RXRG

Summary

RXRG (retinoid X receptor gamma, HGNC:10479) is a protein-coding gene on chromosome 1q23.3, encoding Retinoic acid receptor RXR-gamma (P48443). Receptor for retinoic acid.

This gene encodes a member of the retinoid X receptor (RXR) family of nuclear receptors which are involved in mediating the antiproliferative effects of retinoic acid (RA). This receptor forms dimers with the retinoic acid, thyroid hormone, and vitamin D receptors, increasing both DNA binding and transcriptional function on their respective response elements. This gene is expressed at significantly lower levels in non-small cell lung cancer cells. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 6258 — RefSeq curated summary.

At a glance

• GWAS associations: 27
• Clinical variants (ClinVar): 48 total
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006917

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10479
Approved symbol	RXRG
Name	retinoid X receptor gamma
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	NR2B3, RXRgamma, RXR-gamma
Ensembl gene	ENSG00000143171
Ensembl biotype	protein_coding
OMIM	180247
Entrez	6258

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000359842, ENST00000465764, ENST00000470566, ENST00000619224, ENST00000885409, ENST00000968113

RefSeq mRNA: 3 — MANE Select: NM_006917 NM_001256570, NM_001256571, NM_006917

CCDS: CCDS1248, CCDS72970

Canonical transcript exons

ENST00000359842 — 10 exons

Exon	Start	End
ENSE00000958489	165428719	165428966
ENSE00000958493	165410702	165410831
ENSE00000958495	165408227	165408318
ENSE00000958496	165406812	165406917
ENSE00001068377	165400922	165401410
ENSE00001813843	165444845	165445126
ENSE00002398686	165409558	165409690
ENSE00003612310	165417041	165417220
ENSE00003632302	165410949	165411109
ENSE00003653628	165419870	165420014

Expression profiles

Bgee: expression breadth ubiquitous, 170 present calls, max score 94.07.

FANTOM5 (CAGE): breadth broad, TPM avg 2.5821 / max 314.8577, expressed in 323 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15726	1.1283	214
15730	0.2330	101
15727	0.2180	79
15722	0.2174	93
15728	0.1823	88
15719	0.1579	36
15729	0.1467	71
15718	0.1076	39
15723	0.0788	36
15724	0.0450	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	94.07	gold quality
adenohypophysis	UBERON:0002196	89.56	gold quality
muscle of leg	UBERON:0001383	89.55	gold quality
gastrocnemius	UBERON:0001388	89.35	gold quality
pituitary gland	UBERON:0000007	88.65	gold quality
caudate nucleus	UBERON:0001873	86.46	gold quality
muscle organ	UBERON:0001630	86.13	gold quality
putamen	UBERON:0001874	85.55	gold quality
nucleus accumbens	UBERON:0001882	85.46	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.12	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.06	gold quality
islet of Langerhans	UBERON:0000006	83.65	gold quality
spinal cord	UBERON:0002240	82.29	gold quality
tibial nerve	UBERON:0001323	81.72	gold quality
biceps brachii	UBERON:0001507	79.83	gold quality
hypothalamus	UBERON:0001898	79.34	gold quality
skeletal muscle tissue	UBERON:0001134	79.08	gold quality
apex of heart	UBERON:0002098	78.86	gold quality
amygdala	UBERON:0001876	78.63	gold quality
right frontal lobe	UBERON:0002810	77.32	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	77.18	silver quality
triceps brachii	UBERON:0001509	76.99	gold quality
cingulate cortex	UBERON:0003027	76.85	gold quality
anterior cingulate cortex	UBERON:0009835	76.60	gold quality
muscle tissue	UBERON:0002385	75.98	gold quality
sural nerve	UBERON:0015488	75.73	gold quality
quadriceps femoris	UBERON:0001377	75.45	silver quality
vastus lateralis	UBERON:0001379	75.13	silver quality
prefrontal cortex	UBERON:0000451	74.86	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	74.79	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-98556	yes	302.30
E-MTAB-7316	yes	21.58
E-HCAD-5	yes	15.79
E-GEOD-81547	yes	10.07
E-MTAB-5061	yes	8.82
E-ANND-3	yes	3.65
E-HCAD-30	no	38.10

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
FOXA1
GLI2	Activation
MBP	Activation
NES
PIAS3	Unknown
RBP2
SFTPB	Activation

JASPAR motifs

Motif	Name	Family
MA0856.1	RXRG	RXR-related receptors (NR2)
MA1149.1	RARA::RXRG	Thyroid hormone receptor-related factors (NR1)::RXR-related receptors (NR2)
MA1149.2	RARA::RXRG	Thyroid hormone receptor-related factors (NR1)::RXR-related receptors (NR2)
MA1556.1	RXRG	RXR-related receptors (NR2)

JASPAR matrix evidence (PMIDs): PMID:15019979, PMID:10698945, PMID:14559106

Upstream regulators (CollecTRI, top): E2F1, NR2F1, RARA, RARB

miRNA regulators (miRDB)

31 targeting RXRG, 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-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-12135	98.99	70.26	1814
HSA-MIR-3188	98.58	65.60	878
HSA-MIR-6810-5P	98.29	66.21	975
HSA-MIR-10226	98.25	66.50	811
HSA-MIR-6730-5P	98.03	68.12	1299
HSA-MIR-450A-2-3P	97.91	67.56	1459
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-7112-3P	97.67	68.77	948
HSA-MIR-3184-3P	96.96	66.91	845

