Details for: RARG

Gene ID: 5916

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: RARG

Ensembl ID: ENSG00000172819

Description: retinoic acid receptor gamma

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • chondrocyte CL0000138
    CSI 5.08
    rCSI 8.07%
    PRS 93.11
  • mucosal invariant T cell CL0000940
    CSI 4.98
    rCSI 4.03%
    PRS 98.04
  • mesodermal cell CL0000222
    CSI 4.97
    rCSI 5.96%
    PRS 95.84
  • melanocyte CL0000148
    CSI 4.46
    rCSI 3.3%
    PRS 93.86
  • secretory cell CL0000151
    CSI 4.08
    rCSI 4.26%
    PRS 95.22
  • epithelial cell of lower respiratory tract CL0002632
    CSI 4
    rCSI 3.1%
    PRS 97.21
  • club cell CL0000158
    CSI 3.82
    rCSI 5.6%
    PRS 93.53
  • group 3 innate lymphoid cell CL0001071
    CSI 3.61
    rCSI 2.72%
    PRS 97.33
  • skin fibroblast CL0002620
    CSI 3.38
    rCSI 2.91%
    PRS 95.7
  • respiratory suprabasal cell CL4033048
    CSI 3.23
    rCSI 4.15%
    PRS 96.71
  • nasal mucosa goblet cell CL0002480
    CSI 3.04
    rCSI 3.53%
    PRS 95.37
  • keratinocyte CL0000312
    CSI 2.99
    rCSI 2.51%
    PRS 95.44
  • conjunctival epithelial cell CL1000432
    CSI 2.67
    rCSI 4.08%
    PRS 95.01
  • duct epithelial cell CL0000068
    CSI 2.52
    rCSI 3.69%
    PRS 97.56
  • squamous epithelial cell CL0000076
    CSI 1.99
    rCSI 4.73%
    PRS 92.46
  • keratocyte CL0002363
    CSI 1.95
    rCSI 4.68%
    PRS 96.28
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.94
    rCSI 4.34%
    PRS 88.93
  • mesenchymal cell CL0008019
    CSI 1.41
    rCSI 3.58%
    PRS 93.62

