RARB

Summary

RARB (retinoic acid receptor beta, HGNC:9865) is a protein-coding gene on chromosome 3p24.2, encoding Retinoic acid receptor beta (P10826). Receptor for retinoic acid.

This gene encodes retinoic acid receptor beta, a member of the thyroid-steroid hormone receptor superfamily of nuclear transcriptional regulators. This receptor localizes to the cytoplasm and to subnuclear compartments. It binds retinoic acid, the biologically active form of vitamin A which mediates cellular signalling in embryonic morphogenesis, cell growth and differentiation. It is thought that this protein limits growth of many cell types by regulating gene expression. The gene was first identified in a hepatocellular carcinoma where it flanks a hepatitis B virus integration site. Alternate promoter usage and differential splicing result in multiple transcript variants.

Source: NCBI Gene 5915 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microphthalmia, syndromic 12 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 91
• Clinical variants (ClinVar): 169 total — 6 pathogenic, 16 likely-pathogenic
• Phenotypes (HPO): 19
• Druggable target: yes — 18 molecules with ChEMBL bioactivity
• Transcription factor: yes — 63 downstream targets (CollecTRI)
• MANE Select transcript: NM_000965

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9865
Approved symbol	RARB
Name	retinoic acid receptor beta
Location	3p24.2
Locus type	gene with protein product
Status	Approved
Aliases	HAP, NR1B2, RRB2, RARbeta, RAR-beta
Ensembl gene	ENSG00000077092
Ensembl biotype	protein_coding
OMIM	180220
Entrez	5915

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 15 protein_coding, 7 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000330688, ENST00000383772, ENST00000437042, ENST00000455576, ENST00000458646, ENST00000462272, ENST00000479097, ENST00000480001, ENST00000685523, ENST00000686715, ENST00000687083, ENST00000687353, ENST00000687512, ENST00000687676, ENST00000688892, ENST00000689700, ENST00000690398, ENST00000690576, ENST00000691580, ENST00000691912, ENST00000692640, ENST00000693261, ENST00000693580, ENST00000908036, ENST00000947306

RefSeq mRNA: 8 — MANE Select: NM_000965 NM_000965, NM_001290216, NM_001290217, NM_001290266, NM_001290276, NM_001290277, NM_001290300, NM_016152

CCDS: CCDS2642, CCDS46775, CCDS93227, CCDS93228

Canonical transcript exons

ENST00000330688 — 8 exons

Exon	Start	End
ENSE00001240766	25428263	25428888
ENSE00001498576	25596420	25597932
ENSE00003499027	25461193	25461341
ENSE00003517421	25594520	25594678
ENSE00003625959	25501182	25501323
ENSE00003632613	25593503	25593707
ENSE00003662797	25580546	25580722
ENSE00003685131	25569758	25569918

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 91.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.5180 / max 284.3093, expressed in 943 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35749	2.8364	724
35753	1.7347	560
35745	0.9673	272
35750	0.9246	440
35752	0.4157	228
35751	0.2471	129
35748	0.1708	79
202707	0.1498	81
35747	0.0715	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
choroid plexus epithelium	UBERON:0003911	91.33	gold quality
palpebral conjunctiva	UBERON:0001812	89.33	gold quality
buccal mucosa cell	CL:0002336	88.24	silver quality
metanephros cortex	UBERON:0010533	87.94	gold quality
lower esophagus muscularis layer	UBERON:0035833	87.48	gold quality
lower esophagus	UBERON:0013473	87.42	gold quality
right lung	UBERON:0002167	84.34	gold quality
epithelium of nasopharynx	UBERON:0001951	84.30	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.85	gold quality
nucleus accumbens	UBERON:0001882	83.73	gold quality
caudate nucleus	UBERON:0001873	82.70	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.21	gold quality
right atrium auricular region	UBERON:0006631	82.09	gold quality
calcaneal tendon	UBERON:0003701	81.83	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	81.59	gold quality
cardiac atrium	UBERON:0002081	81.55	gold quality
putamen	UBERON:0001874	81.14	gold quality
heart left ventricle	UBERON:0002084	80.51	gold quality
heart	UBERON:0000948	80.47	gold quality
popliteal artery	UBERON:0002250	80.30	gold quality
tibial artery	UBERON:0007610	80.30	gold quality
cardiac ventricle	UBERON:0002082	80.19	gold quality
apex of heart	UBERON:0002098	80.15	gold quality
right lobe of thyroid gland	UBERON:0001119	79.91	gold quality
endocervix	UBERON:0000458	79.67	gold quality
esophagus	UBERON:0001043	79.65	gold quality
body of uterus	UBERON:0009853	79.39	gold quality
adenohypophysis	UBERON:0002196	79.38	gold quality
adrenal tissue	UBERON:0018303	79.31	gold quality
diaphragm	UBERON:0001103	79.29	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	71770.41
E-HCAD-35	yes	60.65
E-CURD-119	yes	40.59
E-ANND-3	yes	4.95
E-CURD-112	no	2.77

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

63 targets.

Target	Regulation
ACHE
ACTB
ADAM10	Unknown
ADAM2
ADH1C
ADH5	Unknown
AFP	Repression
AKT1
APOA1	Activation
CA2	Repression
CAT
CDH17
CDKN2A
CDKN2B
CKAP2
CRABP2
CRYAB
CYP26A1
DES	Repression
DLST
EGFR
FGFR1
FOLR2
GH1
GLUD1
GNAS
GSTP1
HAP1
HIF1A	Unknown
HOXA5	Repression

JASPAR motifs

Motif	Name	Family
MA1552.1	RARB	Thyroid hormone receptor-related factors (NR1)
MA1552.2	RARB	Thyroid hormone receptor-related factors (NR1)

JASPAR matrix evidence (PMIDs): PMID:1738600

Upstream regulators (CollecTRI, top): CREB1, DNMT1, DNMT3A, DNMT3B, EP300, ESR1, ESR2, FOXD3, HDAC1, HIF1A, JUN, KAT6A, MED1, MYC, MYCN, NCOA2, NCOR1, NCOR2, NR2C1, NR4A1, PBRM1, PPARG, RARA, RARB, RARG, RERE, RUNX1, RXRB, SNW1, SSRP1, STAT5A, TAF1, TBP, TCF3, TGIF1, THRA, VDR, ZHX2

miRNA regulators (miRDB)

159 targeting RARB, 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-1277-5P	100.00	73.95	5056
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-144-3P	99.94	73.98	2698

Literature-anchored findings (GeneRIF, showing 40)

