-[3-[4-(hydroxymethyl)-3-methylsulfonylphenyl]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate	1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assay	ec50	<0.0001	uM
(2’R,3R)-1’-(3,3-dimethylbutanoyl)-2’-[3-[4-(hydroxymethyl)-3-methylsulfonylphenyl]phenyl]spiro[1H-indole-3,3’-pyrrolidine]-2-one	1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assay	ec50	<0.0001	uM
4-[methyl-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)amino]benzoic acid	726704: Agonist activity at RXR (unknown origin) in presence of RAR agonist Am80	ec50	0.0001	uM
(2’S,3S)-1’-(3,3-dimethylbutanoyl)-2’-[3-[4-(hydroxymethyl)-3-methylsulfonylphenyl]phenyl]spiro[1H-indole-3,3’-pyrrolidine]-2-one	1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assay	ec50	0.0001	uM
1’-(3,3-dimethylbutanoyl)-2’-[3-[4-(hydroxymethyl)-3-methylsulfonylphenyl]phenyl]spiro[1H-indole-3,3’-pyrrolidine]-2-one	1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assay	ec50	0.0001	uM
tert-butyl 2’-[3-[3-fluoro-4-(hydroxymethyl)-5-methylsulfonylphenyl]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate	1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assay	ec50	0.0001	uM
tert-butyl (2’R,3R)-2’-[3-[3-fluoro-4-(hydroxymethyl)-5-methylsulfonylphenyl]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate	1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assay	ec50	0.0001	uM
tert-butyl 2’-[3-[4-(hydroxymethyl)-3-methylsulfonylanilino]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate	1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assay	ec50	0.0001	uM
tert-butyl (2’R,3R)-2’-[3-(4-methoxycarbonyl-3-methylsulfonylphenyl)phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate	1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assay	ec50	0.0001	uM
tert-butyl (2’R,3R)-2’-[3-[4-(hydroxymethyl)-3-methylsulfonylanilino]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate	1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assay	ec50	0.0001	uM
N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide	1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assay	ec50	0.0001	uM
4-[(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)-propylamino]benzoic acid	726704: Agonist activity at RXR (unknown origin) in presence of RAR agonist Am80	ec50	0.0001	uM
tert-butyl 2’-[3-[4-(hydroxymethyl)-3-methylsulfonylphenyl]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate	1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assay	ec50	0.0002	uM
2-[(2-chloro-4-fluorophenyl)methyl]-3-(4-fluorophenyl)-7-(trifluoromethyl)indazole	1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assay	ec50	0.0002	uM
2-[3-[3-[[2-chloro-3-(trifluoromethyl)phenyl]methyl-(2,2-diphenylethyl)amino]propoxy]phenyl]acetic acid	1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assay	ec50	0.0002	uM
(2E,4E)-3-methyl-5-[(1S,2S)-2-methyl-2-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)cyclopropyl]penta-2,4-dienoic acid	167582: Transcriptional activation in CV-1 cells expressing retinoid X receptor RXR alpha	ec50	0.0002	uM
4-[1-(4-methylsulfonylphenyl)-5-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)pyrazol-3-yl]benzoic acid	1306249: Displacement of [3H]-TTNPB from RARgamma/RXRalpha (unknown origin) expressed in baculovirus expression system by scintillation proximity assay	ki	0.0003	uM
tert-butyl 2’-[3-(4-methoxycarbonyl-3-methylsulfonylphenyl)phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate	1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assay	ec50	0.0003	uM
tert-butyl (2’S,3S)-2’-[3-[3-fluoro-4-(hydroxymethyl)-5-methylsulfonylphenyl]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate	1691869: Agonist activity at human RXRalpha/LXRalpha expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assay	ec50	0.0003	uM