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [RARG](/details-gene/5916) (Retinoic Acid Receptor Gamma) is a protein-coding gene located on chromosome 12 that encodes a nuclear hormone receptor. As a ligand-dependent transcription factor, [RARG](/details-gene/5916) plays a crucial role in the [retinoic acid receptor signaling pathway](/details-ontology/GO:0048384), translating signals from retinoic acid (a vitamin A metabolite) into changes in gene expression. Its function is fundamental to a wide array of biological processes, including embryonic development, [cell differentiation](/details-ontology/GO:0030154), and the regulation of cell proliferation ([Link](https://doi.org/10.1073/pnas.86.14.5310)). **Overall**, expression data reveals its high significance in cell types critical for structural and barrier tissues, such as [chondrocytes](/details-cell/CL0000138) involved in cartilage formation, as well as various epithelial and immune cells lining mucosal surfaces. Clinical associations for this gene are cataloged under OMIM entry [180190](https://omim.org/entry/180190). ## Cellular Roles and Expression Landscape The expression profile of [RARG](/details-gene/5916) highlights its integral role in the development and maintenance of skeletal, dermal, and mucosal tissues. **Overall**, its most significant expression is observed in [chondrocytes](/details-cell/CL0000138) (CSI: 5.08), which is consistent with its established function in cartilage development and chondrocyte differentiation. A prominent theme in its expression landscape is its importance in barrier tissues and specialized secretory cells. High significance is noted in multiple skin-related cell types, including [melanocytes](/details-cell/CL0000148) (CSI: 4.46), [skin fibroblasts](/details-cell/CL0002620) (CSI: 3.38), and [keratinocytes](/details-cell/CL0000312) (CSI: 2.99). Furthermore, [RARG](/details-gene/5916) is highly significant in various epithelial cells of the respiratory tract, such as [epithelial cell of lower respiratory tract](/details-cell/CL0002632) (CSI: 4.00), [club cells](/details-cell/CL0000158) (CSI: 3.82), and [nasal mucosa goblet cells](/details-cell/CL0002480) (CSI: 3.04). This pattern suggests a central role in maintaining epithelial integrity and function in response to environmental cues. Beyond structural cells, [RARG](/details-gene/5916) is also a significant marker in specific immune cell populations associated with mucosal sites, including [mucosal invariant T cells](/details-cell/CL0000940) (CSI: 4.98) and [group 3 innate lymphoid cells](/details-cell/CL0001071) (CSI: 3.61). This co-expression in both epithelial and resident immune cells points towards a coordinated role for [RARG](/details-gene/5916) in orchestrating mucosal immunity and tissue homeostasis. ## Pathways and Molecular Function Functionally, [RARG](/details-gene/5916) acts as a [nuclear receptor](/details-ontology/GO:0004879) and a [DNA-binding transcription factor](/details-ontology/GO:0003700) that heterodimerizes with retinoid X receptors (RXRs) to regulate target gene transcription ([Link](https://doi.org/10.1210/mend-4-6-837)). Its molecular activities are centered on binding to specific DNA sequences known as retinoic acid response elements (RAREs) within the regulatory regions of genes. This activity is central to its involvement in the [Signaling by retinoic acid](/details-pathway/R-HSA-5362517) pathway. The biological processes governed by [RARG](/details-gene/5916) are extensive, with a strong emphasis on developmental biology ([R-HSA-1266738](https://reactome.org/content/detail/R-HSA-1266738)). Gene Ontology annotations underscore its role in processes such as [anterior/posterior pattern specification](/details-ontology/GO:0009952), [embryonic eye morphogenesis](/details-ontology/GO:0048048), and limb development ([GO:0035116](https://www.ebi.ac.uk/QuickGO/term/GO:0035116)). Its high significance in [chondrocytes](/details-cell/CL0000138) is directly supported by its annotated roles in [trachea cartilage development](/details-ontology/GO:0060534) and the [negative regulation of chondrocyte differentiation](/details-ontology/GO:0032331). Additionally, its functions extend to regulating cell fate decisions, including both [positive regulation of cell population proliferation](/details-ontology/GO:0008284) and the induction of the [apoptotic process](/details-ontology/GO:0006915), highlighting its role as a critical regulator of cellular homeostasis. ## Research Directions The widespread yet specific expression of [RARG](/details-gene/5916) in cells governing structural integrity and mucosal immunity presents several avenues for future research. **Proposed Hypotheses:** 1. Given its high significance in [chondrocytes](/details-cell/CL0000138) and its known role in regulating their differentiation, it is hypothesized that **aberrant [RARG](/details-gene/5916) signaling, potentially due to altered ligand availability or downstream effector mutations, is a contributing factor to the pathogenesis of osteoarthritis by disrupting the homeostatic balance of cartilage matrix synthesis and degradation.** 2. The co-expression of [RARG](/details-gene/5916) in both respiratory epithelial cells and mucosal immune cells like [MAIT cells](/details-cell/CL0000940) and [ILC3s](/details-cell/CL0001071) suggests a coordinating function. Therefore, it is hypothesized that **[RARG](/details-gene/5916) acts as a master regulator of airway mucosal defense, integrating signals from dietary vitamin A to simultaneously bolster epithelial barrier function and prime resident lymphoid cells for rapid response to pathogens.** **Experimental Approach:** To test the second hypothesis regarding the role of [RARG](/details-gene/5916) in airway mucosal defense, a series of experiments using conditional knockout mouse models could be employed. Specifically, a mouse model with a floxed [RARG](/details-gene/5916) allele could be crossed with mice expressing Cre recombinase under the control of an epithelial-specific promoter (e.g., CC10-Cre for club cells) or an ILC3-specific promoter (e.g., Rorc-Cre). Following insult with a respiratory virus (e.g., Influenza A), these conditional knockout mice could be compared to wild-type controls. Key readouts would include measuring epithelial barrier permeability, quantifying viral load, analyzing immune cell infiltration into the bronchoalveolar lavage fluid via flow cytometry, and profiling cytokine and chemokine expression in lung tissue using RNA-sequencing and multiplex protein assays. This approach would elucidate the cell-specific contribution of [RARG](/details-gene/5916) to the integrated mucosal immune response. **Therapeutic Potential:** As a ligand-activated nuclear receptor, [RARG](/details-gene/5916) is an inherently "druggable" target. Its activity can be modulated by small molecule agonists and antagonists, many of which are derivatives of retinoic acid. This presents therapeutic opportunities for a range of diseases. For conditions characterized by impaired epithelial barrier function, such as chronic obstructive pulmonary disease (COPD) or inflammatory bowel disease, selective [RARG](/details-gene/5916) agonists could be developed to promote tissue repair and enhance mucosal resilience. Conversely, in specific cancers where retinoic acid signaling pathways are dysregulated, targeted antagonists could represent a viable therapeutic strategy. Activation would be the preferred approach for degenerative or inflammatory diseases, while inhibition would be relevant for certain malignancies, requiring careful characterization of its context-dependent roles.

