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RORB

gene
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Also known as RZRBNR1F2ROR-BETARORβRZR-BETA

Summary

RORB (RAR related orphan receptor B, HGNC:10259) is a protein-coding gene on chromosome 9q21.13, encoding Nuclear receptor ROR-beta (Q92753). Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5’-AGGTCA-3’ preceded by a short A-T-rich sequence. It is haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is a member of the NR1 subfamily of nuclear hormone receptors. It is a DNA-binding protein that can bind as a monomer or as a homodimer to hormone response elements upstream of several genes to enhance the expression of those genes. The encoded protein has been shown to interact with NM23-2, a nucleoside diphosphate kinase involved in organogenesis and differentiation, and to help regulate the expression of some genes involved in circadian rhythm.

Source: NCBI Gene 6096 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +1 more curated relationship
  • GWAS associations: 13
  • Clinical variants (ClinVar): 461 total — 38 pathogenic, 24 likely-pathogenic
  • Phenotypes (HPO): 15
  • Druggable target: yes — 2 molecules with ChEMBL bioactivity
  • Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
  • MANE Select transcript: NM_006914

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:10259
Approved symbolRORB
NameRAR related orphan receptor B
Location9q21.13
Locus typegene with protein product
StatusApproved
AliasesRZRB, NR1F2, ROR-BETA, RORβ, RZR-BETA
Ensembl geneENSG00000198963
Ensembl biotypeprotein_coding
OMIM601972
Entrez6096

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000376896, ENST00000396204

RefSeq mRNA: 2 — MANE Select: NM_006914 NM_001365023, NM_006914

CCDS: CCDS6646, CCDS94422

Canonical transcript exons

ENST00000376896 — 10 exons

ExonStartEnd
ENSE000007068597464241474642815
ENSE000007068627463463174634772
ENSE000007068667466548874665595
ENSE000007068677466779174667901
ENSE000007068687467178974671901
ENSE000008038077466061774660738
ENSE000008038087466247474662606
ENSE000014720837449733574497983
ENSE000016098207463028274630367
ENSE000037103327468546374693177

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 98.32.

FANTOM5 (CAGE): breadth broad, TPM avg 14.2823 / max 1807.3972, expressed in 664 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter IDTPM avgSamples expressed
9696511.8733565
969641.2961402
2055160.4314109
2055170.328589
2055140.134464
2055150.105848
2055180.069929
969670.02906
969660.00894
969680.00492

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
endothelial cellCL:000011598.32gold quality
Brodmann (1909) area 23UBERON:001355497.59gold quality
middle temporal gyrusUBERON:000277195.87gold quality
parietal lobeUBERON:000187295.02gold quality
postcentral gyrusUBERON:000258194.97gold quality
pigmented layer of retinaUBERON:000178294.96gold quality
primary visual cortexUBERON:000243693.84gold quality
occipital lobeUBERON:000202193.25gold quality
superior frontal gyrusUBERON:000266192.94gold quality
entorhinal cortexUBERON:000272891.58gold quality
endometriumUBERON:000129589.44gold quality
cortical plateUBERON:000534389.42gold quality
seminal vesicleUBERON:000099887.97gold quality
deciduaUBERON:000245085.56silver quality
epithelium of nasopharynxUBERON:000195185.12gold quality
mucosa of paranasal sinusUBERON:000503083.38gold quality
dorsolateral prefrontal cortexUBERON:000983482.92gold quality
frontal cortexUBERON:000187080.38gold quality
neocortexUBERON:000195079.96gold quality
temporal lobeUBERON:000187179.93gold quality
Brodmann (1909) area 9UBERON:001354079.92gold quality
buccal mucosa cellCL:000233679.90gold quality
cerebral cortexUBERON:000095679.46gold quality
prefrontal cortexUBERON:000045179.32gold quality
ventral tegmental areaUBERON:000269178.58gold quality
telencephalonUBERON:000189377.22gold quality
right frontal lobeUBERON:000281077.20gold quality
ventricular zoneUBERON:000305377.12gold quality
lower lobe of lungUBERON:000894976.74silver quality
lateral nuclear group of thalamusUBERON:000273675.73gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-HCAD-35yes900.97
E-HCAD-25yes692.05
E-HCAD-5yes459.00
E-MTAB-10287yes121.20
E-GEOD-137537yes8.10
E-ANND-3no0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

TargetRegulation
BMAL1Unknown
KCNQ5
NAMPT
NRL
OPN1MWActivation
OPN1SWActivation
RORB

JASPAR motifs

MotifNameFamily
MA1150.1RORBThyroid hormone receptor-related factors (NR1)
MA1150.2RORBThyroid hormone receptor-related factors (NR1)

JASPAR matrix evidence (PMIDs): PMID:25500868

Upstream regulators (CollecTRI, top): RORB

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 10)

  • In the suprachiasmatic nucleus, ROR beta mRNA signals showed a peak at early daytime and a trough at early nighttime. ROR beta is a transcription factor possibly related to the circadian pacemaking system. (PMID:11849752)
  • these data demonstrate that Rorbeta regulates known osteogenic pathways, and may represent a novel therapeutic target for age-associated bone loss. (PMID:24125721)
  • associations between NR1D1, RORA and RORB genes and bipolar disorder.( (PMID:25789810)
  • Retinoic acid-related orphan receptor RORbeta, circadian rhythm abnormalities and tumorigenesis (PMID:25816151)
  • Nonsense variant in RORB was identified in four family members with epilepsy. Two de novo RORB deletions identified in patients with behavioral and cognitive impairment and epilepsy. (PMID:27352968)
  • Results show that NRIP2 regulates the activity of the Wnt pathway via RORbeta. RORbeta inhibits tumorigenesis and the self-renewal of cancer initiating cells (CCICs) and targets HBP1 in regulating Wnt pathway to inhibit tumorigenesis and the self-renewal of CCICs. (PMID:28137278)
  • Inherited RORB pathogenic variants: Overlap of photosensitive genetic generalized and occipital lobe epilepsy. (PMID:32162308)
  • RORbeta suppresses the stemness of gastric cancer cells by downregulating the activity of the Wnt signaling pathway. (PMID:34278502)
  • Comprehensive analysis of the prognosis and biological significance of RORbeta in head and neck squamous cell carcinoma. (PMID:37278231)
  • RORB, an Alzheimer’s disease susceptibility gene, is associated with viral encephalitis, an Alzheimer’s disease risk factor. (PMID:37734269)