Literature-anchored findings (GeneRIF, showing 22)

• 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)
• Single nucleotide polymorphism not a factor in resistance to thyroid hormone. (PMID:15186611)
• Retinoid X receptor-gamma and peroxisome proliferator-activated receptor-gamma expression may have roles in apoptosis of thyroid carcinoma (PMID:15299084)
• The retinoid X receptor, gamma expression is mainly restricted to the muscle and brain. (PMID:15608692)
• 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)
• RXRgamma contributes to the genetic background of familial combined hyperlipidemia. (PMID:17272748)
• These data indicate that the RAR/RXR heterodimer is a critical regulator of human hematopoietic stem cell (HSC) differentiation, and pharmacological modulation of RXR signaling prevents the loss of human HSCs that otherwise occurs in short-term culture. (PMID:19106195)
• methylation-associated downregulation of the RXRG gene may play a differential role in the carcinogenesis of non-small cell lung cancer (NSCLC) according to smoking status. (PMID:20113835)
• RXRgamma and PPARgamma ligands acted synergistically to inhibit proliferation and invasiveness in colon cancer cells. (PMID:20510503)
• results indicate that RXR-gamma is a positive regulator of endogenous oligodendrocyte precursor cell differentiation and remyelination. (PMID:21131950)
• The RXR-gamma rs3818569 single nucleotide polymorphisms is associated with diabetic retinopathy development in the Taiwanese population. (PMID:22180072)
• Genetic variation in RXRgamma gene may contribute to the development of HIVLD in combination antiretroviral therapy treated HIV patients. (PMID:23759678)
• loss of RXR-gamma levels appears to provide mechanistic benefits to transformed cells towards the acquisition of resistance to apoptosis hallmark of cancer (PMID:23936423)
• Differences in RAR and RXR subtype mRNA expression patterns in various PTCs may contribute to the immunochemistry data available, and may thus find exploitation in clinical oncology, particularly in the differential diagnosis of thyroid neoplasms. (PMID:23969901)
• Data show that some rexinoids display selective coactivator (CoA) recruitment by the retinoid X receptors (RXRs) homodimer and by the heterodimers nuclear receptor Nur77/RXR and Nurr1/RXR. (PMID:26148973)
• Data show that pregnane X receptor/retinoid X receptor PXR/RXR-[alpha], RXR-[beta], or RXR-[gamma] expression was noted in 9 (16.4%), 9 (16.4%), and 10 (18.2%) pancreatic adenocarcinoma cases, respectively. (PMID:26355550)
• Germline mutations in the RXRG gene are linked to Familial isolated pituitary adenoma in a Brazilian Family. (PMID:27245436)
• Findings indicate that Gc globulin (GC) rs16847024, retinoid X receptor gamma (RXRG) rs17429130 and retinoid X receptor alpha (RXRA) rs4917356 were candidate susceptibility markers for gestational diabetes mellitus (GDM) in Chinese females. (PMID:27636996)
• genetic association studies in a population in Brazil: Data suggest that SNPs in RXRG (rs2134095) and GC (rs7041) are associated with low-density lipoprotein cholesterol levels and hypercholesterolemia in the population studied; there was no apparent association with an SNP in VDR (rs2228570). (RXRG = retinoid X receptor gamma; GC = vitamin D-binding protein; VDR = vitamin D receptor) (PMID:27721113)
• Using a progression model of epithelial ovarian cancer (EOC), a proteomics-based approach identified a specific loss of RXR-gamma driving the progression of EOC. (PMID:31359385)
• Association between Single-nucleotide Polymorphisms of RXRG and Genetic Susceptibility to Type 2 Diabetes in South China. (PMID:31808386)
• Association between functional genetic variants in retinoid X receptor-alpha/gamma and the risk of gestational diabetes mellitus in a southern Chinese population. (PMID:34633445)

Cross-species orthologs

34 orthologs

Organism	Symbol	Gene ID
danio_rerio	rxrgb	ENSDARG00000004697
danio_rerio		ENSDARG00000110856
mus_musculus	Rxrg	ENSMUSG00000015843
rattus_norvegicus	Rxrg	ENSRNOG00000004537
drosophila_melanogaster	usp	FBGN0003964
drosophila_melanogaster	Hnf4	FBGN0004914
drosophila_melanogaster	Hr78	FBGN0015239
drosophila_melanogaster	Hr83	FBGN0037436
caenorhabditis_elegans		WBGENE00003626
caenorhabditis_elegans		WBGENE00003628
caenorhabditis_elegans		WBGENE00003650
caenorhabditis_elegans	nhr-69	WBGENE00003659
caenorhabditis_elegans		WBGENE00003678
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), NR2F6 (ENSG00000160113), HNF4G (ENSG00000164749), NR2F1 (ENSG00000175745), NR2C2 (ENSG00000177463), NR2F2 (ENSG00000185551), RXRA (ENSG00000186350), RXRB (ENSG00000204231), NR2E3 (ENSG00000278570)

Protein

Protein identifiers

Retinoic acid receptor RXR-gamma — P48443 (reviewed: P48443)

Alternative names: Nuclear receptor subfamily 2 group B member 3, Retinoid X receptor gamma

All UniProt accessions (3): P48443, A0A087WZ88, F1D8Q7

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and 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. The high affinity ligand for RXRs is 9-cis retinoic acid.