• The expression of exogenous hRAR beta gene in HL-60R cells could resume their sensitivity to retionoids in inhibiting cell proliferation and inducing granulocytic differentiation. (PMID:11769677)
• PML-RAR fusion protein induces gene hypermethylation and silencing by recruiting DNA methyltransferases to the RARbeta2 promoter (PMID:11834837)
• distinct methylation pattern in bladder cancer with frequent methylation of RARbeta, DAPK, E-cadherin, and p16. (PMID:11839665)
• Results indicate that loss of RAR-beta expression and accumulation of p 53 and Ki67 proteins may serve as biomarkers for early identification of esophageal cancer in the high-risk populations. (PMID:11925591)
• Methylation of the 5’ region of RAR-beta 2 gene may contribute to gene silencing and may be an important and early event in cervical carcinogenesis. (PMID:11945179)
• Endogenous reactivation of the RARbeta2 tumor suppressor gene epigenetically silenced in breast cancer. (PMID:11980632)
• Results show that both RARalpha and RARbeta are mediators in the anticancer function of All-trans retinoic acid via AP-1 activity inhibition. (PMID:12009305)
• downstream codons in mRNAs initiate translation of a protein isoform that disrupts retinoid-activated transcription (PMID:12118004)
• Loss of retinoic acid receptor beta gene expression is linked to aberrant histone H3 acetylation in lung cancer cell lines. (PMID:12124324)
• STAT-1, IRF-1, and RAR-beta expression were enhanced by IFN-gamma and ATRA in combination, and to a greater degree in BALM-3 cells than in BALM-1 cells, suggesting that these IFN-gamma related genes were involved in the induction of apoptosis. (PMID:12191570)
• Present only in basal epithelial nuclei. RAR-beta and -gamma were increased in basal and luminal epithelial nuclei in glands with benign prostatic hyperplasia. (PMID:12399530)
• RARbeta expression may be an indicator of increased risk of lung cancer in heavy smokers. (PMID:12529350)
• RARbeta and RARgamma interact only weakly with SMRT. (PMID:12554770)
• 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)
• ATRA increased RARbeta2 mRNA in non-metastatic breast cancer cells. The same treatment of metastatic cells resulted in an increase in RARbeta4 & a decrease in RARbeta2 mRNA. RARbeta4 may contribute to metastatic properties of breast cancer cell lines. (PMID:12579317)
• RAR beta and RAR gamma receptors appear to adopt a constitutively closed helix 12 conformation in the absence of hormone that may approximate the conformation of RAR alpha when bound to hormone agonist. (PMID:12665583)
• the role of RAR-beta2 induction with respect to clonogenic survival of different human tumor cells under retinoid treatment alone or in combination with irradiation (PMID:12789467)
• c-myc, FOG1, GATA6, glutamate dehydrogenase, glutathione S-transferase homologue (p28), Foxq1, Hic5, Meis1a, Dab2, midkine, and the PDGF-alpha receptor are genes regulated specifically by RARbeta(2) in F9 cells (PMID:12805409)
• The regulatin oexpression of this receptor in cancer cells is affected by ligands of ppargamma. (PMID:12839938)
• Promoter hypermethylation of this gene is demonstrated in esophageal squamous cell carcinoma. (PMID:12839965)
• hypermethylated in invasive and in in situ lobular breast cancer (PMID:14601057)
• Hypermethylation-associated inactivation of retinoic acid receptor beta is associated with esophageal squamous cell carcinoma (PMID:14614007)
• In a 9-cis retinoic acid-dependent fashion in cells in vitro, retinoic acid receptor beta isoform stimulates the expression of reporter constructs containing the site that binds aldehyde dehydrogenase-2. (PMID:14691372)
• The adult RARbeta2 isoform also shows age-related methylation in normal tissues but more variable methylation in colorectal cancer. (PMID:14726683)
• Isoforms are involved in colon cancer cell growth. (PMID:14726690)
• RAR-beta(2) silencing by methylation is an early event in head and neck carcinogenesis. (PMID:15014026)
• Retinoic acid receptor beta2 hypermethylation has a role in prostate cancer [editorial] (PMID:15217922)
• RARbeta2 methylation has a role in development of prostate neoplasms (PMID:15217932)
• Loss of expression of RARbeta is associated with esophageal squamous cell carcinomas (PMID:15255287)
• RARbeta2 acts as a tumor suppressor gene in myelofibrosis with myeloid metaplasia and epigenetic changes are the most significant determinants of RARbeta2 gene activity in these patients. (PMID:15361842)
• Review loss or abnormality of RAR-b in lung cancer cell lines. It may have tumor suppression function. (PMID:15375805)
• (RAR)beta functions as a tumor suppressor gene in various contexts where its absence is associated with tumorigenicity and its presence causes cell cycle arrest. (PMID:15383624)
• Increased acetylation of RARbeta1 is associated with head and neck cancer (PMID:15467435)
• crystal structure of retinoic acid receptor beta (PMID:15502323)
• results show that inactivation of the retinoic acid signaling-associated genes RAR-beta, CRBP1, and TIG1 by DNA methylation occurs frequently in esophageal squamous cell carcinoma (PMID:16128742)
• Hypermethylation of retinoid acid receptor beta is associated with gastric carcinogenesis (PMID:16134180)
• Study demonstrate for the first time a significant and specific overexpression of RAR-beta(1) in chromophobe renal cell carcinoma (PMID:16244585)
• RARbeta2 induces a number of tumor suppressor functions and metastasis suppressors (PMID:16255778)
• RARbeta2 silencing and retinoic acid (RA) resistance are consequent to an impaired integration of RA signal at RARbeta2 chromatin (PMID:16287870)
• In H358 lung cancer cells transiently transfected with RARbeta1’, RA treatment restored target gene expression compared with that in vector-transfected cells and suppressed cell growth compared with that in untreated cells. (PMID:16288117)

Cross-species orthologs

187 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rarb	ENSMUSG00000017491
rattus_norvegicus	Rarb	ENSRNOG00000024061
drosophila_melanogaster	EcR	FBGN0000546
drosophila_melanogaster	Hr96	FBGN0015240
caenorhabditis_elegans		WBGENE00001062
caenorhabditis_elegans	nhr-2	WBGENE00003601
caenorhabditis_elegans		WBGENE00003608
caenorhabditis_elegans		WBGENE00003611
caenorhabditis_elegans		WBGENE00003614
caenorhabditis_elegans		WBGENE00003615
caenorhabditis_elegans		WBGENE00003617
caenorhabditis_elegans		WBGENE00003618
caenorhabditis_elegans		WBGENE00003620
caenorhabditis_elegans	nhr-23	WBGENE00003622
caenorhabditis_elegans		WBGENE00003624
caenorhabditis_elegans		WBGENE00003632
caenorhabditis_elegans		WBGENE00003634
caenorhabditis_elegans		WBGENE00003638
caenorhabditis_elegans		WBGENE00003640
caenorhabditis_elegans		WBGENE00003641
caenorhabditis_elegans		WBGENE00003642
caenorhabditis_elegans		WBGENE00003643
caenorhabditis_elegans		WBGENE00003644
caenorhabditis_elegans		WBGENE00003645
caenorhabditis_elegans		WBGENE00003646
caenorhabditis_elegans		WBGENE00003648
caenorhabditis_elegans		WBGENE00003649
caenorhabditis_elegans		WBGENE00003651
caenorhabditis_elegans		WBGENE00003653
caenorhabditis_elegans		WBGENE00003655
caenorhabditis_elegans		WBGENE00003658
caenorhabditis_elegans		WBGENE00003660
caenorhabditis_elegans		WBGENE00003662
caenorhabditis_elegans	nhr-73	WBGENE00003663
caenorhabditis_elegans	nhr-77	WBGENE00003667
caenorhabditis_elegans		WBGENE00003669
caenorhabditis_elegans	nhr-81	WBGENE00003671
caenorhabditis_elegans	nhr-82	WBGENE00003672
caenorhabditis_elegans		WBGENE00003676
caenorhabditis_elegans		WBGENE00003677
caenorhabditis_elegans		WBGENE00003680
caenorhabditis_elegans		WBGENE00003682
caenorhabditis_elegans		WBGENE00003684
caenorhabditis_elegans		WBGENE00003685
caenorhabditis_elegans		WBGENE00003686
caenorhabditis_elegans		WBGENE00003688
caenorhabditis_elegans		WBGENE00003689
caenorhabditis_elegans		WBGENE00003692
caenorhabditis_elegans		WBGENE00003693
caenorhabditis_elegans		WBGENE00003694
caenorhabditis_elegans		WBGENE00003696
caenorhabditis_elegans		WBGENE00003698
caenorhabditis_elegans		WBGENE00003699
caenorhabditis_elegans		WBGENE00003700
caenorhabditis_elegans		WBGENE00003702
caenorhabditis_elegans		WBGENE00003704
caenorhabditis_elegans		WBGENE00003705
caenorhabditis_elegans		WBGENE00003707
caenorhabditis_elegans		WBGENE00003708
caenorhabditis_elegans		WBGENE00003712
caenorhabditis_elegans		WBGENE00003713
caenorhabditis_elegans		WBGENE00003714
caenorhabditis_elegans		WBGENE00003715
caenorhabditis_elegans		WBGENE00003716
caenorhabditis_elegans		WBGENE00003717
caenorhabditis_elegans		WBGENE00003718
caenorhabditis_elegans		WBGENE00003720
caenorhabditis_elegans		WBGENE00003721
caenorhabditis_elegans		WBGENE00003722
caenorhabditis_elegans		WBGENE00003723
caenorhabditis_elegans		WBGENE00003724
caenorhabditis_elegans		WBGENE00003725
caenorhabditis_elegans		WBGENE00003728
caenorhabditis_elegans		WBGENE00004786
caenorhabditis_elegans		WBGENE00006471
caenorhabditis_elegans	unc-55	WBGENE00006790
caenorhabditis_elegans		WBGENE00007367
caenorhabditis_elegans		WBGENE00008056
caenorhabditis_elegans	nhr-165	WBGENE00008158
caenorhabditis_elegans		WBGENE00008208
caenorhabditis_elegans	nhr-169	WBGENE00008289
caenorhabditis_elegans		WBGENE00008309
caenorhabditis_elegans	nhr-174	WBGENE00008474
caenorhabditis_elegans		WBGENE00008619
caenorhabditis_elegans		WBGENE00008630
caenorhabditis_elegans		WBGENE00008778
caenorhabditis_elegans		WBGENE00008830
caenorhabditis_elegans		WBGENE00008884
caenorhabditis_elegans		WBGENE00008901
caenorhabditis_elegans	nhr-265	WBGENE00009608
caenorhabditis_elegans		WBGENE00010017
caenorhabditis_elegans		WBGENE00010180
caenorhabditis_elegans		WBGENE00010186
caenorhabditis_elegans		WBGENE00010215
caenorhabditis_elegans		WBGENE00010410
caenorhabditis_elegans		WBGENE00010600
caenorhabditis_elegans		WBGENE00010601
caenorhabditis_elegans		WBGENE00010602
caenorhabditis_elegans		WBGENE00010603
caenorhabditis_elegans		WBGENE00010604
caenorhabditis_elegans		WBGENE00011002
caenorhabditis_elegans		WBGENE00011150
caenorhabditis_elegans		WBGENE00011396
caenorhabditis_elegans		WBGENE00011520
caenorhabditis_elegans		WBGENE00011565
caenorhabditis_elegans		WBGENE00011566
caenorhabditis_elegans		WBGENE00011568
caenorhabditis_elegans	nhr-217	WBGENE00011651
caenorhabditis_elegans		WBGENE00011750
caenorhabditis_elegans		WBGENE00012050
caenorhabditis_elegans		WBGENE00012056
caenorhabditis_elegans		WBGENE00012446
caenorhabditis_elegans		WBGENE00012449
caenorhabditis_elegans		WBGENE00012596
caenorhabditis_elegans		WBGENE00012703
caenorhabditis_elegans		WBGENE00013067
caenorhabditis_elegans		WBGENE00013483
caenorhabditis_elegans	nhr-276	WBGENE00013512
caenorhabditis_elegans		WBGENE00013584
caenorhabditis_elegans		WBGENE00013940
caenorhabditis_elegans		WBGENE00014068
caenorhabditis_elegans	nhr-245	WBGENE00014189
caenorhabditis_elegans		WBGENE00014193
caenorhabditis_elegans		WBGENE00015497
caenorhabditis_elegans		WBGENE00015758
caenorhabditis_elegans		WBGENE00015897
caenorhabditis_elegans		WBGENE00015900
caenorhabditis_elegans		WBGENE00015901
caenorhabditis_elegans		WBGENE00015902
caenorhabditis_elegans		WBGENE00016091
caenorhabditis_elegans		WBGENE00016233
caenorhabditis_elegans		WBGENE00016364
caenorhabditis_elegans		WBGENE00016365
caenorhabditis_elegans		WBGENE00016366
caenorhabditis_elegans		WBGENE00016367
caenorhabditis_elegans		WBGENE00016368
caenorhabditis_elegans		WBGENE00016517
caenorhabditis_elegans		WBGENE00016772
caenorhabditis_elegans		WBGENE00016926
caenorhabditis_elegans		WBGENE00016927
caenorhabditis_elegans		WBGENE00017503
caenorhabditis_elegans		WBGENE00017512
caenorhabditis_elegans		WBGENE00017961
caenorhabditis_elegans		WBGENE00018189
caenorhabditis_elegans		WBGENE00018265
caenorhabditis_elegans		WBGENE00018266
caenorhabditis_elegans		WBGENE00018404
caenorhabditis_elegans		WBGENE00018412
caenorhabditis_elegans		WBGENE00018415
caenorhabditis_elegans		WBGENE00018539
caenorhabditis_elegans		WBGENE00018541
caenorhabditis_elegans		WBGENE00018542
caenorhabditis_elegans		WBGENE00018544
caenorhabditis_elegans		WBGENE00018545
caenorhabditis_elegans		WBGENE00018622
caenorhabditis_elegans		WBGENE00019115
caenorhabditis_elegans		WBGENE00019116
caenorhabditis_elegans		WBGENE00019741
caenorhabditis_elegans		WBGENE00019742
caenorhabditis_elegans		WBGENE00019743
caenorhabditis_elegans		WBGENE00020015
caenorhabditis_elegans		WBGENE00020062
caenorhabditis_elegans		WBGENE00020152
caenorhabditis_elegans		WBGENE00020153
caenorhabditis_elegans		WBGENE00020385
caenorhabditis_elegans		WBGENE00020460
caenorhabditis_elegans		WBGENE00020555
caenorhabditis_elegans		WBGENE00020750
caenorhabditis_elegans		WBGENE00020849
caenorhabditis_elegans		WBGENE00020850
caenorhabditis_elegans		WBGENE00020851
caenorhabditis_elegans		WBGENE00020852
caenorhabditis_elegans		WBGENE00021163
caenorhabditis_elegans		WBGENE00021522
caenorhabditis_elegans		WBGENE00021610
caenorhabditis_elegans		WBGENE00021611
caenorhabditis_elegans		WBGENE00021617
caenorhabditis_elegans		WBGENE00022097
caenorhabditis_elegans		WBGENE00022637
caenorhabditis_elegans		WBGENE00022639
caenorhabditis_elegans		WBGENE00022640
caenorhabditis_elegans		WBGENE00022726
caenorhabditis_elegans		WBGENE00022756
caenorhabditis_elegans		WBGENE00022805
caenorhabditis_elegans		WBGENE00044353
caenorhabditis_elegans		WBGENE00044699
caenorhabditis_elegans		WBGENE00045515