Cross-species orthologs

188 orthologs

OrganismSymbolGene ID
danio_reriororbENSDARG00000033498
mus_musculusRorbENSMUSG00000036192
rattus_norvegicusRorbENSRNOG00000013413
drosophila_melanogasterEcRFBGN0000546
drosophila_melanogasterHr96FBGN0015240
caenorhabditis_elegansWBGENE00001062
caenorhabditis_elegansnhr-2WBGENE00003601
caenorhabditis_elegansWBGENE00003608
caenorhabditis_elegansWBGENE00003611
caenorhabditis_elegansWBGENE00003614
caenorhabditis_elegansWBGENE00003615
caenorhabditis_elegansWBGENE00003617
caenorhabditis_elegansWBGENE00003618
caenorhabditis_elegansWBGENE00003620
caenorhabditis_elegansnhr-23WBGENE00003622
caenorhabditis_elegansWBGENE00003624
caenorhabditis_elegansWBGENE00003632
caenorhabditis_elegansWBGENE00003634
caenorhabditis_elegansWBGENE00003638
caenorhabditis_elegansWBGENE00003640
caenorhabditis_elegansWBGENE00003641
caenorhabditis_elegansWBGENE00003642
caenorhabditis_elegansWBGENE00003643
caenorhabditis_elegansWBGENE00003644
caenorhabditis_elegansWBGENE00003645
caenorhabditis_elegansWBGENE00003646
caenorhabditis_elegansWBGENE00003648
caenorhabditis_elegansWBGENE00003649
caenorhabditis_elegansWBGENE00003651
caenorhabditis_elegansWBGENE00003653
caenorhabditis_elegansWBGENE00003655
caenorhabditis_elegansWBGENE00003658
caenorhabditis_elegansWBGENE00003660
caenorhabditis_elegansWBGENE00003662
caenorhabditis_elegansnhr-73WBGENE00003663
caenorhabditis_elegansnhr-77WBGENE00003667
caenorhabditis_elegansWBGENE00003669
caenorhabditis_elegansnhr-81WBGENE00003671
caenorhabditis_elegansnhr-82WBGENE00003672
caenorhabditis_elegansWBGENE00003676
caenorhabditis_elegansWBGENE00003677
caenorhabditis_elegansWBGENE00003680
caenorhabditis_elegansWBGENE00003682
caenorhabditis_elegansWBGENE00003684
caenorhabditis_elegansWBGENE00003685
caenorhabditis_elegansWBGENE00003686
caenorhabditis_elegansWBGENE00003688
caenorhabditis_elegansWBGENE00003689
caenorhabditis_elegansWBGENE00003692
caenorhabditis_elegansWBGENE00003693
caenorhabditis_elegansWBGENE00003694
caenorhabditis_elegansWBGENE00003696
caenorhabditis_elegansWBGENE00003698
caenorhabditis_elegansWBGENE00003699
caenorhabditis_elegansWBGENE00003700
caenorhabditis_elegansWBGENE00003702
caenorhabditis_elegansWBGENE00003704
caenorhabditis_elegansWBGENE00003705
caenorhabditis_elegansWBGENE00003707
caenorhabditis_elegansWBGENE00003708
caenorhabditis_elegansWBGENE00003712
caenorhabditis_elegansWBGENE00003713
caenorhabditis_elegansWBGENE00003714
caenorhabditis_elegansWBGENE00003715
caenorhabditis_elegansWBGENE00003716
caenorhabditis_elegansWBGENE00003717
caenorhabditis_elegansWBGENE00003718
caenorhabditis_elegansWBGENE00003720
caenorhabditis_elegansWBGENE00003721
caenorhabditis_elegansWBGENE00003722
caenorhabditis_elegansWBGENE00003723
caenorhabditis_elegansWBGENE00003724
caenorhabditis_elegansWBGENE00003725
caenorhabditis_elegansWBGENE00003728
caenorhabditis_elegansWBGENE00004786
caenorhabditis_elegansWBGENE00006471
caenorhabditis_elegansunc-55WBGENE00006790
caenorhabditis_elegansWBGENE00007367
caenorhabditis_elegansWBGENE00008056
caenorhabditis_elegansnhr-165WBGENE00008158
caenorhabditis_elegansWBGENE00008208
caenorhabditis_elegansnhr-169WBGENE00008289
caenorhabditis_elegansWBGENE00008309
caenorhabditis_elegansnhr-174WBGENE00008474
caenorhabditis_elegansWBGENE00008619
caenorhabditis_elegansWBGENE00008630
caenorhabditis_elegansWBGENE00008778
caenorhabditis_elegansWBGENE00008830
caenorhabditis_elegansWBGENE00008884
caenorhabditis_elegansWBGENE00008901
caenorhabditis_elegansnhr-265WBGENE00009608
caenorhabditis_elegansWBGENE00010017
caenorhabditis_elegansWBGENE00010180
caenorhabditis_elegansWBGENE00010186
caenorhabditis_elegansWBGENE00010215
caenorhabditis_elegansWBGENE00010410
caenorhabditis_elegansWBGENE00010600
caenorhabditis_elegansWBGENE00010601
caenorhabditis_elegansWBGENE00010602
caenorhabditis_elegansWBGENE00010603
caenorhabditis_elegansWBGENE00010604
caenorhabditis_elegansWBGENE00011002
caenorhabditis_elegansWBGENE00011150
caenorhabditis_elegansWBGENE00011396
caenorhabditis_elegansWBGENE00011520
caenorhabditis_elegansWBGENE00011565
caenorhabditis_elegansWBGENE00011566
caenorhabditis_elegansWBGENE00011568
caenorhabditis_elegansnhr-217WBGENE00011651
caenorhabditis_elegansWBGENE00011750
caenorhabditis_elegansWBGENE00012050
caenorhabditis_elegansWBGENE00012056
caenorhabditis_elegansWBGENE00012446
caenorhabditis_elegansWBGENE00012449
caenorhabditis_elegansWBGENE00012596
caenorhabditis_elegansWBGENE00012703
caenorhabditis_elegansWBGENE00013067
caenorhabditis_elegansWBGENE00013483
caenorhabditis_elegansnhr-276WBGENE00013512
caenorhabditis_elegansWBGENE00013584
caenorhabditis_elegansWBGENE00013940
caenorhabditis_elegansWBGENE00014068
caenorhabditis_elegansnhr-245WBGENE00014189
caenorhabditis_elegansWBGENE00014193
caenorhabditis_elegansWBGENE00015497
caenorhabditis_elegansWBGENE00015758
caenorhabditis_elegansWBGENE00015897
caenorhabditis_elegansWBGENE00015900
caenorhabditis_elegansWBGENE00015901
caenorhabditis_elegansWBGENE00015902
caenorhabditis_elegansWBGENE00016091
caenorhabditis_elegansWBGENE00016233
caenorhabditis_elegansWBGENE00016364
caenorhabditis_elegansWBGENE00016365
caenorhabditis_elegansWBGENE00016366
caenorhabditis_elegansWBGENE00016367
caenorhabditis_elegansWBGENE00016368
caenorhabditis_elegansWBGENE00016517
caenorhabditis_elegansWBGENE00016772
caenorhabditis_elegansWBGENE00016926
caenorhabditis_elegansWBGENE00016927
caenorhabditis_elegansWBGENE00017503
caenorhabditis_elegansWBGENE00017512
caenorhabditis_elegansWBGENE00017961
caenorhabditis_elegansWBGENE00018189
caenorhabditis_elegansWBGENE00018265
caenorhabditis_elegansWBGENE00018266
caenorhabditis_elegansWBGENE00018404
caenorhabditis_elegansWBGENE00018412
caenorhabditis_elegansWBGENE00018415
caenorhabditis_elegansWBGENE00018539
caenorhabditis_elegansWBGENE00018541
caenorhabditis_elegansWBGENE00018542
caenorhabditis_elegansWBGENE00018544
caenorhabditis_elegansWBGENE00018545
caenorhabditis_elegansWBGENE00018622
caenorhabditis_elegansWBGENE00019115
caenorhabditis_elegansWBGENE00019116
caenorhabditis_elegansWBGENE00019741
caenorhabditis_elegansWBGENE00019742
caenorhabditis_elegansWBGENE00019743
caenorhabditis_elegansWBGENE00020015
caenorhabditis_elegansWBGENE00020062
caenorhabditis_elegansWBGENE00020152
caenorhabditis_elegansWBGENE00020153
caenorhabditis_elegansWBGENE00020385
caenorhabditis_elegansWBGENE00020460
caenorhabditis_elegansWBGENE00020555
caenorhabditis_elegansWBGENE00020750
caenorhabditis_elegansWBGENE00020849
caenorhabditis_elegansWBGENE00020850
caenorhabditis_elegansWBGENE00020851
caenorhabditis_elegansWBGENE00020852
caenorhabditis_elegansWBGENE00021163
caenorhabditis_elegansWBGENE00021522
caenorhabditis_elegansWBGENE00021610
caenorhabditis_elegansWBGENE00021611
caenorhabditis_elegansWBGENE00021617
caenorhabditis_elegansWBGENE00022097
caenorhabditis_elegansWBGENE00022637
caenorhabditis_elegansWBGENE00022639
caenorhabditis_elegansWBGENE00022640
caenorhabditis_elegansWBGENE00022726
caenorhabditis_elegansWBGENE00022756
caenorhabditis_elegansWBGENE00022805
caenorhabditis_elegansWBGENE00044353
caenorhabditis_elegansWBGENE00044699
caenorhabditis_elegansWBGENE00045515

