RORC

Summary

RORC (RAR related orphan receptor C, HGNC:10260) is a protein-coding gene on chromosome 1q21.3, encoding Nuclear receptor ROR-gamma (P51449). 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.

The protein encoded by this gene is a DNA-binding transcription factor and is a member of the NR1 subfamily of nuclear hormone receptors. The specific functions of this protein are not known; however, studies of a similar gene in mice have shown that this gene may be essential for lymphoid organogenesis and may play an important regulatory role in thymopoiesis. In addition, studies in mice suggest that the protein encoded by this gene may inhibit the expression of Fas ligand and IL2. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6097 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 13
• Clinical variants (ClinVar): 374 total — 9 pathogenic, 3 likely-pathogenic (top 9% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 5 regions constrained (≈7% of expected missense variation)
• GTEx eGene: eQTL in 9 tissues, sQTL in 7 (q < 0.05)
• Phenotypes (HPO): 10
• Drug target: yes — 1 curated mechanism-of-action drug; 9 molecules with ChEMBL bioactivity
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.35 (moderately constrained)
• Transcription factor: yes — 23 downstream targets (CollecTRI)
• MANE Select transcript: NM_005060

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10260
Approved symbol	RORC
Name	RAR related orphan receptor C
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	RZRG, RORG, NR1F3, TOR
Ensembl gene	ENSG00000143365
Ensembl biotype	protein_coding
OMIM	602943
Entrez	6097

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 14 nonsense_mediated_decay, 9 protein_coding, 4 retained_intron

MANE Select: ENST00000318247

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 2

ENST00000318247, ENST00000356728, ENST00000480719, ENST00000638901, ENST00000651025, ENST00000651814, ENST00000651893, ENST00000652040, ENST00000697811, ENST00000697812, ENST00000697813, ENST00000859918, ENST00000859919, ENST00000859920, ENST00000859921, ENST00000859922, ENST00000982012, ENST00000982014, ENST00000982015, ENST00000982017, ENST00000982018, ENST00000982019, ENST00000982020, ENST00001010139, ENST00001106841, ENST00001116456, ENST00001120914

RefSeq mRNA: 2 — MANE Select: NM_005060 NM_001001523, NM_005060

CCDS: CCDS1004, CCDS30856

Canonical transcript exons

ENST00000318247 — 11 exons

Exon	Start	End
ENSE00000959584	151816664	151816805
ENSE00000959585	151814913	151815425
ENSE00000959586	151814574	151814695
ENSE00000959587	151813488	151813620
ENSE00000959588	151813239	151813346
ENSE00000959589	151812947	151813057
ENSE00001072282	151811325	151811434
ENSE00001423028	151829429	151829458
ENSE00001681892	151817195	151817280
ENSE00001873959	151806071	151807633
ENSE00003843865	151831725	151831802

Expression profiles

Bgee: expression breadth ubiquitous, 209 present calls, max score 96.46.

FANTOM5 (CAGE): breadth broad, TPM avg 2.1497 / max 188.7946, expressed in 361 samples.

Highest expression (Bgee): gastrocnemius, male germ line stem cell (sensu Vertebrata) in testis, hindlimb stylopod muscle, lobe of liver, muscle of leg.

Genetic regulation across tissues (GTEx eQTL / sQTL)

RORC is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 9 tissues and its splicing (sQTL) in 7 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

16 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	sqtl	5.1e-16	+0.40	1:151812518:C:T
Muscle Skeletal	eqtl	1.2e-09	-0.18	1:151812071:G:A
Pancreas	sqtl	1.0e-07	-0.92	1:151830163:C:T
Esophagus Mucosa	eqtl	8.2e-05	-0.24	1:151831288:G:C
Thyroid	sqtl	9.3e-04	-0.53	1:151825217:C:T
Testis	eqtl	3.3e-03	-0.43	1:151170747:A:G
Skin Sun Exposed Lower leg	sqtl	4.7e-03	-0.24	1:151809236:TA:T
Whole Blood	eqtl	1.5e-02	+0.16	1:151501194:G:A
Breast Mammary Tissue	eqtl	1.7e-02	-0.49	1:152313912:G:A
Spleen	sqtl	1.7e-02	-0.52	1:151420468:C:T
Nerve Tibial	eqtl	2.4e-02	-0.37	1:151832539:G:A
Testis	sqtl	2.6e-02	-0.57	1:151829475:G:A
Brain Cerebellum	eqtl	2.8e-02	-0.18	1:151811121:C:T
Brain Nucleus accumbens basal ganglia	eqtl	3.2e-02	-0.41	1:152806082:C:T
Adrenal Gland	sqtl	4.4e-02	-1.68	1:152568139:T:C
Brain Cortex	eqtl	4.8e-02	+0.32	1:152024132:C:T

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
14466	1.6002	291
14462	0.3754	61
14463	0.0760	38
14467	0.0579	25
14465	0.0256	15
14461	0.0145	6

Top tissues by expression

showing 100 of 289 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	96.46	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	96.00	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.92	gold quality
right lobe of liver	UBERON:0001114	95.19	gold quality
muscle of leg	UBERON:0001383	94.77	gold quality
right uterine tube	UBERON:0001302	94.25	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.94	gold quality
parotid gland	UBERON:0001831	93.04	gold quality
muscle organ	UBERON:0001630	92.90	gold quality
body of pancreas	UBERON:0001150	92.81	gold quality
liver	UBERON:0002107	90.87	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.78	gold quality
vastus lateralis	UBERON:0001379	89.08	gold quality
skeletal muscle tissue	UBERON:0001134	88.90	gold quality
quadriceps femoris	UBERON:0001377	88.72	silver quality
skin of leg	UBERON:0001511	88.24	gold quality
pancreas	UBERON:0001264	87.97	gold quality
saliva-secreting gland	UBERON:0001044	87.95	gold quality
gluteal muscle	UBERON:0002000	87.50	silver quality
skin of abdomen	UBERON:0001416	87.19	gold quality
thyroid gland	UBERON:0002046	86.89	gold quality
minor salivary gland	UBERON:0001830	86.71	gold quality
left lobe of thyroid gland	UBERON:0001120	86.66	gold quality
pituitary gland	UBERON:0000007	86.59	gold quality
adult mammalian kidney	UBERON:0000082	86.52	gold quality
apex of heart	UBERON:0002098	86.46	gold quality
deltoid	UBERON:0001476	86.37	silver quality
diaphragm	UBERON:0001103	86.25	gold quality
tibialis anterior	UBERON:0001385	86.11	silver quality
adenohypophysis	UBERON:0002196	86.10	gold quality
zone of skin	UBERON:0000014	85.37	gold quality
body of tongue	UBERON:0011876	85.24	gold quality
muscle tissue	UBERON:0002385	85.17	gold quality
biceps brachii	UBERON:0001507	85.15	gold quality
right lobe of thyroid gland	UBERON:0001119	85.02	gold quality
mouth mucosa	UBERON:0003729	84.78	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	84.71	gold quality
heart right ventricle	UBERON:0002080	84.05	silver quality
germinal epithelium of ovary	UBERON:0001304	83.84	gold quality
metanephros cortex	UBERON:0010533	83.42	gold quality
renal medulla	UBERON:0000362	83.31	gold quality
rectum	UBERON:0001052	82.89	gold quality
tongue	UBERON:0001723	82.60	gold quality
superior surface of tongue	UBERON:0007371	82.60	gold quality
islet of Langerhans	UBERON:0000006	82.49	gold quality
amniotic fluid	UBERON:0000173	82.35	gold quality
mucosa of transverse colon	UBERON:0004991	81.85	gold quality
nasal cavity mucosa	UBERON:0001826	81.62	gold quality
cardia of stomach	UBERON:0001162	81.48	gold quality
cardiac ventricle	UBERON:0002082	81.29	gold quality
heart left ventricle	UBERON:0002084	81.24	gold quality
prostate gland	UBERON:0002367	80.88	gold quality
ileal mucosa	UBERON:0000331	80.60	silver quality
mucosa of paranasal sinus	UBERON:0005030	80.54	gold quality
duodenum	UBERON:0002114	80.23	gold quality
pylorus	UBERON:0001166	80.18	gold quality
thymus	UBERON:0002370	80.06	silver quality
jejunum	UBERON:0002115	79.97	gold quality
right testis	UBERON:0004534	79.92	gold quality
trachea	UBERON:0003126	79.89	gold quality
left testis	UBERON:0004533	79.44	gold quality
body of stomach	UBERON:0001161	79.21	gold quality
pharyngeal mucosa	UBERON:0000355	78.55	gold quality
kidney	UBERON:0002113	78.48	gold quality
stomach	UBERON:0000945	78.23	gold quality
bronchial epithelial cell	CL:0002328	78.02	gold quality
tonsil	UBERON:0002372	78.02	gold quality
lower esophagus mucosa	UBERON:0035834	77.89	gold quality
bronchus	UBERON:0002185	77.54	gold quality
testis	UBERON:0000473	77.52	gold quality
epithelium of bronchus	UBERON:0002031	77.39	gold quality
small intestine	UBERON:0002108	76.91	gold quality
endometrium	UBERON:0001295	76.77	gold quality
upper arm skin	UBERON:0004263	76.77	silver quality
small intestine Peyer’s patch	UBERON:0003454	76.75	gold quality
cerebellar hemisphere	UBERON:0002245	76.48	gold quality
cerebellar cortex	UBERON:0002129	76.33	gold quality
jejunal mucosa	UBERON:0000399	76.04	gold quality
mammary duct	UBERON:0001765	76.01	silver quality
gall bladder	UBERON:0002110	75.99	gold quality
fundus of stomach	UBERON:0001160	75.94	gold quality
nipple	UBERON:0002030	75.80	gold quality
right hemisphere of cerebellum	UBERON:0014890	75.69	gold quality
cerebellum	UBERON:0002037	75.37	gold quality
transverse colon	UBERON:0001157	75.29	gold quality
left ventricle myocardium	UBERON:0006566	75.21	gold quality
right lung	UBERON:0002167	75.12	gold quality
pancreatic ductal cell	CL:0002079	74.88	silver quality
myocardium	UBERON:0002349	74.86	gold quality
upper lobe of left lung	UBERON:0008952	74.66	gold quality
sperm	CL:0000019	74.60	gold quality
seminal vesicle	UBERON:0000998	74.55	gold quality
heart	UBERON:0000948	74.53	gold quality
esophagus mucosa	UBERON:0002469	74.29	gold quality
palpebral conjunctiva	UBERON:0001812	74.23	gold quality
male germ cell	CL:0000015	74.00	gold quality
esophagus squamous epithelium	UBERON:0006920	73.82	silver quality
epithelium of mammary gland	UBERON:0003244	73.74	silver quality
caput epididymis	UBERON:0004358	73.60	gold quality
colonic mucosa	UBERON:0000317	73.55	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	11.63
E-ANND-3	yes	7.10
E-CURD-112	no	2.73

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 72 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Skeletal muscle	tissue	67.8
Liver	tissue	62.6
Tongue	tissue	52.4
Pancreas	tissue	50.7
Thymus	tissue	47.3
Salivary gland	tissue	37.8
Parathyroid gland	tissue	30.8
Thyroid gland	tissue	23.9
Fallopian tube	tissue	19.4
Stomach 1	tissue	17.6
Kidney	tissue	14.3
Pituitary gland	tissue	13.8
Prostate	tissue	12.7
Skin 1	tissue	11.5
Lung	tissue	11.4
Small intestine	tissue	11.2
Seminal vesicle	tissue	10.1
Duodenum	tissue	9.9
Rectum	tissue	8.4
Choroid plexus	tissue	8.4
Colon	tissue	8.2
Breast	tissue	6.9
Cervix	tissue	6.1
Testis	tissue	6.1
Heart muscle	tissue	5.5
Adrenal gland	tissue	4.4
Esophagus	tissue	4.2
Gallbladder	tissue	3.1
Periaqueductal gray	tissue	2.9
Vagina	tissue	2.7
Hippocampal formation	tissue	2.3
Amygdala	tissue	2.2
Tonsil	tissue	2.2
Urinary bladder	tissue	2.1
Cerebellum	tissue	2.1
Spinal cord	tissue	2.1
Epididymis	tissue	2.0
Medulla oblongata	tissue	2.0
Hypothalamus	tissue	2.0
Caudate putamen	tissue	1.9
Basal ganglia	tissue	1.8
Endometrium 1	tissue	1.6
Superior colliculi	tissue	1.6
Substantia nigra	tissue	1.6
Olfactory bulb	tissue	1.6
Cerebral cortex	tissue	1.5
Pons	tissue	1.5
Midbrain	tissue	1.5
Corpus callosum	tissue	1.5
Insular cortex	tissue	1.5
Septum	tissue	1.4
Appendix	tissue	1.4
Thalamus	tissue	1.3
Ventral forebrain	tissue	1.3
Retrosplenial cortex	tissue	1.3
Entorhinal cortex	tissue	1.2
Retrosplenial and cingulate cortex	tissue	1.2
Temporal cortex	tissue	1.2
Prefrontal cortex	tissue	1.1
Motor cortex	tissue	1.0