tert-butyl (2’S,3S)-2’-[3-[4-(hydroxymethyl)-3-methylsulfonylphenyl]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate	1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assay	ec50	0.0004	uM
tert-butyl (2’R,3R)-2’-[3-[3-chloro-4-(dimethylcarbamoyl)phenyl]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate	1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assay	ec50	0.0004	uM
tert-butyl (2’R,3R)-2’-[3-[4-(hydroxymethyl)phenyl]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate	1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assay	ec50	0.0004	uM
tretinoin	35839: Binding affinity for retinoic acid receptor RAR alpha	ki	0.0004	uM
tert-butyl (2’S,3S)-2’-[3-[4-(hydroxymethyl)-3-methylsulfonylanilino]phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate	1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assay	ec50	0.0005	uM
4-[N-ethyl-3-(2-methylpropoxy)-4-propan-2-ylanilino]benzoic acid	1925145: Inhibition of RXRalpha (unknown origin)	ec50	0.0006	uM
tert-butyl (2’S,3S)-2-oxo-2’-(3-phenylphenyl)spiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate	1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assay	ec50	0.0006	uM
tert-butyl (2’R,3R)-2’-[3-(3-methylsulfonylphenyl)phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate	1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assay	ec50	0.0007	uM
trans-(1R,2R)-2-[5-[3,5-bis(trifluoromethyl)phenyl]-4-phenyl-1,3-oxazol-2-yl]cyclopropane-1-carboxylic acid	2024928: Agonist activity at full length human RXR alpha expressed in HEK293T cells measured after 16 hrs by Dual-glo luciferase assay	ec50	0.0007	uM
(E)-3-[4-hydroxy-3-(3-propan-2-ylphenyl)phenyl]prop-2-enoic acid	1925168: Inhibition of Nurr1-RXRalpha (unknown origin) by BRET assay	ec50	0.0008	uM
(2E,4E,6Z)-7-[2-(2,2-difluoroethoxy)-3-propan-2-yl-5-thiophen-2-ylphenyl]-3-methylocta-2,4,6-trienoic acid	199352: Binding affinity against RXR alpha receptor using [3H]9-cis-RA as radioligand in CV-1 cells	ki	0.0008	uM
(2E,4E,6Z)-7-[2-(2,2-difluoroethoxy)-5-(4-fluorophenyl)-3-propan-2-ylphenyl]-3-methylocta-2,4,6-trienoic acid	199352: Binding affinity against RXR alpha receptor using [3H]9-cis-RA as radioligand in CV-1 cells	ki	0.0008	uM
(5Z)-5-[[3-(1-ethyl-4,4,6-trimethyl-2-oxo-3H-quinolin-7-yl)-4-(trifluoromethoxy)phenyl]methylidene]-1,3-thiazolidine-2,4-dione	307669: Activity at RXRalpha by GAL4DNA cotransfection assay	ec50	0.0009	uM
tert-butyl (2’S,3S)-2’-[3-(4-methoxycarbonyl-3-methylsulfonylphenyl)phenyl]-2-oxospiro[1H-indole-3,3’-pyrrolidine]-1’-carboxylate	1691870: Agonist activity at human RXRalpha/LXRbeta expressed in HEK293 cells measured after 20 hrs by dual luciferase reporter gene assay	ec50	0.0009	uM
(2E,4E,6Z)-7-[2-(2,2-difluoroethoxy)-3,5-di(propan-2-yl)phenyl]-3-methylocta-2,4,6-trienoic acid	199489: Inhibitory activity against Retinoic acid receptor RXR-alpha antagonist was determined in vitro	ic50	0.0010	uM
(2E,4E,6Z)-7-[2-ethoxy-3,5-di(propan-2-yl)phenyl]-3-methylocta-2,4,6-trienoic acid	47191: Transcriptional activity against RXR:PPAR-gamma synergy was determined in vitro	ec50	0.0010	uM
(2E,4E,6Z)-7-[2-methoxy-3,5-di(propan-2-yl)phenyl]-3-methylocta-2,4,6-trienoic acid	199494: Binding affinity against Retinoic acid receptor RXR-alpha was determined in vitro by using [3H]9-cis-RA as radioligand	ki	0.0010	uM
(2E,4E,6Z)-7-[2-(2-fluoroethoxy)-3,5-di(propan-2-yl)phenyl]-3-methylocta-2,4,6-trienoic acid	199494: Binding affinity against Retinoic acid receptor RXR-alpha was determined in vitro by using [3H]9-cis-RA as radioligand	ki	0.0010	uM
(2E,4E,6Z)-7-[2-(2,2-difluoroethoxy)-5-(3-fluorophenyl)-3-propan-2-ylphenyl]-3-methylocta-2,4,6-trienoic acid	199352: Binding affinity against RXR alpha receptor using [3H]9-cis-RA as radioligand in CV-1 cells	ki	0.0010	uM
2-[2-[(2-chlorophenyl)methyl]-1-[4-(3-methylsulfonylphenyl)phenyl]imidazol-4-yl]propan-2-ol	1172001: Binding affinity to LXRbeta-RXRalpha heterodimer (unknown origin) expressed in insect cells by scintillation proximity assay	ki	0.0010	uM