Paralogs (18): NR1H4 (ENSG00000012504), NR1H3 (ENSG00000025434), RORA (ENSG00000069667), RARB (ENSG00000077092), VDR (ENSG00000111424), PPARD (ENSG00000112033), THRA (ENSG00000126351), NR1D1 (ENSG00000126368), NR1H2 (ENSG00000131408), RARA (ENSG00000131759), PPARG (ENSG00000132170), NR1I3 (ENSG00000143257), RORC (ENSG00000143365), NR1I2 (ENSG00000144852), THRB (ENSG00000151090), RARG (ENSG00000172819), NR1D2 (ENSG00000174738), PPARA (ENSG00000186951)

Protein

Protein identifiers

Nuclear receptor ROR-beta — Q92753 (reviewed: Q92753)

Alternative names: Nuclear receptor RZR-beta, Nuclear receptor subfamily 1 group F member 2, Retinoid-related orphan receptor-beta

All UniProt accessions (3): Q92753, A0A1L4FMK7, Q58EY0

UniProt curated annotations — full annotation on UniProt →

Function. Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5’-AGGTCA-3’ preceded by a short A-T-rich sequence. Considered to have intrinsic transcriptional activity, have some natural ligands such as all-trans retinoic acid (ATRA) and other retinoids which act as inverse agonists repressing the transcriptional activity. Required for normal postnatal development of rod and cone photoreceptor cells. Modulates rod photoreceptors differentiation at least by inducing the transcription factor NRL-mediated pathway. In cone photoreceptor cells, regulates transcription of OPN1SW. Involved in the regulation of the period length and stability of the circadian rhythm. May control cytoarchitectural patterning of neocortical neurons during development. May act in a dose-dependent manner to regulate barrel formation upon innervation of layer IV neurons by thalamocortical axons. May play a role in the suppression of osteoblastic differentiation through the inhibition of RUNX2 transcriptional activity. Isoform 1 is critical for hindlimb motor control and for the differentiation of amacrine and horizontal cells in the retina. Regulates the expression of PTF1A synergistically with FOXN4.

Subunit / interactions. Monomer. Interacts with CRX.

Subcellular location. Nucleus. Nucleoplasm.

Disease relevance. Epilepsy, idiopathic generalized 15 (EIG15) [MIM:618357] An autosomal dominant form of idiopathic generalized epilepsy, a disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures. EIG15 is characterized by onset of variable types of seizures in the first decade of life. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Domain organisation. AF-2 (activation function-2) motif is required for recruiting coregulators containing the LXXLL motif, such as NCOA1, and control the transactivational activity.

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

Isoforms (2)

UniProt IDNamesCanonical?
Q92753-22yes
Q92753-11

RefSeq proteins (2): NP_001351952, NP_008845* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000536Nucl_hrmn_rcpt_lig-bdDomain
IPR001628Znf_hrmn_rcptDomain
IPR001723Nuclear_hrmn_rcptFamily
IPR003079ROR_rcptFamily
IPR013088Znf_NHR/GATAHomologous_superfamily
IPR035500NHR-like_dom_sfHomologous_superfamily
IPR044101NR_DBD_RORDomain

Pfam: PF00104, PF00105

UniProt features (17 total): sequence conflict 5, sequence variant 3, zinc finger region 2, chain 1, domain 1, DNA-binding region 1, region of interest 1, short sequence motif 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q92753-F179.480.59

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

IDPathway
R-HSA-383280Nuclear Receptor transcription pathway
R-HSA-9931509Expression of BMAL (ARNTL), CLOCK, and NPAS2
R-HSA-212436Generic Transcription Pathway
R-HSA-73857RNA Polymerase II Transcription
R-HSA-74160Gene expression (Transcription)

MSigDB gene sets: 240 (showing top): GOBP_CIRCADIAN_RHYTHM, AAGCAAT_MIR137, WWTAAGGC_UNKNOWN, GOBP_CELLULAR_RESPONSE_TO_LIPID, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_OSTEOBLAST_DIFFERENTIATION, TATTATA_MIR374, GOBP_NEUROGENESIS, HNF1_Q6, GOBP_NEURAL_RETINA_DEVELOPMENT, LHX3_01, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, CHANDRAN_METASTASIS_DN, MORF_RAD51L3, GOBP_REGULATION_OF_CIRCADIAN_RHYTHM

GO Biological Process (19): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), visual perception (GO:0007601), amacrine cell differentiation (GO:0035881), eye photoreceptor cell development (GO:0042462), regulation of circadian rhythm (GO:0042752), negative regulation of osteoblast differentiation (GO:0045668), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), retinal rod cell development (GO:0046548), retinal cone cell development (GO:0046549), rhythmic process (GO:0048511), retina development in camera-type eye (GO:0060041), cellular response to retinoic acid (GO:0071300), G protein-coupled receptor signaling pathway (GO:0007186), regulation of gene expression (GO:0010468), intracellular receptor signaling pathway (GO:0030522), retinal rod cell differentiation (GO:0060221)

GO Molecular Function (12): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), nuclear receptor activity (GO:0004879), zinc ion binding (GO:0008270), melatonin receptor activity (GO:0008502), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-4 pathways:

