RORC Gene: Retinoic Acid Receptor-Related Orphan Receptor C
Key transcription factor in immune regulation, thymopoiesis, and metabolic processes; implicated in autoimmune and inflammatory diseases.
Gene Information Card
| Symbol | RORC |
|---|---|
| Full Name | RAR-related orphan receptor C |
| Gene Type | protein-coding |
| Chromosomal Location | 1q21.3 |
| NCBI Gene ID | 6097 ncbi.nlm.nih.gov/gene/6097 |
| Ensembl ID | ENSG00000143365 |
| UniProt ID | P51449 |
| OMIM ID | 602943 |
| HGNC ID | 10260 |
| Aliases | RORG, RZRG, RORgamma, RAR-related orphan receptor C, NR1F3 |
Description
The RORC gene encodes a nuclear receptor transcription factor, RORγ (and its isoform RORγt), which is critical for the development and function of several immune cell types, including T helper 17 (Th17) cells, regulatory T cells, and innate lymphoid cells. It also plays roles in circadian rhythm, metabolism, and thymopoiesis. RORC is a key therapeutic target for autoimmune diseases and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autoimmune diseases (e.g., multiple sclerosis, rheumatoid arthritis) | RORγt drives Th17 cell differentiation and IL-17 production, promoting inflammation | PMID: 16973390; 20581886 |
| Inflammatory bowel disease (IBD) | RORγt-mediated Th17 responses contribute to intestinal inflammation | PMID: 20581886; 24162849 |
| Psoriasis | IL-17/IL-22 axis regulated by RORγt is central to skin inflammation | PMID: 22105173 |
| Asthma | RORγt promotes Th2/Th17 responses and airway inflammation | PMID: 20581886 |
| Cancer (e.g., colorectal, breast) | RORγt can modulate tumor immunity; RORγ expression in tumor cells may affect proliferation | PMID: 28397828; 30510156 |
| Immunodeficiency (rare, autosomal recessive) | Loss-of-function mutations in RORC cause susceptibility to mycobacterial and candidal infections | PMID: 26047134 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Thymus | High | High expression in thymocytes and developing T cells |
| Lymph nodes | Moderate | Expression in T cells and innate lymphoid cells |
| Spleen | Moderate | Expression in T cells and ILC3s |
| Skin | Low | Expression in skin-resident T cells |
| Liver | Low | Expression in hepatocytes (RORγ isoform) |
| Muscle | Low | Expression in skeletal muscle (RORγ) |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Th17 cells | High | Key transcription factor for Th17 differentiation |
| Regulatory T cells (Tregs) | Moderate | RORγt expression in a subset of Tregs |
| Innate lymphoid cells (ILC3) | High | RORγt is essential for ILC3 development |
| γδ T cells | High | RORγt expression in IL-17-producing γδ T cells |
| Jurkat (T cell leukemia) | Low | Expression in T cell lines |
| HepG2 (liver cancer) | Low | Expression of RORγ isoform |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1225C>T (p.Arg409Ter) | Nonsense | Rare | Loss of function; causes immunodeficiency with candidiasis and mycobacteriosis |
| c.937C>T (p.Arg313Ter) | Nonsense | Rare | Loss of function; similar phenotype |
| c.1183G>A (p.Gly395Arg) | Missense | Rare | Loss of function; impaired DNA binding |
| c.1226G>A (p.Arg409Gln) | Missense | Rare | Loss of function; reduced transcriptional activity |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that impair DNA binding or transcriptional activation lead to loss of RORγt function, causing immunodeficiency and increased susceptibility to infections.
Gain of Function (GOF)
No clear gain-of-function mutations reported; overexpression of RORγt is associated with enhanced Th17 responses in autoimmune diseases.
Dominant Negative (DN)
Some missense mutations may act in a dominant-negative manner, but evidence is limited; most reported mutations are recessive.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • zinc ion binding | • steroid hormone receptor activity |
| • nuclear receptor activity | • transcription coregulator binding |
| • protein homodimerization activity | • sequence-specific DNA binding |
Pathways
• Th17 cell differentiation
• IL-17 signaling
• Circadian rhythm
• Nuclear receptor transcription pathway
• T cell receptor signaling
Protein Summary
RORγ is a nuclear receptor with a DNA-binding domain and a ligand-binding domain. It functions as a ligand-dependent transcription factor, though its natural ligand is debated. The isoform RORγt is a truncated variant that lacks the N-terminal domain and is specifically expressed in the immune system. RORγt regulates the expression of IL-17 and other cytokines, and is essential for the differentiation of Th17 cells and the development of lymphoid tissues. It also plays a role in metabolic regulation and circadian rhythm.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RORC Knockout HEK293 Cell Line | EDJ-KQ2549 | Human | 6097 | Details Get a Quote |
| RORC Knockout HeLa Cell Line | EDJ-KQ23196 | Human | 6097 | Details Get a Quote |
| RORC Knockout A-549 Cell Line | EDJ-KQ62830 | Human | 6097 | Details Get a Quote |
| RORC Knockout HCT 116 Cell Line | EDJ-KQ71297 | Human | 6097 | Details Get a Quote |
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