Subunit / interactions. Homodimer. Heterodimer with a RAR molecule. Binds DNA preferentially as a RAR/RXR heterodimer. Interacts with RARA.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in aortic endothelial cells (at protein level).

Post-translational modifications. Acetylated by EP300.

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

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

RefSeq proteins (3): NP_001243499, NP_001243500, NP_008848* (*=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 (24 total): helix 13, region of interest 3, strand 2, zinc finger region 2, chain 1, domain 1, DNA-binding region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7A79	X-RAY DIFFRACTION	2.05
2GL8	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48443-F1	75.28	0.55

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-383280	Nuclear Receptor transcription pathway
R-HSA-5362517	Signaling by Retinoic Acid
R-HSA-162582	Signal Transduction
R-HSA-212436	Generic Transcription Pathway
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9006931	Signaling by Nuclear Receptors

MSigDB gene sets: 197 (showing top): MYAATNNNNNNNGGC_UNKNOWN, BENPORATH_ES_WITH_H3K27ME3, GGTGTGT_MIR329, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, MORF_MSH3, GOBP_CELLULAR_RESPONSE_TO_LIPID, HOFMANN_CELL_LYMPHOMA_UP, GCANCTGNY_MYOD_Q6, MORF_BRCA1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, AP4_Q6, MORF_ESR1, MODULE_404, CAGCTG_AP4_Q5, MORF_RAD51L3

GO Biological Process (6): nervous system development (GO:0007399), cell differentiation (GO:0030154), positive regulation of transcription by RNA polymerase II (GO:0045944), retinoic acid receptor signaling pathway (GO:0048384), regulation of DNA-templated transcription (GO:0006355), nuclear receptor-mediated steroid hormone signaling pathway (GO:0030518)

GO Molecular Function (12): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), nuclear steroid receptor activity (GO:0003707), nuclear receptor activity (GO:0004879), zinc ion binding (GO:0008270), retinoic acid-responsive element binding (GO:0044323), molecular condensate scaffold activity (GO:0140693), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (5): chromatin (GO:0000785), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), RNA polymerase II transcription regulator complex (GO:0090575), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Generic Transcription Pathway	1
Signaling by Nuclear Receptors	1
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of transcription by RNA polymerase II	2
nuclear receptor-mediated signaling pathway	2
system development	1
cellular developmental process	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
hormone-mediated signaling pathway	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
steroid hormone receptor signaling pathway	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
nuclear receptor activity	1
nuclear receptor-mediated steroid hormone signaling pathway	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
intracellular receptor signaling pathway	1
signaling receptor activity	1
ligand-modulated transcription factor activity	1
transition metal ion binding	1
RNA polymerase II cis-regulatory region sequence-specific DNA binding	1
protein-macromolecule adaptor activity	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
regulation of DNA-templated transcription	1
transcription regulator activity	1
binding	1
DNA binding	1
cation binding	1
chromosome	1
nuclear lumen	1
intracellular anatomical structure	1
transcription regulator complex	1
nuclear protein-containing complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1412 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RXRG	THRB	P10828	665
RXRG	RARB	P10826	630
RXRG	NR1H4	Q96RI1	601
RXRG	NR1H3	Q13133	570
RXRG	CYP7A1	P22680	554
RXRG	DRD2	P14416	554
RXRG	XPR1	Q9UBH6	547
RXRG	RARS1	P54136	490
RXRG	FOS	P01100	487
RXRG	CRX	O43186	476
RXRG	RARA	P10276	476
RXRG	ZNF423	Q2M1K9	470
RXRG	POU3F1	Q03052	468
RXRG	FABP4	P15090	463
RXRG	BMAL1	O00327	462

IntAct

217 interactions, top by confidence:

A	B	Type	Score
RARA	RXRG	psi-mi:“MI:0915”(physical association)	0.940
RXRG	RARA	psi-mi:“MI:0915”(physical association)	0.940
NR1H2	RXRG	psi-mi:“MI:0915”(physical association)	0.810
RXRG	NR1H2	psi-mi:“MI:0915”(physical association)	0.810
RARA	NCOR1	psi-mi:“MI:0914”(association)	0.800
RARB	RXRG	psi-mi:“MI:0915”(physical association)	0.780
RXRG	RARB	psi-mi:“MI:0915”(physical association)	0.780
NR1H3	RXRG	psi-mi:“MI:0915”(physical association)	0.740

BioGRID (67): RXRG (Two-hybrid), RXRG (Two-hybrid), RXRG (Two-hybrid), NR1H2 (Two-hybrid), NR1H3 (Two-hybrid), RXRG (Affinity Capture-Western), RXRG (Affinity Capture-Western), RXRG (Affinity Capture-Western), RXRG (Two-hybrid), SRF (Two-hybrid), RXRG (Two-hybrid), RXRG (Two-hybrid), NR1H2 (Two-hybrid), NR1H3 (Two-hybrid), RARA (Two-hybrid)

ESM2 similar proteins: A0A1L8GWK2, A0A571BF63, A0JMA8, A0JNE3, A2BGA0, A4IIG7, O00443, P13056, P24781, P28701, P28705, P43354, P45448, P48443, P51128, P51129, Q04913, Q06219, Q07917, Q08E53, Q09555, Q0GFF6, Q0IHW3, Q0VC20, Q1LVF3, Q26622, Q33E94, Q505F1, Q5BJR8, Q5FWP2, Q5R5Y4, Q5RAY1, Q5RCZ5, Q5REL6, Q5RJH6, Q61194, Q64287, Q68F67, Q6DHP9, 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

7 interactions.