CategoryPathways
Generic Transcription Pathway1
Circadian clock1
RNA Polymerase II Transcription1
Gene expression (Transcription)1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
regulation of DNA-templated transcription4
DNA-templated transcription3
RNA polymerase II transcription regulatory region sequence-specific DNA binding3
transcription by RNA polymerase II2
regulation of transcription by RNA polymerase II2
eye photoreceptor cell development2
G protein-coupled receptor activity2
DNA-binding transcription factor activity, RNA polymerase II-specific2
cellular anatomical structure2
regulation of gene expression1
regulation of RNA biosynthetic process1
sensory perception of light stimulus1
neural retina development1
central nervous system neuron differentiation1
eye photoreceptor cell differentiation1
photoreceptor cell development1
circadian rhythm1
regulation of biological process1
osteoblast differentiation1
negative regulation of cell differentiation1
regulation of osteoblast differentiation1
negative regulation of RNA biosynthetic process1
positive regulation of RNA biosynthetic process1
positive regulation of DNA-templated transcription1
retinal rod cell differentiation1
retinal cone cell differentiation1
biological_process1
camera-type eye development1
anatomical structure development1
response to retinoic acid1
cellular response to lipid1
cellular response to oxygen-containing compound1
signal transduction1
gene expression1
regulation of macromolecule biosynthetic process1
intracellular signal transduction1
camera-type eye photoreceptor cell differentiation1
cis-regulatory region sequence-specific DNA binding1
chromatin1
DNA-binding transcription factor activity1

Protein interactions and networks

STRING

1426 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
RORBPER3P56645937
RORBBMAL1O00327925
RORBPER2O15055922
RORBNPAS2Q99743921
RORBCRY1Q16526919
RORBNFIL3Q16649903
RORBBHLHE41Q9C0J9856
RORBBHLHE40O14503856
RORBCLOCKO15516844
RORBCRY2Q49AN0842
RORBTIMELESSQ9UNS1725
RORBCUX2O14529668
RORBCSNK1EP49674649
RORBOTX2P32243623
RORBCRXO43186615

IntAct

6 interactions, top by confidence:

ABTypeScore
RORBClockpsi-mi:“MI:0915”(physical association)0.510
RORBRORCpsi-mi:“MI:0915”(physical association)0.000
RORBClockpsi-mi:“MI:0915”(physical association)0.000
RORBCSNK2Bpsi-mi:“MI:0915”(physical association)0.000
BHLHE40RORBpsi-mi:“MI:0915”(physical association)0.000

ESM2 similar proteins: A0A3Q0KHE7, A2YPT7, A2Z8S0, A3KPF2, B0W3L6, B3M1E1, B3P4N5, B4GZ20, B4HJC0, B4JXV2, B4KA23, B4LVS8, B4NKI9, B4PVH6, B4QVW6, F1QLY4, O73630, P31396, P45446, Q08A71, Q0J7U6, Q0WV90, Q10NY2, Q174R2, Q24151, Q27GK7, Q29B63, Q2HVD6, Q4AE70, Q5NBT9, Q5RGQ2, Q5XK84, Q63369, Q6DC04, Q75G68, Q7Q2B7, Q7XI75, Q84JM4, Q84W92, Q86X55

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

SIGNOR signaling

4 interactions.

AEffectBMechanism
“all-trans-retinoic acid”“down-regulates activity”RORB“chemical inhibition”
RORB“up-regulates quantity by expression”ARNTL“transcriptional regulation”
RORB“up-regulates quantity by expression”OPN1MW“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic38
Likely pathogenic24
Uncertain significance207
Likely benign134
Benign14

Top pathogenic / likely-pathogenic (30)

Variant IDHGVSClassification
1327473NM_006914.4(RORB):c.202C>T (p.Gln68Ter)Pathogenic
1384338NM_006914.4(RORB):c.673G>T (p.Glu225Ter)Pathogenic
1404805NM_006914.4(RORB):c.78_79del (p.Thr26_Cys27insTer)Pathogenic
1413758NM_006914.4(RORB):c.631G>T (p.Glu211Ter)Pathogenic
1452736NM_006914.4(RORB):c.445del (p.Leu149fs)Pathogenic
1456655NM_006914.4(RORB):c.1114C>T (p.Arg372Ter)Pathogenic
1458677NC_000009.11:g.(?77112893)(77112919_?)delPathogenic
1459201NC_000009.11:g.(?77112893)(77502772_?)delPathogenic
1678868NM_006914.4(RORB):c.61del (p.His21fs)Pathogenic
1700119NM_006914.4(RORB):c.423T>G (p.Tyr141Ter)Pathogenic
2023022NM_006914.4(RORB):c.816C>A (p.Tyr272Ter)Pathogenic
2028548NM_006914.4(RORB):c.463dup (p.Tyr155fs)Pathogenic
2134793NM_006914.4(RORB):c.41dup (p.Asp15fs)Pathogenic
225115NM_006914.4(RORB):c.218T>C (p.Leu73Pro)Pathogenic
2501689NM_006914.4(RORB):c.1069del (p.Glu357fs)Pathogenic
2580352GRCh37/hg19 9q21.13(chr9:77112742-77113051)x1Pathogenic
2662614NM_006914.4(RORB):c.566del (p.Val189fs)Pathogenic
2718853NM_006914.4(RORB):c.304C>T (p.Gln102Ter)Pathogenic
2729731NM_006914.4(RORB):c.777G>A (p.Trp259Ter)Pathogenic
2770599NM_006914.4(RORB):c.2T>G (p.Met1Arg)Pathogenic
2810239NM_006914.4(RORB):c.538C>T (p.Gln180Ter)Pathogenic
2825215NM_006914.4(RORB):c.3G>C (p.Met1Ile)Pathogenic
2830166NM_006914.4(RORB):c.564del (p.Val189fs)Pathogenic
2838413NM_006914.4(RORB):c.347_359del (p.Glu116fs)Pathogenic
2864839NM_006914.4(RORB):c.1215del (p.Leu406fs)Pathogenic
3363344NM_006914.4(RORB):c.1121G>A (p.Trp374Ter)Pathogenic
3376020NM_006914.4(RORB):c.1A>G (p.Met1Val)Pathogenic
3721234NM_006914.4(RORB):c.175A>T (p.Arg59Ter)Pathogenic
4291106NM_006914.4(RORB):c.682C>T (p.Gln228Ter)Pathogenic
4538480NM_006914.4(RORB):c.694del (p.Glu232fs)Pathogenic

SpliceAI

2054 predictions. Top by Δscore:

