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Key regulator of cellular differentiation, immunity, peripheral circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism (PubMed:19381306, PubMed:19965867, PubMed:20203100, PubMed:22789990, PubMed:26160376). 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 (PubMed:19965867, PubMed:22789990). 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 (PubMed:19965867). 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 (PubMed:19965867). Regulates the rhythmic expression of PROX1 and promotes its nuclear localization (PubMed:19381306, PubMed:19965867, PubMed:20203100, PubMed:22789990, PubMed:26160376). Plays an indispensable role in the induction of IFN-gamma dependent anti-mycobacterial systemic immunity (PubMed:26160376)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P51450"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21499262"}],"value":"Nuclear receptor essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes and Peyer's patches (PubMed:21499262). Required for the generation of LTi (lymphoid tissue inducer) cells (By similarity). Regulates thymocyte survival through DNA-binding on ROREs of target gene promoter regions and recruitment of coactivaros via the AF-2 (By similarity). 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 (PubMed:21499262). 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 (PubMed:21499262). 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 (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity)"}],"commentType":"FUNCTION","molecule":"Isoform 2"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P51450"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18368049"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20211758"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22170608"}],"value":"Interacts (via AF-2 motif) with the coactivator NCOA2 (via LXXLL motif) (PubMed:20211758). Interacts with the corepressor NCOR1 (By similarity). Interacts with CRY1 (PubMed:22170608). Interacts (via AF-2 motif) with the coactivators NCOA1 and PPARGC1A (via LXXLL motif) (By similarity). Interacts (via AF-2 motif) with PROX1 (By similarity). Interacts with FOXP3 (PubMed:18368049). Interacts with NR0B2 (By similarity)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P51449","intActId":"EBI-3908771"},"interactantTwo":{"uniProtKBAccession":"Q15788","geneName":"NCOA1","intActId":"EBI-455189"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P51449","intActId":"EBI-3908771"},"interactantTwo":{"uniProtKBAccession":"P62195","geneName":"PSMC5","intActId":"EBI-357745"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P51449","intActId":"EBI-3908771"},"interactantTwo":{"uniProtKBAccession":"Q9WTL8","geneName":"Bmal1","intActId":"EBI-644534"},"numberOfExperiments":2,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P51449","intActId":"EBI-3908771"},"interactantTwo":{"uniProtKBAccession":"O08785","geneName":"Clock","intActId":"EBI-79859"},"numberOfExperiments":2,"organismDiffer":true}]},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26160376"}],"value":"Nucleus","id":"SL-0191"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative promoter usage"],"isoforms":[{"name":{"value":"1"},"isoformIds":["P51449-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"synonyms":[{"value":"RORgT"},{"value":"RORgammaT"}],"isoformIds":["P51449-2"],"sequenceIds":["VSP_010632","VSP_010633"],"isoformSequenceStatus":"Described"}]},{"texts":[{"value":"Isoform 1 is widely expressed in many tissues, including liver and adipose, and highly expressed in skeletal muscle. 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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.","diseaseCrossReference":{"database":"MIM","id":"616622"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26160376"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the nuclear hormone receptor family. 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