RORA [The Human Chemical-Genetic Interaction Map Project]

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======= RORA =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: RORA
  * **<color #00a2e8>Official Name</color>**: RAR related orphan receptor A
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=6095|6095]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P35398|P35398]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=RORA&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20RORA|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/600825|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The protein encoded by this gene is a member of the NR1 subfamily of nuclear hormone receptors. It can bind as a monomer or as a homodimer to hormone response elements upstream of several genes to enhance the expression of those genes. The encoded protein has been shown to interact 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. Also, it has been shown to aid in the transcriptional regulation of some genes involved in circadian rhythm. Four transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2014]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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. {ECO:0000269|PubMed:10478845, ECO:0000269|PubMed:11053433, ECO:0000269|PubMed:11252722, ECO:0000269|PubMed:11554739, ECO:0000269|PubMed:12467577, ECO:0000269|PubMed:14570920, ECO:0000269|PubMed:15781255, ECO:0000269|PubMed:15790933, ECO:0000269|PubMed:16462772, ECO:0000269|PubMed:17512500, ECO:0000269|PubMed:18005000, ECO:0000269|PubMed:18354202, ECO:0000269|PubMed:18658046, ECO:0000269|PubMed:19965867, ECO:0000269|PubMed:21499262, ECO:0000269|PubMed:7926749, ECO:0000269|PubMed:9328355, ECO:0000269|PubMed:9862959}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|zf-C4|
|Hormone recep|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|ligand-activated transcription factor activity|
|oxysterol binding|
|cell proliferation in external granule layer|
|cerebellar granule cell precursor proliferation|
|cell proliferation in hindbrain|
|T-helper 17 type immune response|
|T-helper 17 cell differentiation|
|cerebellar Purkinje cell differentiation|
|cerebellar Purkinje cell layer formation|
|nitric oxide biosynthetic process|
|transcription corepressor binding|
|cerebellar Purkinje cell layer morphogenesis|
|nitric oxide metabolic process|
|regulation of transcription involved in cell fate commitment|
|positive regulation of circadian rhythm|
|cGMP metabolic process|
|cell differentiation in hindbrain|
|reactive nitrogen species metabolic process|
|transcription coactivator binding|
|cerebellar cortex formation|
|cellular response to sterol|
|cerebellar Purkinje cell layer development|
|reactive oxygen species biosynthetic process|
|CD4-positive, alpha-beta T cell differentiation involved in immune response|
|T-helper cell differentiation|
|alpha-beta T cell activation involved in immune response|
|alpha-beta T cell differentiation involved in immune response|
|positive regulation of vascular endothelial growth factor production|
|cerebellar cortex morphogenesis|
|response to sterol|
|T cell differentiation involved in immune response|
|regulation of vascular endothelial growth factor production|
|CD4-positive, alpha-beta T cell differentiation|
|triglyceride homeostasis|
|acylglycerol homeostasis|
|cerebellum morphogenesis|
|CD4-positive, alpha-beta T cell activation|
|cyclic nucleotide metabolic process|
|hindbrain morphogenesis|
|negative regulation of I-kappaB kinase/NF-kappaB signaling|
|neurotransmitter biosynthetic process|
|negative regulation of fat cell differentiation|
|cerebellar cortex development|
|nuclear receptor activity|
|alpha-beta T cell differentiation|
|steroid hormone receptor activity|
|regulation of macrophage activation|
|alpha-beta T cell activation|
|circadian regulation of gene expression|
|T cell activation involved in immune response|
|neural precursor cell proliferation|
|regulation of smoothened signaling pathway|
|cholesterol homeostasis|
|sterol homeostasis|
|beta-catenin binding|
|neurotransmitter metabolic process|
|cerebellum development|
|lymphocyte activation involved in immune response|
|metencephalon development|
|reactive oxygen species metabolic process|
|regulation of glucose metabolic process|
|regulation of steroid metabolic process|
|regulation of circadian rhythm|
|steroid hormone mediated signaling pathway|
|regulation of fat cell differentiation|
|xenobiotic metabolic process|
|lipid homeostasis|
|T cell differentiation|
|negative regulation of inflammatory response|
|regulation of cellular carbohydrate metabolic process|
|circadian rhythm|
|hindbrain development|
|intracellular receptor signaling pathway|
|hormone-mediated signaling pathway|
|cellular response to interleukin-1|
|transcription initiation from RNA polymerase II promoter|
|central nervous system neuron differentiation|
|cellular response to xenobiotic stimulus|
|cellular response to hypoxia|