VariantEffectΔscore
9:74497981:GAG:Gdonor_gain1.0000
9:74497981:GAGGT:Gdonor_loss1.0000
9:74497983:GGT:Gdonor_loss1.0000
9:74497984:GTAA:Gdonor_loss1.0000
9:74497985:T:Adonor_loss1.0000
9:74630277:TTCA:Tacceptor_loss1.0000
9:74630279:CA:Cacceptor_loss1.0000
9:74630280:A:AGacceptor_gain1.0000
9:74630280:AGCAC:Aacceptor_loss1.0000
9:74630281:G:GCacceptor_gain1.0000
9:74630281:GCA:Gacceptor_gain1.0000
9:74630281:GCAC:Gacceptor_gain1.0000
9:74630281:GCACA:Gacceptor_gain1.0000
9:74634628:AAG:Aacceptor_gain1.0000
9:74634628:AAGG:Aacceptor_gain1.0000
9:74634629:A:Gacceptor_gain1.0000
9:74634629:AG:Aacceptor_gain1.0000
9:74634630:GG:Gacceptor_gain1.0000
9:74634769:GATG:Gdonor_gain1.0000
9:74642407:A:AGacceptor_gain1.0000
9:74642408:A:Gacceptor_gain1.0000
9:74642412:A:AGacceptor_gain1.0000
9:74642413:G:GAacceptor_gain1.0000
9:74642812:ATCGG:Adonor_loss1.0000
9:74642814:CGG:Cdonor_loss1.0000
9:74642816:G:GGdonor_gain1.0000
9:74642816:GTA:Gdonor_loss1.0000
9:74642817:TAAGT:Tdonor_loss1.0000
9:74642818:A:AGdonor_loss1.0000
9:74660614:C:Gacceptor_gain1.0000

AlphaMissense

3046 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
9:74630297:T:AI19K1.000
9:74630297:T:CI19T1.000
9:74630297:T:GI19R1.000
9:74630302:T:AC21S1.000
9:74630302:T:CC21R1.000
9:74630302:T:GC21G1.000
9:74630303:G:AC21Y1.000
9:74630303:G:CC21S1.000
9:74630303:G:TC21F1.000
9:74630304:C:GC21W1.000
9:74630308:A:TI23F1.000
9:74630309:T:AI23N1.000
9:74630309:T:CI23T1.000
9:74630309:T:GI23S1.000
9:74630311:T:AC24S1.000
9:74630311:T:CC24R1.000
9:74630311:T:GC24G1.000
9:74630312:G:AC24Y1.000
9:74630312:G:CC24S1.000
9:74630312:G:TC24F1.000
9:74630313:T:GC24W1.000
9:74630315:G:AG25D1.000
9:74630315:G:TG25V1.000
9:74630317:G:CD26H1.000
9:74630318:A:CD26A1.000
9:74630318:A:GD26G1.000
9:74630318:A:TD26V1.000
9:74630320:A:GK27E1.000
9:74630322:G:CK27N1.000
9:74630322:G:TK27N1.000

dbSNP variants (sampled 300 via entrez): RS1000009199 (9:74622846 C>A), RS1000032587 (9:74690248 TGACAC>T), RS1000034451 (9:74536241 C>T), RS1000043683 (9:74669333 G>C,T), RS1000076622 (9:74552270 A>T), RS1000095340 (9:74530189 C>G), RS1000098202 (9:74542398 C>T), RS1000113724 (9:74583906 T>A), RS1000128855 (9:74684050 T>C), RS1000143518 (9:74502035 G>A), RS1000151266 (9:74662321 T>A), RS1000175123 (9:74555558 A>T), RS1000177307 (9:74681250 A>T), RS1000185379 (9:74517369 C>G,T), RS1000194208 (9:74655191 A>G,T)

Disease associations

OMIM: gene MIM:601972 | disease phenotypes: MIM:618357, MIM:609056

GenCC curated gene-disease

DiseaseClassificationInheritance
epilepsy, idiopathic generalized, susceptibility to, 15StrongAutosomal dominant
complex neurodevelopmental disorderModerateAutosomal dominant

ClinGen Gene-Disease Validity (1)

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

DiseaseClassificationInheritance
complex neurodevelopmental disorderDefinitiveAD

Mondo (4): epilepsy, idiopathic generalized, susceptibility to, 15 (MONDO:0032699), GM3 synthase deficiency (MONDO:0018274), epilepsy (MONDO:0005027), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (3): Amish infantile epilepsy syndrome (Orphanet:171714), GM3 synthase deficiency (Orphanet:370933), Salt-and-pepper syndrome (Orphanet:370938)

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPOTerm
HP:0000006Autosomal dominant inheritance
HP:0000708Atypical behavior
HP:0000718Aggressive behavior
HP:0000750Delayed speech and language development
HP:0000992Cutaneous photosensitivity
HP:0001250Seizure
HP:0001263Global developmental delay
HP:0001336Myoclonus
HP:0002069Bilateral tonic-clonic seizure
HP:0002121Generalized non-motor (absence) seizure
HP:0003593Infantile onset
HP:0003621Juvenile onset
HP:0003829Typified by incomplete penetrance
HP:0011463Childhood onset
HP:0025097Eyelid myoclonus

GWAS associations

13 associations (top):

StudyTraitp-value
GCST001524_7Visceral adipose tissue/subcutaneous adipose tissue ratio9.000000e-06
GCST001858_13Refractive error4.000000e-08
GCST003219_50Advanced age-related macular degeneration3.000000e-09
GCST006291_47Spherical equivalent or myopia (age of diagnosis)1.000000e-11
GCST006976_103Macular thickness3.000000e-13
GCST007328_50Alcohol consumption (drinks per week)3.000000e-08
GCST007576_7Chronotype1.000000e-12
GCST007830_3Anti-thyroid peroxidase (TPOAb) levels in Hashimoto’s thyroiditis1.000000e-06
GCST007851_6Anti-thyroid peroxidase (TPOAb) and anti-thyroglobulin (TgAb) levels in Hashimoto’s thyroiditis5.000000e-06
GCST010002_321Refractive error6.000000e-36
GCST012400_101Low myopia vs hyperopia4.000000e-07
GCST012401_15Hyperopia8.000000e-08
GCST90002387_337Immature fraction of reticulocytes2.000000e-10

EFO canonical traits (4, from GWAS)

EFO IDTrait name
EFO:0004767visceral:subcutaneous adipose tissue ratio
EFO:1001492atrophic macular degeneration
EFO:0004847age at onset
EFO:0008328chronotype measurement

MeSH disease descriptors (1)

DescriptorNameTree numbers
D004827EpilepsyC10.228.140.490

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3091268 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 194,757 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL38TRETINOIN4194,008
CHEMBL4472508CINTIRORGON1749

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: nhr — 1F. Retinoic acid-related orphans

Most potent curated ligand interactions (3 total), top 3:

LigandActionAffinityParameter
ALRT 1550Antagonist10.4pIC50
CD2314Agonist6.84pKd
all-trans-4-oxo-retinoic acidAntagonist6.1pKi

