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  3. RORA

RORA (RAR related orphan receptor A)

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Summary of RORA

The gene codes for a protein, RAR related orphan receptor A. The protein interacts with NM23-2, a nucleoside diphosphate kinase involved in organogenesis and differentiation, as well as with NM23-1, the product of a tumor metastasis suppressor candidate gene. It aids in the transcriptional regulation of genes related to circadian rhythm [R].

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The Function of RORA

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 embryonic development, cellular differentiation, immunity, 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 genes regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts. Regulates genes involved in photoreceptor development including OPN1SW, OPN1SM and ARR3 and skeletal muscle development with MYOD1. Required for proper cerebellum development, regulates SHH gene expression, among others, to induce granule cells proliferation as well as expression of genes involved in calcium-mediated signal transduction. Regulates the circadian expression of several clock genes, including CLOCK, ARNTL/BMAL1, NPAS2 and CRY1. Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as ARNTL/BMAL1, CRY1 and NR1D1 itself, resulting in NR1D1-mediated repression or RORA-mediated activation of clock genes expression, leading to the circadian pattern of clock genes expression. Therefore influences the period length and stability of the clock. Regulates genes involved in lipid metabolism such as apolipoproteins APOA1, APOA5, APOC3 and PPARG. In liver, has specific and redundant functions with RORC 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 CYP7B1 and SULT2A1. Induces a rhythmic expression of some of these genes. In addition, interplays functionally with NR1H2 and NR1H3 for the regulation of genes involved in cholesterol metabolism. Also involved in the regulation of hepatic glucose metabolism through the modulation of G6PC and PCK1. In adipose tissue, plays a role as negative regulator of adipocyte differentiation, probably acting through dual mechanisms. May suppress CEBPB-dependent adipogenesis through direct interaction and PPARG-dependent adipogenesis through competition for DNA-binding. Downstream of IL6 and TGFB and synergistically with RORC isoform 2, is implicated in the 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. Involved in hypoxia signaling by interacting with and activating the transcriptional activity of HIF1A. May inhibit cell growth in response to cellular stress. May exert an anti-inflammatory role by inducing CHUK expression and inhibiting NF-kappa-B signaling.

Protein names

Recommended name:

Nuclear receptor ROR-alpha

Alternative name(s):

Nuclear receptor RZR-alpha
Nuclear receptor subfamily 1 group F member 1
RAR-related orphan receptor A
Retinoid-related orphan receptor-alpha

RORA SNPs

    To see your genotype, you should be logged in and have a file with your genotype uploaded.

  1. RS11071559 (RORA) ??
  2. RS11631179 (RORA) ??
  3. RS12591650 (RORA) ??
  4. RS12912233 (RORA) ??
  5. RS1902618 (RORA) ??
  6. RS2028122 (RORA) ??
  7. RS339969 (RORA) ??
  8. RS339978 (RORA) ??
  9. RS340005 (RORA) ??
  10. RS340029 (RORA) ??
  11. RS3743266 (RORA) ??
  12. RS3784609 (RORA) ??
  13. RS4775301 (RORA) ??
  14. RS664910 (RORA) ??
  15. RS7168987 (RORA) ??
  16. RS7172342 (RORA) ??
  17. RS7179259 (RORA) ??
  18. RS782947 (RORA) ??
  19. RS8024133 (RORA) ??
  20. RS8041061 (RORA) ??
  21. RS8042149 (RORA) ??
  22. RS809736 (RORA) ??
  23. RS877228 (RORA) ??
  24. RS980000 (RORA) ??

Top Gene-Substance Interactions

RORA Interacts with These Diseases

Disease Score

Substances That Increase RORA

Substances Interaction Organism Category

Substances That Decrease RORA

Substances Interaction Organism Category

Conditions with Increased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Conditions with Decreased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Technical

The following transcription factors affect gene expression:

  • AP-1
  • Arnt
  • RORalpha2
  • c-Jun
  • ARP-1
  • Sp1
  • AP-2gamma
  • p300

Tissue specificity:

Widely expressed in a number of tissues. Expressed in both regulatory T-cells (Treg) and effector T-cells (Teff).

Gene Pathways:

  • Gene Expression
  • Circadian Clock
  • Mus musculus biological processes
  • Circadian rhythm - mammal

Induction:

Induced by oxidative stress and DNA damage. Isoform 4 is induced by hypoxia (through transactivation by HIF1A and SP1), but not isoform 1.

Molecular Function:

  • Core Promoter Sequence-Specific Dna Binding
  • Dna Binding
  • Oxysterol Binding
  • Rna Polymerase Ii Regulatory Region Sequence-Specific Dna Binding
  • Rna Polymerase Ii Transcription Factor Activity, Ligand-Activated Sequence-Specific Dna Binding
  • Sequence-Specific Dna Binding
  • Steroid Hormone Receptor Activity
  • Transcription Coactivator Binding
  • Transcription Corepressor Binding
  • Transcription Factor Activity, Direct Ligand Regulated Sequence-Specific Dna Binding
  • Transcription Factor Activity, Sequence-Specific Dna Binding
  • Transcription Factor Binding
  • Zinc Ion Binding

Biological Processes:

  • Angiogenesis
  • Cellular Response To Hypoxia
  • Cellular Response To Interleukin-1
  • Cellular Response To Sterol
  • Cellular Response To Tumor Necrosis Factor
  • Cerebellar Granule Cell Precursor Proliferation
  • Cerebellar Purkinje Cell Differentiation
  • Cgmp Metabolic Process
  • Circadian Regulation Of Gene Expression
  • Intracellular Receptor Signaling Pathway
  • Muscle Cell Differentiation
  • Negative Regulation Of Fat Cell Differentiation
  • Negative Regulation Of I-Kappab Kinase/Nf-Kappab Signaling
  • Negative Regulation Of Inflammatory Response
  • Nitric Oxide Biosynthetic Process
  • Positive Regulation Of Circadian Rhythm
  • Positive Regulation Of Transcription, Dna-Templated
  • Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
  • Positive Regulation Of Vascular Endothelial Growth Factor Production
  • Regulation Of Cholesterol Homeostasis
  • Regulation Of Glucose Metabolic Process
  • Regulation Of Macrophage Activation
  • Regulation Of Smoothened Signaling Pathway
  • Regulation Of Steroid Metabolic Process
  • Regulation Of Transcription, Dna-Templated
  • Regulation Of Transcription Involved In Cell Fate Commitment
  • T-Helper 17 Cell Differentiation
  • Transcription Initiation From Rna Polymerase Ii Promoter
  • Triglyceride Homeostasis
  • Xenobiotic Metabolic Process
*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

hypothetical protein| A306_15262| AS27_06142| AS28_07291| CB1_000598017| D623_10029423| H920_12589| M91_19101| M959_05234| MDA_GLEAN10013429| N300_15032| N301_08257| N302_04875| N303_01374| N305_08259| N306_15241| N307_11132| N308_02808| N309_01955| N310_05384| N311_10823| N312_06935| N320_03908| N321_11731| N322_12929| N324_01458| N325_05943| N326_00205| N327_09407| N329_02670| N330_05407| N331_00330| N333_07073| N334_00440| N335_02724| N336_02065| N339_02996| N340_11299| N341_07235| nmf267| NR1F1| nuclear receptor ROR-alpha| nuclear receptor RZR-alpha| nuclear receptor subfamily 1 group F member 1| PAL_GLEAN10023414| PANDA_012073| RAR-related orphan receptor A| RAR-related orphan receptor alpha| RAR-related orphan receptor A protein| retinoic acid receptor-related orphan receptor alpha| retinoic acid related-orphan receptor alpha| retinoic acid-related orphan receptor alpha| retinoid-related orphan receptor alpha| retinoid-related orphan receptor-alpha| ROR1| ROR2| ROR3| ror-alpha| RORalpha1| rzra| rzr-alpha| sg| staggerer| thyroid hormone nuclear receptor alpha variant 4| tmgc26| transcription factor RZR-alpha| UY3_19067| Y1Q_014658| Y956_05530| Z169_06607| rora

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