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Aliases for RORC Gene

Aliases for RORC Gene

  • RAR Related Orphan Receptor C 2 3
  • RAR-Related Orphan Receptor C 2 3 4 5
  • Nuclear Receptor Subfamily 1 Group F Member 3 3 4
  • Nuclear Receptor RZR-Gamma 3 4
  • NR1F3 3 4
  • RORG 3 4
  • RZRG 3 4
  • RAR-Related Orphan Nuclear Receptor Variant 2 3
  • Retinoid-Related Orphan Receptor Gamma 3
  • Retinoid-Related Orphan Receptor-Gamma 4
  • Retinoic Acid-Binding Receptor Gamma 3
  • RZR-GAMMA 3
  • IMD42 3
  • TOR 3

External Ids for RORC Gene

Previous GeneCards Identifiers for RORC Gene

  • GC01M149620
  • GC01M147561
  • GC01M148553
  • GC01M148995
  • GC01M148997
  • GC01M148592
  • GC01M150040
  • GC01M150046
  • GC01M151778
  • GC01M123155

Summaries for RORC Gene

Entrez Gene Summary for RORC Gene

  • The protein encoded by this gene is a DNA-binding transcription factor and is a member of the NR1 subfamily of nuclear hormone receptors. The specific functions of this protein are not known; however, studies of a similar gene in mice have shown that this gene may be essential for lymphoid organogenesis and may play an important regulatory role in thymopoiesis. In addition, studies in mice suggest that the protein encoded by this gene may inhibit the expression of Fas ligand and IL2. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GeneCards Summary for RORC Gene

RORC (RAR Related Orphan Receptor C) is a Protein Coding gene. Diseases associated with RORC include immunodeficiency 42 and red color blindness. Among its related pathways are Gene Expression and Innate Lymphoid Cell Differentiation Pathways. GO annotations related to this gene include transcription factor activity, sequence-specific DNA binding and steroid hormone receptor activity. An important paralog of this gene is NR1D2.

UniProtKB/Swiss-Prot for RORC Gene

  • 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 cellular differentiation, immunity, peripheral circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism (PubMed:19381306, PubMed:19965867, PubMed:22789990, PubMed:26160376, PubMed:20203100). 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, ARNTL/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 ARNTL/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 also a role in the regulation of hepatocyte glucose metabolism through the regulation of G6PC and PCK1 (PubMed:19965867). Regulates the rhythmic expression of PROX1 and promotes its nuclear localization (PubMed:19381306, PubMed:19965867, PubMed:22789990, PubMed:26160376, PubMed:20203100). Plays an indispensable role in the induction of IFN-gamma dependent anti-mycobacterial systemic immunity (PubMed:26160376).

  • Isoform 2: Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes and Peyers patches. Required for the generation of LTi (lymphoid tissue inducer) cells. Regulates thymocyte survival through DNA-binding on ROREs of target gene promoter regions and recruitment of coactivaros via the AF-2. 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. 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. 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.

Tocris Summary for RORC Gene

  • Retinoic acid-related Orphan Receptors (RORs) are a family of orphan nuclear receptors that are believed to play a role in numerous physiological processes, including circadian rhythm and bone metabolism. The endogenous ligand for these receptors is not yet known.

Gene Wiki entry for RORC Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for RORC Gene

Genomics for RORC Gene

Regulatory Elements for RORC Gene

Promoters for RORC Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around RORC on UCSC Golden Path with GeneCards custom track

Transcription factor binding sites by QIAGEN in the RORC gene promoter:

Genomic Location for RORC Gene

Chromosome:
1
Start:
151,806,071 bp from pter
End:
151,832,238 bp from pter
Size:
26,168 bases
Orientation:
Minus strand

Genomic View for RORC Gene

Genes around RORC on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RORC Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RORC Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RORC Gene

Proteins for RORC Gene

  • Protein details for RORC Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P51449-RORG_HUMAN
    Recommended name:
    Nuclear receptor ROR-gamma
    Protein Accession:
    P51449
    Secondary Accessions:
    • Q5SZR9
    • Q8N5V7
    • Q8NCY8

    Protein attributes for RORC Gene

    Size:
    518 amino acids
    Molecular mass:
    58195 Da
    Quaternary structure:
    • Interacts (via AF-2 motif) with the coactivator NCOA2 (via LXXLL motif). Interacts with the corepressor NCOR1. Interacts with CRY1. 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.
    SequenceCaution:
    • Sequence=AAA64751.1; Type=Frameshift; Positions=516; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for RORC Gene

    Alternative splice isoforms for RORC Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RORC Gene

Proteomics data for RORC Gene at MOPED

Post-translational modifications for RORC Gene

  • Ubiquitination at Lys 279
  • Modification sites at PhosphoSitePlus

Other Protein References for RORC Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • R&D Systems Antibodies for RORC (ROR gamma t/RORC2/NR1F3)
  • R&D Systems Antibodies for RORC (ROR gamma/RORC/NR1F3)

No data available for DME Specific Peptides for RORC Gene

Domains & Families for RORC Gene

Gene Families for RORC Gene

Graphical View of Domain Structure for InterPro Entry

P51449

UniProtKB/Swiss-Prot:

