Alt. symbols: TONEBP | KIAA0827 | NFATL1 | OREBP | NFATZ | NF-AT5

Approved name: nuclear factor of activated T cells 5
Alt. names: nuclear factor of activated T-cells 5, tonicity-responsive, nuclear factor of activated T-cells 5 | tonicity-responsive enhancer binding protein

Location: 16q22.1: 69565094 - 69704666 (+)
Gene type: protein_coding, 17 transcripts.

Scores: LoFtool: 0.439000 | pLI: 0.99999094 | LOEUF: 0.205

HGNC: 7774

NCBI: 10725, RefSeq: NG_029600.1

Ensembl: ENSG00000102908.23

LRG_1332 | Status: public

OMIM: 604708

Expression | ProteinAtlas

The nuclear factor of activated T-cells 5 (NFAT5), was originally identified as a key transcription factor involved in the regulation of genes involved in osmotic stress to maintain cellular homeostasis against hypertonic and hyperosmotic environments. However, there is evidence that NFAT5 plays a role in the development and activation of immune cells, especially T cells and macrophages. In these immune cells NFAT5 induces the expression of different target genes and signalling pathways in both tonicity-dependent and -independent manners: i) In response to hyperosmotic stress, NFAT5 induces the generation of pathogenic TH17 cells and pro-inflammatory macrophages, contributing to autoimmune and inflammatory diseases. ii) NFAT5 can also be activated in tonicity-independent stimuli (Toll-like receptor activation and inflammatory cytokines) and promote immune cell survival, proliferation, migration, and angiogenesis (Lee, N. et al. 2019).

Haploinsufficiency of NFAT5 has been reported to be associated with autoimmune enterocolopathy (AIE) (Boland 2015 J Immunol, PMID:25667416). Boland and colleagues described the case of a male patient with immunodeficiency and AIE, who started to present IBD-like symptoms at the age of 7 years. He was discovered to carry a de-novo heterozygous 559-kb deletion at 16q22.1 that included NFAT5 and 7 additional genes. The patient showed a 6-fold reduction in NFAT5 protein expression and 5-fold reducti on in mRNA levels. Subsequently, the authors identified 3 patients with AIE that also presented loss of NFAT5 heterozygosity. Finally, testing NFAT5 mRNA expression in rectal biopsies from IBD patients (7 with UC and 6 with CD), they observed that all of them had half the expression of the 7 controls tested. Moreover, NFAT5 has been implicated in the pathogenesis of rheumatoid arthritis, as its knockdown seems to reduce synovial proliferation and angiogenesis in chronic arthritis human cells and mice models (Yoon H. et al. 2011). [Load More]