Genular Protein ID: 3527835060

Symbol: RARG_HUMAN

Name: Retinoic acid receptor gamma

UniProtKB Accession Codes:

P13631 B7Z492 B7Z4F1 B7ZAE4 J3KNP6 P22932 Q15281 Q52LZ8 Q9BYX8 Q9H1I3 Q9UJ38

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 4 CDD 2 CTD 1 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 17 DrugCentral 1 EMBL 16 Ensembl 4 EvolutionaryTrace 1 ExpressionAtlas 1 GO 48 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 8 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 11 PDBsum 11 PIR 2 PRINTS 3 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 Reactome 3 RefSeq 4 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 2546152

Title: A third human retinoic acid receptor, hRAR-gamma.

PubMed ID: 2546152

DOI: 10.1073/pnas.86.14.5310

PubMed ID: 2172793

Title: A functional retinoic acid receptor encoded by the gene on human chromosome 12.

PubMed ID: 2172793

DOI: 10.1210/mend-4-6-837

PubMed ID: 1849262

Title: Genomic organization of the retinoic acid receptor gamma gene.

PubMed ID: 1849262

DOI: 10.1093/nar/19.3.573

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16541075

Title: The finished DNA sequence of human chromosome 12.

PubMed ID: 16541075

DOI: 10.1038/nature04569

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 2157210

Title: Murine isoforms of retinoic acid receptor gamma with specific patterns of expression.

PubMed ID: 2157210

DOI: 10.1073/pnas.87.7.2700

PubMed ID: 1320193

Title: RAR-gamma-2 expression is regulated through a retinoic acid response element embedded in Sp1 sites.

PubMed ID: 1320193

DOI: 10.1128/mcb.12.7.2976-2985.1992

PubMed ID: 28112733

Title: Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.

PubMed ID: 28112733

DOI: 10.1038/nsmb.3366

PubMed ID: 7501014

Title: Crystal structure of the RAR-gamma ligand-binding domain bound to all-trans retinoic acid.

PubMed ID: 7501014

DOI: 10.1038/378681a0

PubMed ID: 9501913

Title: Conformational adaptation of agonists to the human nuclear receptor RAR gamma.

PubMed ID: 9501913

DOI: 10.1038/nsb0398-199

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

PubMed ID: 28167758

Title: MicroRNA-10a is crucial for endothelial response to different flow patterns via interaction of retinoid acid receptors and histone deacetylases.