RORG_HUMAN :
  • The AF-2 (activation function-2) motif is required for recruiting coregulators containing LXXLL motifs such as NCOA1 and NCOA2.
  • Belongs to the nuclear hormone receptor family. NR1 subfamily.
Domain:
  • The AF-2 (activation function-2) motif is required for recruiting coregulators containing LXXLL motifs such as NCOA1 and NCOA2.
  • Contains 1 nuclear receptor DNA-binding domain.
Family:
  • Belongs to the nuclear hormone receptor family. NR1 subfamily.
genes like me logo Genes that share domains with RORC: view

Function for RORC Gene

Molecular function for RORC Gene

GENATLAS Biochemistry:
RAR related orphan receptor,ligand activated transcription factor,highly expressed in skeletal muscle,steroid/thyroid retinoic receptor superfamily
UniProtKB/Swiss-Prot Function:
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 cellular differentiation, immunity, peripheral circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism (PubMed:19381306, PubMed:19965867, PubMed:22789990, PubMed:26160376, PubMed:20203100). 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, ARNTL/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 ARNTL/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 also a role in the regulation of hepatocyte glucose metabolism through the regulation of G6PC and PCK1 (PubMed:19965867). Regulates the rhythmic expression of PROX1 and promotes its nuclear localization (PubMed:19381306, PubMed:19965867, PubMed:22789990, PubMed:26160376, PubMed:20203100). Plays an indispensable role in the induction of IFN-gamma dependent anti-mycobacterial systemic immunity (PubMed:26160376).
UniProtKB/Swiss-Prot Function:
Isoform 2: Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes and Peyers patches. Required for the generation of LTi (lymphoid tissue inducer) cells. Regulates thymocyte survival through DNA-binding on ROREs of target gene promoter regions and recruitment of coactivaros via the AF-2. 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. 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. 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.
UniProtKB/Swiss-Prot Induction:
Up-regulated in the state of obesity.

Gene Ontology (GO) - Molecular Function for RORC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003707 steroid hormone receptor activity IEA --
GO:0008142 oxysterol binding IDA 19965867
GO:0043565 sequence-specific DNA binding ISS --
genes like me logo Genes that share ontologies with RORC: view
genes like me logo Genes that share phenotypes with RORC: view

Animal Models for RORC Gene

MGI Knock Outs for RORC:

Animal Model Products

miRNA for RORC Gene

Targeted motifs for RORC Gene
HOMER Transcription Factor Regulatory Elements motif RORC
  • Consensus sequence: AAYTAGGTCA Submotif: canonical Cell Type: EL4 GEO ID: GSE56019

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology and Transcription Factor Targets for RORC Gene

Localization for RORC Gene

Subcellular locations from UniProtKB/Swiss-Prot for RORC Gene

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for RORC Gene COMPARTMENTS Subcellular localization image for RORC gene
Compartment Confidence
nucleus 5
cytosol 2
extracellular 1

No data available for Gene Ontology (GO) - Cellular Components for RORC Gene

Pathways & Interactions for RORC Gene

genes like me logo Genes that share pathways with RORC: view

Gene Ontology (GO) - Biological Process for RORC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006805 xenobiotic metabolic process ISS --
GO:0010467 gene expression TAS --
GO:0030522 intracellular receptor signaling pathway TAS 7811290
GO:0036315 cellular response to sterol IDA 19965867
genes like me logo Genes that share ontologies with RORC: view

No data available for SIGNOR curated interactions for RORC Gene

Drugs & Compounds for RORC Gene

(3) Drugs for RORC Gene - From: IUPHAR and DGIdb

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Tretinoin Approved, Investigational Nutra Full agonist, Agonist, binder 210
25-Hydroxycholesterol Pharma Agonist 0
ALRT 1550 Pharma Antagonist 0

(4) Additional Compounds for RORC Gene - From: Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
retinoic acid
302-79-4
SR 1001
1335106-03-0
SR 1078
1246525-60-9
SR 2211
1359164-11-6
genes like me logo Genes that share compounds with RORC: view

Transcripts for RORC Gene

Unigene Clusters for RORC Gene

RAR-related orphan receptor C:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for RORC Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5a · 5b ^ 6a · 6b ^ 7a · 7b ^ 8a · 8b ^ 9a · 9b ^ 10 ^ 11 ^ 12a · 12b
SP1: - - - - - -
SP2: - - - -
SP3: -
SP4:
SP5: -
SP6:

Relevant External Links for RORC Gene

GeneLoc Exon Structure for
RORC
ECgene alternative splicing isoforms for
RORC

Expression for RORC Gene

mRNA expression in normal human tissues for RORC Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for RORC Gene

This gene is overexpressed in Muscle - Skeletal (x12.1), Liver (x6.7), and Pancreas (x5.9).