Brain sub-regions (HPA Brain Atlas): detected in 104; highest nTPM — Cerebellar cortex (4.3), Flocculonodular lobe (4.2), Vermis (3.4), Periaquaductal grey, lateral (2.5), Ventral hippocampus (2.3).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

23 targets:

Target	Regulation
BCL2L1	Activation
BMAL1	Activation
CCR6	Unknown
CYP2C19	Activation
CYP2C8	Activation
CYP2C9	Activation
FASLG	Repression
FOXP3	Repression
IFNG	Activation
IL17A	Unknown
IL17F	Activation
IL1R1	Activation
IL2	Repression
IL21	Activation
IL22	Unknown
IL23R	Repression
IL6	Activation
KLRB1	Unknown
PTGER2	Unknown
RORA	Activation
TBXT
TNF	Activation
TOB1

JASPAR motifs

Motif	Name	Family
MA1151.1	RORC	Thyroid hormone receptor-related factors (NR1)
MA1151.2	RORC	Thyroid hormone receptor-related factors (NR1)

JASPAR matrix evidence (PMIDs): PMID:25500868

Upstream regulators (CollecTRI, top): AHR, GLI2, ID1, NCOR2, NR1D1, PPARG, PROX1, RUNX1, STAT3, USF1, USF2

miRNA regulators (miRDB)

Targeting RORC by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 84 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-186-5P	99.99	70.83	3707
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4487	99.96	64.58	1252
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-6739-5P	99.80	67.87	2806

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.351, missense Z 2.9 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000318247 splits into 5 regions with different missense tolerance; 1 is missense-constrained (≈7% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
1:151,807,475–151,812,963	93 / 116.6	0.80	no
1:151,812,964–151,814,677	100 / 190.8	0.52	no
1:151,814,678–151,816,796	241 / 295.5	0.82	no
1:151,816,797–151,829,447	13 / 46.0	0.28	yes (p 1.1e-06)
1:151,829,448–151,831,764	21 / 20.6	1.02	no

Literature-anchored findings (GeneRIF, showing 40)

• We review here recent studies on the glucocorticoid receptor and the orphan receptors Nur77 and RORgamma (PMID:11983153)
• data suggest that RORC cannot explain the linkage of type 2 diabetes in the 1q21-q23 region (PMID:12855222)
• transcription factor driving the development of IL-17-producing T cells (PMID:17240331)
• Review highlights the regulation of IL-17 production by orphan nuclear receptor ROR gamma t, which dictates the differentiation of pro-inflammatory T helper 17 (TH17) cells and is a therapeutic target for intervention of inflammatory autoimmunity. (PMID:17504012)
• Foxp3 inhibits RORgammat-mediated IL-17A mRNA transcription through direct interaction with RORgammat (PMID:18434325)
• Expression of the transcription factor RORgammat defined a previously unknown subset of NKp46+CD3- lymphocytes. (PMID:19029904)
• the authors identify the upregulation of the TH17 lymphocyte subset transcription factor retinoid orphan receptor gamma T in contact sensitivity (PMID:19112760)
• human memory Tregs secrete IL-17 ex vivo and constitutively express RORgamma t (PMID:19439651)
• Findings demonstrate that expression of RORC2 in T cells has functional consequences beyond altering cytokine production and provides insight into the factors regulating the development of human Th17 cells. (PMID:19449310)
• There is an increased synovial expression of the transcription factor of Th17, RORC2, in juvenile idiopathic arthritis and an inverse relationship with FOXP3 mRNA. (PMID:19648312)
• Encephalitogenic T cells can be divided into those that are ROR gamma t negative and those that are positive. (PMID:19692128)
• RORalpha and RORgamma are ligand-regulated members of the NR superfamily and may serve as sensors for 7-oxygenated sterols. (PMID:19965867)
• higher expression in peripheral blood lymphocytes and decidua of recurrent spontaneous abortion patients (PMID:20106535)
• Data showed that hydroxycholesterols promote the recruitment of coactivators by RORgamma, crystal structures reveal the binding modes of various hydroxycholesterols in the RORgamma pocket, with the receptors adopting the canonical active conformation. (PMID:20203100)
• RORalpha and RORgamma display an overlapping ligand preference with another class of oxysterol nuclear receptors, the liver X receptors (LXRalpha [NR1H3] and LXRbeta [NR1H2]). (PMID:20211758)
• this study identifies RORC2 as a polarizing factor in transcriptional cross-regulation (PMID:20427770)
• Compared with healthy volunteers, patients with gastric cancer showed higher levels of RORgammat and FoxP3 in PBMC. (PMID:20450585)
• Studies indicate that innate lymphocyte subset co-expressing RORgammat, NK cell receptors, and Il-22 has been identified. (PMID:21391996)
• RORC2 and IL-17 are involved in the inflammatory response of allergic rhinitis and can be used as an indicator to judge the severity. (PMID:21426710)
• RORgammat determined Th17 cell might be involved with increased IL-17A in Behcet’s Disease. (PMID:21455110)
• Ursolic acid suppresses interleukin-17 (IL-17) production by selectively antagonizing the function of RORgamma t protein. (PMID:21566134)
• Our data show a decreased Foxp3 expression and an increased ROR gamma t expression in COPD patients and normal smokers that parallels the aggravation of the disease. (PMID:21791252)
• By allying with HIF1alpha, RORgammat wins the fight against FoxP3 and Treg cell commitment. (PMID:22058032)
• RORgammat repressor isoform, RORgammat-Delta(5-8) may arbitrate IL-17 production in human T cells. (PMID:22237416)
• High IL4I1 mRNA expression was detectable in Th17 cell precursors and was strictly dependent on Th17 cell master gene, the retinoid acid related orphan receptor (RORC). (PMID:22326581)
• Single nucleotide polymorphisms in RORC gene is associated with lymphedema after breast cancer. (PMID:22404826)
• Analysis of human RORgammaT promoter demonstrates the role of USF-1 and USF-2 transcription factors in regulating the expression of RORgammaT in human lymphocytes. (PMID:22891280)
• Data indicate that the dominance of the SLAMF3/SLAMF6 pathway in inducing IL-17A production can be attributed to an increased nuclear abundance and recruitment of RORgammat to the IL17A promoter. (PMID:22989874)
• study to evaluate gene expression of RORalpha and RORgammat and their potential role in acute-on-chronic hepatitis B liver failure (ACHBLF); mRNA level of RORgammat was positively correlated with model of end-stage liver disease (MELD) score; RORgammat plays an important role in the pathogenesis of ACHBLF (PMID:23043388)
• SULT2A1 as a novel ROR-alpha and ROR-gamma target gene. (PMID:23211525)
• Data suggest that expression of RORC and interleukin-17 is up-regulated in mononuclear cells cultured with interleukin-23 but only in cells from subjects with Graves disease; this response is independent of thyroid function (i.e., euthyroid or not). (PMID:23327801)
• Collectively, these data suggest that FoxP3 interacts with RORgammat transcription factor in a viral load-dependent fashion and brings about negative impact on IL-17 production in HIV-1 infection. (PMID:23409930)
• Defective TH17 development in human neonatal T cells involves reduced RORC2 mRNA content (PMID:23726039)
• Expression of RORC in nasal epithelial cells was higher in nasal polyps compared to control mucosa. (PMID:23765061)
• Increased plasmacytoid dendritic cells and RORgammat-expressing immune effectors in cutaneous acute graft-versus-host disease. (PMID:23990625)
• Neutrophils, but not mast cells, coexpressed the IL-17-associated transcription factor RORgammat and were able to form extracellular traps. (PMID:24317395)
• Data suggest that RORgammat is a tractable drug target for the treatment of cutaneous inflammatory disorders. (PMID:24516202)
• 20(OH)D3 and 20,23(OH)2D3 act as antagonists or inverse agonists of RORalpha and RORgamma. (PMID:24668754)
• In Th17 cells, RORC repressed EP2 by directly silencing PTGER2 transcription, and knock down of RORC restored EP2 expression in Th17 cells. (PMID:24812667)
• This study demonstrates the role and significant correlation between a histone methyltransferase (PRMT2)-dependent signature, RORgamma, the cell-cycle regulation, DNA repair circuits, and breast cancer survival outcomes. (PMID:24911119)

Cross-species orthologs

188 orthologs

Organism	Symbol	Gene ID
danio_rerio	rorc	ENSDARG00000087195
mus_musculus	Rorc	ENSMUSG00000028150
rattus_norvegicus	Rorc	ENSRNOG00000020836
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), RARB (ENSG00000077092), VDR (ENSG00000111424), PPARD (ENSG00000112033), THRA (ENSG00000126351), NR1D1 (ENSG00000126368), NR1H2 (ENSG00000131408), RARA (ENSG00000131759), PPARG (ENSG00000132170), NR1I3 (ENSG00000143257), NR1I2 (ENSG00000144852), THRB (ENSG00000151090), RARG (ENSG00000172819), NR1D2 (ENSG00000174738), PPARA (ENSG00000186951), RORB (ENSG00000198963)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:104856) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 65 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased CD4-positive, alpha-beta T cell number	4
absent Peyer’s patches	3
decreased double-positive T cell number	3
absent lymph nodes	3
decreased CD8-positive, alpha-beta T cell number	3
decreased IgG level	2
decreased IgM level	2
abnormal T cell differentiation	2
abnormal gut-associated lymphoid tissue morphology	2
abnormal CD4-positive, alpha beta T cell morphology	2
abnormal lymph organ development	2
increased thymocyte apoptosis	2
increased effector memory CD4-positive, alpha-beta T cell number	2
decreased response to antigen	2
impaired humoral immune response	2
abnormal colon morphology	1
decreased salivation	1
enlarged spleen	1
decreased thymocyte number	1
demyelination	1
weight loss	1
colonic necrosis	1
thymus hypoplasia	1
lung inflammation	1
salivary gland inflammation	1

+40 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Ovis aries	B3SV56	99.3%	Diamond
Bos taurus	Q08E02	99.3%	Diamond
Pongo abelii	Q5RAP4	99.2%	Diamond
Macaca fascicularis	Q95K90	98.8%	Diamond
Oncorhynchus mykiss	Q9W6I9	98.6%	Diamond
Sus scrofa	A0P8Z4	98.4%	Diamond
Notophthalmus viridescens	P18515	97.4%	Diamond
Gallus gallus	O42101	97.2%	Diamond
Xenopus laevis	P70033	97.0%	Diamond
Xenopus tropicalis	Q66JK1	97.0%	Diamond
Equus caballus	Q9GKL2	96.5%	Diamond
Callorhinus ursinus	P62044	95.4%	Diamond
Drosophila virilis	O16845	94.9%	Diamond
Galleria mellonella	P49868	89.6%	Diamond
Manduca sexta	Q08882	89.6%	Diamond
Cavia porcellus	O35507	88.9%	Diamond
Oryzias latipes	Q9YGL3	85.1%	Diamond
Notamacropus eugenii	Q95L87	80.4%	Diamond
Strongylocentrotus purpuratus	Q26622	65.8%	Diamond
Bombyx mori	P49867	65.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
C2CD4D	protein-coding	100191040
THEM4	protein-coding	117145
THEM5	protein-coding	284486
LINGO4	protein-coding	339398
C2CD4D-AS1	ncRNA	100132111
TDRKH	protein-coding	11022
OAZ3	protein-coding	51686
MRPL9	protein-coding	65005
TDRKH-AS1	ncRNA	109729141

Protein

Protein identifiers

Nuclear receptor ROR-gamma — P51449 (reviewed: P51449)

Alternative names: Nuclear receptor RZR-gamma, Nuclear receptor subfamily 1 group F member 3, RAR-related orphan receptor C, Retinoid-related orphan receptor-gamma

All UniProt accessions (9): A0A1W2PRM4, A0A494C0H2, A0A494C0S6, A0A494C174, A0A8V8TL94, B6ZGS6, F1D8P6, P51449, Q6I9R9

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. Key regulator of cellular differentiation, immunity, peripheral circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respectively. Recruits distinct combinations of cofactors to target gene regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts. Regulates the circadian expression of clock genes such as CRY1, BMAL1 and NR1D1 in peripheral tissues and in a tissue-selective manner. Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as BMAL1, CRY1 and NR1D1 itself, resulting in NR1D1-mediated repression or RORC-mediated activation of the expression, leading to the circadian pattern of clock genes expression. Therefore influences the period length and stability of the clock. Involved in the regulation of the rhythmic expression of genes involved in glucose and lipid metabolism, including PLIN2 and AVPR1A. Negative regulator of adipocyte differentiation through the regulation of early phase genes expression, such as MMP3. Controls adipogenesis as well as adipocyte size and modulates insulin sensitivity in obesity. In liver, has specific and redundant functions with RORA as positive or negative modulator of expression of genes encoding phase I and Phase II proteins involved in the metabolism of lipids, steroids and xenobiotics, such as SULT1E1. Also plays a role in the regulation of hepatocyte glucose metabolism through the regulation of G6PC1 and PCK1. Regulates the rhythmic expression of PROX1 and promotes its nuclear localization. Plays an indispensable role in the induction of IFN-gamma dependent anti-mycobacterial systemic immunity. Nuclear receptor essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes and Peyer’s patches. Required for the generation of LTi (lymphoid tissue inducer) cells. Regulates thymocyte survival through DNA-binding on ROREs of target gene promoter regions and recruitment of coactivaros via the AF-2. Also plays a key role, downstream of IL6 and TGFB and synergistically with RORA, for lineage specification of uncommitted CD4(+) T-helper (T(H)) cells into T(H)17 cells, antagonizing the T(H)1 program. Probably regulates IL17 and IL17F expression on T(H) by binding to the essential enhancer conserved non-coding sequence 2 (CNS2) in the IL17-IL17F locus. Plays a key role in tolerance to gut microbiota and foreign antigens in food by mediating differentiation of peripherally-induced regulatory T-cells (pTreg), which suppress inflammatory responses to commensal microorganisms and food proteins. Specifically expressed in antigen-presenting cell populations, such as (1) type 3 innate lymphoid cells (ILC3s), which are required for tolerance to gut microbiota, (2) Thetis cells, also named Janus cells, which are enriched in gut lymph nodes during early life and are required for oral tolerance, and (3) a subset of dendritic cells. Following activation by an unknown ligand in antigen-presenting cells, promotes recruitment of transcription regulators, such as PRDM16 or ZBTB46, and drives differentiation of pTreg cells, which maintain immune tolerance and prevent autoimmune diseases. May also play a role in the pre-TCR activation cascade leading to the maturation of alpha/beta T-cells and may participate in the regulation of DNA accessibility in the TCR-J(alpha) locus.

Subunit / interactions. Interacts (via AF-2 motif) with the coactivator NCOA2 (via LXXLL motif). Interacts with the corepressor NCOR1. Interacts with CRY1. Interacts (via AF-2 motif) with the coactivators NCOA1 and PPARGC1A (via LXXLL motif). Interacts (via AF-2 motif) with PROX1. Interacts with FOXP3. Interacts with NR0B2.

Subcellular location. Nucleus.

Tissue specificity. Isoform 1 is widely expressed in many tissues, including liver and adipose, and highly expressed in skeletal muscle. Isoform 2 is primarily expressed in immature thymocytes.

Disease relevance. Immunodeficiency 42 (IMD42) [MIM:616622] An autosomal recessive primary immunodeficiency characterized by increased susceptibility to concomitant candidiasis and mycobacteriosis. Candidiasis is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida. Mycobacteriosis is characterized by infections caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. IMD42 patients vaccinated with BCG are particularly at risk for developing disseminated mycobacterial infections. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The AF-2 (activation function-2) motif is required for recruiting coregulators containing LXXLL motifs such as NCOA1 and NCOA2.

Induction. Up-regulated in the state of obesity.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P51449-1	1	yes
P51449-2	2, RORgT, RORgammaT

RefSeq proteins (2): NP_001001523, NP_005051* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000536	Nucl_hrmn_rcpt_lig-bd	Domain
IPR001628	Znf_hrmn_rcpt	Domain
IPR001723	Nuclear_hrmn_rcpt	Family
IPR003079	ROR_rcpt	Family
IPR013088	Znf_NHR/GATA	Homologous_superfamily
IPR035500	NHR-like_dom_sf	Homologous_superfamily
IPR044101	NR_DBD_ROR	Domain

Pfam: PF00104, PF00105

UniProt features (41 total): helix 18, strand 4, mutagenesis site 3, region of interest 3, compositionally biased region 2, splice variant 2, turn 2, zinc finger region 2, chain 1, domain 1, sequence variant 1, DNA-binding region 1, short sequence motif 1

Structure

Experimental structures (PDB)

showing 30 of 162 structures by resolution:

PDB	Title	Method	Resolution (Å)
7NPC	ROR(gamma)t ligand binding domain in complex with allosteric ligand FM156	X-RAY DIFFRACTION	1.47
6T4X	ROR(gamma)t ligand binding domain in complex with 25-hydroxycholesterol and allosteric …	X-RAY DIFFRACTION	1.48
5APH	Ligand complex of RORg LBD	X-RAY DIFFRACTION	1.54
6R7K	Ligand complex of RORg LBD	X-RAY DIFFRACTION	1.54
7NP5	ROR(gamma)t ligand binding domain in complex with allosteric ligand FM216	X-RAY DIFFRACTION	1.55
6W9I	SUBSTITUTED BENZYLOXYTRICYCLIC COMPOUNDS AS RETINOIC ACID-RELATED ORPHAN RECEPTOR GAMMA T …	X-RAY DIFFRACTION	1.61
6SAL	ROR(gamma)t ligand binding domain in complex with allosteric ligand FM26	X-RAY DIFFRACTION	1.61
7OFK	Ligand complex of RORg LBD	X-RAY DIFFRACTION	1.61
6T4T	ROR(gamma)t ligand binding domain in complex with 20-alpha-hydroxycholesterol and …	X-RAY DIFFRACTION	1.62
7KXD	CRYSTAL STRUCTURE OF RAR-RELATED ORPHAN RECEPTOR C (NHIS-RORGT(244-487)-L6-SRC1(678-692)) …	X-RAY DIFFRACTION	1.62
9N9L	An RORgt Inverse agonist for treatment of Psoriasis	X-RAY DIFFRACTION	1.64
5NTW	Structural states of RORgt: X-ray elucidation of molecular mechanisms and binding …	X-RAY DIFFRACTION	1.64
6G07	RORGT (264-518;C455S) IN COMPLEX WITH INVERSE AGONIST ““CPD-9"” AND RIP140 PEPTIDE AT …	X-RAY DIFFRACTION	1.66
5NTP	Structural states of RORgt: X-ray elucidation of molecular mechanisms and binding …	X-RAY DIFFRACTION	1.7
4WLB	Crystal structure of RORc in complex with a partial inverse agonist compound	X-RAY DIFFRACTION	1.7
6T4W	ROR(gamma)t ligand binding domain in complex with 20-alpha-hydroxycholesterol and …	X-RAY DIFFRACTION	1.71
5G42	Ligand complex of RORg LBD	X-RAY DIFFRACTION	1.72
3L0L	Crystal structure of orphan nuclear receptor RORgamma in complex with natural ligand	X-RAY DIFFRACTION	1.74
5G46	Ligand complex of RORg LBD	X-RAY DIFFRACTION	1.76
6TLQ	ROR(gamma)t ligand binding domain in complex with cholesterol and allosteric ligand …	X-RAY DIFFRACTION	1.76
5C4T	Identification of a Novel Allosteric Binding Site for RORgt Inhibitors	X-RAY DIFFRACTION	1.77
5M96	Synthesis and biological evaluation of new triazolo and imidazolopyridine RORgt inverse …	X-RAY DIFFRACTION	1.77
7W3P	Crystal structure of RORgamma in complex with natural inverse agonist	X-RAY DIFFRACTION	1.77
6T4J	ROR(gamma)t ligand binding domain in complex with desmosterol and allosteric ligand FM26	X-RAY DIFFRACTION	1.79
6FZU	RORGT (264-518;C455S) IN COMPLEX WITH THE FRAGMENT (““CPD-1"”) AND RIP140 PEPTIDE AT 1.80A	X-RAY DIFFRACTION	1.8
5NIB	Ligand complex of RORg LBD	X-RAY DIFFRACTION	1.82
5G44	Ligand complex of RORg LBD	X-RAY DIFFRACTION	1.84
6ESN	Ligand complex of RORg LBD	X-RAY DIFFRACTION	1.84
6R7J	Ligand complex of RORg LBD	X-RAY DIFFRACTION	1.84
6T4I	ROR(gamma)t ligand binding domain in complex with cholesterol and allosteric ligand MRL871	X-RAY DIFFRACTION	1.84

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51449-F1	75.42	0.57

Human Protein Atlas

Protein class: Nuclear receptors, Predicted intracellular proteins, Transcription factors, Zinc-coordinating DNA-binding domains, Disease related genes, Human disease related genes, Primary immunodeficiency

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nuclear bodies

Antibody reliability (HPA): IF supported

Functional residue map

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

Mutagenesis-validated functional residues (3)

Position	Phenotype
327	completely abolishes transcriptional activity.
378	completely abolishes transcriptional activity.
397	nearly abolishes transcriptional activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 13; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

13 pathways:

ID	Pathway	Evidence
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling	curated
R-HSA-383280	Nuclear Receptor transcription pathway	curated
R-HSA-9909396	Circadian clock	—
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-9931509	Expression of BMAL (ARNTL), CLOCK, and NPAS2	electronic
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-168256	Immune System	—
R-HSA-9931510	Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock genes	electronic
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-9933387	RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression	electronic
R-HSA-8949275	RUNX3 Regulates Immune Response and Cell Migration	electronic
R-HSA-449147	Signaling by Interleukins	—

MSigDB gene sets: 315 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_TOLERANCE_INDUCTION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GCANCTGNY_MYOD_Q6, ATACCTC_MIR202, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, GOBP_LYMPH_NODE_DEVELOPMENT, GOBP_REGULATION_OF_LYMPHOCYTE_APOPTOTIC_PROCESS, GOBP_CIRCADIAN_REGULATION_OF_GENE_EXPRESSION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, USF_C

GO Biological Process (24): negative regulation of transcription by RNA polymerase II (GO:0000122), tolerance induction in gut-associated lymphoid tissue (GO:0002394), DNA-templated transcription (GO:0006351), regulation of transcription by RNA polymerase II (GO:0006357), xenobiotic metabolic process (GO:0006805), regulation of glucose metabolic process (GO:0010906), regulation of steroid metabolic process (GO:0019218), circadian regulation of gene expression (GO:0032922), cellular response to sterol (GO:0036315), T-helper cell differentiation (GO:0042093), positive regulation of circadian rhythm (GO:0042753), regulatory T cell differentiation (GO:0045066), regulation of fat cell differentiation (GO:0045598), positive regulation of DNA-templated transcription (GO:0045893), lymph node development (GO:0048535), Peyer’s patch development (GO:0048541), adipose tissue development (GO:0060612), negative regulation of thymocyte apoptotic process (GO:0070244), T-helper 17 cell differentiation (GO:0072539), regulation of DNA-templated transcription (GO:0006355), circadian rhythm (GO:0007623), regulation of gene expression (GO:0010468), intracellular receptor signaling pathway (GO:0030522), rhythmic process (GO:0048511)

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 transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription factor activity (GO:0003700), nuclear receptor activity (GO:0004879), oxysterol binding (GO:0008142), zinc ion binding (GO:0008270), ligand-modulated transcription factor activity (GO:0098531), 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 (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear body (GO:0016604)

Reactome top-level categories

8 top-level categories:

Category	Pathways
Circadian clock	3
Generic Transcription Pathway	1
Signaling by Interleukins	1
Transcriptional regulation by RUNX3	1
Immune System	1
RNA Polymerase II Transcription	1
Cytokine Signaling in Immune system	1
Gene expression (Transcription)	1

GO top-level categories

showing 60 of 66 GO namespaces:

Category	Terms
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
circadian rhythm	2
regulation of gene expression	2
DNA-templated transcription	2
DNA-binding transcription factor activity	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
immune response in gut-associated lymphoid tissue	1
tolerance induction in mucosal-associated lymphoid tissue	1
gene expression	1
RNA biosynthetic process	1
metabolic process	1
cellular response to xenobiotic stimulus	1
glucose metabolic process	1
regulation of carbohydrate metabolic process	1
regulation of small molecule metabolic process	1
steroid metabolic process	1
regulation of lipid metabolic process	1
response to sterol	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
CD4-positive, alpha-beta T cell differentiation	1
regulation of circadian rhythm	1
positive regulation of biological process	1
T cell differentiation	1
fat cell differentiation	1
regulation of cell differentiation	1
positive regulation of RNA biosynthetic process	1
hematopoietic or lymphoid organ development	1
mucosa-associated lymphoid tissue development	1
animal organ development	1
connective tissue development	1
negative regulation of T cell apoptotic process	1
thymocyte apoptotic process	1
regulation of thymocyte apoptotic process	1
alpha-beta T cell activation involved in immune response	1
T cell differentiation involved in immune response	1
T-helper cell differentiation	1
T-helper 17 type immune response	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription repressor activity	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
intracellular receptor signaling pathway	1
signaling receptor activity	1
ligand-modulated transcription factor activity	1
sterol binding	1
transition metal ion binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
DNA binding	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 10 of 41 annotations. The rest are phylogenetic / computational / electronic (IEA).

10 experimentally-supported GO terms:

GO term	NS	Evidence
T-helper 17 cell differentiation	BP	direct assay
cellular response to sterol	BP	direct assay
negative regulation of transcription by RNA polymerase II	BP	direct assay
nuclear body	CC	direct assay
nucleus	CC	direct assay
DNA-binding transcription repressor activity, RNA polymerase II-specific	MF	direct assay
RNA polymerase II cis-regulatory region sequence-specific DNA binding	MF	direct assay
ligand-modulated transcription factor activity	MF	direct assay
oxysterol binding	MF	direct assay
sequence-specific double-stranded DNA binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,392 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RORC	TBX21	Q9UL17	894
RORC	IL17A	Q16552	882
RORC	NFIL3	Q16649	871
RORC	IL17F	Q96PD4	868
RORC	CRY1	Q16526	857
RORC	PER3	P56645	854
RORC	NPAS2	Q99743	853
RORC	IL23R	Q5VWK5	851
RORC	BMAL1	O00327	830
RORC	IL22	Q9GZX6	826
RORC	PER2	O15055	822
RORC	FOXP3	Q9BZS1	818
RORC	BHLHE40	O14503	815
RORC	CD4	P01730	802
RORC	BHLHE41	Q9C0J9	798

IntAct

Human interaction partners of RORC in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

25 partners by confidence:

Partner	Interaction type	MIscore	Records
PSMC5	physical association	0.560	3
NCOA1	direct interaction	0.440	2
CREBBP	direct interaction	0.440	1
PPARGC1A	direct interaction	0.440	1
FOXP3	physical association	0.400	1
IL17A	physical association	0.370	2
IL17F	physical association	0.370	2
IL25	physical association	0.370	2
IL26	physical association	0.370	2
EVI2A	physical association	0.370	1
GLB1	association	0.350	1
BHLHE40	physical association	0.000	1
BMAL2	physical association	0.000	1
FBXL15	physical association	0.000	1
NPAS2	physical association	0.000	1
NR1D2	physical association	0.000	1
PPP1CA	physical association	0.000	1
PPP1CB	physical association	0.000	1
PPP1CC	physical association	0.000	1
PPP2CA	physical association	0.000	1
PPP2R1A	physical association	0.000	1
PPP2R1B	physical association	0.000	1
PPP2R5D	physical association	0.000	1
PPP2R5E	physical association	0.000	1
RORB	physical association	0.000	1

BioGRID (48 interactions; top human partners by supporting records): ANKHD1-EIF4EBP3 (Affinity Capture-MS; 2 records), ARNTL (Two-hybrid; 2 records), CLOCK (Two-hybrid; 2 records), CUL4B (Affinity Capture-Western; 2 records), GLB1 (Affinity Capture-MS; 2 records), HDAC1 (Affinity Capture-Western; 2 records), PSMC5 (Two-hybrid; 2 records), TRAF5 (Affinity Capture-Western; 2 records), ARNTL2 (Two-hybrid), BHLHE41 (Two-hybrid), CIPC (Two-hybrid), CSNK1E (Two-hybrid), CTSA (Affinity Capture-MS), DEC1 (Two-hybrid), EP300 (Affinity Capture-Western)

SIGNOR signaling

6 signaling interactions:

A	Effect	B	Mechanism
STAT3	up-regulates	RORC
SMAD2/STAT3/EP300	up-regulates	RORC
RORC	up-regulates	Th17
RORC	up-regulates	IL17A	“transcriptional regulation”
RORC	“up-regulates quantity by expression”	ARNTL	“transcriptional regulation”
PROX1	down-regulates	RORC

Ligand–receptor pairs (CellPhoneDB) (4)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

4 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
DHCR24	receptor	Signaling by Cholesterol/Desmosterol
DHCR7	receptor	Signaling by Cholesterol/Desmosterol
CEL	receptor	Signaling by Cholesterol
LIPA	receptor	Signaling by Cholesterol

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 25 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
Signaling by GSK3beta mutants	5	158.6×	3e-09
CTNNB1 S33 mutants aren’t phosphorylated	5	158.6×	3e-09
CTNNB1 S37 mutants aren’t phosphorylated	5	158.6×	3e-09
CTNNB1 S45 mutants aren’t phosphorylated	5	158.6×	3e-09
CTNNB1 T41 mutants aren’t phosphorylated	5	158.6×	3e-09
Beta-catenin phosphorylation cascade	5	139.9×	5e-09
Platelet sensitization by LDL	5	139.9×	5e-09
Co-inhibition by CTLA4	5	108.1×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
regulation of circadian rhythm	7	75.6×	9e-10
circadian regulation of gene expression	7	68.3×	9e-10

Disease & clinical

Genetic variants

Variant evidence for RORC: 374 ClinVar records (12 pathogenic / likely pathogenic); 13 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	3
Uncertain significance	137
Likely benign	161
Benign	19

Top pathogenic / likely-pathogenic (12)

Showing all 12 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
2697193	NM_005060.4(RORC):c.292C>T (p.Arg98Ter)	Pathogenic	criteria provided, single submitter	1
2860649	NM_005060.4(RORC):c.682C>T (p.Arg228Ter)	Pathogenic	criteria provided, single submitter	1
3722087	NM_005060.4(RORC):c.908del (p.Glu303fs)	Pathogenic	criteria provided, single submitter	1
4720711	NM_005060.4(RORC):c.990C>A (p.Tyr330Ter)	Pathogenic	criteria provided, single submitter	1
4725563	NM_005060.4(RORC):c.205_208del (p.Arg69fs)	Pathogenic	criteria provided, single submitter	1
4734088	NM_005060.4(RORC):c.811G>T (p.Glu271Ter)	Pathogenic	criteria provided, single submitter	1
1068314	NM_005060.4(RORC):c.934-1G>A	Likely pathogenic	criteria provided, single submitter	1
2585221	NM_005060.4(RORC):c.1165C>T (p.Arg389Ter)	Likely pathogenic	criteria provided, single submitter	1
4813333	NM_005060.4(RORC):c.991G>A (p.Val331Met)	Likely pathogenic	criteria provided, single submitter	1
217445	NM_005060.4(RORC):c.113C>T (p.Ser38Leu)	Pathogenic	no assertion criteria provided	1
217446	NM_005060.4(RORC):c.985C>T (p.Gln329Ter)	Pathogenic	no assertion criteria provided	1
217447	NM_005060.4(RORC):c.1321C>T (p.Gln441Ter)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore RORC’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 999):

Position(s)	Effect	Δscore	Sites
1:151811323–151811324	donor_loss	1.0000	5
1:151811454–151811455	acceptor_gain	1.0000	2
1:151811458	acceptor_gain	1.0000
1:151813353–151813354	acceptor_gain	1.0000	2
1:151814572–151814573	donor_loss	1.0000	5
1:151814576	donor_gain	1.0000
1:151814703–151814704	acceptor_gain	1.0000	2
1:151817193–151817194	donor_loss	1.0000	3
1:151817281–151817282	acceptor_loss	1.0000	6
1:151811435–151811436	acceptor_loss	0.9900	5

AlphaMissense

1,032 missense substitutions predicted likely pathogenic (of 3,376 scored), across 232 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M96	9	0.984	1.000
M106	9	0.922	0.998
H42	8	0.994	0.999
F55	8	0.990	0.999
F54	8	0.984	1.000
D36	8	0.979	0.996
D348	8	0.978	0.995
F388	8	0.972	0.993
F341	8	0.970	0.996
F506	8	0.963	0.991
F498	8	0.953	0.991
F334	8	0.950	0.997
H479	8	0.950	0.988
F103	8	0.944	0.998
F486	8	0.931	0.990
F378	8	0.927	0.984
N81	8	0.890	0.984
S58	8	0.849	0.991
D99	8	0.831	0.950
F450	8	0.812	0.976

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

5 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.87e-10
Head and Neck Squamous Cell Carcinoma (TCGA)	favorable	5.45e-05
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000111
Liver Hepatocellular Carcinoma (validation)	favorable	0.000416
Liver Hepatocellular Carcinoma (TCGA)	favorable	0.000587

Disease associations

OMIM: gene MIM:602943 | disease phenotypes: MIM:616622

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency	Strong	Autosomal recessive	4
lymphatic malformation	Moderate	Autosomal dominant

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (3 panels, 2 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

3 panels:

Panel	Rating
COVID-19 research	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green
Primary lymphoedema	amber

Mondo (2): autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency (MONDO:0014710), lymphatic malformation (MONDO:0019313)

Orphanet (1): Mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency (Orphanet:477857)

HPO phenotypes

10 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000778	Hypoplasia of the thymus
HP:0001744	Splenomegaly
HP:0002240	Hepatomegaly
HP:0003593	Infantile onset
HP:0009098	Recurrent oral thrush
HP:0011107	Recurrent aphthous stomatitis
HP:0011370	Recurrent cutaneous fungal infections
HP:0011463	Childhood onset
HP:0020087	BCGosis

GWAS associations

13 associations:

Study	Trait	p-value
GCST90013407_174	Liver enzyme levels (gamma-glutamyl transferase)	5e-37
GCST008916_2	Asthma	5e-27
GCST008916_34	Asthma	1e-25
GCST005537_235	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	2e-16
GCST007800_12	Asthma (childhood onset)	2e-16
GCST001725_34	Inflammatory bowel disease	4e-16
GCST007798_16	Asthma	3e-14
GCST004131_15	Inflammatory bowel disease	7e-14
GCST008916_27	Asthma	1e-12
GCST005038_69	Allergic disease (asthma, hay fever or eczema)	2e-12
GCST004133_27	Ulcerative colitis	2e-11
GCST002755_3	Depressive symptoms (SSRI exposure interaction)	3e-7
GCST004132_67	Crohn’s disease	6e-7

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0007006	depressive symptom measurement
EFO:0007010	drug use measurement
EFO:0007011	SSRI use measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1741186 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the RORC protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

1 curated-mechanism drugs:

Drug	Modality	Max phase
JTE-151	Unknown	1

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,100,839 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

9 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL705	ALITRETINOIN	4	39,748
CHEMBL1751	DIGOXIN	4	67,871
CHEMBL38	TRETINOIN	4	195,980
CHEMBL112570	CHOLESTEROL	2	754,612
CHEMBL169	URSOLIC ACID	2	21,155
CHEMBL269277	BETULINIC ACID	1	20,637
CHEMBL4634542	BMS-986251	1	12
CHEMBL4472508	CINTIRORGON	1	774
CHEMBL4225088	GSK2981278	1	50

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

4 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs2280471	regorafenib	Toxicity	Allele G is associated with decreased likelihood of Erythema multiforme when treated with regorafenib in people with Colorectal Neoplasms and Metastatic neoplasm as compared to allele A.	PMID:41284062
rs12145375	regorafenib	Toxicity	Allele T is associated with decreased likelihood of Erythema multiforme when treated with regorafenib in people with Colorectal Neoplasms and Metastatic neoplasm as compared to allele C.	PMID:41284062
rs55841824	regorafenib	Toxicity	Allele T is associated with decreased likelihood of Erythema multiforme when treated with regorafenib in people with Colorectal Neoplasms and Metastatic neoplasm as compared to allele C.	PMID:41284062
rs12144914	regorafenib	Toxicity	Allele G is associated with decreased likelihood of Erythema multiforme when treated with regorafenib in people with Colorectal Neoplasms and Metastatic neoplasm as compared to allele T.	PMID:41284062

GtoPdb / IUPHAR curated pharmacology

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

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

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

Ligand	Action	Affinity	Parameter
compound 32 [PMID: 31638797]	Inverse agonist	10.44	pIC50
compound 25 [Zhang et al., 2020]	Negative	9.0	pIC50
TAK-828F	Inverse agonist	8.72	pIC50
GSK2981278	Inverse agonist	8.49	pIC50
compound 14 [Schnute et al., 2023]	Inverse agonist	8.03	pIC50
GNE-3500	Inverse agonist	7.92	pEC50
MRL-871	Inverse agonist	7.8	pEC50
RORC2 inverse agonist 66 [PMID: 30130103]	Inverse agonist	7.78	pIC50
AZD0284	Inverse agonist	7.39	pIC50
T0901317	Inverse agonist	7.29	pKi
SR2211	Inverse agonist	6.98	pKi
SR1001	Inverse agonist	6.95	pKi
cintirorgon	Agonist	6.3	pEC50
XY101	Inverse agonist	6.12	pKd
SR1555	Inverse agonist	6.0	pIC50

Binding affinities (BindingDB)

5622 measured of 6082 human assays (6100 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
[4-chloro-2-methoxy-3-[[4-(trifluoromethyl)phenyl]methyl]quinolin-6-yl]-bis(2,3-dimethylimidazol-4-yl)methanol	KD	0.017 nM	US-9290476: Methylene linked quinolinyl modulators of RORγt
(R)-[4-chloro-2-methoxy-3-[[4-(trifluoromethyl)piperidin-1-yl]methyl]quinolin-6-yl]-(2,6-dimethyl-4-pyridinyl)-(3-methyltriazol-4-yl)methanol	KD	0.02 nM	US-10201546: Quinolinyl modulators of RORγt
[4-chloro-2-methoxy-3-[[4-(trifluoromethyl)phenyl]methyl]quinolin-6-yl]-(2,3-dimethylimidazol-4-yl)-(3-methyltriazol-4-yl)methanol	KD	0.026 nM	US-9290476: Methylene linked quinolinyl modulators of RORγt
6-[(2,6-dimethyl-3-pyridinyl)-hydroxy-(3-methyltriazol-4-yl)methyl]-3-[[4-(trifluoromethyl)phenyl]methyl]quinoline-2,4-dicarbonitrile	KD	0.04 nM	US-9290476: Methylene linked quinolinyl modulators of RORγt
6-[(2,3-dimethylimidazol-4-yl)-hydroxy-(3-methyltriazol-4-yl)methyl]-2-methoxy-3-[[4-(trifluoromethyl)phenyl]methyl]quinoline-4-carbonitrile	KD	0.05 nM	US-9290476: Methylene linked quinolinyl modulators of RORγt
[4-chloro-2-methoxy-3-[[4-(trifluoromethyl)phenyl]methyl]quinolin-6-yl]-(2,6-dimethyl-3-pyridinyl)-(3-methyltriazol-4-yl)methanol	KD	0.14 nM	US-9290476: Methylene linked quinolinyl modulators of RORγt
[4-chloro-2-ethyl-3-[[4-(trifluoromethyl)phenyl]methyl]quinolin-6-yl]-(1-methylsulfonylazetidin-3-yl)-(3-methyltriazol-4-yl)methanol	KD	0.23 nM	US-9290476: Methylene linked quinolinyl modulators of RORγt
6-[(2,6-dimethyl-3-pyridinyl)-hydroxy-(3-methyltriazol-4-yl)methyl]-2-methoxy-3-[[4-(trifluoromethyl)phenyl]methyl]quinoline-4-carbonitrile	KD	0.28 nM	US-9290476: Methylene linked quinolinyl modulators of RORγt
[4-chloro-2-methoxy-8-methyl-3-[(4-pyrazol-1-ylphenyl)methyl]quinolin-6-yl]-bis(3-methylimidazol-4-yl)methanol	KD	0.29 nM	US-9290476: Methylene linked quinolinyl modulators of RORγt
1-[3-[[4-chloro-2-ethyl-3-[[4-(trifluoromethyl)phenyl]methyl]quinolin-6-yl]-hydroxy-(3-methyltriazol-4-yl)methyl]azetidin-1-yl]ethanone	KD	0.32 nM	US-9290476: Methylene linked quinolinyl modulators of RORγt
4-{(6R or S)-1-({2- chloro-6-[1- (difluoromethyl)cyclo propyl]phenyl}car- bonyl)-6-[(3- methoxyazetidin-1- yl)carbonyl]-4,5,6,7- tetrahydro-1H- indazol-3-yl}-3- fluorobenzoic acid	IC50	0.5 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
(R or S)-4-(1-(2- chloro-6-(1- (trifluoromethyl)cyclo- propyl)benzoyl)-6- (1-methyl-1,4,5,6- tetrahydropyrrolo[3,4- c]pyrazole-5- carbonyl)-4,5,6,7- tetrahydro-1H- indazol-3-yl)-3- fluorobenzoic acid	IC50	0.5 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
(R or S)-4-(1-(2- chloro-6-(1- (trifluoromethyl)cyclo- propyl)benzoyl)-6- (2-methyl-4,5,6,7- tetrahydro-2H- pyrazolo[4,3- c]pyridine-5- carbonyl)-4,5,6,7- tetrahydro-1H- indazol-3-yl)-3- fluorobenzoic acid	IC50	0.5 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
(R or S)-4-(1-(2- chloro-6-(1- (trifluoromethyl)cyclo- propyl)benzoyl)-6- (5,6,7,8-tetrahydro- [1,2,4]triazolo[1,5- a]pyrazine-7- carbonyl)-4,5,6,7- tetrahydro-1H- indazol-3-yl)-3- fluorobenzoic acid	IC50	0.5 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
3-[5-[5-[4-(tert-butylsulfamoyl)-2,3-dichlorophenyl]-4-(cyclohexylmethyl)-1,3-thiazol-2-yl]-1,3,4-oxadiazol-2-yl]-2,2-dimethylpropanoic acid	KD	0.55 nM	US-10080744: Thiazoles as modulators of RORγt
4-[(6R or S)-1-({2- chloro-6-[1- (trifluoromethyl)cyclo- propyl]phenyl}car- bonyl)-6-(1-oxa-7- azaspiro[4.4]non-7- ylcarbonyl)-4,5,6,7- tetrahydro-1H- indazol-3-yl]-3- fluorobenzoic acid	IC50	0.6 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
4-{(6R or S)-1-({2- chloro-6-[1- (trifluoromethyl)cyclo- propyl]phenyl}car- bonyl)-6-[(3-methoxy- 3-methylazetidin-1- yl)carbonyl]-4,5,6,7- tetrahydro-1H- indazol-3-yl}-3- fluorobenzoic acid	IC50	0.6 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
4-{(6R or S)-1-({2- chloro-6-[1- (difluoromethyl)cyclo propyl]phenyl}car- bonyl)-6-[(3-methoxy- 3-methylazetidin-1- yl)carbonyl]-4,5,6,7- tetrahydro-1H- indazol-3-yl}-3- fluorobenzoic acid	IC50	0.6 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
(R or S)-4-(1-(2- chloro-6-(1- (trifluoromethyl)cyclo- propyl)benzoyl)-6- (4,5,6,7-tetrahydro- 1H-pyrazolo[4,3- c]pyridine-5- carbonyl)-4,5,6,7- tetrahydro-1H- indazol-3-yl)-3- fluorobenzoic acid	IC50	0.6 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
(R or S)-4-(1-(2- chloro-6-(1- (trifluoromethyl)cyclo- propyl)benzoyl)-6- (2-methyl-1,4,5,6- tetrahydropyrrolo[3,4- d]imidazole-5- carbonyl)-4,5,6,7- tetrahydro-1H- indazol-3-yl)-3- fluorobenzoic acid	IC50	0.6 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
(R or S)-4-(1-(2- chloro-6-(1- (trifluoromethyl)cyclo- propyl)benzoyl)-6- (methyl(1-methyl- 1H-pyrazol-4- yl)carbamoyl)- 4,5,6,7-tetrahydro- 1H-indazol-3-yl)-3- fluorobenzoic acid	IC50	0.6 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
4-[3-(2,6-dichlorobenzoyl)-7-fluoro-3a,7a-dihydroindol-1-yl]-3-fluorobenzoic acid	IC50	0.615 nM	US-9855229: Treatment of respiratory disorders using ROR-gamma inhibitors
[4-chloro-2-methoxy-3-[[4-(trifluoromethyl)phenyl]methyl]quinolin-6-yl]-(2,4-dimethyl-1,3-oxazol-5-yl)-(3-methyltriazol-4-yl)methanol	KD	0.63 nM	US-9290476: Methylene linked quinolinyl modulators of RORγt
1-[3-[[4-chloro-2-methoxy-3-[[4-(trifluoromethyl)phenyl]methyl]quinolin-6-yl]-hydroxy-(3-methyltriazol-4-yl)methyl]azetidin-1-yl]ethanone	KD	0.64 nM	US-9290476: Methylene linked quinolinyl modulators of RORγt
4-[1-[2-chloro-6-[1-(trifluoromethyl)cyclopropyl]benzoyl]-6-(2-oxa-7-azaspiro[3.4]octane-7-carbonyl)-4,5,6,7-tetrahydroindazol-3-yl]-3-fluorobenzoic acid	IC50	0.7 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
4-[(6R or S)-1-({2- chloro-6-[1- (trifluoromethyl)cyclo- propyl]phenyl}car- bonyl)-6-(5-oxa-2- azaspiro[3.4]oct-2- ylcarbonyl)-4,5,6,7- tetrahydro-1H- indazol-3-yl]-3- fluorobenzoic acid	IC50	0.7 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
4-[(6R or S)-1-({2- chloro-6-[1- (trifluoromethyl)cyclo- propyl]phenyl}car- bonyl)-6-{[4- (dimethylamino)-3,3- difluoropyrrolidin-1- yl]carbonyl}-4,5,6,7- tetrahydro-1H- indazol-3-yl]-3- fluorobenzoic acid	IC50	0.7 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
4-[(6R or S)-1-({2- chloro-6-[1- (trifluoromethyl)cyclo- propyl]phenyl}car- bonyl)-6-{[(3S,4S)-3- hydroxy-4- methoxypyrrolidin-1- yl]carbonyl}-4,5,6,7- tetrahydro-1H- indazol-3-yl]-3- fluorobenzoic acid	IC50	0.7 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
(R or S)-4-(1-(2- chloro-6-(1- (trifluoromethyl)cyclo- propyl)benzoyl)-6- (2-oxa-6- azaspiro[3.3]heptane- 6-carbonyl)-4,5,6,7- tetrahydro-1H- indazol-3-yl)-3- fluorobenzoic acid	IC50	0.7 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
(S)-(4-chloro-3-cyclopentyl-2-methoxyquinolin-6-yl)-(2,3-dimethylimidazol-4-yl)-(3-methyltriazol-4-yl)methanol	KD	0.75 nM	US-10201546: Quinolinyl modulators of RORγt
tert-butyl 3-[[4-chloro-2-ethyl-3-[[4-(trifluoromethyl)phenyl]methyl]quinolin-6-yl]-hydroxy-(3-methyltriazol-4-yl)methyl]azetidine-1-carboxylate	KD	0.77 nM	US-9290476: Methylene linked quinolinyl modulators of RORγt
4-{(6R or S)-1-({2- chloro-6-[1- (trifluoromethyl)cyclo- propyl]phenyl}car- bonyl)-6-[(3- methoxyazetidin-1- yl)carbonyl]-4,5,6,7- tetrahydro-1H- indazol-3-yl}-3- fluorobenzoic acid	IC50	0.8 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
4-[(6R or S)-1-({2- chloro-6-[1- (difluoromethyl)cyclo propyl]phenyl}car- bonyl)-6-(2-oxa-6- azaspiro[3.4]oct-6- ylcarbonyl)-4,5,6,7- tetrahydro-1H- indazol-3-yl]-3- fluorobenzoic acid	IC50	0.8 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
4-[(6R or S)-1-({2- chloro-6-[1- (difluoromethyl)cyclo propyl]phenyl)car- bonyl)-6-{[(3S,4R)-3- fluoro-4- hydroxypyrrolidin-1- yl]carbonyl}-4,5,6,7- tetrahydro-1H- indazol-3-yl]-3- fluorobenzoic acid	IC50	0.8 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
(R or S)-4-(1-(2- chloro-6-(1- (trifluoromethyl)cyclo- propyl)benzoyl)-6- (methyl((1-methyl- 1H-pyrazol-4- yl)methyl)carbamoyl)- 4,5,6,7-tetrahydro- 1H-indazol-3-yl)-3- fluorobenzoic acid	IC50	0.8 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
4-[(6R or S)-1-({2- chloro-6-[1- (trifluoromethyl)cyclo- propyl]phenyl}car- bonyl)-6-{[(3S,4S)-3- (dimethylamino)-4- hydroxypyrrolidin-1- yl]carbonyl}-4,5,6,7- tetrahydro-1H- indazol-3-yl]-3- fluorobenzoic acid	IC50	0.8 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
4-{(6R or S)-1-({2- chloro-6-[1- (trifluoromethyl)cyclo- propyl]phenyl}car- bonyl)-6-[(3- hydroxyazetidin-1- yl)carbonyl]-4,5,6,7- tetrahydro-1H- indazol-3-yl}-3- fluorobenzoic acid	IC50	0.8 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
[2,4-dichloro-3-[(4-chlorophenyl)methyl]quinolin-6-yl]-pyridin-3-yl-(1,3-thiazol-5-yl)methanol	KD	0.83 nM	US-9290476: Methylene linked quinolinyl modulators of RORγt
3-cyano-N-[1-methyl-3-[1-[(2S)-thiolane-2-carbonyl]piperidin-4-yl]-4-(trifluoromethyl)pyrrolo[2,3-b]pyridin-5-yl]benzamide	IC50	0.9 nM	US-9670201: Methyl- and trifluoromethyl-substituted pyrrolopyridine modulators of RORC2 and methods of use thereof
4-[1-[2-chloro-6-[1-(trifluoromethyl)cyclopropyl]benzoyl]-6-[(3R)-3-(dimethylamino)pyrrolidine-1-carbonyl]-4,5,6,7-tetrahydroindazol-3-yl]-3-fluorobenzoic acid	IC50	0.9 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
(R or S)-4-(1-(2- chloro-6-(1- (trifluoromethyl)cyclo- propyl)benzoyl)-6- (1-methyl-3- (trifluoromethyl)- 4,5,6,7-tetrahydro- 1H-pyrazolo[4,3- c]pyridine-5- carbonyl)-4,5,6,7- tetrahydro-1H- indazol-3-yl)-3- fluorobenzoic acid	IC50	0.9 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
(R or S)-4-(6-(((1H- pyrazol-5- yl)methyl)(methyl)car- bamoyl)-1-(2- chloro-6-(1- (trifluoromethyl)cyclo- propyl)benzoyl)- 4,5,6,7-tetrahydro- 1H-indazol-3-yl)-3- fluorobenzoic acid	IC50	0.9 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
(R or S)-4-(1-(2- chloro-6-(1- (trifluoromethyl)cyclo- propyl)benzoyl)-6- (methyl(2-(1-methyl- 1H-pyrazol-4- yl)ethyl)carbamoyl)- 4,5,6,7-tetrahydro- 1H-indazol-3-yl)-3- fluorobenzoic acid	IC50	0.9 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
4-[(6R or S)-1-({2- chloro-6-[1- (trifluoromethyl)cyclo- propyl]phenyl}car- bonyl)-6-{[(3R)-3- cyanopyrrolidin-1- yl]carbonyl}-4,5,6,7- tetrahydro-1H- indazol-3-yl]-3- fluorobenzoic acid	IC50	0.9 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
(R or S)-4-(1-(2- chloro-6-(1- (trifluoromethyl)cyclo- propyl)benzoyl)-6- (3-fluoro-[1,3’- biazetidine]-1’- carbonyl)-4,5,6,7- tetrahydro-1H- indazol-3-yl)-3- fluorobenzoic acid	IC50	0.9 nM	US-10221142: Substituted pyrazole compounds as RORgammaT inhibitors and uses thereof
4-[6-(azetidine-1-carbonyl)-1-[[2-chloro-6-(trifluoromethyl)phenyl]methyl]-4-fluoroindazol-3-yl]-5-fluoro-2-hydroxybenzoic acid	IC50	1 nM	US-9556168: N-alkylated indole and indazole compounds as RORgammaT inhibitors and uses thereof
(3S,4R)-1-[1-(2-chloro-6-cyclopropylbenzoyl)-4-fluoroindazol-3-yl]-3-hydroxypiperidine-4-carboxylic acid	IC50	1 nM	US-9663522: 3-aminocycloalkyl compounds as RORgammaT inhibitors and uses thereof
4-(1-(2-chloro-6- (trifluoromethyl)benzoyl)-6- (3-methoxy-azetidine-1- carbonyl)-1H-indol-3-yl)-3- fluorobenzoic acid	IC50	1 nM	US-10196354: 4-heteroaryl substituted benzoic acid compounds as RORgammaT inhibitors and uses thereof
(3S,6R)-2-[[2,5-difluoro-4-[(1R,5S)- 6-(1,2,4-triazol-4-yl)-3- azabicyclo[3.1.0]hexan-3- yl]phenyl]methyl]-3-ethyl-6- phenyl-thiazinane 1,1-dioxide	IC50	1 nM	US-9751873: Aryl sultam derivatives as RORc modulators
(7R)-2-[[2,5-difluoro-4-[(1R,5S)- 6-(1,2,4-triazol-4-yl)-3- azabicyclo[3.1.0]hexan-3- yl]phenyl]methyl]-7-phenyl- thiazepane 1,1-dioxide	IC50	1 nM	US-9751873: Aryl sultam derivatives as RORc modulators

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.77	Kd	0.017	nM	CHEMBL3929357
10.72	Kd	0.019	nM	CHEMBL5821593
10.70	Kd	0.02	nM	CHEMBL4441287
10.70	Kd	0.02	nM	CHEMBL5766445
10.70	Kd	0.02	nM	CHEMBL5848238
10.70	Kd	0.02	nM	CHEMBL5948510
10.62	Kd	0.024	nM	CHEMBL3358455
10.62	Kd	0.024	nM	CHEMBL5782981
10.60	Kd	0.025	nM	CHEMBL4642631
10.59	Kd	0.026	nM	CHEMBL3910514
10.52	Kd	0.03	nM	CHEMBL4642631
10.52	Kd	0.03	nM	CHEMBL5999201
10.44	Kd	0.036	nM	CHEMBL5812593
10.42	Kd	0.038	nM	CHEMBL4637144
10.41	Kd	0.039	nM	CHEMBL5787501
10.40	Kd	0.04	nM	CHEMBL3969443
10.40	Kd	0.04	nM	CHEMBL4637144
10.40	Kd	0.04	nM	CHEMBL5948255
10.36	Kd	0.044	nM	CHEMBL6060307
10.35	Kd	0.045	nM	CHEMBL5870061
10.30	Kd	0.05	nM	CHEMBL3978521
10.30	Kd	0.05	nM	CHEMBL3314002
10.30	Kd	0.05	nM	CHEMBL4635066
10.30	Kd	0.05	nM	CHEMBL4647899
10.30	Kd	0.05	nM	CHEMBL5974922
10.30	Kd	0.05	nM	CHEMBL5772558
10.24	Kd	0.058	nM	CHEMBL6015906
10.24	Kd	0.058	nM	CHEMBL6171702
10.22	Kd	0.06	nM	CHEMBL4643698
10.22	Kd	0.06	nM	CHEMBL6046148
10.22	Kd	0.06	nM	CHEMBL6033780
10.22	Kd	0.06	nM	CHEMBL5943144
10.20	Kd	0.063	nM	CHEMBL5800104
10.15	Kd	0.07	nM	CHEMBL4646424
10.15	Kd	0.07	nM	CHEMBL4633899
10.15	Kd	0.07	nM	CHEMBL5745122
10.15	Kd	0.07	nM	CHEMBL5807349
10.15	Kd	0.07	nM	CHEMBL5869679
10.11	Kd	0.077	nM	CHEMBL4128575
10.11	Kd	0.078	nM	CHEMBL4635866
10.10	Kd	0.08	nM	CHEMBL5945490
10.10	Kd	0.08	nM	CHEMBL5901158
10.08	Kd	0.083	nM	CHEMBL5849731
10.00	Kd	0.1	nM	CHEMBL4442831
10.00	Kd	0.1	nM	CHEMBL3905654
10.00	IC50	0.1	nM	CHEMBL4635823
10.00	Kd	0.1	nM	CHEMBL5854700
10.00	Kd	0.1	nM	CHEMBL5757627
9.96	Kd	0.11	nM	CHEMBL3910514
9.96	Kd	0.11	nM	CHEMBL4126366

PubChem BioAssay actives

3559 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[4-chloro-2-methoxy-3-[[4-(trifluoromethyl)piperidin-1-yl]methyl]quinolin-6-yl]-(2,6-dimethyl-4-pyridinyl)-(3-methyltriazol-4-yl)methanol	1544476: Displacement of thermofluor from human recombinant N-terminal TEV cleavage site-fused-His-tagged RORgammat LBD expressed in Escherichia coli assessed as equilibrium binding constants by fluorescence-based thermal shift assay	kd	<0.0001	uM
3-[5-[4-(cyclopentylmethyl)-5-[2-(difluoromethyl)-3-fluoro-4-[[(2S)-1,1,1-trifluorobutan-2-yl]sulfamoyl]phenyl]-1,3-thiazol-2-yl]-1,3,4-oxadiazol-2-yl]-2,2-dimethylpropanoic acid	1662523: Binding affinity to RORgammat (unknown origin) assessed as dissociation constant by thermal shift binding assay	kd	<0.0001	uM
3-[5-[4-(cyclohexylmethyl)-5-[2-(difluoromethyl)-3-fluoro-4-[[(2S)-1,1,1-trifluorobutan-2-yl]sulfamoyl]phenyl]-1,3-thiazol-2-yl]-1,3,4-oxadiazol-2-yl]-2,2-dimethylpropanoic acid	1662523: Binding affinity to RORgammat (unknown origin) assessed as dissociation constant by thermal shift binding assay	kd	<0.0001	uM
3-[5-[5-[2-(difluoromethyl)-3-fluoro-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]phenyl]-4-[(2S)-2-methylpiperidine-1-carbonyl]-1,3-thiazol-2-yl]-1,3,4-oxadiazol-2-yl]-2,2-dimethylpropanoic acid	1662523: Binding affinity to RORgammat (unknown origin) assessed as dissociation constant by thermal shift binding assay	kd	<0.0001	uM
[4-chloro-3-[(4,4-difluorocyclohexyl)methyl]-2-methoxyquinolin-6-yl]-(2,6-dimethyl-3-pyridinyl)-(3-methyltriazol-4-yl)methanol	1544476: Displacement of thermofluor from human recombinant N-terminal TEV cleavage site-fused-His-tagged RORgammat LBD expressed in Escherichia coli assessed as equilibrium binding constants by fluorescence-based thermal shift assay	kd	0.0001	uM
3-[[5-[4-(tert-butylsulfamoyl)-5,6,7,8-tetrahydronaphthalen-1-yl]-4-(cyclohexylmethyl)-1,3-thiazole-2-carbonyl]amino]cyclobutane-1-carboxylic acid	1494612: Binding affinity to recombinant human RORgamma LBD (237 to 497 residues) expressed in Escherichia coli BL21 (DE3) GOLD by 1,8-ANS dye-based thermofluor assay	kd	0.0001	uM
3-[[4-(cyclohexylmethyl)-5-[4-(2-methylbutan-2-ylsulfamoyl)naphthalen-1-yl]-1,3-thiazole-2-carbonyl]amino]cyclobutane-1-carboxylic acid	1494612: Binding affinity to recombinant human RORgamma LBD (237 to 497 residues) expressed in Escherichia coli BL21 (DE3) GOLD by 1,8-ANS dye-based thermofluor assay	kd	0.0001	uM
5-[2-(difluoromethyl)-4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-N-(2-hydroxy-2-methylpropyl)-4-[(2S)-2-methylpiperidine-1-carbonyl]-1,3-thiazole-2-carboxamide	2263034: Inverse agonist activity at N-terminal his-tagged wild type human RORgammat LBD domain expressed in Escherichia coli assessed as dissociation constant by thermofluor assay	kd	0.0001	uM
3-[5-[5-[2-(difluoromethyl)-3-fluoro-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]phenyl]-4-[(4-fluorophenyl)methyl]-1,3-thiazol-2-yl]-1,3,4-oxadiazol-2-yl]-2,2-dimethylpropanoic acid	1662523: Binding affinity to RORgammat (unknown origin) assessed as dissociation constant by thermal shift binding assay	kd	0.0001	uM
5-[2,3-dichloro-4-[[(2S)-1,1,1-trifluorobutan-2-yl]sulfamoyl]phenyl]-4-(4-fluoropiperidine-1-carbonyl)-N-(6-oxaspiro[2.5]octan-2-yl)-1,3-thiazole-2-carboxamide	1660035: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay	kd	0.0001	uM
5-[2,3-dichloro-4-[[1-(trifluoromethyl)cyclopropyl]sulfamoyl]phenyl]-4-(4,4-difluoropiperidine-1-carbonyl)-N-(2-hydroxy-2-methylpropyl)-1,3-thiazole-2-carboxamide	1660035: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay	kd	0.0001	uM
5-[2,3-dichloro-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]phenyl]-4-[(2S,4R)-4-fluoro-2-methylpiperidine-1-carbonyl]-N-(2-hydroxy-2-methylpropyl)-1,3-thiazole-2-carboxamide	1660035: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay	kd	0.0001	uM
5-[2,3-dichloro-4-[[(2S)-1,1,1-trifluoro-3,3-dimethylbutan-2-yl]sulfamoyl]phenyl]-4-(4-fluoropiperidine-1-carbonyl)-N-(2-hydroxy-2-methylpropyl)-1,3-thiazole-2-carboxamide	1660035: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay	kd	0.0001	uM
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 acid	1662523: Binding affinity to RORgammat (unknown origin) assessed as dissociation constant by thermal shift binding assay	kd	0.0001	uM
5-[2-chloro-4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-N-(2-hydroxy-2-methylpropyl)-4-[(2S)-2-methylpiperidine-1-carbonyl]-1,3-thiazole-2-carboxamide	2263034: Inverse agonist activity at N-terminal his-tagged wild type human RORgammat LBD domain expressed in Escherichia coli assessed as dissociation constant by thermofluor assay	kd	0.0001	uM
4-(6-azaspiro[2.5]octane-6-carbonyl)-5-[2,3-dichloro-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]phenyl]-N-(2-hydroxy-2-methylpropyl)-1,3-thiazole-2-carboxamide	1660035: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay	kd	0.0002	uM
3-[[4-(cyclohexylmethyl)-5-[4-[(4-fluoro-2-methylbutan-2-yl)sulfamoyl]naphthalen-1-yl]-1,3-thiazole-2-carbonyl]amino]cyclobutane-1-carboxylic acid	1494612: Binding affinity to recombinant human RORgamma LBD (237 to 497 residues) expressed in Escherichia coli BL21 (DE3) GOLD by 1,8-ANS dye-based thermofluor assay	kd	0.0002	uM
5-[2,3-dichloro-4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-4-[(2S)-4,4-difluoro-2-methylpyrrolidine-1-carbonyl]-N-(2-hydroxy-2-methylpropyl)-1,3-thiazole-2-carboxamide	2263034: Inverse agonist activity at N-terminal his-tagged wild type human RORgammat LBD domain expressed in Escherichia coli assessed as dissociation constant by thermofluor assay	kd	0.0002	uM
4-N-cyclobutyl-5-[2,3-dichloro-4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-4-N-ethyl-2-N-(2-hydroxy-2-methylpropyl)-1,3-thiazole-2,4-dicarboxamide	2263034: Inverse agonist activity at N-terminal his-tagged wild type human RORgammat LBD domain expressed in Escherichia coli assessed as dissociation constant by thermofluor assay	kd	0.0002	uM
5-[2,3-dichloro-4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-4-[(2S,4S)-4-fluoro-2-methylpiperidine-1-carbonyl]-N-(2-hydroxy-2-methylpropyl)-1,3-thiazole-2-carboxamide	2263034: Inverse agonist activity at N-terminal his-tagged wild type human RORgammat LBD domain expressed in Escherichia coli assessed as dissociation constant by thermofluor assay	kd	0.0002	uM
5-[6-(2,2-dimethylpropylamino)-4-(trifluoromethyl)-3-pyridinyl]-N-(2-hydroxy-2-methylpropyl)-4-[(2S)-2-methylpiperidine-1-carbonyl]-1,3-thiazole-2-carboxamide	1960093: Inhibition of human RORgammmat LBD expressed in Escherichia coli by ThermoFluro assay	kd	0.0002	uM
N-[3-[(2R,4R)-2,4-dimethylpiperidine-1-carbonyl]-4,5,6,7-tetrahydro-1-benzothiophen-2-yl]pyridine-3-carboxamide	1989383: Inverse agonist activity at GST-tagged RORgammaT LBD (unknown origin) expressed in insect cells assessed as inhibition of biotinyl-NH-Ahx NSHQKVTLLQLLLGHKNEEN-CONH coactivator peptide recruitment at pH 7.4 at 293K by TR-FRET assay	ic50	0.0002	uM
5-[2,3-dichloro-4-[[(2S)-1,1,1-trifluoro-3-methylbutan-2-yl]sulfamoyl]phenyl]-4-(4-fluoropiperidine-1-carbonyl)-N-(2-hydroxy-2-methylpropyl)-1,3-thiazole-2-carboxamide	1660035: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay	kd	0.0002	uM
4-N-(1-bicyclo[1.1.1]pentanyl)-5-[2,3-dichloro-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]phenyl]-4-N-ethyl-2-N-(2-hydroxy-2-methylpropyl)-1,3-thiazole-2,4-dicarboxamide	1660035: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay	kd	0.0002	uM
[4-chloro-2-methoxy-3-[(4-pyrazol-1-ylphenyl)methyl]quinolin-6-yl]-bis(2,3-dimethylimidazol-4-yl)methanol	1366775: Displacement of 1,8-ANS from human N-terminal His-tagged RORgammat LBD (850 to 1635 residues) expressed in Escherichia coli by thermofluor assay	kd	0.0003	uM
[4-chloro-2-methoxy-3-[[4-(trifluoromethyl)piperidin-1-yl]methyl]quinolin-6-yl]-(3-methylimidazol-4-yl)-[2-(trifluoromethyl)-4-pyridinyl]methanol	1544476: Displacement of thermofluor from human recombinant N-terminal TEV cleavage site-fused-His-tagged RORgammat LBD expressed in Escherichia coli assessed as equilibrium binding constants by fluorescence-based thermal shift assay	kd	0.0003	uM
3-[5-[4-(cyclobutylmethyl)-5-[4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]naphthalen-1-yl]-1,3-thiazol-2-yl]-1,3,4-oxadiazol-2-yl]-2,2-dimethylpropanoic acid	1662523: Binding affinity to RORgammat (unknown origin) assessed as dissociation constant by thermal shift binding assay	kd	0.0003	uM
5-[2,3-dichloro-4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-N-(2-hydroxy-2-methylpropyl)-4-[(2S)-2-methylpyrrolidine-1-carbonyl]-1,3-thiazole-2-carboxamide	2263034: Inverse agonist activity at N-terminal his-tagged wild type human RORgammat LBD domain expressed in Escherichia coli assessed as dissociation constant by thermofluor assay	kd	0.0003	uM
5-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-2-methylphenyl]-N-(2-hydroxy-2-methylpropyl)-4-[(2S)-2-methylpiperidine-1-carbonyl]-1,3-thiazole-2-carboxamide	2263034: Inverse agonist activity at N-terminal his-tagged wild type human RORgammat LBD domain expressed in Escherichia coli assessed as dissociation constant by thermofluor assay	kd	0.0003	uM
5-[4-(tert-butylsulfamoyl)naphthalen-1-yl]-4-(cyclohexylmethyl)-N-[(4-ethylsulfonylphenyl)methyl]-1,3-thiazole-2-carboxamide	1494612: Binding affinity to recombinant human RORgamma LBD (237 to 497 residues) expressed in Escherichia coli BL21 (DE3) GOLD by 1,8-ANS dye-based thermofluor assay	kd	0.0003	uM
5-[2,3-dichloro-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]phenyl]-N-(2-hydroxy-2-methylpropyl)-4-[(2S)-2-methylpiperidine-1-carbonyl]-1,3-thiazole-2-carboxamide	1660035: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay	kd	0.0003	uM
5-[2,3-dichloro-4-[[(2S)-1,1,1-trifluorobutan-2-yl]sulfamoyl]phenyl]-4-(4,4-difluoropiperidine-1-carbonyl)-N-(2-hydroxy-2-methylpropyl)-1,3-thiazole-2-carboxamide	1660035: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay	kd	0.0003	uM
5-[2,3-dichloro-4-[[(2S)-1,1,1-trifluorobutan-2-yl]sulfamoyl]phenyl]-4-N,4-N-diethyl-2-N-(2-hydroxy-2-methylpropyl)-1,3-thiazole-2,4-dicarboxamide	1660035: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay	kd	0.0003	uM
5-[2,3-dichloro-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]phenyl]-4-(4-fluoropiperidine-1-carbonyl)-N-[2-methyl-2-(5-oxo-4H-1,2,4-oxadiazol-3-yl)propyl]-1,3-thiazole-2-carboxamide	1660035: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay	kd	0.0003	uM
3-[4-(cyclobutylmethyl)-5-[2-(difluoromethyl)-3-fluoro-4-[[(2S)-1,1,1-trifluorobutan-2-yl]sulfamoyl]phenyl]-1,3-thiazol-2-yl]-2,2-dimethylpropanoic acid	1662523: Binding affinity to RORgammat (unknown origin) assessed as dissociation constant by thermal shift binding assay	kd	0.0003	uM
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 acid	1662523: Binding affinity to RORgammat (unknown origin) assessed as dissociation constant by thermal shift binding assay	kd	0.0003	uM
5-[2,3-dichloro-4-[[(2S)-1,1,1-trifluorobutan-2-yl]sulfamoyl]phenyl]-N-(1,1-dioxothian-4-yl)-4-(4-fluoropiperidine-1-carbonyl)-1,3-thiazole-2-carboxamide	1660035: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay	kd	0.0003	uM
[4-chloro-2-methoxy-3-[(4-pyrazol-1-ylphenyl)methyl]quinolin-6-yl]-(2,3-dimethylimidazol-4-yl)-(3-methyltriazol-4-yl)methanol	1366775: Displacement of 1,8-ANS from human N-terminal His-tagged RORgammat LBD (850 to 1635 residues) expressed in Escherichia coli by thermofluor assay	kd	0.0004	uM
5-[4-(tert-butylsulfamoyl)naphthalen-1-yl]-4-(cyclohexylmethyl)-N-(oxan-4-yl)-1,3-thiazole-2-carboxamide	1494612: Binding affinity to recombinant human RORgamma LBD (237 to 497 residues) expressed in Escherichia coli BL21 (DE3) GOLD by 1,8-ANS dye-based thermofluor assay	kd	0.0004	uM
N-(3-amino-2,2-dimethyl-3-oxopropyl)-5-[4-(tert-butylsulfamoyl)naphthalen-1-yl]-4-(cyclohexylmethyl)-1,3-thiazole-2-carboxamide	1494614: Inverse agonist activity at human GAL4 DBD-fused RORgammat LBD (237 to 497 residues) expressed in HEK293T cells assessed as reduction in ROR mediated transcriptional activity after 24 hrs by dual glo luciferase reporter gene assay	ic50	0.0004	uM
3-[[5-[4-(tert-butylsulfamoyl)-2,3-dichlorophenyl]-4-(cyclohexylmethyl)-1,3-thiazole-2-carbonyl]amino]cyclobutane-1-carboxylic acid	1494612: Binding affinity to recombinant human RORgamma LBD (237 to 497 residues) expressed in Escherichia coli BL21 (DE3) GOLD by 1,8-ANS dye-based thermofluor assay	kd	0.0004	uM
3-[3-[4-(cyclobutylmethyl)-5-[2,3-dichloro-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]phenyl]-1,3-thiazol-2-yl]-1,2,4-oxadiazol-5-yl]-2,2-dimethylpropanoic acid	1662523: Binding affinity to RORgammat (unknown origin) assessed as dissociation constant by thermal shift binding assay	kd	0.0004	uM
4-N-cyclobutyl-5-[2,3-dichloro-4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-2-N-(2-hydroxy-2-methylpropyl)-4-N-methyl-1,3-thiazole-2,4-dicarboxamide	2263034: Inverse agonist activity at N-terminal his-tagged wild type human RORgammat LBD domain expressed in Escherichia coli assessed as dissociation constant by thermofluor assay	kd	0.0004	uM
N-[3-(benzylcarbamoyl)-4,5,6,7-tetrahydro-1-benzothiophen-2-yl]-5-chloro-2-methylsulfanylpyrimidine-4-carboxamide	1989383: Inverse agonist activity at GST-tagged RORgammaT LBD (unknown origin) expressed in insect cells assessed as inhibition of biotinyl-NH-Ahx NSHQKVTLLQLLLGHKNEEN-CONH coactivator peptide recruitment at pH 7.4 at 293K by TR-FRET assay	ic50	0.0004	uM
5-[2-chloro-3-fluoro-4-[[(2S)-1,1,1-trifluorobutan-2-yl]sulfamoyl]phenyl]-4-(4,4-difluoropiperidine-1-carbonyl)-N-(2-hydroxy-2-methylpropyl)-1,3-thiazole-2-carboxamide	1660035: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay	kd	0.0004	uM
5-[2,3-dichloro-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]phenyl]-4-N-ethyl-2-N-(2-hydroxy-2-methylpropyl)-4-N-(2,2,2-trifluoroethyl)-1,3-thiazole-2,4-dicarboxamide	1660035: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay	kd	0.0004	uM
3-[4-(cyclobutylmethyl)-5-[2,3-dichloro-4-[[(2S)-1,1,1-trifluoropropan-2-yl]sulfamoyl]phenyl]-1,3-thiazol-2-yl]-2,2-dimethylpropanoic acid	1662523: Binding affinity to RORgammat (unknown origin) assessed as dissociation constant by thermal shift binding assay	kd	0.0004	uM
(2,4-dichloro-3-phenylquinolin-6-yl)-(3-methylimidazol-4-yl)-quinolin-4-ylmethanol	1366775: Displacement of 1,8-ANS from human N-terminal His-tagged RORgammat LBD (850 to 1635 residues) expressed in Escherichia coli by thermofluor assay	kd	0.0005	uM
5-[4-(tert-butylsulfamoyl)naphthalen-1-yl]-4-(cyclohexylmethyl)-N-(1,1-dioxothietan-3-yl)-1,3-thiazole-2-carboxamide	1494612: Binding affinity to recombinant human RORgamma LBD (237 to 497 residues) expressed in Escherichia coli BL21 (DE3) GOLD by 1,8-ANS dye-based thermofluor assay	kd	0.0005	uM
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 acid	1662523: Binding affinity to RORgammat (unknown origin) assessed as dissociation constant by thermal shift binding assay	kd	0.0005	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	3
Estradiol	affects cotreatment, decreases expression	3
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	3
25-hydroxycholesterol	affects binding, decreases reaction	2
2-(1’H-indole-3’-carbonyl)thiazole-4-carboxylic acid methyl ester	affects expression, affects cotreatment, increases expression, decreases expression	2
Nickel	decreases expression	2
Aflatoxin B1	affects expression, decreases expression, decreases methylation	2
dihydroouabain	affects binding, increases reaction, increases expression	1
triptolide	decreases expression	1
bufotalin	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects binding, decreases activity, decreases reaction	1
helveticoside	increases expression	1
lead acetate	decreases expression	1
sulforaphane	decreases expression	1
3-phenoxybenzoic acid	affects binding	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
cupric chloride	decreases expression	1
fluvalinate	affects binding	1
cyhalothrin	affects binding	1
tryptanthrine	decreases reaction, increases expression	1
azoxystrobin	increases activity	1
bifenthrin	affects binding	1
6-formylindolo(3,2-b)carbazole	affects expression	1
rofecoxib	decreases expression	1
dihydroxy-vitamin D3	decreases response to substance, increases expression	1
T0901317	affects binding, decreases activity, decreases reaction	1