ChEMBL bioactivities

237 potent at pChembl≥5 of 291 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
9.82IC500.15nMTRETINOIN
8.48Kd3.3nMCHEMBL4129790
8.47IC503.4nMCHEMBL4128427
8.33Kd4.7nMCHEMBL4130294
8.04Kd9.1nMCHEMBL4128427
8.00Kd10nMCHEMBL4126690
7.89IC5013nMCHEMBL4130294
7.89Kd13nMCHEMBL4128042
7.82IC5015nMCHEMBL4292343
7.80IC5016nMCHEMBL4129790
7.80IC5016nMCHEMBL4632490
7.75Kd18nMCHEMBL4126534
7.58IC5026nMCHEMBL4289114
7.47IC5034nMCHEMBL4284016
7.40IC5040nMCHEMBL4276720
7.37Kd43nMCHEMBL4127926
7.30IC5050nMCHEMBL4649210
7.28IC5053nMCHEMBL4126690
7.23IC5059nMCHEMBL4225808
7.21Kd62nMCHEMBL4642674
7.20IC5063.1nMCHEMBL3105681
7.20IC5063nMCHEMBL4226645
7.19IC5064nMCHEMBL3105681
7.12IC5076nMCHEMBL4291888
7.10IC5079.43nMCHEMBL3105681
7.08IC5083nMCHEMBL4128042
7.07Kd86nMCHEMBL4127282
7.06IC5087nMCHEMBL4284644
7.05IC5090nMCHEMBL4225823
7.05IC5090nMCHEMBL4293341
7.05IC5090nMCHEMBL4286904
7.03IC5094nMCHEMBL4288028
6.96IC50110nMCHEMBL4226392
6.94IC50115nMCHEMBL4126534
6.94Kd115nMCHEMBL4647899
6.92IC50119nMCHEMBL4127926
6.92IC50120nMCHEMBL4227190
6.90IC50125.9nMTRETINOIN
6.89IC50130nMCHEMBL4228640
6.89IC50130nMCHEMBL4281271
6.85IC50140nMCHEMBL4227927
6.83IC50148nMCHEMBL4645288
6.82Ki151nMCHEMBL5902122
6.81IC50154nMCHEMBL4126366
6.80IC50160nMCHEMBL4225264
6.80IC50160nMCHEMBL4227867
6.79IC50164nMCHEMBL4128926
6.79IC50163nMCHEMBL4128262
6.75IC50176nMCHEMBL4130137
6.75IC50180nMCHEMBL4290788

