RORC Gene

The RORC gene (RFORC stands for "RAR Related Orphan Receptor C") is a protein coding gene located on chromosome 1q21. Two transcript variants encoding different isoforms have been found for this gene.

The RORC protein encoded by the RORC gene is a DNA-binding transcription factor, belongs to the NR1 subfamily of nuclear hormone receptors, and is the major transcription factor responsible for the differentiation of T helper 17 cells.

Furthermore, the RORC gene plays a role in lymphoid organogenesis, thymopoiesis, and lymph node organogenesis (Michelini S et al. 2021). In addition, the RORC protein is thought to inhibit the expression of Fas ligand as well as IL-2. Signaling pathways utilized include cytokine signaling in the immune system and cytokine production by Th17 cells in cystic fibrosis.

Diseases associated with RORC include:

Autosomal recessive immunodeficiency 42 (IMD42; see also Mendelian susceptibility to mycobacterial diseases), a rare immunodeficiency syndrome caused by a mutation in the RORC gene.

and

secondary progressive multiple sclerosis.

Mutations in RORC may predispose to lymphedema (Michelini S et al.2021).

1. Ivanov II et al (2006) The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126:1121-1133
2. Kurebayashi S et al (2000) Retinoid-related orphan receptor gamma (ROR-gamma) is essential for lymphoid organogenesis and controls apoptosis during thymopoiesis. Proc Nat Acad Sc. 97: 10132-10137.
3. Leija-Martínez JJ et al. (2020) Decreased methylation profiles in the TNFA gene promoters in type 1 macrophages and in the IL17A and RORC gene promoters in Th17 lymphocytes have a causal association with non-atopic asthma caused by obesity: A hypothesis" Med. Hypotheses 2020 144:110181.
4. Michelini S et al (2021) Possible Role of the RORC Gene in Primary and Secondary Lymphedema: Review of the Literature and Genetic Study of Two Rare Causative Variants. Lymphat Res Biol 19:129-133.
5. Okada S et al (2015) Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations. Science 349: 606-613.