(2E,4E)-3-methyl-5-[(2S)-2-methyl-2-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)cyclopropyl]penta-2,4-dienoic acid	1925171: Inhibition of human full length Nurr1-RXRalpha transfected in COS7 cells	ec50	0.0010	uM
(2E,4E,6Z)-7-(3,5-ditert-butyl-2-methoxyphenyl)-3-methylocta-2,4,6-trienoic acid	199494: Binding affinity against Retinoic acid receptor RXR-alpha was determined in vitro by using [3H]9-cis-RA as radioligand	ki	0.0010	uM
4-[5-(3-tert-butylphenyl)-1-(4-methylsulfonylphenyl)pyrazol-3-yl]benzoic acid	1306249: Displacement of [3H]-TTNPB from RARgamma/RXRalpha (unknown origin) expressed in baculovirus expression system by scintillation proximity assay	ki	0.0011	uM
4-[5-(3-tert-butyl-5-methylphenyl)-1-(4-methylsulfonylphenyl)pyrazol-3-yl]benzoic acid	1306249: Displacement of [3H]-TTNPB from RARgamma/RXRalpha (unknown origin) expressed in baculovirus expression system by scintillation proximity assay	ki	0.0011	uM
4-[5-(3,5-ditert-butylphenyl)-1-[4-(4-methylpiperazine-1-carbonyl)phenyl]pyrazol-3-yl]benzoic acid	1306249: Displacement of [3H]-TTNPB from RARgamma/RXRalpha (unknown origin) expressed in baculovirus expression system by scintillation proximity assay	ki	0.0011	uM
3-[4-(trifluoromethoxy)-3-[4,4,6-trimethyl-2-oxo-1-(2,2,2-trifluoroethyl)-3H-quinolin-7-yl]phenyl]propanoic acid	307699: Activity at RXRalpha by GAL4DNA cotransfection assay	ec50	0.0014	uM
4-[1-(4-carbamoylphenyl)-5-(3,5-ditert-butylphenyl)pyrazol-3-yl]benzoic acid	1306249: Displacement of [3H]-TTNPB from RARgamma/RXRalpha (unknown origin) expressed in baculovirus expression system by scintillation proximity assay	ki	0.0014	uM
alitretinoin	167582: Transcriptional activation in CV-1 cells expressing retinoid X receptor RXR alpha	ec50	0.0015	uM
(2E,4E,6Z)-7-[3,5-ditert-butyl-2-(2,2-difluoroethoxy)phenyl]-3-methylocta-2,4,6-trienoic acid	199352: Binding affinity against RXR alpha receptor using [3H]9-cis-RA as radioligand in CV-1 cells	ki	0.0015	uM
(2E,4E)-3-methyl-5-[2-methyl-2-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)cyclopropyl]penta-2,4-dienoic acid	167583: Inhibition of [3H]9-cis-retinoic acid binding to baculovirus expressed retinoic acid receptor RXR-alpha	kd	0.0015	uM
(E)-3-[3-(3,5-ditert-butyl-2-propoxyphenyl)-1H-indol-5-yl]but-2-enoic acid	199350: Ability to displace [3H]9-cis-RA from Retinoid X receptor alpha in CV-1 cells	ki	0.0016	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	increases expression, decreases expression, increases phosphorylation, affects localization, increases activity (+9 more)	30
Alitretinoin	affects activity, increases stability, decreases degradation, decreases reaction, decreases expression (+9 more)	23
Calcitriol	increases expression, affects response to substance, affects binding, affects cotreatment, increases stability (+5 more)	11
Benzo(a)pyrene	increases reaction, increases methylation, affects methylation, affects cotreatment, decreases expression (+2 more)	8
sodium arsenite	affects methylation, decreases expression, increases expression	7
Rosiglitazone	affects binding, affects cotreatment, decreases reaction, decreases expression, increases expression	6
Bexarotene	increases activity, increases expression, increases reaction, affects reaction, affects binding	6
tributyltin	decreases response to substance, affects binding, decreases reaction, affects reaction, increases activity (+1 more)	5
bisphenol A	increases expression, affects binding, affects cotreatment	4
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression, increases stability, affects cotreatment, affects localization, decreases reaction (+2 more)	4
LG 100268	affects binding, increases activity, increases expression, decreases reaction, increases reaction	4