A	Effect	B	Mechanism
RARA	up-regulates	RXRG	binding
RARA	“up-regulates quantity by expression”	RXRG	“transcriptional regulation”
“all-trans-retinoic acid”	“up-regulates activity”	RXRG	“chemical activation”
bexarotene	“up-regulates activity”	RXRG	“chemical activation”
“9-cis-retinoic acid”	“up-regulates activity”	RXRG	“chemical activation”
RXRG	“up-regulates quantity”	MBP	“transcriptional regulation”
RXRG	“up-regulates quantity”	GLI2	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 43 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
SUMOylation of intracellular receptors	6	56.0×	8e-08
Nuclear Receptor transcription pathway	10	55.6×	2e-13
Chemokine receptors bind chemokines	5	26.0×	6e-05
SARS-CoV-2 activates/modulates innate and adaptive immune responses	6	14.9×	7e-05
PPARA activates gene expression	5	13.1×	8e-04
Activation of anterior HOX genes in hindbrain development during early embryogenesis	5	12.7×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
intracellular receptor signaling pathway	5	123.9×	9e-08
retinoic acid receptor signaling pathway	6	97.2×	1e-08
mRNA transcription by RNA polymerase II	5	41.3×	8e-06
cellular response to virus	6	30.1×	5e-06
adaptive immune response	7	14.8×	2e-05
defense response to virus	6	10.4×	4e-04
inflammatory response	9	8.5×	3e-05
negative regulation of cell population proliferation	6	6.3×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1716 predictions. Top by Δscore:

Variant	Effect	Δscore
1:165401408:AACC:A	acceptor_loss	1.0000
1:165401410:CCT:C	acceptor_loss	1.0000
1:165401411:C:G	acceptor_loss	1.0000
1:165401412:T:A	acceptor_loss	1.0000
1:165408221:GGTTA:G	donor_loss	1.0000
1:165408223:TTA:T	donor_loss	1.0000
1:165408224:TAC:T	donor_loss	1.0000
1:165408314:GGACT:G	acceptor_gain	1.0000
1:165408315:GACT:G	acceptor_gain	1.0000
1:165408316:ACT:A	acceptor_gain	1.0000
1:165408317:CT:C	acceptor_gain	1.0000
1:165408317:CTC:C	acceptor_gain	1.0000
1:165408318:TC:T	acceptor_loss	1.0000
1:165408318:TCT:T	acceptor_gain	1.0000
1:165408319:C:CC	acceptor_gain	1.0000
1:165408320:T:A	acceptor_loss	1.0000
1:165408326:C:CT	acceptor_gain	1.0000
1:165408327:A:T	acceptor_gain	1.0000
1:165410697:TTTA:T	donor_loss	1.0000
1:165410698:TTACC:T	donor_loss	1.0000
1:165410699:TA:T	donor_loss	1.0000
1:165410827:TTTGT:T	acceptor_gain	1.0000
1:165410828:TTGT:T	acceptor_gain	1.0000
1:165410829:TGT:T	acceptor_gain	1.0000
1:165410830:GT:G	acceptor_gain	1.0000
1:165410830:GTCT:G	acceptor_loss	1.0000
1:165410831:TCTGA:T	acceptor_loss	1.0000
1:165410832:C:CC	acceptor_gain	1.0000
1:165410832:CT:C	acceptor_loss	1.0000
1:165410833:T:C	acceptor_loss	1.0000

AlphaMissense

3032 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:165401288:A:G	L456S	1.000
1:165401300:A:G	L452P	1.000
1:165401300:A:T	L452H	1.000
1:165401302:G:C	F451L	1.000
1:165401302:G:T	F451L	1.000
1:165401303:A:G	F451S	1.000
1:165401304:A:G	F451L	1.000
1:165401312:A:T	I448N	1.000
1:165401330:A:G	L442P	1.000
1:165401330:A:T	L442H	1.000
1:165401335:G:C	F440L	1.000
1:165401335:G:T	F440L	1.000
1:165401337:A:G	F440L	1.000
1:165401341:G:C	F438L	1.000
1:165401341:G:T	F438L	1.000
1:165401343:A:G	F438L	1.000
1:165401345:A:G	L437P	1.000
1:165401351:T:A	E435V	1.000
1:165401356:G:C	C433W	1.000
1:165401357:C:T	C433Y	1.000
1:165401358:A:G	C433R	1.000
1:165401366:C:A	G430V	1.000
1:165401366:C:T	G430D	1.000
1:165401367:C:G	G430R	1.000
1:165401369:A:T	I429N	1.000
1:165401373:A:G	S428P	1.000
1:165401375:C:G	R427P	1.000
1:165401376:G:T	R427S	1.000
1:165401378:A:C	L426R	1.000
1:165401378:A:G	L426P	1.000

dbSNP variants (sampled 300 via entrez): RS1000019504 (1:165421692 G>A), RS1000032845 (1:165417973 T>C), RS1000105281 (1:165402119 T>C), RS1000114227 (1:165408149 C>G,T), RS1000255420 (1:165411420 C>A), RS1000285820 (1:165421336 C>G), RS1000336592 (1:165408358 G>A,C), RS1000514375 (1:165413139 A>T), RS1000588045 (1:165412859 A>G), RS1000698472 (1:165418247 T>G), RS1000884709 (1:165443901 C>A,T), RS1000991882 (1:165439313 G>A), RS1001039057 (1:165437451 A>G), RS1001108391 (1:165446089 G>A), RS1001108742 (1:165403568 A>C,G)