Paralogs (18): NR1H4 (ENSG00000012504), NR1H3 (ENSG00000025434), RORA (ENSG00000069667), VDR (ENSG00000111424), PPARD (ENSG00000112033), THRA (ENSG00000126351), NR1D1 (ENSG00000126368), NR1H2 (ENSG00000131408), RARA (ENSG00000131759), PPARG (ENSG00000132170), NR1I3 (ENSG00000143257), RORC (ENSG00000143365), NR1I2 (ENSG00000144852), THRB (ENSG00000151090), RARG (ENSG00000172819), NR1D2 (ENSG00000174738), PPARA (ENSG00000186951), RORB (ENSG00000198963)

Protein

Protein identifiers

Retinoic acid receptor beta — P10826 (reviewed: P10826)

Alternative names: HBV-activated protein, Nuclear receptor subfamily 1 group B member 2, RAR-epsilon

All UniProt accessions (14): P10826, A0A8I5KNZ0, A0A8I5KQX3, A0A8I5KSR9, A0A8I5KUH8, A0A8I5KVJ9, A0A8I5KVN9, A0A8I5KVP8, A0A8I5KWP3, A0A8I5KXD0, A0A8I5KXT3, D6RBI3, F1D8S6, Q5QHG3

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 RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5’-AGGTCA-3’ sites known as DR1-DR5. In the absence or presence of hormone ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. The RXRA/RARB heterodimer can act as a repressor on the DR1 element and as an activator on the DR5 element. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function.

Subunit / interactions. Homodimer. Heterodimer; with a RXR molecule. Binds DNA preferentially as a RAR/RXR heterodimer. Heterodimerizes (via NR LBD) with RXRA. Interacts weakly with NCOR2.

Subcellular location. Nucleus. Cytoplasm Nucleus Nucleus Cytoplasm.

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

Disease relevance. Microphthalmia, syndromic, 12 (MCOPS12) [MIM:615524] A form of microphthalmia, a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. MCOPS12 patients manifest variable features, including diaphragmatic hernia, pulmonary hypoplasia, and cardiac abnormalities. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. The DNA-binding nuclear receptor domain and the NR LBD domain are required for binding of the RARB/RXRA heterodimer to both DR1 and DR5 DNA elements.

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

Isoforms (4)

UniProt ID	Names	Canonical?
P10826-1	Beta-1	yes
P10826-2	Beta-2
P10826-4	Beta-3
P10826-3	Beta-4

RefSeq proteins (8): NP_000956, NP_001277145, NP_001277146, NP_001277195, NP_001277205, NP_001277206, NP_001277229, NP_057236 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000536	Nucl_hrmn_rcpt_lig-bd	Domain
IPR001628	Znf_hrmn_rcpt	Domain
IPR001723	Nuclear_hrmn_rcpt	Family
IPR003078	Retinoic_acid_rcpt	Family
IPR013088	Znf_NHR/GATA	Homologous_superfamily
IPR035500	NHR-like_dom_sf	Homologous_superfamily
IPR047158	NR_LBD_RAR	Domain
IPR047159	NR_DBD_RAR	Domain

Pfam: PF00104, PF00105

UniProt features (63 total): helix 15, mutagenesis site 14, strand 9, sequence variant 5, sequence conflict 4, region of interest 4, compositionally biased region 3, splice variant 2, zinc finger region 2, chain 1, domain 1, modified residue 1, DNA-binding region 1, turn 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
4DM6	X-RAY DIFFRACTION	1.9
4JYI	X-RAY DIFFRACTION	1.9
1XAP	X-RAY DIFFRACTION	2.1
4DM8	X-RAY DIFFRACTION	2.3
6SSQ	X-RAY DIFFRACTION	2.3
4JYG	X-RAY DIFFRACTION	2.35
4JYH	X-RAY DIFFRACTION	2.6
5UAN	X-RAY DIFFRACTION	3.51
1HRA	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10826-F1	80.68	0.68

Functional residue map

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

Post-translational modifications (1): 77

Mutagenesis-validated functional residues (14):