PubChem BioAssay actives

215 with measured affinity, of 606 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
3-[[4-(cyclohexylmethyl)-5-[3-(1-methylcyclopropyl)-5-[[(2S)-1,1,1-trifluorobutan-2-yl]carbamoyl]phenyl]-1,3-thiazole-2-carbonyl]amino]cyclobutane-1-carboxylic acid1494613: Binding affinity to recombinant human RORbeta LBD (201 to 452 residues) expressed in Escherichia coli BL21 (DE3) GOLD by 1,8-ANS dye-based thermofluor assaykd0.0033uM
3-[[5-[3-tert-butyl-5-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]phenyl]-4-(cyclohexylmethyl)-1,3-thiazole-2-carbonyl]amino]cyclobutane-1-carboxylic acid1494616: Inverse agonist activity at human GAL4 DBD-fused RORbeta LBD (201 to 452 residues) expressed in HEK293T cells assessed as reduction in ROR mediated transcriptional activity after 24 hrs by dual glo luciferase reporter gene assayic500.0034uM
5-[4-(tert-butylsulfamoyl)naphthalen-1-yl]-4-(cyclohexylmethyl)-N-[(4-ethylsulfonylphenyl)methyl]-1,3-thiazole-2-carboxamide1494613: Binding affinity to recombinant human RORbeta LBD (201 to 452 residues) expressed in Escherichia coli BL21 (DE3) GOLD by 1,8-ANS dye-based thermofluor assaykd0.0047uM
3-[[5-[3-tert-butyl-5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-4-(cyclohexylmethyl)-1,3-thiazole-2-carbonyl]amino]cyclobutane-1-carboxylic acid1494613: Binding affinity to recombinant human RORbeta LBD (201 to 452 residues) expressed in Escherichia coli BL21 (DE3) GOLD by 1,8-ANS dye-based thermofluor assaykd0.0100uM
[5-amino-3-(3,5-dichlorophenyl)thiophen-2-yl]-(2-chlorophenyl)methanone1420199: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by TopCount scintillation proximity assayic500.0100uM
3-[[4-(cyclohexylmethyl)-5-[3-(1-methylcyclopropyl)-5-[[(2S)-1,1,1-trifluoropropan-2-yl]carbamoyl]phenyl]-1,3-thiazole-2-carbonyl]amino]cyclobutane-1-carboxylic acid1494613: Binding affinity to recombinant human RORbeta LBD (201 to 452 residues) expressed in Escherichia coli BL21 (DE3) GOLD by 1,8-ANS dye-based thermofluor assaykd0.0130uM
[3-(3-bromo-5-propan-2-yloxyphenyl)thiophen-2-yl]-(2-chlorophenyl)methanone1420199: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by TopCount scintillation proximity assayic500.0150uM
3-[5-[4-(cyclobutylmethyl)-5-[2,3-dichloro-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]phenyl]-1,3-thiazol-2-yl]-1,3,4-thiadiazol-2-yl]-2,2-dimethylpropanoic acid1662537: Binding affinity to recombinant human RORbeta transfected in human HEK293T cells incubated for 24 hrs by dual-glo luciferase reporter gene assayic500.0160uM
3-[[5-[3-(tert-butylcarbamoyl)-5-(1-methylcyclopropyl)phenyl]-4-(cyclohexylmethyl)-1,3-thiazole-2-carbonyl]amino]cyclobutane-1-carboxylic acid1494613: Binding affinity to recombinant human RORbeta LBD (201 to 452 residues) expressed in Escherichia coli BL21 (DE3) GOLD by 1,8-ANS dye-based thermofluor assaykd0.0180uM
[4-[3-bromo-5-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]-(2-chlorophenyl)methanone1420199: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by TopCount scintillation proximity assayic500.0260uM
(2-chlorophenyl)-[4-[3-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methanone1420199: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by TopCount scintillation proximity assayic500.0340uM
[5-amino-3-[3-(trifluoromethyl)phenyl]thiophen-2-yl]-(2-chlorophenyl)methanone1420199: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by TopCount scintillation proximity assayic500.0400uM
3-[[5-[3-tert-butyl-5-[[(2S)-1,1,1-trifluoropropan-2-yl]carbamoyl]phenyl]-4-(cyclohexylmethyl)-1,3-thiazole-2-carbonyl]amino]cyclobutane-1-carboxylic acid1494613: Binding affinity to recombinant human RORbeta LBD (201 to 452 residues) expressed in Escherichia coli BL21 (DE3) GOLD by 1,8-ANS dye-based thermofluor assaykd0.0430uM
3-[6-[4-(cyclobutylmethyl)-5-[2,3-dichloro-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]phenyl]-1,3-thiazol-2-yl]pyrimidin-4-yl]-2,2-dimethylpropanoic acid1662537: Binding affinity to recombinant human RORbeta transfected in human HEK293T cells incubated for 24 hrs by dual-glo luciferase reporter gene assayic500.0500uM
N-[5-(2-chlorobenzoyl)-4-(2-chlorophenyl)-1,3-thiazol-2-yl]-2-(4-ethylsulfonylphenyl)acetamide1390733: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) at after 1 hr by scintillation proximity assayic500.0590uM
3-[5-[5-[2-(difluoromethyl)-3-fluoro-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]phenyl]-4-[(3,3-difluoropiperidin-1-yl)methyl]-1,3-thiazol-2-yl]-1,3,4-oxadiazol-2-yl]-2,2-dimethylpropanoic acid1662569: Binding affinity to RORbeta (unknown origin) assessed as dissociation constant by thermal shift binding assaykd0.0620uM
[2-amino-4-[3-bromo-5-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]-(2-chlorophenyl)methanone1390733: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) at after 1 hr by scintillation proximity assayic500.0630uM
N-[5-(2-chlorobenzoyl)-4-(3-chlorophenyl)-1,3-thiazol-2-yl]-2-(4-ethylsulfonylphenyl)acetamide1168691: Inverse agonist activity at RORbeta (unknown origin) by M1H assayic500.0631uM
[5-amino-3-[3-(trifluoromethyl)phenyl]thiophen-2-yl]-(2-methoxyphenyl)methanone1420199: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by TopCount scintillation proximity assayic500.0760uM
3-[[4-(cyclohexylmethyl)-5-[4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]naphthalen-1-yl]-1,3-thiazole-2-carbonyl]amino]cyclobutane-1-carboxylic acid1494613: Binding affinity to recombinant human RORbeta LBD (201 to 452 residues) expressed in Escherichia coli BL21 (DE3) GOLD by 1,8-ANS dye-based thermofluor assaykd0.0860uM
(2-chlorophenyl)-[3-(2-chloro-4-pyridinyl)thiophen-2-yl]methanone1420199: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by TopCount scintillation proximity assayic500.0870uM
[2-amino-4-[3-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]-[2-(trifluoromethyl)phenyl]methanone1390733: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) at after 1 hr by scintillation proximity assayic500.0900uM
[4-amino-2-[3-(trifluoromethyl)phenyl]phenyl]-(2-chlorophenyl)methanone1420199: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by TopCount scintillation proximity assayic500.0900uM
(2-chlorophenyl)-(3-naphthalen-1-ylthiophen-2-yl)methanone1420199: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by TopCount scintillation proximity assayic500.0900uM
(2-methoxyphenyl)-[4-[3-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methanone1420199: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by TopCount scintillation proximity assayic500.0940uM
[2-amino-4-[3-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]-(2-bromophenyl)methanone1390733: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) at after 1 hr by scintillation proximity assayic500.1100uM
3-[4-(cyclobutylmethyl)-5-[2,3-dichloro-4-[[(2S)-1,1,1-trifluorobutan-2-yl]sulfamoyl]phenyl]-1,3-thiazol-2-yl]-2,2-dimethylpropanoic acid1662569: Binding affinity to RORbeta (unknown origin) assessed as dissociation constant by thermal shift binding assaykd0.1150uM
[2-amino-4-[4-chloro-3-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]-(2-chlorophenyl)methanone1390733: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) at after 1 hr by scintillation proximity assayic500.1200uM
tretinoin1168691: Inverse agonist activity at RORbeta (unknown origin) by M1H assayic500.1259uM
[2-amino-4-[3-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]-[2-fluoro-6-(trifluoromethyl)phenyl]methanone1390733: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) at after 1 hr by scintillation proximity assayic500.1300uM
[5-amino-3-(3-chlorophenyl)thiophen-2-yl]-(2-methoxyphenyl)methanone1420199: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by TopCount scintillation proximity assayic500.1300uM
[2-amino-4-[3-chloro-5-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]-(2-chlorophenyl)methanone1390733: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) at after 1 hr by scintillation proximity assayic500.1400uM
3-[5-[4-(cyclobutylmethyl)-5-[2,3-dichloro-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]phenyl]-1,3-thiazol-2-yl]-1,3-thiazol-2-yl]-2,2-dimethylpropanoic acid1662537: Binding affinity to recombinant human RORbeta transfected in human HEK293T cells incubated for 24 hrs by dual-glo luciferase reporter gene assayic500.1480uM
3-[[5-[4-(tert-butylsulfamoyl)-5,6,7,8-tetrahydronaphthalen-1-yl]-4-(cyclohexylmethyl)-1,3-thiazole-2-carbonyl]amino]cyclobutane-1-carboxylic acid1494616: Inverse agonist activity at human GAL4 DBD-fused RORbeta LBD (201 to 452 residues) expressed in HEK293T cells assessed as reduction in ROR mediated transcriptional activity after 24 hrs by dual glo luciferase reporter gene assayic500.1540uM
[2-amino-4-[4-chloro-3-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]-(2-methoxyphenyl)methanone1390733: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) at after 1 hr by scintillation proximity assayic500.1600uM
[2-amino-4-[3-bromo-5-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]-(2-methoxyphenyl)methanone1390733: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) at after 1 hr by scintillation proximity assayic500.1600uM
5-[4-[(1-cyanocyclopropyl)sulfamoyl]naphthalen-1-yl]-4-(cyclohexylmethyl)-N-(2-hydroxy-2-methylpropyl)-1,3-thiazole-2-carboxamide1494616: Inverse agonist activity at human GAL4 DBD-fused RORbeta LBD (201 to 452 residues) expressed in HEK293T cells assessed as reduction in ROR mediated transcriptional activity after 24 hrs by dual glo luciferase reporter gene assayic500.1630uM
3-[[5-[4-(tert-butylsulfamoyl)naphthalen-1-yl]-4-(cyclohexylmethyl)-1,3-thiazole-2-carbonyl]amino]cyclobutane-1-carboxylic acid1494616: Inverse agonist activity at human GAL4 DBD-fused RORbeta LBD (201 to 452 residues) expressed in HEK293T cells assessed as reduction in ROR mediated transcriptional activity after 24 hrs by dual glo luciferase reporter gene assayic500.1640uM
4-[(3,3-difluorocyclobutyl)methyl]-N-(2-hydroxy-2-methylpropyl)-5-[4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]naphthalen-1-yl]-1,3-thiazole-2-carboxamide1494616: Inverse agonist activity at human GAL4 DBD-fused RORbeta LBD (201 to 452 residues) expressed in HEK293T cells assessed as reduction in ROR mediated transcriptional activity after 24 hrs by dual glo luciferase reporter gene assayic500.1760uM
(2-chlorophenyl)-[2-[3-(trifluoromethyl)phenyl]phenyl]methanone1420199: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by TopCount scintillation proximity assayic500.1800uM
[3-(3-chlorophenyl)thiophen-2-yl]-(2-methoxyphenyl)methanone1420199: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by TopCount scintillation proximity assayic500.1800uM
5-[2,3-dichloro-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]phenyl]-4-[(4-fluorophenyl)methyl]-N-(2-hydroxy-2-methylpropyl)-1,3-thiazole-2-carboxamide1494616: Inverse agonist activity at human GAL4 DBD-fused RORbeta LBD (201 to 452 residues) expressed in HEK293T cells assessed as reduction in ROR mediated transcriptional activity after 24 hrs by dual glo luciferase reporter gene assayic500.1840uM
3-[3-[4-(cyclobutylmethyl)-5-[2,3-dichloro-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]phenyl]-1,3-thiazol-2-yl]-1,2-oxazol-5-yl]-2,2-dimethylpropanoic acid1662537: Binding affinity to recombinant human RORbeta transfected in human HEK293T cells incubated for 24 hrs by dual-glo luciferase reporter gene assayic500.1890uM
3-[[4-(cyclobutylmethyl)-5-[4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]naphthalen-1-yl]-1,3-thiazole-2-carbonyl]amino]cyclobutane-1-carboxylic acid1494613: Binding affinity to recombinant human RORbeta LBD (201 to 452 residues) expressed in Escherichia coli BL21 (DE3) GOLD by 1,8-ANS dye-based thermofluor assaykd0.2000uM
[5-amino-3-(3,5-dichlorophenyl)thiophen-2-yl]-(2-methoxyphenyl)methanone1420199: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by TopCount scintillation proximity assayic500.2000uM
(2-methoxyphenyl)-[3-[3-(trifluoromethyl)phenyl]thiophen-2-yl]methanone1420199: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by TopCount scintillation proximity assayic500.2200uM
[3-(2-chloro-4-pyridinyl)thiophen-2-yl]-(2-methoxyphenyl)methanone1420199: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by TopCount scintillation proximity assayic500.2300uM
(2-chlorophenyl)-[3-[3-(trifluoromethyl)phenyl]thiophen-2-yl]methanone1420199: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by TopCount scintillation proximity assayic500.2300uM
3-[[4-(cyclohexylmethyl)-5-[4-(2-methylbutan-2-ylsulfamoyl)naphthalen-1-yl]-1,3-thiazole-2-carbonyl]amino]cyclobutane-1-carboxylic acid1494613: Binding affinity to recombinant human RORbeta LBD (201 to 452 residues) expressed in Escherichia coli BL21 (DE3) GOLD by 1,8-ANS dye-based thermofluor assaykd0.2400uM
[5-amino-3-[3,5-bis(trifluoromethyl)phenyl]thiophen-2-yl]-(2-chlorophenyl)methanone1420199: Displacement of [3H]-T0901317 from recombinant human His-SUMO-tagged RORbeta LBD (71 to 459 residues) expressed in Escherichia coli BL21(DE3) after 1 hr by TopCount scintillation proximity assayic500.2400uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Valproic Aciddecreases expression, increases expression4
Progesteroneaffects cotreatment, increases expression3
arseniteaffects binding, decreases reaction, increases methylation2
Benzo(a)pyreneaffects methylation, increases methylation2
Lipopolysaccharidesaffects cotreatment, decreases expression, decreases reaction, increases expression, affects response to substance2
Tretinoinaffects binding, decreases expression2
Aflatoxin B1affects expression, increases methylation2
pirinixic acidaffects binding, decreases expression, increases activity1
bisphenol Aaffects cotreatment, increases methylation1
trichostatin Aincreases expression1
benzo(e)pyreneincreases methylation1
aflatoxin B2increases methylation1
triadimefonincreases expression1
S-(1,2-dichlorovinyl)cysteineaffects response to substance, increases expression, affects cotreatment1
beta-methylcholineaffects expression1
tebufenozideincreases activity1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, decreases expression1
ICG 001decreases expression, affects expression, affects reaction1
dorsomorphinaffects cotreatment, decreases expression1
licochalcone Bdecreases expression1
bisphenol Saffects cotreatment, increases methylation1
(+)-JQ1 compoundincreases expression1
Sevofluranedecreases expression, decreases reaction, increases expression1
Temozolomideincreases expression1
Arsenic Trioxideaffects expression, affects reaction, decreases expression, increases expression1
Fulvestrantaffects cotreatment, increases methylation1
Acetaminophenincreases expression1
Estradiolaffects cotreatment, increases expression1
Methapyrileneincreases methylation1
Methotrexateincreases expression1