Disease associations

OMIM: gene MIM:180247 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST000487_5	AIDS	4.000000e-06
GCST000880_16	Menarche (age at onset)	1.000000e-13
GCST000995_7	Personality traits in bipolar disorder	4.000000e-07
GCST002541_32	Menarche (age at onset)	2.000000e-24
GCST003993_22	Menarche (age at onset)	4.000000e-15
GCST004001_5	Bipolar disorder or attention deficit hyperactivity disorder	2.000000e-07
GCST004002_3	Bipolar disorder (age of onset <21) or attention deficit hyperactivity disorder	7.000000e-06
GCST005867_14	Menarche (age at onset)	5.000000e-08
GCST006976_88	Macular thickness	4.000000e-09
GCST009391_107	Metabolite levels	1.000000e-06
GCST009391_195	Metabolite levels	9.000000e-06
GCST010796_4809	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_4810	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_4811	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_4812	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_4813	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_4814	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_4815	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_4816	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_4821	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_4822	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST010796_4823	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_4824	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_4825	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-09
GCST010917_2	Proportion of activated microglia (midfrontal cortex)	9.000000e-06
GCST012226_582	Waist circumference adjusted for body mass index	1.000000e-09
GCST90020029_1234	Waist circumference adjusted for body mass index	2.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0004365	personality trait
EFO:0010491	glycocholate measurement
EFO:0010482	gamma-aminoisobutyric acid measurement
EFO:0004327	electrocardiography
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2004 (SINGLE PROTEIN), CHEMBL2363070 (PROTEIN FAMILY), CHEMBL2363071 (PROTEIN FAMILY), CHEMBL2363072 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 326,531 (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
CHEMBL38	TRETINOIN	4	194,008
CHEMBL705	ALITRETINOIN	4	39,246
CHEMBL295416	PIRINIXIC ACID	2	830
CHEMBL75133	IRX-4204	2	452

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

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs380518	RXRG		0.00	0
rs4657437	RXRG		0.00	0
rs283695	RXRG		0.00	0
rs3767344	RXRG		0.00	0
rs157880	RXRG		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 (7 total), top 7:

Ligand	Action	Affinity	Parameter
LG100268	Agonist	8.52	pIC50
AGN194204	Agonist	8.4	pKd
alitretinoin	Agonist	8.0	pIC50
LG100754	Antagonist	7.9	pKi
[3H]9-cis-retinoic acid	Full agonist	7.9	pKd
bexarotene	Agonist	7.54	pIC50
compound 28 [Heitel et al., 2019]	Agonist	5.8	pEC50

ChEMBL bioactivities

335 potent at pChembl≥5 of 395 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.10	EC50	0.08	nM	IRX-4204
9.89	EC50	0.13	nM	CHEMBL2325917
9.85	EC50	0.14	nM	CHEMBL2321917
9.22	EC50	0.6	nM	CHEMBL5404648
9.00	EC50	1	nM	CHEMBL69091
8.85	Ki	1.4	nM	TRETINOIN
8.74	Kd	1.8	nM	CHEMBL69091
8.70	EC50	2	nM	CHEMBL96184
8.70	EC50	2	nM	TRETINOIN
8.59	EC50	2.6	nM	CHEMBL5404648
8.55	Ki	2.8	nM	CHEMBL337393
8.54	Ki	2.9	nM	CHEMBL130232
8.52	EC50	3	nM	CHEMBL5289973
8.42	Kd	3.8	nM	IRX-4204
8.40	EC50	4	nM	CHEMBL423465
8.40	EC50	4	nM	CHEMBL5404648
8.40	Ki	4	nM	CHEMBL111589
8.40	EC50	4	nM	CHEMBL109581
8.40	IC50	4	nM	ALITRETINOIN
8.40	EC50	4	nM	CHEMBL328481
8.37	EC50	4.3	nM	ALITRETINOIN
8.35	EC50	4.5	nM	ALITRETINOIN
8.30	Ki	5	nM	CHEMBL92284
8.30	Ki	5	nM	CHEMBL162334
8.25	Ki	5.6	nM	CHEMBL133915
8.25	Ki	5.6	nM	CHEMBL130374
8.22	Ki	6	nM	CHEMBL93518
8.22	Kd	6	nM	CHEMBL90674
8.22	EC50	6	nM	CHEMBL308377
8.15	EC50	7	nM	CHEMBL92284
8.15	EC50	7	nM	CHEMBL166244
8.15	EC50	7	nM	CHEMBL162334
8.15	EC50	7	nM	CHEMBL109847
8.11	Ki	7.7	nM	CHEMBL133896
8.10	Kd	8	nM	CHEMBL89331
8.10	Ki	8	nM	CHEMBL423465
8.10	EC50	7.9	nM	CHEMBL4547228
8.10	EC50	8	nM	CHEMBL114640
8.08	Ki	8.3	nM	BEXAROTENE
8.05	EC50	9	nM	CHEMBL166201
8.05	EC50	9	nM	CHEMBL111589
8.03	Ki	9.3	nM	CHEMBL89241
8.00	Ki	10	nM	CHEMBL208316
8.00	IC50	10	nM	CHEMBL424636
8.00	IC50	10	nM	CHEMBL284937
7.96	EC50	11	nM	CHEMBL164902
7.96	EC50	11	nM	CHEMBL5565773
7.96	Ki	10.9	nM	CHEMBL422088
7.96	Ki	11	nM	ALITRETINOIN
7.92	Ki	12	nM	CHEMBL41890