Position	Phenotype
106	as a heterodimer with rxra, abolishes transcriptional repression on dr1, reduces transcriptional activation on dr5 and b
113	as a heterodimer with rxra, abolishes transcriptional repression on dr1 and reduces transcriptional activation on dr5.
120	as a heterodimer with rxra, reduces transcriptional repression on dr1 and reduces transcriptional activation on dr5. red
123	reduces transcriptional repression on dr1 and reduces transcriptional activation on dr5; when associated with e-369 and
188	no effect on transcriptional activation in the absence of hormone.
191	no effect on transcriptional activation in the absence of hormone.
222	reduced transcriptional activation in the absence of hormone. even greater reduction in transcriptional activation in th
223	greatly reduced transcriptional activation in the absence of hormone. even greater reduction in transcriptional activati
232	reduced transcriptional activation in the absence of hormone. some further reduction of transcriptional activity in the
365	as a heterodimer with rxra, reduces transcriptional repression on dr1 and reduces transcriptional activation on dr5. red
366	as a heterodimer with rxra, reduces binding affinity for dr5 dna element and no change in binding to dr1. reduces transc
367	as a heterodimer with rxra, reduces transcriptional repression on dr1 and reduces transcriptional activation on dr5. red
369	reduces transcriptional repression on dr1 and reduces transcriptional activation on dr5; when associated with v-123 and
370	reduces transcriptional repression on dr1 and reduced transcriptional activation on dr5; when associated with v-123 and

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-383280	Nuclear Receptor transcription pathway
R-HSA-5362517	Signaling by Retinoic Acid
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis

MSigDB gene sets: 446 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_OUTFLOW_TRACT_SEPTUM_MORPHOGENESIS, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GOBP_REGULATION_OF_CARTILAGE_DEVELOPMENT, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_HINDLIMB_MORPHOGENESIS, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN

GO Biological Process (30): negative regulation of transcription by RNA polymerase II (GO:0000122), ureteric bud development (GO:0001657), glandular epithelial cell development (GO:0002068), outflow tract septum morphogenesis (GO:0003148), growth plate cartilage development (GO:0003417), apoptotic process (GO:0006915), signal transduction (GO:0007165), striatum development (GO:0021756), neurogenesis (GO:0022008), cell differentiation (GO:0030154), regulation of myelination (GO:0031641), negative regulation of chondrocyte differentiation (GO:0032331), embryonic hindlimb morphogenesis (GO:0035116), multicellular organism growth (GO:0035264), positive regulation of apoptotic process (GO:0043065), negative regulation of apoptotic process (GO:0043066), positive regulation of transcription by RNA polymerase II (GO:0045944), embryonic eye morphogenesis (GO:0048048), retinoic acid receptor signaling pathway (GO:0048384), embryonic digestive tract development (GO:0048566), ventricular cardiac muscle cell differentiation (GO:0055012), neural precursor cell proliferation (GO:0061351), stem cell proliferation (GO:0072089), negative regulation of stem cell proliferation (GO:2000647), regulation of DNA-templated transcription (GO:0006355), cell population proliferation (GO:0008283), programmed cell death (GO:0012501), positive regulation of programmed cell death (GO:0043068), bone development (GO:0060348), negative regulation of cartilage development (GO:0061037)

GO Molecular Function (13): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), nuclear receptor activity (GO:0004879), zinc ion binding (GO:0008270), protein-containing complex binding (GO:0044877), nuclear retinoid X receptor binding (GO:0046965), heterocyclic compound binding (GO:1901363), sequence-specific double-stranded DNA binding (GO:1990837), 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), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Generic Transcription Pathway	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
regulation of transcription by RNA polymerase II	3
cellular anatomical structure	3
transcription by RNA polymerase II	2
regulation of cellular process	2
apoptotic process	2
regulation of apoptotic process	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
binding	2
negative regulation of DNA-templated transcription	1
mesonephric tubule development	1
columnar/cuboidal epithelial cell development	1
glandular epithelial cell differentiation	1
outflow tract morphogenesis	1
cardiac septum morphogenesis	1
endochondral bone growth	1
cartilage development involved in endochondral bone morphogenesis	1
connective tissue development	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
subpallium development	1
anatomical structure development	1
nervous system development	1
cell differentiation	1
cellular developmental process	1
myelination	1
regulation of nervous system development	1
chondrocyte differentiation	1
regulation of chondrocyte differentiation	1
negative regulation of cell differentiation	1
negative regulation of cartilage development	1
embryonic limb morphogenesis	1
hindlimb morphogenesis	1
multicellular organismal process	1
developmental growth	1
positive regulation of programmed cell death	1

Protein interactions and networks

STRING

2121 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RARB	RARS1	P54136	959
RARB	CRABP2	P29373	938
RARB	RARG	P13631	824
RARB	RASSF1	Q9NS23	789
RARB	CRABP1	P29762	762
RARB	RXRB	P28702	755
RARB	CYP26A1	O43174	731
RARB	DAPK1	P53355	724
RARB	RERE	Q9P2R6	715
RARB	RBP1	P09455	701
RARB	MGMT	P16455	697
RARB	GSTP1	P09211	668
RARB	CDKN2A	P42771	666
RARB	FHIT	P49789	664
RARB	CDH13	P55290	652

IntAct

23 interactions, top by confidence:

A	B	Type	Score
RARB	RXRG	psi-mi:“MI:0915”(physical association)	0.550
RARB	ASXL1	psi-mi:“MI:0407”(direct interaction)	0.440
ZNF423	RARB	psi-mi:“MI:0915”(physical association)	0.400
RARA	RARB	psi-mi:“MI:0915”(physical association)	0.400
RARB	bipA	psi-mi:“MI:0915”(physical association)	0.370
IL25	RARB	psi-mi:“MI:0915”(physical association)	0.370
IL31	RARB	psi-mi:“MI:0915”(physical association)	0.370
	RARB	psi-mi:“MI:0915”(physical association)	0.370
RARB	HR	psi-mi:“MI:0915”(physical association)	0.370
GATA3	RARB	psi-mi:“MI:0915”(physical association)	0.370
RARB	RXRB	psi-mi:“MI:0915”(physical association)	0.370
CCNH	RARB	psi-mi:“MI:0915”(physical association)	0.370
RARB	SMAD2	psi-mi:“MI:0915”(physical association)	0.370
RARB	PRKD2	psi-mi:“MI:0915”(physical association)	0.370
ITGB1BP2	PLOD2	psi-mi:“MI:0914”(association)	0.350
ESR1	TUBAL3	psi-mi:“MI:0914”(association)	0.350
ESR2	PSMD11	psi-mi:“MI:0914”(association)	0.350
DISC1	RARB	psi-mi:“MI:0915”(physical association)	0.000
RARB		psi-mi:“MI:0915”(physical association)	0.000
RSPH1	RARB	psi-mi:“MI:0915”(physical association)	0.000
NRIP1	RARB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (41): RARB (Two-hybrid), RXRB (Two-hybrid), RXRG (Two-hybrid), RARB (Reconstituted Complex), RARB (Reconstituted Complex), RARB (Reconstituted Complex), RARB (Reconstituted Complex), PSMC5 (Two-hybrid), RARB (Affinity Capture-MS), RARB (Co-localization), RARB (Co-localization), RARB (Co-localization), RARB (Two-hybrid), PSMC5 (Two-hybrid), PPARGC1A (Two-hybrid)

ESM2 similar proteins: A2T928, D3ZHS6, O42132, O75916, O88974, O93511, O97716, P03373, P10276, P10826, P10827, P11416, P13631, P18113, P18119, P18514, P18516, P18911, P22448, P22605, P28699, P37242, P49805, P51126, P57753, P63058, P63059, Q15047, Q1LUC3, Q28571, Q28C33, Q5FBR4, Q5RAP4, Q69ZT9, Q7ZTI3, Q80TJ7, Q90271, Q90966, Q91392, Q92831

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

SIGNOR signaling

20 interactions.