PubMed ID: 28167758

DOI: 10.1073/pnas.1621425114

Sequence Information:

  • Length: 454
  • Mass: 50342
  • Checksum: 1EE27B22772D4AFD
  • Sequence:
    • MATNKERLFA AGALGPGSGY PGAGFPFAFP GALRGSPPFE MLSPSFRGLG QPDLPKEMAS 
LSVETQSTSS EEMVPSSPSP PPPPRVYKPC FVCNDKSSGY HYGVSSCEGC KGFFRRSIQK 
NMVYTCHRDK NCIINKVTRN RCQYCRLQKC FEVGMSKEAV RNDRNKKKKE VKEEGSPDSY 
ELSPQLEELI TKVSKAHQET FPSLCQLGKY TTNSSADHRV QLDLGLWDKF SELATKCIIK 
IVEFAKRLPG FTGLSIADQI TLLKAACLDI LMLRICTRYT PEQDTMTFSD GLTLNRTQMH 
NAGFGPLTDL VFAFAGQLLP LEMDDTETGL LSAICLICGD RMDLEEPEKV DKLQEPLLEA 
LRLYARRRRP SQPYMFPRML MKITDLRGIS TKGAERAITL KMEIPGPMPP LIREMLENPE 
MFEDDSSQPG PHPNASSEDE VPGGQGKGGL KSPA

Genular Protein ID: 978391113

Symbol: B7Z4B4_HUMAN

Name: N/A

UniProtKB Accession Codes:

B7Z4B4

Database IDs:

ARBA 8 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 8 Gene3D 2 InterPro 7 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 2 PROSITE 4 PeptideAtlas 1 Pfam 2 RefSeq 1 SAM 1 SMART 2 SUPFAM 1

Sequence Information:

  • Length: 333
  • Mass: 37539
  • Checksum: 5974D8CE3C55D05F
  • Sequence:
    • MVYTCHRDKN CIINKVTRNR CQYCRLQKCF EVGMSKEAVR NDRNKKKKEV KEEGSPDSYE 
LSPQLEELIT KVSKAHQETF PSLCQLGKYT TNSSADHRVQ LDLGLWDKFS ELATKCIIKI 
VEFAKRLPGF TGLSIADQIT LLKAACLDIL MLRICTRYTP EQDTMTFSDG LTLNRTQMRN 
AGFGPLTDLV FAFAGQLLPL EMDDTETGLL SAICLICGDR MDLEEPEKVD KLQEPLLEAL 
RLYARRRRPS QPYMFPRMLM KITDLRGIST KGAERAITLK MEIPGPMPPL IREMLENPEM 
FEDDSSQPGP HPNASSEDEV PGGQGKGGLK SPA

Genular Protein ID: 180951686

Symbol: F1D8P1_HUMAN

Name: N/A

UniProtKB Accession Codes:

F1D8P1

Database IDs:

ARBA 9 AlphaFoldDB 1 Antibodypedia 1 BioGRID-ORCS 1 CDD 2 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 ExpressionAtlas 1 GO 8 Gene3D 2 InterPro 8 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 3 PROSITE 5 Pfam 2 RefSeq 1 RuleBase 1 SAM 1 SMART 2 SMR 1 SUPFAM 2 VEuPathDB 1

Sequence Information:

  • Length: 443
  • Mass: 49308
  • Checksum: 4D709194F5111E86
  • Sequence:
    • MYDCMETFAP GPRRLYGAAG PGAGLLRRAT GGSCFAGLES FAWPQPASLQ SVETQSTSSE 
EMVPSSPSPP PPPRVYKPCF VCNDKSSGYH YGVSSCEGCK GFFRRSIQKN MVYTCHRDKN 
CIINKVTRNR CQYCRLQKCF EVGMSKEAVR NDRNKKKKEV KEEGSPDSYE LSPQLEELIT 
KVSKAHQETF PSLCQLGKYT TNSSADHRVQ LDLGLWDKFS ELATKCIIKI VEFAKRLPGF 
TGLSIADQIT LLKAACLDIL MLRICTRYTP EQDTMTFSDG LTLNRTQMHN AGFGPLTDLV 
FAFAGQLLPL EMDDTETGLL SAICLICGDR MDLEEPEKVD KLQEPLLEAL RLYARRRRPS 
QPYMFPRMLM KITDLRGIST KGAERAITLK MEIPGPMPPL IREMLENPEM FEDDSSQPGP 
HPNASSEDEV PGGQGKGGLK SPA