PubChem BioAssay actives

300 with measured affinity, of 896 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
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
(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	167594: Transcriptional activation in CV-1 cells expressing retinoid X receptor RXR gamma	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
trans-(1R,2R)-2-[5-[3,5-bis(trifluoromethyl)phenyl]-4-phenyl-1,3-oxazol-2-yl]cyclopropane-1-carboxylic acid	2024930: Agonist activity at full length human RXR gamma expressed in HEK293T cells measured after 16 hrs by Dual-glo luciferase assay	ec50	0.0006	uM
tretinoin	73356: Binding affinity for retinoic acid receptor RAR gamma	ki	0.0014	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	167595: Inhibition of [3H]9-cis-retinoic acid binding to baculovirus expressed retinoic acid receptor RXR-gamma	kd	0.0018	uM
4-[1-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)ethenyl]benzoic acid	199960: Effective concentrations against Retinoic acid receptor RXR-gamma	ec50	0.0020	uM
(2E,4E,6Z)-7-[2-(2,2-difluoroethoxy)-5-(3,5-difluorophenyl)-3-propan-2-ylphenyl]-3-methylocta-2,4,6-trienoic acid	199816: Binding affinity against RXR gamma receptor using [3H]9-cis-RA as radioligand in CV-1 cells	ki	0.0028	uM
(2E,4E,6Z)-7-[2-(2,2-difluoroethoxy)-5-(3-fluorophenyl)-3-propan-2-ylphenyl]-3-methylocta-2,4,6-trienoic acid	199816: Binding affinity against RXR gamma receptor using [3H]9-cis-RA as radioligand in CV-1 cells	ki	0.0029	uM
4-[N-ethyl-3-(2-methylpropoxy)-4-propan-2-ylanilino]benzoic acid	1925147: Inhibition of RXRgamma (unknown origin)	ec50	0.0030	uM
(2E,4E,6Z)-7-(3-methoxy-5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)-3-methylocta-2,4,6-trienoic acid	199944: Inhibition of [3H]targretin binding to Retinoid X receptor RXR gamma	ki	0.0040	uM
alitretinoin	199380: Binding affinity against retinoic Acid X gamma receptor using [3H]- -9-cis-Retinoic Acid in competitive binding assay	ic50	0.0040	uM
(2E,4E,6Z)-3-methyl-7-(5,5,8,8-tetramethyl-3-propoxy-6,7-dihydronaphthalen-2-yl)octa-2,4,6-trienoic acid	199942: Transcriptional activation of Retinoid X receptor RXR gamma	ec50	0.0040	uM
4-[(E)-N-methoxy-C-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)carbonimidoyl]benzoic acid	199961: Transcriptional activity was evaluated in CV-1 cells transfected with expression vector for Retinoic acid receptor RXR-gamma	ec50	0.0040	uM
4-[(E)-N-hydroxy-C-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)carbonimidoyl]benzoic acid	199966: Binding affinity towards recombinantly expressed Retinoic acid receptor RXR-gamma in baculoviral system, by using 5 nM [3H]targretin in a competitive binding assay	ki	0.0050	uM
(2E,4E,6Z)-7-[2-(2,2-difluoroethoxy)-3-propan-2-yl-5-thiophen-2-ylphenyl]-3-methylocta-2,4,6-trienoic acid	199816: Binding affinity against RXR gamma receptor using [3H]9-cis-RA as radioligand in CV-1 cells	ki	0.0056	uM
(2E,4E,6Z)-7-[2-(2,2-difluoroethoxy)-5-(4-fluorophenyl)-3-propan-2-ylphenyl]-3-methylocta-2,4,6-trienoic acid	199816: Binding affinity against RXR gamma receptor using [3H]9-cis-RA as radioligand in CV-1 cells	ki	0.0056	uM
(2E,4E)-3-methyl-5-[(1R,2R)-2-methyl-2-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)cyclopropyl]penta-2,4-dienoic acid	167594: Transcriptional activation in CV-1 cells expressing retinoid X receptor RXR gamma	ec50	0.0060	uM
(2E,4E)-3-methyl-6-[1-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)cyclopentyl]hexa-2,4-dienoic acid	199954: Inhibition of [3H]-9-cis-RA binding to human Retinoid X receptor RXR gamma	kd	0.0060	uM
4-[(E)-C-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)-N-prop-2-enoxycarbonimidoyl]benzoic acid	199961: Transcriptional activity was evaluated in CV-1 cells transfected with expression vector for Retinoic acid receptor RXR-gamma	ec50	0.0070	uM
(2E,4E,6Z)-7-(3-ethoxy-5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)-3-methylocta-2,4,6-trienoic acid	199942: Transcriptional activation of Retinoid X receptor RXR gamma	ec50	0.0070	uM
(2E,4E,6Z)-7-[2-ethoxy-5-(1,1,2,2,2-pentafluoroethyl)-3-propan-2-ylphenyl]-3-methylocta-2,4,6-trienoic acid	199816: Binding affinity against RXR gamma receptor using [3H]9-cis-RA as radioligand in CV-1 cells	ki	0.0077	uM
4-[ethyl-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)amino]benzoic acid	1630288: Agonist activity at human RXR binding domain and activation domain expressed in human HCT116 cells assessed as rexinoid activity incubated for 24 hrs by luciferase reporter gene based mammalian two-hybrid assay	ec50	0.0079	uM
2-[cyclopropylmethyl-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)amino]pyrimidine-5-carboxylic acid	1925147: Inhibition of RXRgamma (unknown origin)	ec50	0.0080	uM
(2E,4E)-3-methyl-6-[1-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)cyclopropyl]hexa-2,4-dienoic acid	199954: Inhibition of [3H]-9-cis-RA binding to human Retinoid X receptor RXR gamma	kd	0.0080	uM
Bexarotene	199368: Selective activity towards retinoid X receptor-gamma	ki	0.0083	uM
4-[(E)-N-ethoxy-C-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)carbonimidoyl]benzoic acid	199961: Transcriptional activity was evaluated in CV-1 cells transfected with expression vector for Retinoic acid receptor RXR-gamma	ec50	0.0090	uM
(2E,4E,6E)-7-(3,5-ditert-butylphenyl)-3-methylocta-2,4,6-trienoic acid	199967: Inhibition of [3H]9-cis-RA binding to Retinoid X receptor RXR gamma	ki	0.0093	uM
4-[(E)-2-(3-ethyl-5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)prop-1-enyl]benzoic acid	199380: Binding affinity against retinoic Acid X gamma receptor using [3H]- -9-cis-Retinoic Acid in competitive binding assay	ic50	0.0100	uM
4-[(E)-2-(5,5,8,8-tetramethyl-3-propan-2-yl-6,7-dihydronaphthalen-2-yl)prop-1-enyl]benzoic acid	199380: Binding affinity against retinoic Acid X gamma receptor using [3H]- -9-cis-Retinoic Acid in competitive binding assay	ic50	0.0100	uM
(2E,4E)-6-[(6-tert-butyl-1,1-dimethyl-2,3-dihydroinden-4-yl)-propylamino]-3-methylhexa-2,4-dienoic acid	263925: Binding affinity to RXRgamma	ki	0.0100	uM
(2E,4E,6Z)-7-[2-(2,2-difluoroethoxy)-5-(2-fluorophenyl)-3-propan-2-ylphenyl]-3-methylocta-2,4,6-trienoic acid	199816: Binding affinity against RXR gamma receptor using [3H]9-cis-RA as radioligand in CV-1 cells	ki	0.0109	uM
3-[4-chloro-6-(4,4-dimethyl-2,3-dihydroquinolin-1-yl)pyrimidin-2-yl]oxypropanoic acid	2099262: Partial agonist activity at recombinant human RXR gamma LBD (233 to 463 residues) expressed in Escherichia coli Rosetta incubated for 16 hrs by Gal4-hybrid reporter gene based Dual-glo luciferase assay	ec50	0.0110	uM
4-[(E)-N-(cyanomethoxy)-C-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)carbonimidoyl]benzoic acid	199961: Transcriptional activity was evaluated in CV-1 cells transfected with expression vector for Retinoic acid receptor RXR-gamma	ec50	0.0110	uM
(E)-3-[4-[2-ethoxy-3,5-di(propan-2-yl)phenyl]-1-benzothiophen-2-yl]but-2-enoic acid	199189: Displacement of [3H]9-cis-RA from retinoic X receptor gamma	ki	0.0120	uM
6-[1-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)cyclopropyl]pyridine-3-carboxylic acid	199189: Displacement of [3H]9-cis-RA from retinoic X receptor gamma	ki	0.0120	uM
(2E,4E,6E)-7-[3,5-ditert-butyl-2-(2,2,2-trifluoroethoxy)phenyl]-6-fluoro-3-methylocta-2,4,6-trienoic acid	199816: Binding affinity against RXR gamma receptor using [3H]9-cis-RA as radioligand in CV-1 cells	ki	0.0124	uM
(2E,4E,6E)-7-[3,5-ditert-butyl-2-(2,2-difluoroethoxy)phenyl]-6-fluoro-3-methylocta-2,4,6-trienoic acid	199816: Binding affinity against RXR gamma receptor using [3H]9-cis-RA as radioligand in CV-1 cells	ki	0.0132	uM
6-[ethyl-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)amino]pyridine-3-carboxylic acid	1630288: Agonist activity at human RXR binding domain and activation domain expressed in human HCT116 cells assessed as rexinoid activity incubated for 24 hrs by luciferase reporter gene based mammalian two-hybrid assay	ec50	0.0138	uM
6-[ethyl-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)amino]pyridine-3-carboxylic acid	1630288: Agonist activity at human RXR binding domain and activation domain expressed in human HCT116 cells assessed as rexinoid activity incubated for 24 hrs by luciferase reporter gene based mammalian two-hybrid assay	ec50	0.0138	uM
(2E,4E)-3-methyl-5-[2-[(E)-2-(2,6,6-trimethylcyclohexen-1-yl)ethenyl]furan-3-yl]penta-2,4-dienoic acid	199964: Inhibition of [3H]-9-cis RA binding to Retinoid X receptor RXR gamma	kd	0.0140	uM