ChEMBL screening assays

90 unique, capped per target: 87 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL3097486BindingInverse agonist activity at GAL4-fused human RORb expressed in HEK293T cells assessed as suppression of basal transcriptional activity after 20 hrs by dual-glo luciferase reporter gene assayStructure-based design of substituted hexafluoroisopropanol-arylsulfonamides as modulators of RORc. — Bioorg Med Chem Lett
CHEMBL5723472FunctionalAffinity On-target Cellular interaction: (Reporter gene assay (HEK293T cells)) EUB0001157a RORBAffinity On-target Cellular Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 induced pluripotent stem cell

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

CellosaurusNameCategorySex
CVCL_A4ZUZZUNEUi019-AInduced pluripotent stem cellFemale
CVCL_A5W8SEES3-1V human RORB, clone1Embryonic stem cellMale
CVCL_A5W9SEES3-1V human RORB, clone2Embryonic stem cellMale
CVCL_A5X0SEES3-1V human RORB, clone3Embryonic stem cellMale

Clinical trials (associated diseases)

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

TrialPhaseStatusTitle
NCT00004637PHASE4COMPLETEDDouble-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914PHASE4COMPLETEDMeasurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223PHASE4UNKNOWNEffects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081PHASE4UNKNOWNStudy to Improve the Treatment of Epilepsy (SITE)
NCT00137709PHASE4UNKNOWNHormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076PHASE4COMPLETEDA Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828PHASE4TERMINATEDEfficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116PHASE4COMPLETEDLevetiracetam for Benign Rolandic Epilepsy
NCT00207935PHASE4COMPLETEDUse of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592PHASE4COMPLETEDOpen Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604PHASE4COMPLETEDA Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639PHASE4COMPLETEDLyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676PHASE4UNKNOWNCompare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947PHASE4COMPLETEDMethylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411PHASE4COMPLETEDStudy of Valproate in Young Patients Suffering From Epilepsy
NCT00522418PHASE4TERMINATEDStudy Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940PHASE4COMPLETEDComparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526PHASE4UNKNOWNKetogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915PHASE4COMPLETEDRCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155PHASE4COMPLETEDTrial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195PHASE4COMPLETEDRNS® System LTT Study
NCT00610532PHASE4TERMINATEDEvaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357PHASE4COMPLETEDTrial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630PHASE4COMPLETEDStudy on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968PHASE4COMPLETEDS.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150PHASE4COMPLETEDA Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958PHASE4COMPLETEDZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622PHASE4COMPLETEDComparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989PHASE4COMPLETEDThe Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884PHASE4COMPLETEDThe Safety of Intravenous Lacosamide
NCT00869622PHASE4COMPLETEDAntiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987PHASE4COMPLETEDLamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081PHASE4COMPLETEDA Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455PHASE4TERMINATEDTrial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165PHASE4COMPLETEDLow and High Dose Zonisamide in Children as Monotherapy
NCT01127256PHASE4COMPLETEDComparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867PHASE4COMPLETEDOpen-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954PHASE4COMPLETEDCognitive and Behavioral Effects of Lacosamide
NCT01229735PHASE4COMPLETEDLevetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724PHASE4TERMINATEDLexapro for Major Depression in Patients With Epilepsy

About this page

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

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This page pulls from 80 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot