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FLASH GENE
Symbol RORA contributors: mct/ - updated : 06-06-2018
HGNC name RAR-related orphan receptor A
HGNC id 10258
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
11 - 10828 59 523 broadly expressed in various tissues and organs during embryonic development 2011 21480365
  • also called ROR alpha 1
  • implicated in the regulation of adipogenesis and lipoprotein metabolism
  • disrupted by t(4;15)(q22.3-q21.3)in severe obesity (haploinsufficiency of ROR1A and/or gain of function mediated by the fusion gene RORA1-UNC5C)
  • regulate the inflammatory responses via inhibition of the nuclear factor-kappaB signaling pathway in endothelial cells
  • RORA1 over-expression increased alkaline phosphatase, osteocalcin, cell mineralization, and collagen type I mRNA and protein expression, while RORA1 RNA silencing inhibited these responses
  • 12 - 10998 63 556 - 2004 14742449
    also called ROR alpha 2
    11 - 10974 62.1 548 - 2004 14742449
    also called ROR alpha 3
    10 - 10669 53.4 468 most abundantly expressed transcript in the human CNS, is prominently expressed by keratinocytes in a manner that increases with differentiation 2004 14742449
  • also called RZR-alpha, RORA4
  • regulate the inflammatory responses via inhibition of the nuclear factor-kappaB signaling pathway in endothelial cells
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine   
     mouthtongue   
    Endocrineneuroendocrinepituitary  highly
    Hearing/Equilibriumear   highly
    Nervousbrain   highly Homo sapiens
    Urinarykidney    
    Visualeyeretina    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousastrocyte Homo sapiens
    Nervousglia Homo sapiens
    Nervousneuron Homo sapiens
    Visualganglion cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a frizzled domain
  • an immunoglobulin-like C2-type domain
  • a kringle domain
  • a protein kinase domain
  • mono polymer monomer
    HOMOLOGY
    interspecies homolog to RAR orphan receptor alpha
    Homologene
    FAMILY
  • steroid/thyroid nuclear receptor superfamily
  • nuclear hormone receptor family
  • NR1 subfamily
  • CATEGORY transcription factor , receptor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • having ligand-dependent nuclear receptor activity, and involved in signal transduction
  • plays a crucial role in cone development by directly regulating multiple cone genes
  • pluripotent molecular player in constitutive and adaptive astrocyte physiology, exerting a bi-directional regulation of IL6 in resting and reactive astrocytes
  • cholesterol signalling through increased RORA expression stimulates chondrocyte hypertrophy and partially mediates responses of cartilage to actin dynamics
  • play a critical role in responses to cellular stress
  • contributes to the basal expression of FGF21
  • involved in regulating the Akt2-AMPK signaling pathways in the context of lipid homeostasis in skeletal muscle
  • operates at the nexus of pathways controlling the association between lipid homeostasis (lipogenesis, and fatty acid oxidation), Akt2 signaling (glucose tolerance and uptake) and AMPK signaling
  • RORA is a key molecular player in hypoxia, protecting neurons through its dual action in neurons and astrocytes
  • role of RORA in diverse pathological processes including oxidative stress-induced apoptosis and cerebral hypoxia
  • plays an important role in regulation of the circadian rhythm and metabolism
  • is a retinoid-related orphan nuclear receptor that regulates inflammation, lipid metabolism, and cellular differentiation of several non-epithelial tissues
  • RORA is a transcriptional activator of insulin, suggesting novel therapeutic opportunities for management of the diabetes
  • RORA and NR1D1 coordinately regulate the expression of the positive arm of the circadian rhythm feedback loop (
  • is a potent tumor suppressor that reduces cell proliferation and inhibits tumor growth
  • nuclear melatonin receptor RORA is a novel endogenous protective receptor against MI/R injury and an important mediator of melatonin-exerted cardioprotection
  • plays important roles in lipid, glucose metabolism, as well as the inflammatory response
  • RORA-induced ER stress response potentially contributes to the adipose tissue inflammation that can be mitigated by treatment with chemical chaperones
  • is an important regulator of various biological processes, including cerebellum development, circadian rhythm and cancer
  • has a pivotal role in the regulation of hepatic lipid homeostasis
  • 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
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with EP300 and MYOD1 in myogenesis
  • interacting with NR1D1
  • target for hypoxia-inducible factor 1(HIF1A, HIF1B)
  • FOXP3 interacts with RORA, and this interaction inhibits transcriptional activation mediated by RORA
  • link between RORA, a key regulator of the mammalian clock, and FGF21, an important hormone regulating glucose and lipid homeostasis
  • T3 action on the early Purkinje cell dendritic differentiation process is mediated by RORalpha
  • CS is a direct RORA target gene and one mechanism by which RORA regulates lipid metabolism is via regulation of CS expression
  • cholesterol sulfate induces expression of the skin barrier protein filaggrin in normal human epidermal keratinocytes through induction of RORA
  • pro-differentiation function of RORA is mediated at least in part by FOXN1, a well-known pro-differentiation transcription factor that we establish as a novel direct target of RORA in keratinocytes
  • RORA bound to the heptad repeat and marked box region of E2F1 and suppressed E2F1-regulated transcription in epithelial cells
  • directly suppressed the gene transcription of suppressors of cytokine signaling 3 (SOCS3), a critical negative regulator of inflammation
  • RORA regulates macrophage M2 polarization via activation of AMPKA, which may provide a novel beneficial effect of RORA against inflammation
  • RORA interacts with the CLDND1 promoter to enhance transcription, and CLDND1 is a direct RORA target 9)
  • RORA functions as an important mediator of HIF1A activities in regulating keratinocyte differentiation/survival and epidermal barrier function during the oxygen sensing stage
  • RORA is a novel transcriptional regulator of SEMA3E-mediated neurovascular coupling in pathological retinal angiogenesis
  • RORA directly bound to a specific ROR response element on the promoter of SEMA3E and negatively regulated SEMA3E promoter-driven luciferase expression
  • hepatic RORA controls lipid homeostasis by negatively regulating transcriptional activity of PPARG that mediates hepatic lipid metabolism
  • cell & other
    REGULATION
    activated by SUMOylation which may positively regulate transcriptional function of RORA
    ASSOCIATED DISORDERS
    corresponding disease(s) NDDCMB
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    in multiple tumors
    constitutional     --low  
    in the autistic brain
    constitutional       loss of function
    led to decreased levels of proinflammatory cytokines and increased levels of antiinflammatory cytokines in retinopathy
    tumoral     --low  
    down-regulated and/or hypoactivated in breast cancer compared to normal mammary tissue
    Susceptibility to orofacial cleft
    Variant & Polymorphism other
  • variants in SHH, RORA, MRPL53, ACVR1, and GDF11 may contribute to risk of orofacial clefts
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    digestiveliver 
    melatonin directly suppresses hepatic stellate cells (HSC) activation via RORA-mediated inhibition of ALOX5 expression, which provides novel drug targets to treat liver fibrosis
    neurosensorialvisualretina
    RORA inhibition may represent a new way to treat ocular neovascularizatio
    cancerreproductivebreast
    potential therapeutic target for breast cancer
    ANIMAL & CELL MODELS
  • (sg/sg) mouse,with a staggerer mutation consisting of an intragenic CNV that results in a 122-bp frameshifting deletion that truncates the ligand binding domain, leading to the loss of Rora activity (this phenotype is similar to Rora-/- mice)
  • liver-specific Rora-deficient mice develop hepatic steatosis, obesity and insulin resistance when challenged with a high-fat diet (HFD)
  • mice lacking a functional ROR&
  • 945; display a range of metabolic abnormalities including decreased serum cholesterol and plasma triglycerides