(2E,4E)-6-[1-(3,5-ditert-butylphenyl)cyclopropyl]-3-methylhexa-2,4-dienoic acid	199954: Inhibition of [3H]-9-cis-RA binding to human Retinoid X receptor RXR gamma	kd	0.0160	uM
trans-(1S,2S)-2-[5-[3,5-bis(trifluoromethyl)phenyl]-4-phenyl-1,3-oxazol-2-yl]cyclopropane-1-carboxylic acid	2024930: Agonist activity at full length human RXR gamma expressed in HEK293T cells measured after 16 hrs by Dual-glo luciferase assay	ec50	0.0170	uM
2-[ethyl-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)amino]pyrimidine-5-carboxylic acid	1630288: Agonist activity at human RXR binding domain and activation domain expressed in human HCT116 cells assessed as rexinoid activity incubated for 24 hrs by luciferase reporter gene based mammalian two-hybrid assay	ec50	0.0182	uM
(E)-3-[4-[3,5-di(propan-2-yl)-2-propoxyphenyl]-1-benzothiophen-2-yl]but-2-enoic acid	199189: Displacement of [3H]9-cis-RA from retinoic X receptor gamma	ki	0.0200	uM
(E)-3-[4-[3,5-ditert-butyl-2-(2,2-difluoroethoxy)phenyl]-1-benzothiophen-2-yl]but-2-enoic acid	199189: Displacement of [3H]9-cis-RA from retinoic X receptor gamma	ki	0.0200	uM
(E)-3-[4-[3,5-ditert-butyl-2-(2,2,2-trifluoroethoxy)phenyl]-1-benzothiophen-2-yl]but-2-enoic acid	199189: Displacement of [3H]9-cis-RA from retinoic X receptor gamma	ki	0.0200	uM
(E)-3-[4-[3,5-ditert-butyl-2-(3-fluoropropoxy)phenyl]-1-benzothiophen-2-yl]but-2-enoic acid	199189: Displacement of [3H]9-cis-RA from retinoic X receptor gamma	ki	0.0210	uM
(2E,4E)-6-[1-(6-tert-butyl-1,1-dimethyl-2,3-dihydroinden-4-yl)cyclopropyl]-3-methylhexa-2,4-dienoic acid	199954: Inhibition of [3H]-9-cis-RA binding to human Retinoid X receptor RXR gamma	kd	0.0220	uM
(2E,4E,6Z)-7-[2-(2,2-difluoroethoxy)-3-phenyl-5-propan-2-ylphenyl]-3-methylocta-2,4,6-trienoic acid	199816: Binding affinity against RXR gamma receptor using [3H]9-cis-RA as radioligand in CV-1 cells	ki	0.0225	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	affects binding, decreases expression, increases activity, increases expression	5
bisphenol A	affects binding, decreases methylation, increases expression	4
Alitretinoin	affects activity, affects binding, decreases expression	3
cadmium sulfate	increases expression	2
Fenretinide	decreases expression, increases expression	2
2-hydroxyphytanic acid	affects binding	1
diethyl phthalate	affects binding	1
triphenyltin hydroxide	affects activity, affects binding	1
mono-(2-ethylhexyl)phthalate	affects binding	1
3-phenoxybenzoic acid	affects binding	1
fenvalerate	affects binding	1
dimethyl phthalate	affects binding	1
di-n-hexyl phthalate	affects binding	1
butylbenzyl phthalate	affects binding	1
phthalic acid	affects binding	1
di-n-pentyl phthalate	affects binding	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
diheptyl phthalate	affects binding	1
CGP 52608	affects binding, increases reaction	1
di-n-propylphthalate	affects binding	1
AGN 194204	increases activity, affects binding	1
5-OH,11-O-hydrophenanthrene	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
bisphenol S	increases methylation	1
bisphenol AF	affects binding	1
Rosiglitazone	affects binding	1
Sunitinib	increases expression	1
Fulvestrant	decreases methylation	1
Bexarotene	affects binding	1
Ethanol	increases expression	1

ChEMBL screening assays

193 unique, capped per target: 169 binding, 24 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1024630	Functional	Agonist activity at RXRgamma 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
CHEMBL1029807	Binding	Activity at RXRgamma ligand binding domain expressed in COS7 cells co-transfected with Gal4-DBD assessed as transcriptional activation after 16 hrs by Gal4 response element-driven luciferase reporter gene assay	Novel non-carboxylic acid retinoids: 1,2,4-oxadiazol-5-one derivatives. — Bioorg Med Chem Lett

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A6A0	SEES3-1V human RXRG, clone1	Embryonic stem cell	Male
CVCL_A6A1	SEES3-1V human RXRG, clone2	Embryonic stem cell	Male
CVCL_A6A2	SEES3-1V human RXRG, clone3	Embryonic stem cell	Male
CVCL_KZ08	PathHunter CHO-K1 RXRgamma Protein Interaction	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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