A	Effect	B	Mechanism
PBRM1	“up-regulates quantity by expression”	RARB	“transcriptional regulation”
RARB	up-regulates	THRA	binding
THRA	up-regulates	RARB	binding
RARB	up-regulates	RXRA	binding
RARB	up-regulates	RXRB	binding
RXRA	up-regulates	RARB	binding
RXRB	up-regulates	RARB	binding
RXRB	“up-regulates quantity by expression”	RARB	“transcriptional regulation”
GATA6	“up-regulates quantity by expression”	RARB
“all-trans-retinoic acid”	“up-regulates activity”	RARB	“chemical activation”
adapalene	“up-regulates activity”	RARB	“chemical activation”
“9-cis-retinoic acid”	“up-regulates activity”	RARB	“chemical activation”
THR	“up-regulates activity”	RARB	binding
RARB	“up-regulates activity”	THR	binding
RARB	“up-regulates quantity by expression”	OXT	“transcriptional regulation”
RARB	up-regulates	THR	binding
THR	up-regulates	RARB	binding
tazarotene	“up-regulates activity”	RARB	“chemical activation”
“4-{[(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)carbonyl]amino}benzoic acid”	“up-regulates activity”	RARB	“chemical activation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 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	5	58.9×	4e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	16
Uncertain significance	69
Likely benign	26
Benign	23

Top pathogenic / likely-pathogenic (22)

Variant ID	HGVS	Classification
1710327	NM_000965.5(RARB):c.654G>C (p.Trp218Cys)	Pathogenic
1710328	NM_000965.5(RARB):c.1151-1G>C	Pathogenic
430023	NM_000965.5(RARB):c.1160G>T (p.Arg387Leu)	Pathogenic
88760	NM_000965.5(RARB):c.355C>T (p.Arg119Ter)	Pathogenic
88761	NM_000965.5(RARB):c.1205_1206dup (p.Ile403fs)	Pathogenic
88763	NM_000965.5(RARB):c.1159C>A (p.Arg387Ser)	Pathogenic
1338852	NM_000965.5(RARB):c.881G>T (p.Gly294Val)	Likely pathogenic
1710325	NM_000965.5(RARB):c.307G>T (p.Gly103Cys)	Likely pathogenic
1710326	NM_000965.5(RARB):c.624_635del (p.Asp208_Arg212delinsGlu)	Likely pathogenic
1710329	NM_000965.5(RARB):c.1205T>C (p.Leu402Pro)	Likely pathogenic
218338	NM_000965.5(RARB):c.887G>C (p.Gly296Ala)	Likely pathogenic
2579398	NM_000965.5(RARB):c.1220T>C (p.Leu407Pro)	Likely pathogenic
2687744	NM_000965.5(RARB):c.749A>G (p.Gln250Arg)	Likely pathogenic
3342605	NM_000965.5(RARB):c.553C>T (p.Arg185Ter)	Likely pathogenic
3376953	NM_000965.5(RARB):c.640G>T (p.Asp214Tyr)	Likely pathogenic
3377400	NM_000965.5(RARB):c.1199C>T (p.Pro400Leu)	Likely pathogenic
3776082	NM_000965.5(RARB):c.1205_1206del (p.Leu402fs)	Likely pathogenic
4755515	NM_000965.5(RARB):c.674C>A (p.Ala225Asp)	Likely pathogenic
559901	NM_000965.5(RARB):c.872A>T (p.His291Leu)	Likely pathogenic
800775	NM_000965.5(RARB):c.1180G>T (p.Glu394Ter)	Likely pathogenic
870386	NM_000965.5(RARB):c.835T>G (p.Phe279Val)	Likely pathogenic
988076	NM_000965.5(RARB):c.1151G>A (p.Gly384Asp)	Likely pathogenic

SpliceAI

725 predictions. Top by Δscore:

Variant	Effect	Δscore
3:25461175:A:AG	acceptor_gain	1.0000
3:25461176:C:G	acceptor_gain	1.0000
3:25461192:GC:G	acceptor_gain	1.0000
3:25461192:GCA:G	acceptor_gain	1.0000
3:25501179:CA:C	acceptor_loss	1.0000
3:25501180:A:AG	acceptor_gain	1.0000
3:25501180:AG:A	acceptor_gain	1.0000
3:25501180:AGG:A	acceptor_gain	1.0000
3:25501181:G:GA	acceptor_gain	1.0000
3:25501181:GG:G	acceptor_gain	1.0000
3:25501181:GGG:G	acceptor_gain	1.0000
3:25501181:GGGC:G	acceptor_gain	1.0000
3:25501181:GGGCT:G	acceptor_gain	1.0000
3:25501319:AGAAT:A	donor_gain	1.0000
3:25501320:GAAT:G	donor_gain	1.0000
3:25501320:GAATG:G	donor_gain	1.0000
3:25501321:AATGT:A	donor_loss	1.0000
3:25501322:AT:A	donor_gain	1.0000
3:25501322:ATG:A	donor_loss	1.0000
3:25501323:TGT:T	donor_loss	1.0000
3:25501324:G:GG	donor_gain	1.0000
3:25501324:GTAA:G	donor_loss	1.0000
3:25501325:T:G	donor_loss	1.0000
3:25461180:A:AG	acceptor_gain	0.9900
3:25461181:T:G	acceptor_gain	0.9900
3:25461189:ATAGC:A	acceptor_loss	0.9900
3:25461191:A:AG	acceptor_gain	0.9900
3:25461192:G:GG	acceptor_gain	0.9900
3:25461192:G:GT	acceptor_loss	0.9900
3:25461192:GCAA:G	acceptor_gain	0.9900

AlphaMissense

2954 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000000006 (3:25021738 G>A), RS1000000351 (3:25057599 T>C), RS1000002115 (3:25284500 C>G,T), RS1000007369 (3:24837453 C>T), RS1000019152 (3:24865715 C>T), RS1000021333 (3:25407154 T>A), RS1000023528 (3:25118615 T>G), RS1000025314 (3:25441584 G>A,C), RS1000027855 (3:25547016 G>A,T), RS1000030989 (3:25137107 A>G), RS1000035411 (3:25582117 G>C), RS1000037609 (3:25396954 A>G), RS1000041141 (3:25233978 G>A,C), RS1000041474 (3:25553241 G>A), RS1000041879 (3:25431940 T>C)

Disease associations

OMIM: gene MIM:180220 | disease phenotypes: MIM:615524, MIM:617751

GenCC curated gene-disease

Disease	Classification	Inheritance
microphthalmia, syndromic 12	Definitive	Autosomal dominant
Matthew-Wood syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
microphthalmia, syndromic 12	Definitive	AD

Mondo (6): microphthalmia, syndromic 12 (MONDO:0014229), microphthalmia (MONDO:0021129), coloboma (MONDO:0001476), intellectual disability, autosomal dominant 48 (MONDO:0030913), intellectual disability (MONDO:0001071), Matthew-Wood syndrome (MONDO:0011010)

Orphanet (5): Matthew-Wood syndrome (Orphanet:2470), Microphthalmia-motor delay-language delay-brain anomalies-diaphragmatic hernia syndrome (Orphanet:689829), OBSOLETE: Ocular coloboma (Orphanet:194), Microcephaly-corpus callosum and cerebellar vermis hypoplasia-facial dysmorphism-intellectual disability syndrom (Orphanet:500159), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

19 total (19 of 19 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000175	Cleft palate
HP:0000278	Retrognathia
HP:0000347	Micrognathia
HP:0000431	Wide nasal bridge
HP:0000455	Broad nasal tip
HP:0000528	Anophthalmia
HP:0000568	Microphthalmia
HP:0000776	Congenital diaphragmatic hernia
HP:0000813	Bicornuate uterus
HP:0001249	Intellectual disability
HP:0001629	Ventricular septal defect
HP:0002089	Pulmonary hypoplasia
HP:0002566	Intestinal malrotation
HP:0003577	Congenital onset
HP:0003811	Neonatal death
HP:0005156	Hypoplastic left atrium

GWAS associations

91 associations (top):

Study	Trait	p-value
GCST000426_2	Obesity (extreme)	4.000000e-06
GCST001248_8	Pulmonary function	4.000000e-14
GCST001356_2	Gout	1.000000e-07
GCST001621_6	Airflow obstruction	9.000000e-07
GCST001784_46	Pulmonary function (smoking interaction)	7.000000e-11
GCST002724_3	Airway responsiveness in chronic obstructive pulmonary disease	3.000000e-06
GCST002763_13	Optic disc area	3.000000e-07
GCST002763_4	Optic disc area	2.000000e-08
GCST002783_152	Body mass index	2.000000e-09
GCST002783_205	Body mass index	8.000000e-10
GCST002783_560	Body mass index	8.000000e-07
GCST002911_6	Calcium levels	4.000000e-06
GCST002937_1	Molybdenum levels	2.000000e-07
GCST003030_1	Oppositional defiant disorder dimensions in attention-deficit hyperactivity disorder	5.000000e-06
GCST003264_647	Post bronchodilator FEV1/FVC ratio	4.000000e-06
GCST004076_14	Optic disc area	2.000000e-07
GCST004076_29	Optic disc area	1.000000e-08
GCST004147_5	Chronic obstructive pulmonary disease	2.000000e-08
GCST004495_91	BMI (adjusted for smoking behaviour)	1.000000e-07
GCST004497_33	Body mass index (joint analysis main effects and smoking interaction)	1.000000e-08
GCST004498_21	BMI in smokers	9.000000e-06
GCST004557_127	Body mass index	3.000000e-09
GCST004557_158	Body mass index	2.000000e-09
GCST004557_178	Body mass index	1.000000e-09
GCST004557_41	Body mass index	6.000000e-11
GCST004558_126	Body mass index (joint analysis main effects and physical activity interaction)	4.000000e-09
GCST004558_225	Body mass index (joint analysis main effects and physical activity interaction)	2.000000e-11
GCST004558_34	Body mass index (joint analysis main effects and physical activity interaction)	3.000000e-08
GCST004558_77	Body mass index (joint analysis main effects and physical activity interaction)	1.000000e-09
GCST004559_118	Body mass index in physically active individuals	1.000000e-06