|cellular response to steroid hormone stimulus|
|cellular response to decreased oxygen levels|
|response to interleukin-1|
|regulation of carbohydrate metabolic process|
|negative regulation of defense response|
|cellular response to oxygen levels|
|DNA-templated transcription, initiation|
|regulation of I-kappaB kinase/NF-kappaB signaling|
|T cell activation|
|lymphocyte differentiation|
|cellular response to tumor necrosis factor|
|muscle cell differentiation|
|cell fate commitment|
|response to tumor necrosis factor|
|rhythmic process|
|adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|response to xenobiotic stimulus|
|purine ribonucleotide metabolic process|
|RNA polymerase II regulatory region sequence-specific DNA binding|
|angiogenesis|
|ribonucleotide metabolic process|
|response to steroid hormone|
|purine nucleotide metabolic process|
|leukocyte differentiation|
|transcription factor binding|
|ribose phosphate metabolic process|
|regulation of inflammatory response|
|response to hypoxia|
|regulation of neurotransmitter levels|
|response to decreased oxygen levels|
|negative regulation of response to external stimulus|
|purine-containing compound metabolic process|
|response to oxygen levels|
|lymphocyte activation|
|regulation of lipid metabolic process|
|blood vessel morphogenesis|
|sequence-specific DNA binding|
|regulation of small molecule metabolic process|
|nucleotide metabolic process|
|DNA-binding transcription activator activity, RNA polymerase II-specific|
|positive regulation of cytokine production|
|nucleoside phosphate metabolic process|
|muscle structure development|
|transcription by RNA polymerase II|
|blood vessel development|
|drug metabolic process|
|RNA polymerase II proximal promoter sequence-specific DNA binding|
|negative regulation of intracellular signal transduction|
|vasculature development|
|cardiovascular system development|
|cellular response to lipid|
|nucleobase-containing small molecule metabolic process|
|cellular response to organic cyclic compound|
|cell population proliferation|
|hemopoiesis|
|regulation of leukocyte activation|
|cellular response to hormone stimulus|
|hematopoietic or lymphoid organ development|
|adaptive immune response|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|transcription, DNA-templated|
|regulation of cell activation|
|nucleic acid-templated transcription|
|immune system development|
|RNA biosynthetic process|
|tube morphogenesis|
|cytokine-mediated signaling pathway|
|DNA-binding transcription factor activity|
|regulation of cytokine production|
|negative regulation of cell differentiation|
|brain development|
|regulation of defense response|
|head development|
|zinc ion binding|
|tube development|
|response to lipid|
|circulatory system development|
|organophosphate metabolic process|
|anatomical structure formation involved in morphogenesis|
|response to hormone|
|response to organic cyclic compound|
|leukocyte activation|
|negative regulation of developmental process|
|central nervous system development|
|cellular response to cytokine stimulus|
|neuron differentiation|
|carbohydrate derivative metabolic process|
|cellular response to oxygen-containing compound|
|cell activation|
|immune effector process|
|regulation of response to external stimulus|
|nucleobase-containing compound biosynthetic process|
|response to cytokine|
|chemical homeostasis|
|response to abiotic stimulus|
|heterocycle biosynthetic process|
|aromatic compound biosynthetic process|
|positive regulation of transcription by RNA polymerase II|
|cellular response to endogenous stimulus|
|negative regulation of signal transduction|
|organic cyclic compound biosynthetic process|
|negative regulation of cell communication|
|negative regulation of signaling|
|DNA binding|
|response to endogenous stimulus|
|regulation of response to stress|
|generation of neurons|
|positive regulation of transcription, DNA-templated|
|response to oxygen-containing compound|
|DNA-binding transcription factor activity, RNA polymerase II-specific|
|negative regulation of response to stimulus|
|neurogenesis|
|cellular nitrogen compound biosynthetic process|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|homeostatic process|
|regulation of immune system process|
|RNA metabolic process|
|cellular response to stress|
|cellular macromolecule biosynthetic process|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|small molecule metabolic process|
|macromolecule biosynthetic process|
|regulation of cell differentiation|
|regulation of intracellular signal transduction|
|immune response|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|gene expression|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp42|BI-6727 0.001μM R01 exp42]]|-1.76|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 18317
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 2.95 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='RORA Expression in NALM6 Cells: 2.95'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>