ChEMBL screening assays

758 unique, capped per target: 707 binding, 50 functional, 1 unclassified

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1738628	Unclassified	PUBCHEM_BIOASSAY: Late stage results from the probe development effort to identify novel modulators of the Retinoic acid receptor-related Orphan Receptors (ROR). (Class of assay: screening) [Related pubchem assays (depositor defined):AID213	PubChem BioAssay data set
CHEMBL1961836	Binding	Effect on RORG(NR1F3) dependent reporter activity in HEK293 cells at 20 uM	Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. — *Nature*
CHEMBL2114768	Functional	PubChem BioAssay. Late stage assay provider counterscreen from the probe development effort to identify selective inverse agonists of the Retinoic acid receptor-related Orphan Receptor Gamma (RORC): radioligand binding for ROR gamma using S	PubChem BioAssay data set

Cellosaurus cell lines

7 cell lines: 3 embryonic stem cell, 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A5X1	SEES3-1V human RORC, clone1	Embryonic stem cell	Male
CVCL_A5X2	SEES3-1V human RORC, clone2	Embryonic stem cell	Male
CVCL_A5X3	SEES3-1V human RORC, clone3	Embryonic stem cell	Male
CVCL_B2E2	Abcam HeLa RORC KO	Cancer cell line	Female
CVCL_B8NW	Abcam HCT 116 RORC KO	Cancer cell line	Male
CVCL_B9R8	Abcam A-549 RORC KO	Cancer cell line	Male
CVCL_D7HD	Ubigene HEK293T RORC KO	Transformed cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

29 trials:

NCT	Phase	Status	Title
NCT07728825	Phase 4	COMPLETED	Intralesional Bleomycin Sclerotherapy for Low-Flow Vascular Malformations of the Head and Neck
NCT07285005	Phase 3	RECRUITING	A Study to Investigate Efficacy and Safety of KP-001 Compared With Placebo in Patients Aged ≥2 Years With Common VM, Common LM, or KTS/CLOVES Syndrome
NCT02335242	Phase 2	COMPLETED	Sildenafil for the Treatment of Lymphatic Malformations
NCT03243019	Phase 2	RECRUITING	Efficacy of Rapamycin in the Treatment of Cervico-facial Lymphatic Malformations
NCT03427619	Phase 2	COMPLETED	OK432 (Picibanil) in the Treatment of Lymphatic Malformations
NCT03972592	Phase 2	COMPLETED	Topical Sirolimus in Cutaneous Lymphatic Malformations
NCT04861064	Phase 2	RECRUITING	Weekly Sirolimus Therapy
NCT05871970	Phase 2	RECRUITING	Safety and Efficacy Study of Intracystic TARA-002 for the Treatment of Lymphatic Malformations in Participants 6 Months to Less Than 18 Years of Age
NCT05983159	Phase 2	RECRUITING	A Trial of Targeted Therapies for Patients With Slow-Flow or Fast-Flow Vascular Malformations
NCT06437158	Phase 2	RECRUITING	Use of Bleomycin in the Sclerotherapy of Lymphatic Malformations for Pediatric Patients
NCT06789913	Phase 2	RECRUITING	A Phase 2 Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, in Adults and Children With PIK3CA Related Overgrowth Spectrum and Malformations Driven by PIK3CA Mutation (The ReInspire Study)
NCT01212965	Phase 1	TERMINATED	Selenium in the Treatment of Complicated Lymphatic Malformations
NCT04994002	Phase 1	WITHDRAWN	A Pharmacokinetic, Pharmacodynamic, Safety and Tolerability Study of CERC-006 in Adults With Complex Lymphatic Malformations
NCT00010452	Phase 2/3	COMPLETED	Study of Picibanil (OK432) Sclerotherapy in Children With Macrocystic Lymphatic Malformations
NCT05948943	Phase 2/3	RECRUITING	Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation.
NCT06673290	Phase 2/3	RECRUITING	Different Doses of Sirolimus for the Treatment of Cystic Lymphatic Malformations
NCT04409145	Phase 1/2	TERMINATED	First in Human Trial of Topical VT30 in Pts With Venous/Lymphatic Malformations Assoc With PIK3CA or TEK Gene Mutations
NCT00577213	Not specified	COMPLETED	Diagnosis of Hemangiomas and Vascular Malformations
NCT00866827	Not specified	COMPLETED	Airway Vascular Lesions
NCT02399527	Not specified	RECRUITING	Lymphatic Anomalies Registry for the Assessment of Outcome Data
NCT04836884	Not specified	COMPLETED	Vascular Anomaly Pathology and Genomics Biopsy Study
NCT05563831	Not specified	COMPLETED	National Evaluation of Patients With PIK3CA-Related Overgrowth Spectrum (PROS)
NCT06257719	Not specified	COMPLETED	Clinical Characteristics of Lymphatic Malformations
NCT06275022	Not specified	RECRUITING	A Prospective Study on the Treatment of cLM Based on ICG Imaging
NCT06755905	Not specified	COMPLETED	Indocyanine Green Lymphography in Management of Lingual Lymphatic Malformation
NCT06892964	Not specified	RECRUITING	Institution of an Italian Registry and Biobank for Biological Sample Collection
NCT06943703	Not specified	COMPLETED	Bleomycin as an Effective and Curative Adjunct Therapy for Lymphangioma
NCT06994260	Not specified	NOT_YET_RECRUITING	Diagnostic Imaging of Vascular Malformations Using MSOT and ULM
NCT07189832	Not specified	COMPLETED	Bleomycin Intralesional Injections of Cystic Hygromas

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for RORC across ~30M SureChEMBL compounds — explore on Sugi Predict.