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FLASH GENE
Symbol RORC contributors: mct - updated : 08-09-2019
HGNC name RAR-related orphan receptor C
HGNC id 10260
Corresponding disease
IMD42 Immunodeficiency 42
Location 1q21      Physical location : 151.778.547 - 151.804.348
Synonym name
  • nuclear receptor ROR-gamma
  • RAR-related orphan receptor gamma
  • retinoic acid-binding receptor gamma
    • Synonym symbol(s) RORG, NR1F3, TOR, RZRG, MGC129539
    DNA
    TYPE functioning gene
    STRUCTURE 24.00 kb     11 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 3084 58.2 518 - 2012 22237416
    10 - 3054 - 497 thymus 2012 22237416
    - - - - - - 2012 22237416
  • lacks the hinge-encoding exons 5-8 and represses potently IL17 and IL21 gene transcription
  • acts as a dominant-negative regulator of RORC-mediated gene regulation and the balance between the full-length RORC and the novel repressor isoform may arbitrate IL17 production in human T cells
    		•
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node    
     thymus    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticthymocyte
    Lymphoid/Immunelymphocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal conserved domain
  • a central bipartite zinc finger with differential DNA binding activities
  • a C terminal ligand binding domain
    • HOMOLOGY
    intraspecies homolog to RAR orphan receptor
    Homologene
    FAMILY steroid/thyroid retinoic receptor superfamily
    CATEGORY receptor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies
    basic FUNCTION
  • ligand activated transcription factor, essential for lymphoid organogenesis (lymph nodes and Peyer's patches) and playing an important regulatory role in thymopoeisis
  • functions as an important link between the circadian clock and the transcriptional regulation of several metabolic genes
  • both RORC-overexpressed CD4(+) T cells and reduced Treg cells might contribute to the development of Sjögren syndrome (SS)-like sialadenitis
  • plays a significant role in the dysregulated immune response associated with systemic lupus erythematosus (SLE)
  • is critical for the differentiation and proliferation of Th17 cells associated with several chronic autoimmune diseases
  • RORC/IL17A axis influences VEGFA production and neovascular retinopathy by mechanisms involving neuroglia
  • directs the differentiation of Th17 cells, that mediate pathological immune responses responsible for autoimmune diseases, including psoriasis and multiple sclerosis
  • master regulator of the Th17/IL17 pathway that plays crucial roles in the pathogenesis of autoimmunity
  • RORC, and RORA are expressed in Th17 cells and have been suggested to play a role in Th17 differentiation
  • overlapping role of RORC and RORA in human Th17 cell differentiation through regulation of a defined common set of Th17 genes
  • RORB and RORC are part of the molecular cascade that regulates insulin secretion in pancreatic beta cells
    • CELLULAR PROCESS cell life, cell death/apoptosis
    cell life, antiapoptosis
    cell organization/biogenesis
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ID2 and RORC are sequentially up-regulated during lymphoid tissue inducer (LTi) cell development, matching two waves of differentiation with opposite requirements for NOTCH1 signaling
  • LY9/SLAMF6 signaling mediates increased nuclear abundance and recruitment of RORC to the proximal IL17A promoter, resulting in increased trans-activation and gene expression
  • transcription factor NFIL3 suppresses T(H)17 cell development by directly binding and repressing the RORC promoter
  • USP17 stabilizes RORC protein expression by reducing RORC polyubiquitination at its Lys-360 residue
  • SOX5 and MAF cooperatively induce Th17 cell differentiation via the induction of RORC as downstream targets of STAT3
  • SIRT1 increases RORC transcriptional activity, enhancing Th17 cell generation and function
  • TRAF5, known as an E3 ubiquitin protein ligase and signal transducer, interacts with and ubiquitinates RORC via Lys-63-linked polyubiquitination, and stabilizes the RORC protein level depending on its RING finger domain
  • is a key transcription factor involved in Th17 cell differentiation through direct transcriptional activation of interleukin 17(A) (IL17A)
  • EP300, which has histone acetyltransferase (HAT) activity, interacts with and acetylates RORC at its K81 residue
  • USP15 interacted with RORC, removed ubiquitin from K446, and stimulated RORC activity by enhancing coactivator SRC recruitment (positive role for USP15-mediated deubiquitination of RORC in Th17 differentiation)
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) IMD42
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyautoimmune 
    highly promising target for treatment of a number of autoimmune diseases
    neurosensorialvisual 
    inhibition of RORC and IL17A may have potential for the improved treatment of neovascular retinopathies
    ANIMAL & CELL MODELS