SOURCE GeneReport for Unigene cluster for RORC Gene Hs.256022

mRNA Expression by UniProt/SwissProt for RORC Gene

P51449-RORG_HUMAN
Tissue specificity: Isoform 1 is widely expressed in many tissues, including liver and adipose, and highly expressed in skeletal muscle. Isoform 2 is primarily expressed in immature thymocytes.
genes like me logo Genes that share expression patterns with RORC: view

In Situ Assay Products

No data available for Protein differential expression in normal tissues , Protein expression and Protein tissue co-expression partners for RORC Gene

Orthologs for RORC Gene

This gene was present in the common ancestor of animals.

Orthologs for RORC Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia RORC 36
  • 88 (a)
OneToOne
RORC 35
  • 99.55 (n)
  • 99.23 (a)
cow
(Bos Taurus)
Mammalia RORC 35
  • 90.38 (n)
  • 89.72 (a)
RORC 36
  • 90 (a)
OneToOne
dog
(Canis familiaris)
Mammalia RORC 36
  • 86 (a)
OneToOne
RORC 35
  • 88.35 (n)
  • 85.52 (a)
mouse
(Mus musculus)
Mammalia Rorc 16
Rorc 35
  • 87.21 (n)
  • 89.15 (a)
Rorc 36
  • 89 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia RORC 36
  • 82 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia RORC 36
  • 56 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia LOC102556141 35
  • 87.52 (n)
  • 88.71 (a)
chicken
(Gallus gallus)
Aves RORC 36
  • 55 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia RORC 36
  • 56 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii RORC 36
  • 46 (a)
OneToOne
LOC100004847 35
  • 55.65 (n)
  • 51.2 (a)
fruit fly
(Drosophila melanogaster)
Insecta Hr46 36
  • 18 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea nhr-23 36
  • 24 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 25 (a)
OneToMany
Species with no ortholog for RORC:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for RORC Gene

ENSEMBL:
Gene Tree for RORC (if available)
TreeFam:
Gene Tree for RORC (if available)

Paralogs for RORC Gene

Paralogs for RORC Gene

genes like me logo Genes that share paralogs with RORC: view

Variants for RORC Gene

Sequence variations from dbSNP and Humsavar for RORC Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type
VAR_073725 -
rs939594 -- 151,811,121(+) CCAAT(C/T)CCAGG intron-variant
rs939595 -- 151,811,212(+) CAGAG(A/C)GTGGT intron-variant
rs949969 -- 151,820,338(-) TCTCC(C/T)AGGGG intron-variant
rs1521177 -- 151,809,654(-) AAGCA(A/C)ATCCG intron-variant

Structural Variations from Database of Genomic Variants (DGV) for RORC Gene

Variant ID Type Subtype PubMed ID
nsv516369 CNV Gain 19592680
nsv160848 CNV Loss 16902084

Variation tolerance for RORC Gene

Residual Variation Intolerance Score: 36.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.59; 65.28% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for RORC Gene

HapMap Linkage Disequilibrium report
RORC
Human Gene Mutation Database (HGMD)
RORC

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RORC Gene

Disorders for RORC Gene

MalaCards: The human disease database

(4) MalaCards diseases for RORC Gene - From: OMIM, ClinVar, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
immunodeficiency 42
  • imd42
red color blindness
  • protan defect
anus cancer
  • anal cancer
behcet's disease
  • adamantiades-behcet disease
- elite association - COSMIC cancer census association via MalaCards
Search RORC in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

RORG_HUMAN
  • Note=Biallelic RORC mutations are a cause of immunodeficiency resulting in concomitant candidiasis and mycobacteriosis. Candidiasis is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida. 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. {ECO:0000269 PubMed:26160376}.

Relevant External Links for RORC

Genetic Association Database (GAD)
RORC
Human Genome Epidemiology (HuGE) Navigator
RORC
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
RORC
genes like me logo Genes that share disorders with RORC: view

No data available for Genatlas for RORC Gene

Publications for RORC Gene

  1. ROR gamma: the third member of ROR/RZR orphan receptor subfamily that is highly expressed in skeletal muscle. (PMID: 7811290) Hirose T. … Jetten A.M. (Biochem. Biophys. Res. Commun. 1994) 2 3 4 67
  2. Molecular screening and association studies of retinoid-related orphan receptor gamma (RORC): a positional and functional candidate for type 2 diabetes. (PMID: 12855222) Wang H. … Elbein S.C. (Mol. Genet. Metab. 2003) 3 23
  3. Genomic structure and chromosomal mapping of the nuclear orphan receptor ROR gamma (RORC) gene. (PMID: 9403063) Medvedev A. … Jetten A.M. (Genomics 1997) 3 23
  4. Demethylation of the RORC2 and IL17A in human CD4+ T lymphocytes defines Th17 origin of nonclassic Th1 cells. (PMID: 25740946) Mazzoni A. … Annunziato F. (J. Immunol. 2015) 3
  5. IL-17 Producing Cells and RORI^t mRNA Transcriptional Factor in Cirrhotic and HCC Egyptian Patients. (PMID: 26415373) El Bassuoni M.A. … Al Gazar A. (Egypt J Immunol 2015) 3

Products for RORC Gene

Sources for RORC Gene

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