Rifampin	affects binding, affects cotreatment, increases activity, increases reaction, decreases reaction (+2 more)	4
Valproic Acid	decreases methylation, increases methylation, affects expression	4
Aflatoxin B1	affects methylation, affects localization, decreases reaction, affects binding, decreases expression	4
pirinixic acid	affects cotreatment, decreases expression, increases activity, increases expression	3
AGN 194204	affects binding, increases activity, increases response to substance	3
Acetaminophen	decreases expression	3
Lithocholic Acid	affects binding, increases reaction	3
Tetrachlorodibenzodioxin	increases expression	3
Fenretinide	increases expression, increases reaction, decreases expression, affects binding	3
diisononyl phthalate	affects binding	2
triphenyltin chloride	affects reaction, increases activity, increases expression, affects binding, decreases reaction	2
perfluorooctanoic acid	increases expression, affects cotreatment	2
1,4-bis(2-(3,5-dichloropyridyloxy))benzene	affects binding, affects cotreatment, increases reaction	2
triphenyltin	affects reaction, increases activity, affects binding	2
9-cis-retinal	increases reaction, increases expression, affects binding	2
1,25-dihydroxyvitamin D	decreases expression, affects binding, increases reaction	2
U 0126	increases reaction, affects binding, decreases degradation, decreases reaction, increases phosphorylation	2
Arsenic Trioxide	increases expression, increases phosphorylation, decreases reaction	2
Troglitazone	decreases reaction, decreases response to substance, increases response to substance, affects binding, increases activity (+1 more)	2

ChEMBL screening assays

846 unique, capped per target: 703 binding, 138 functional, 5 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1015266	Binding	Increase in transcriptional activity of RXRalpha ligand binding domain expressed in human Hep G2 cells co-transfected with Gal4-DBD by luciferase reporter gene assay	Crystal 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
CHEMBL1024628	Functional	Agonist activity at RXRalpha expressed in african green monkey COS1 cells by luciferase reporter gene assay relative to LGD1069	Replacing alkyl sulfonamide with aromatic sulfonamide in sulfonamide-type RXR agonists favors switch towards antagonist activity. — Bioorg Med Chem Lett
CHEMBL4430357	ADMET	Agonist activity at human RXRalpha/LXRalpha expressed in human HCT116 cells assessed as reduction in SREBP-mediated transcription activity at 100 nM incubated for 24 hrs by luciferase reporter gene assay relative to bexarotene	Modeling, Synthesis, and Biological Evaluation of Potential Retinoid X Receptor (RXR)-Selective Agonists: Analogues of 4-[1-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic Acid (Bexarotene) and 6-(Ethyl(5,5,8,8-tetrahydronaphthalen-2-yl)amino)nicotinic Acid (NEt-TMN). — J Med Chem

Cellosaurus cell lines

28 cell lines: 15 cancer cell line, 9 transformed cell line, 4 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_6355	2V6.11	Transformed cell line	Female
CVCL_7261	EcR-293	Transformed cell line	Female
CVCL_A5Z4	SEES3-1V human RXRA, clone1	Embryonic stem cell	Male
CVCL_A5Z5	SEES3-1V human RXRA, clone2	Embryonic stem cell	Male
CVCL_A5Z6	SEES3-1V human RXRA, clone3	Embryonic stem cell	Male
CVCL_B1E4	Abcam HCT 116 RXRA KO	Cancer cell line	Male
CVCL_BW94	ES-R1 CAG-S-hRXRalpha	Embryonic stem cell	Male
CVCL_D3XP	EcR-293-LacZ	Transformed cell line	Female
CVCL_D3XR	Neuro2a-RXR	Cancer cell line	Male
CVCL_D3YR	Neuro2a-tNhtt-EGFP-16Q	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00104104	PHASE4	COMPLETED	A Multiple Myeloma Trial in Patients With Bone Metastases
NCT00211211	PHASE4	COMPLETED	FREE Study - Fracture Reduction Evaluation
NCT00242528	PHASE4	WITHDRAWN	Open-label Study, to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Bone Lesions Secondary to Multiple Myeloma.
NCT00257114	PHASE4	COMPLETED	Evaluation of VELCADE Given as Retreatment to Multiple Myeloma Patients for Efficacy, Safety and Tolerability
NCT00352703	PHASE4	COMPLETED	PROMPT - Palifermin in Reduction of Oral Mucositis in PBSC Transplantation
NCT00361140	PHASE4	COMPLETED	Busulfan Safety/Efficacy as Conditioning Prior to Hematopoietic Cell Transplantation (HCT)
NCT00622505	PHASE4	COMPLETED	Zoledronic Acid Treatment (Every 4 or 12 Weeks) to Prevent Skeletal Complications in Advanced Multiple Myeloma Participants
NCT00652041	PHASE4	COMPLETED	Bortezomib/Adriamycine/Melfalan/Prednisone (VAMP)/Thalidomide/Cyclophosphamide/Dexamethasone (TaCyDex) or Bortezomib/Melfalan/Prednisone (V-MP)/TaCyDex) in Refractary or Relapsed Multiple Myeloma
NCT00733538	PHASE4	COMPLETED	Stage I Multiple Myeloma Treatment
NCT01087008	PHASE4	COMPLETED	Zoledronic Acid in Patients With Multiple Myeloma and Asymptomatic Biochemical Relapse
NCT01249690	PHASE4	UNKNOWN	Efficacy Study of PAD and TAD in Newly Diagnosed Multiple Myeloma
NCT01410929	PHASE4	WITHDRAWN	Evaluation of Vertebral Compression Fracture Fixation With RF Kyphoplasty in Patients With Multiple Myeloma
NCT01731886	PHASE4	COMPLETED	Lenalidomide and Dexamethasone With/Without Stem Cell Transplant in Patients With Multiple Myeloma
NCT01868828	PHASE4	UNKNOWN	A Study of PAD Versus Velcade, Cyclophosphamide and Dexamethasone (VCD) Treatment in Subjects With Multiple Myeloma
NCT02268890	PHASE4	COMPLETED	A Pharmacokinetic Study of Bortezomib in Taiwanese Participants With Multiple Myeloma
NCT02286830	PHASE4	COMPLETED	Prolonged Protection From Bone Disease in Multiple Myeloma
NCT02559154	PHASE4	UNKNOWN	Modified Bortezomib-based Combination Therapy for Multiple Myeloma
NCT02577783	PHASE4	UNKNOWN	PDD vs PAD to Treat Initially Diagnosed MM
NCT02773550	PHASE4	TERMINATED	Treatment With a Scheme With Low Doses of Bortezomib / Melphalan / Prednisone (MPV) in Patients With Multiple Myeloma
NCT02958969	PHASE4	COMPLETED	Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma
NCT03173092	PHASE4	TERMINATED	A Study of Ixazomib (NINLARO®) in Combination With Lenalidomide and Dexamethasone (IRD) for the Treatment of Participants With Multiple Myeloma (MM)
NCT03619252	PHASE4	COMPLETED	Pneumococcal Vaccination of Multiple Myeloma Patients on Novel Agents
NCT03768960	PHASE4	COMPLETED	A Study of DARZALEX (Daratumumab) In Indian Participants With Relapsed and Refractory Multiple Myeloma, Whose Prior Therapy Included a Proteasome Inhibitor and an Immunomodulatory Agent
NCT03829371	PHASE4	ACTIVE_NOT_RECRUITING	STUDY COMPARING TWO STANDARD TREATMENTS IN AUTOLOGOUS STEM CELL TRANSPLANTATION INELIGIBLE POPULATION AFFECTED BY MULTIPLE MYELOMA
NCT03908138	PHASE4	UNKNOWN	RDD Versus VDD in Newly Diagnosed Patients With Multiple Myeloma
NCT04217967	PHASE4	COMPLETED	Ixazomib, Lenalidomide, and Combination for Maintenance in NDMM Patients
NCT04952766	PHASE4	COMPLETED	Study Evaluating SARS-CoV-2 (COVID-19) Humoral Response After BNT162b2 Vaccine in Immunocompromised Adults Compared to Healthy Adults