EFO canonical traits (35, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004713	FEV/FVC ratio
EFO:0006897	airway responsiveness measurement
EFO:0004340	body mass index
EFO:0004838	calcium measurement
EFO:0007679	oppositional defiant disorder measurement
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0008433	pursuit maintenance gain measurement
EFO:0009270	heel bone mineral density
EFO:0003939	energy intake
EFO:0004695	intraocular pressure measurement
EFO:0004747	protein measurement
EFO:0005188	CCL11 measurement
EFO:0005939	parental genotype effect measurement
EFO:0007964	gestational serum measurement
EFO:0008579	risk-taking behaviour
EFO:0004312	vital capacity
EFO:0009718	peak expiratory flow
EFO:0004314	forced expiratory volume
EFO:0008328	chronotype measurement
EFO:0010078	dentures
EFO:0008475	mood instability measurement
EFO:0010101	decreased susceptibility to hepatitis C infection
EFO:0006781	coffee consumption measurement
EFO:0009282	sodium measurement
EFO:0005670	smoking initiation
EFO:0006939	cup-to-disc ratio measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0009819	comparative body size at age 10, self-reported

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D003103	Coloboma	C11.250.110; C11.270.147; C16.131.384.282
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008850	Microphthalmos	C11.250.566; C16.131.384.666
C537768	Anophthalmia with pulmonary hypoplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2008 (SINGLE PROTEIN), CHEMBL2363069 (PROTEIN FAMILY), CHEMBL2363071 (PROTEIN FAMILY), CHEMBL3885631 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

18 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,020,147 (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
CHEMBL1082	AMOXICILLIN	4	113,048
CHEMBL1265	ADAPALENE	4	12,179
CHEMBL1324	TOLCAPONE	4	13,819
CHEMBL157101	KETOCONAZOLE	4	75,361
CHEMBL160	CYCLOSPORINE	4	168,247
CHEMBL1657	TAZAROTENE	4	26,405
CHEMBL25202	TAMIBAROTENE	4	5,139
CHEMBL3707313	TRIFAROTENE	4	224
CHEMBL38	TRETINOIN	4	194,008
CHEMBL408	TROGLITAZONE	4	38,856
CHEMBL428	TROVAFLOXACIN	4	17,587
CHEMBL495	ALPROSTADIL	4	13,450
CHEMBL521	IBUPROFEN	4	228,490
CHEMBL603	ZAFIRLUKAST	4	23,220
CHEMBL705	ALITRETINOIN	4	39,246
CHEMBL191703	CONESSINE	2	437
CHEMBL383634	GLIQUIDONE	2	9,480

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10865801	RARB, TOP2B		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: nhr — 1B. Retinoic acid receptors

Most potent curated ligand interactions (17 total), top 17:

Ligand	Action	Affinity	Parameter
alitretinoin	Agonist	9.7	pKi
tretinoin	Agonist	9.4	pKi
[3H]9-cis-retinoic acid	Full agonist	9.4	pKd
tazarotene	Agonist	9.1	pEC50
KCL-286	Agonist	8.72	pEC50
AGN193109	Inverse agonist	8.7	pIC50
BMS641	Agonist	8.6	pIC50
BMS493	Inverse agonist	8.54	pIC50
AC261066	Full agonist	8.1	pEC50
Ro 40-6055	Agonist	8.07	pEC50
TTNPB	Agonist	8.0	pIC50
adapalene	Agonist	7.47	pKi
AC55649	Full agonist	7.3	pEC50
trifarotene	Agonist	6.9	pEC50
tamibarotene	Agonist	6.63	pEC50
CD666	Agonist	5.64	pKd
YCT-529	Antagonist	5.48	pIC50

Binding affinities (BindingDB)

18 measured of 19 human assays (19 total across all organisms); most potent 18 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
9-cis retinoic acid	KD	0.3 nM
Ch 80	KD	0.4 nM
BMS 961	KI	1.5 nM
4-[(E)-2-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid	EC50	5.5 nM	US-10188615: Alkoxy compounds for disease treatment
6-[3-Adamantan-1-yl-4-(3-hydroxy-propyl)-phenyl]-naphthalene-2-carboxylic acid	KI	21 nM
6-(3-adamantan-1-yl-4-methoxyphenyl)naphthalene-2-carboxylic acid	KI	34 nM
4-[(E)-2-(3-Adamantan-1-yl-4-hydroxy-phenyl)-vinyl]-benzoic acid	KI	70 nM
4-[(E)-2-(3-Adamantan-1-yl-4-methoxy-phenyl)-propenyl]-benzoic acid	KI	105 nM
CD564	KD	118 nM
(E)-4-[3-(1-adamantyl)-4-hydroxyphenyl]cinnamic acid	EC50	200 nM
6-[3-Adamantan-1-yl-4-(1,2-dihydroxy-ethyl)-phenyl]-naphthalene-2-carboxylic acid	KI	288 nM
CD666	KD	2240 nM
BMS184394-S	KD	7500 nM
BMS184394	KD	7500 nM
(E)-3-(3’-Adamantan-1-yl-4’-hydroxy-biphenyl-4-yl)-N-(4-hydroxy-phenyl)-acrylamide	EC50	7700 nM
BMS184394-R	KD	16000 nM
(E)-3-(3’-Adamantan-1-yl-4’-hydroxy-biphenyl-4-yl)-N-(2-amino-phenyl)-acrylamide	EC50	17600 nM
9-cis-retinoic acid (9cRA)	IC50	27100 nM

ChEMBL bioactivities

500 potent at pChembl≥5 of 514 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.52	EC50	0.3	nM	CHEMBL451835
9.52	EC50	0.3	nM	CHEMBL5997757
9.40	Ki	0.4	nM	TRETINOIN
9.40	EC50	0.4	nM	CHEMBL12585
9.40	EC50	0.4	nM	CHEMBL441231
9.40	Kd	0.4	nM	TRETINOIN
9.30	Ki	0.5	nM	CHEMBL275311
9.30	Ki	0.5	nM	TRETINOIN
9.30	Ki	0.5	nM	ALITRETINOIN
9.30	EC50	0.5	nM	CHEMBL285179
9.15	Ki	0.7	nM	ALITRETINOIN
9.15	Ki	0.7	nM	CHEMBL89241
9.10	EC50	0.8	nM	ALITRETINOIN
9.10	EC50	0.8	nM	TAZAROTENE
9.05	IC50	0.9	nM	TRETINOIN
9.03	IC50	0.94	nM	TRETINOIN
9.00	EC50	1	nM	TRETINOIN
9.00	EC50	1	nM	CHEMBL275311
8.96	Kd	1.1	nM	CHEMBL82716
8.92	Kd	1.2	nM	CHEMBL309282
8.82	EC50	1.5	nM	TRETINOIN
8.77	Kd	1.7	nM	CHEMBL78587
8.73	EC50	1.88	nM	CHEMBL1235644
8.72	EC50	1.9	nM	CHEMBL5946099
8.71	EC50	1.94	nM	CHEMBL4459692
8.70	IC50	2	nM	CHEMBL165629
8.70	Kd	2	nM	CHEMBL3945228
8.70	EC50	2	nM	ADAPALENE
8.70	EC50	2	nM	CHEMBL151870
8.70	EC50	2	nM	TRETINOIN
8.70	EC50	2	nM	CHEMBL5899376
8.70	EC50	2	nM	CHEMBL5877402
8.70	AC50	2	nM	ALITRETINOIN
8.70	Kd	2	nM	CHEMBL358145
8.69	EC50	2.05	nM	CHEMBL4459692
8.66	EC50	2.2	nM	CHEMBL4449668
8.66	EC50	2.2	nM	CHEMBL89241
8.60	EC50	2.5	nM	CHEMBL4212472
8.60	EC50	2.5	nM	CHEMBL4439399
8.60	IC50	2.5	nM	CHEMBL131925
8.57	EC50	2.7	nM	CHEMBL5818566
8.54	EC50	2.9	nM	CHEMBL5947674
8.54	EC50	2.9	nM	CHEMBL5840509
8.52	Ki	3	nM	CHEMBL36768
8.52	EC50	3	nM	CHEMBL80271
8.52	EC50	3	nM	CHEMBL275311
8.52	EC50	3	nM	ALITRETINOIN
8.51	EC50	3.1	nM	CHEMBL5940771
8.48	EC50	3.3	nM	CHEMBL44478
8.48	EC50	3.3	nM	ALITRETINOIN

PubChem BioAssay actives

355 with measured affinity, of 1121 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
alitretinoin	1799183: Retinoid Competition Binding Assay from Article 10.1006/jmbi.2000.4032: “Structural basis for isotype selectivity of the human retinoic acid nuclear receptor.”	kd	0.0002	uM
4-[2-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)ethynyl]benzoic acid	396777: Activity at human RARbeta 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	ec50	0.0003	uM
tretinoin	1799183: Retinoid Competition Binding Assay from Article 10.1006/jmbi.2000.4032: “Structural basis for isotype selectivity of the human retinoic acid nuclear receptor.”	kd	0.0004	uM
(2E,4E,6E)-7-(3,5-ditert-butylphenyl)-3-methylocta-2,4,6-trienoic acid	198547: Inhibition of [3H]ATRA binding to Retinoic acid receptor RAR beta	ki	0.0007	uM
Tazarotene	396777: Activity at human RARbeta 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	ec50	0.0008	uM
6-[1-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)ethenyl]naphthalene-2-carboxylic acid	198215: Apparent binding constant for Retinoic acid receptor beta in HeLa cellGAL-4 transactivation assay	kd	0.0011	uM
6-(5,5,8,8-tetramethyl-6,7-dihydronaphthalene-2-carbonyl)naphthalene-2-carboxylic acid	1799183: Retinoid Competition Binding Assay from Article 10.1006/jmbi.2000.4032: “Structural basis for isotype selectivity of the human retinoic acid nuclear receptor.”	kd	0.0012	uM
6-[2,2-difluoro-1-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)ethenyl]naphthalene-2-carboxylic acid	198215: Apparent binding constant for Retinoic acid receptor beta in HeLa cellGAL-4 transactivation assay	kd	0.0017	uM
4-[2,2-dimethyl-4-(4-methylphenyl)benzo[g]thiochromen-7-yl]benzoic acid	228584: Antagonistic activity against RAR beta in transcriptional activation assay with 10 nM TTNPB	ic50	0.0020	uM
4-[2-[5,5-dimethyl-8-(4-methylphenyl)-6H-naphthalen-2-yl]ethynyl]benzoic acid	198540: Binding constant for baculovirus-expressed Retinoic acid receptor RAR beta	kd	0.0020	uM
Adapalene	1380634: Agonist activity at GAL4 DNA-binding domain-tagged RARbeta (unknown origin) ligand-binding domain expressed in human HG5LN cells incubated for 18 hrs by luciferase reporter gene assay	ec50	0.0020	uM
4-[5-(4,7-dimethyl-1-benzofuran-2-yl)-1,2,4-oxadiazol-3-yl]benzoic acid	1602875: Transactivation of GAL4 DBD-fused human RARbeta-LBD expressed in HEK293 cells by beta-lactamase reporter gene based assay	ec50	0.0021	uM
4-[5-(5,5,8,8-tetramethyl-6,7-dihydroquinoxalin-2-yl)furan-3-yl]benzoic acid	198213: Binding affinity for Retinoic Acid Receptor beta (RAR beta)	ic50	0.0025	uM
6-[2-(4,4-dimethyl-2,3-dihydrothiochromen-6-yl)ethynyl]pyridine-2-carboxylic acid	1380634: Agonist activity at GAL4 DNA-binding domain-tagged RARbeta (unknown origin) ligand-binding domain expressed in human HG5LN cells incubated for 18 hrs by luciferase reporter gene assay	ec50	0.0025	uM
4-(5,5,8,8-tetramethyl-6,7-dihydroanthracen-2-yl)benzoic acid	198222: Binding affinity to retinoic acid receptor beta using [3H]CD 367 as radioligand	ki	0.0030	uM
4-[(E)-2-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)prop-1-enyl]benzoic acid	199386: Binding affinity against retinoic Acid beta receptors co-transfected into CV-1 cells	ec50	0.0030	uM
4-[(E)-3-oxo-3-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)prop-1-enyl]benzoic acid	1799183: Retinoid Competition Binding Assay from Article 10.1006/jmbi.2000.4032: “Structural basis for isotype selectivity of the human retinoic acid nuclear receptor.”	kd	0.0035	uM
4-[4-(3-hydroxypropoxy)-3-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)phenyl]benzoic acid	1380634: Agonist activity at GAL4 DNA-binding domain-tagged RARbeta (unknown origin) ligand-binding domain expressed in human HG5LN cells incubated for 18 hrs by luciferase reporter gene assay	ec50	0.0038	uM
4-[5,5-dimethyl-8-(4-methylphenyl)-6H-anthracen-2-yl]benzoic acid	228586: Binding affinity of [3H]- RA to baculovirus expressed human Retinoic acid receptor beta	kd	0.0040	uM
4-[(E)-4-[2-(4-ethylphenyl)-6,6-dimethylcyclohexen-1-yl]but-3-en-1-ynyl]benzoic acid	198539: Binding affinity towards retinoic acid receptor beta was determined using [3H]ATRA (5 nM) as radioligand	kd	0.0040	uM
4-[5-(3-tert-butylphenyl)-1-(4-methylsulfonylphenyl)pyrazol-3-yl]benzoic acid	1306248: Displacement of [3H]-TTNPB from RARbeta/RXRalpha (unknown origin) expressed in baculovirus expression system by scintillation proximity assay	ki	0.0043	uM
4-[5-(5,5,8,8-tetramethyl-6,7-dihydroquinoxalin-2-yl)thiophen-3-yl]benzoic acid	198213: Binding affinity for Retinoic Acid Receptor beta (RAR beta)	ic50	0.0045	uM
4-[(1E,3E)-2-methyl-4-(2,6,6-trimethylcyclohexen-1-yl)buta-1,3-dienyl]benzoic acid	198522: Effective concentration against Retinoic acid receptor beta	ec50	0.0050	uM
4-[4-methoxy-3-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)phenyl]benzoic acid	1380634: Agonist activity at GAL4 DNA-binding domain-tagged RARbeta (unknown origin) ligand-binding domain expressed in human HG5LN cells incubated for 18 hrs by luciferase reporter gene assay	ec50	0.0050	uM
4-[(E)-3-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)prop-1-enyl]benzoic acid	198539: Binding affinity towards retinoic acid receptor beta was determined using [3H]ATRA (5 nM) as radioligand	kd	0.0050	uM
4-[(Z)-2-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)prop-1-enyl]benzoic acid	198536: Binding affinity for baculovirus-expressed Retinoic acid receptor RAR beta	kd	0.0050	uM
4-[1-(4-methylsulfonylphenyl)-5-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)pyrazol-3-yl]benzoic acid	1306248: Displacement of [3H]-TTNPB from RARbeta/RXRalpha (unknown origin) expressed in baculovirus expression system by scintillation proximity assay	ki	0.0052	uM
4-[5,5-dimethyl-8-(5-methylthiophen-2-yl)-6H-anthracen-2-yl]benzoic acid	228586: Binding affinity of [3H]- RA to baculovirus expressed human Retinoic acid receptor beta	kd	0.0060	uM
4-[(E)-4-[6,6-dimethyl-2-(4-methylphenyl)cyclohexen-1-yl]but-3-en-1-ynyl]benzoic acid	198539: Binding affinity towards retinoic acid receptor beta was determined using [3H]ATRA (5 nM) as radioligand	kd	0.0060	uM
4-[2,2-dimethyl-4-(5-methylthiophen-2-yl)benzo[g]chromen-7-yl]benzoic acid	228584: Antagonistic activity against RAR beta in transcriptional activation assay with 10 nM TTNPB	ic50	0.0065	uM
4-[4-(4-hydroxybutoxy)-3-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)phenyl]benzoic acid	1380634: Agonist activity at GAL4 DNA-binding domain-tagged RARbeta (unknown origin) ligand-binding domain expressed in human HG5LN cells incubated for 18 hrs by luciferase reporter gene assay	ec50	0.0068	uM
4-[(E)-4-(2,6,6-trimethylcyclohexen-1-yl)but-3-en-1-ynyl]benzoic acid	198377: Ability to inhibit TTNPB-induced transactivation at retinoic acid receptor beta	ec50	0.0070	uM
4-[2,2-dimethyl-4-(4-methylphenyl)benzo[g]chromen-7-yl]benzoic acid	228586: Binding affinity of [3H]- RA to baculovirus expressed human Retinoic acid receptor beta	kd	0.0070	uM
4-[(E)-2-(5,5-dimethyl-8-phenyl-6H-naphthalen-2-yl)ethenyl]benzoic acid	2141843: Agonist activity at recombinant human RAR-beta expressed in mammalian cells by luciferase reporter gene based transactivation assay	ec50	0.0076	uM
4-[4-(2-butoxyethoxy)-5-methyl-1,3-thiazol-2-yl]-2-fluorobenzoic acid	394804: Agonist activity at RARbeta2 expressed in mouse NIH3T3 cells by R-SAT assay	ec50	0.0079	uM
(2E,4E,6Z)-7-(3-methoxy-5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)-3-methylocta-2,4,6-trienoic acid	198202: Transcriptional activation of Retinoic acid receptor RAR beta	ec50	0.0080	uM
4-[(5,5,8,8-tetramethyl-6,7-dihydronaphthalene-2-carbonyl)amino]benzoic acid	396777: Activity at human RARbeta 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	ec50	0.0086	uM
4-[4-hydroxy-3-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)phenyl]benzoic acid	1380634: Agonist activity at GAL4 DNA-binding domain-tagged RARbeta (unknown origin) ligand-binding domain expressed in human HG5LN cells incubated for 18 hrs by luciferase reporter gene assay	ec50	0.0086	uM
4-[4-(4-hydroxybutoxy)-3-[4-pyrrolidin-1-yl-3-(trifluoromethyl)phenyl]phenyl]benzoic acid	1380640: Inverse agonist activity at GAL4 DNA-binding domain-tagged RARabetaa (unknown origin) ligand-binding domain expressed in human HG5LN cells incubated for 18 hrs by luciferase reporter gene assay	ec50	0.0095	uM
4-[2-[8-(4-ethylphenyl)-5,5-dimethyl-6H-naphthalen-2-yl]ethynyl]benzoic acid	198535: Ability to displace 3H-retinoic acid (5 nM) from beta retinoic acid receptor (beta RAR) using transactivation assay	kd	0.0100	uM
4-[5-(3-tert-butyl-5-methylphenyl)-1-(4-methylsulfonylphenyl)pyrazol-3-yl]benzoic acid	1306248: Displacement of [3H]-TTNPB from RARbeta/RXRalpha (unknown origin) expressed in baculovirus expression system by scintillation proximity assay	ki	0.0100	uM
4-[2-(4-tert-butylphenyl)ethynyl]benzoic acid	396777: Activity at human RARbeta 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	ec50	0.0100	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	198202: Transcriptional activation of Retinoic acid receptor RAR beta	ec50	0.0100	uM
4-[2-[5,5-dimethyl-8-(4-propan-2-ylphenyl)-6H-naphthalen-2-yl]ethynyl]benzoic acid	198535: Ability to displace 3H-retinoic acid (5 nM) from beta retinoic acid receptor (beta RAR) using transactivation assay	kd	0.0110	uM
4-[5-methyl-4-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)-1,3-thiazol-2-yl]benzoic acid	1389199: Transactivation of GST-tagged RARbeta LBD (unknown origin) assessed as fluorescein-labelled coactivator peptide recruitment measured after 4 hrs by TR-FRET analysis	ec50	0.0110	uM
4-[(E)-2-(3-tert-butyl-4-methoxyphenyl)prop-1-enyl]benzoic acid	198222: Binding affinity to retinoic acid receptor beta using [3H]CD 367 as radioligand	ki	0.0120	uM
ethyl 4-[5-methyl-4-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)-1,3-thiazol-2-yl]benzoate	1389199: Transactivation of GST-tagged RARbeta LBD (unknown origin) assessed as fluorescein-labelled coactivator peptide recruitment measured after 4 hrs by TR-FRET analysis	ec50	0.0121	uM
4-[4-[3-(cyclopropylamino)propoxy]-3-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)phenyl]benzoic acid	1380634: Agonist activity at GAL4 DNA-binding domain-tagged RARbeta (unknown origin) ligand-binding domain expressed in human HG5LN cells incubated for 18 hrs by luciferase reporter gene assay	ec50	0.0130	uM
6-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)naphthalene-2-carboxylic acid	198222: Binding affinity to retinoic acid receptor beta using [3H]CD 367 as radioligand	ki	0.0130	uM
4-[2,2-dimethyl-4-(5-methylthiophen-2-yl)benzo[g]thiochromen-7-yl]benzoic acid	228586: Binding affinity of [3H]- RA to baculovirus expressed human Retinoic acid receptor beta	kd	0.0130	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	decreases reaction, increases expression, affects cotreatment, affects binding, decreases expression (+5 more)	54
Decitabine	affects expression, affects methylation, affects cotreatment, increases reaction, decreases metabolic processing (+4 more)	7
Alitretinoin	affects cotreatment, affects expression, decreases expression, affects binding, increases activity (+1 more)	6
Valproic Acid	affects methylation, decreases methylation, increases expression	5
trichostatin A	affects reaction, increases expression, increases reaction, affects binding, affects cotreatment	4
Arsenic Trioxide	decreases expression, decreases reaction, increases expression	4
AGN 193109	affects binding, decreases activity, decreases reaction, increases expression	3
Estradiol	decreases expression, increases response to substance, increases expression, increases reaction	3
CD2665	increases reaction, decreases activity, decreases reaction, increases expression	2
4-oxoretinoic acid	increases activity, increases expression	2
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	affects binding, increases activity	2
mercuric bromide	increases expression, affects cotreatment	2
epigallocatechin gallate	decreases metabolic processing, decreases methylation, increases expression	2
tamibarotene	increases expression, increases reaction	2
4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-anthracenyl)benzoic acid	affects binding, increases expression, decreases reaction	2
15-deoxy-delta(12,14)-prostaglandin J2	increases expression, increases reaction, decreases reaction	2
entinostat	increases expression, affects cotreatment	2
bisphenol S	increases expression, increases methylation	2
Vorinostat	affects cotreatment, increases expression	2
Bexarotene	increases expression, increases reaction, decreases reaction	2
Panobinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation	2
Doxorubicin	increases expression, increases response to substance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Vitamin A	decreases expression, increases expression	2
Isotretinoin	increases expression, affects cotreatment, increases acetylation, increases reaction	2
Aflatoxin B1	decreases methylation, increases methylation	2
Fenretinide	increases expression, increases reaction	2

ChEMBL screening assays

278 unique, capped per target: 199 binding, 78 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1011120	Binding	Activity at human RARbeta ligand binding domain expressed in COS7 cells co-transfected with Gal4-DBD assessed as transcriptional activation at 10 uM after 16 hrs by Gal4 response element-driven luciferase reporter gene assay relative to all	Novel non-carboxylic acid retinoids: 1,2,4-oxadiazol-5-one derivatives. — Bioorg Med Chem Lett
CHEMBL1022109	Functional	Agonist activity at RARbeta2 expressed in mouse NIH3T3 cells by R-SAT assay relative to Am-580	Design, synthesis, and structure-activity analysis of isoform-selective retinoic acid receptor beta ligands. — J Med Chem
CHEMBL3224187	ADMET	Inhibition of RAR beta (unknown origin)	Overcoming retinoic acid receptor- based testicular toxicity in the optimisation of glucokinase activators — Medchemcomm

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_A5S6	SEES3-1V human RARB, clone1	Embryonic stem cell	Male
CVCL_A5S7	SEES3-1V human RARB, clone2	Embryonic stem cell	Male
CVCL_A5S8	SEES3-1V human RARB, clone3	Embryonic stem cell	Male
CVCL_B8NN	Abcam HCT 116 RARB KO	Cancer cell line	Male
CVCL_B9B0	Abcam MCF-7 RARB KO	Cancer cell line	Female
CVCL_B9QZ	Abcam A-549 RARB KO	Cancer cell line	Male
CVCL_KY93	PathHunter CHO-K1 RARbeta Protein Interaction	Spontaneously immortalized cell line	Female
CVCL_LF51	GeneBLAzer RARbeta-UAS-bla HEK 293T	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01778543	Not specified	RECRUITING	Pathogenesis and Genetics of Microphthalmia, Anophthalmia and Uveal Coloboma (MAC)
NCT03748732	Not specified	UNKNOWN	Extensive Circumferential Partial Thickness Sclerectomy in Nanophthalmic Eyes
NCT04759560	Not specified	UNKNOWN	Biometric Characteristics of the Eye With Microcornea/Microphthalmia and Congenital Cataract Before And After Cataract Extraction
NCT05954403	Not specified	RECRUITING	National Cohort on Congenital Defects of the Eye
NCT06293560	Not specified	RECRUITING	Microphthalmia, Anophthalmia, and Coloboma Genetic Epidemiology in Children
NCT00368004	Not specified	TERMINATED	Family Studies of Uveal Coloboma
NCT04833361	Not specified	COMPLETED	Potential Environmental Causes of Uveal Coloboma
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients