NFAT5: Nuclear Factor of Activated T Cells 5
A key osmoregulatory transcription factor involved in immune response and cellular adaptation to hypertonic stress.
Gene Information Card
| Symbol | NFAT5 |
|---|---|
| Full Name | Nuclear Factor of Activated T Cells 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q22.1 |
| NCBI Gene ID | 10725 ncbi.nlm.nih.gov/gene/10725 |
| Ensembl ID | ENSG00000102974 |
| UniProt ID | O94916 |
| OMIM ID | 604708 |
| HGNC ID | 7774 |
| Aliases | TonEBP, NFATL1, OREBP, KIAA0824 |
Description
NFAT5 (Nuclear Factor of Activated T Cells 5) encodes a transcription factor that belongs to the Rel family. It is the only member of the NFAT family that is not regulated by calcium/calcineurin signaling. Instead, NFAT5 is activated by hypertonic stress and plays a critical role in cellular osmoregulation by inducing the expression of osmoprotective genes such as aldose reductase and betaine/GABA transporter. It also participates in immune cell development, T-cell activation, and inflammatory responses. NFAT5 is widely expressed and its dysregulation is implicated in autoimmune diseases, cancer, and kidney disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autoimmune diseases (e.g., rheumatoid arthritis, inflammatory bowel disease) | NFAT5 promotes pro-inflammatory cytokine expression in T cells and macrophages under hypertonic conditions, contributing to chronic inflammation. | PMID: 23454738, PMID: 25687263 |
| Renal medullary carcinoma | NFAT5 overexpression in renal medullary cells under hyperosmotic stress may drive cell proliferation and survival. | PMID: 29127259 |
| Breast cancer | NFAT5 upregulation in breast cancer cells enhances invasion and metastasis via osmotic stress adaptation. | PMID: 30266947 |
| Diabetic nephropathy | NFAT5 activation in renal cells under hyperglycemic/hyperosmotic conditions contributes to fibrosis and inflammation. | PMID: 27582087 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | High |
| Thymus | 8.3 | Medium |
| Spleen | 7.1 | Medium |
| Lung | 6.8 | Medium |
| Liver | 5.2 | Low |
| Brain | 4.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | Embryonic kidney cells; high baseline expression |
| Jurkat | 9.8 | T-cell leukemia line; induced by hypertonicity |
| HeLa | 7.5 | Cervical carcinoma; moderate expression |
| MCF7 | 6.1 | Breast cancer; upregulated under osmotic stress |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2140C>T (p.Arg714Trp) | Missense | Rare (0.01%) | Unknown functional impact; reported in ClinVar |
| c.2875G>A (p.Gly959Ser) | Missense | Rare (0.005%) | Predicted benign; no known disease association |
| c.1234_1235insA (p.Thr412Asnfs*3) | Frameshift | Very rare | Loss of function; reported in COSMIC for colorectal cancer |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations (e.g., p.Thr412Asnfs*3) lead to truncated protein and loss of DNA-binding activity.
Gain of Function (GOF)
Not well characterized; some missense variants may increase transcriptional activity under hypertonic stress.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Hypertonic stress response (TonEBP/NFAT5 pathway)
• NFAT signaling in immune response
• Osmotic stress-induced gene expression
Protein Summary
NFAT5 (TonEBP) is a 1455-amino acid transcription factor with a Rel homology domain (RHD) for DNA binding and dimerization, and a transactivation domain (TAD) at the C-terminus. It binds to tonicity-responsive enhancer (TonE) elements in target gene promoters. Under isotonic conditions, NFAT5 is predominantly cytoplasmic; hypertonic stress induces its nuclear translocation and transcriptional activity. The protein is post-translationally modified by phosphorylation and sumoylation, which modulate its stability and activity. NFAT5 is essential for cellular adaptation to high salt environments and plays roles in T-cell development, macrophage activation, and cancer cell survival.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NFAT5 Knockout HEK293 Cell Line | EDJ-KQ7142 | Human | 10725 | Details Get a Quote |
| NFAT5 Knockout A-549 Cell Line | EDJ-KQ32033 | Human | 10725 | Details Get a Quote |
| NFAT5 Knockout HCT 116 Cell Line | EDJ-KQ32034 | Human | 10725 | Details Get a Quote |
| NFAT5 Knockout HeLa Cell Line | EDJ-KQ32035 | Human | 10725 | Details Get a Quote |
