NFATC4 Gene: Nuclear Factor of Activated T Cells 4
Key regulator of immune response, cardiac development, and cancer signaling
Gene Information Card
| Symbol | NFATC4 |
|---|---|
| Full Name | Nuclear Factor of Activated T Cells 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q11.2 |
| NCBI Gene ID | 4776 ncbi.nlm.nih.gov/gene/4776 |
| Ensembl ID | ENSG00000100968 |
| UniProt ID | Q14934 |
| OMIM ID | 602698 |
| HGNC ID | 7777 |
| Aliases | NFAT3 |
Description
NFATC4 (Nuclear Factor of Activated T Cells 4) encodes a member of the nuclear factor of activated T cells (NFAT) family of transcription factors. The protein plays a critical role in inducible gene transcription during immune response, cardiac development, and cellular differentiation. It is activated by calcium-dependent calcineurin signaling and translocates to the nucleus to regulate target genes. NFATC4 is implicated in cardiac hypertrophy, cancer progression, and inflammatory disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cardiac Hypertrophy | NFATC4 is activated by calcineurin; sustained nuclear localization promotes hypertrophic gene expression in cardiomyocytes. | PMID: 11782478; OMIM 602698 |
| Breast Cancer | NFATC4 overexpression correlates with poor prognosis; promotes cell migration and invasion via transcriptional activation of target genes. | PMID: 25636800; COSMIC |
| Colorectal Cancer | NFATC4 amplification and increased expression linked to tumor progression and metastasis. | PMID: 27562872; COSMIC |
| Inflammatory Bowel Disease | NFATC4 variants associated with altered immune regulation and chronic inflammation. | ClinVar; PMID: 23128233 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Skeletal Muscle | 8.3 | Low |
| Brain | 6.1 | Low |
| Lung | 4.7 | Low |
| Kidney | 3.9 | Low |
| Liver | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression in embryonic kidney cells |
| HeLa | 9.8 | Moderate expression in cervical cancer cells |
| MCF7 | 7.4 | Moderate expression in breast cancer cells |
| Jurkat | 5.1 | Low expression in T-cell leukemia line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1003C>T (p.Arg335Trp) | Missense | 0.01% | Altered DNA-binding affinity; potential loss of function |
| c.1456G>A (p.Glu486Lys) | Missense | 0.005% | Unknown functional impact; reported in ClinVar |
| c.1789_1791del (p.Lys597del) | In-frame deletion | 0.002% | May affect nuclear localization signal |
Mutation functional classification
Loss of Function (LOF)
Rare missense variants (e.g., p.Arg335Trp) reduce transcriptional activity and DNA binding.
Gain of Function (GOF)
Amplification or overexpression in cancers leads to constitutive activation of target genes.
Dominant Negative (DN)
Truncating mutations that lack transactivation domain may interfere with wild-type NFATC4 function.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity (GO:0000981) | • nucleus (GO:0005634) |
| • cytoplasm (GO:0005737) | • transcription factor binding (GO:0008134) |
| • positive regulation of transcription by RNA polymerase II (GO:0045944) | • signal transduction (GO:0007165) |
| • cellular response to chemical stimulus (GO:0070887) |
Pathways
• Calcineurin-NFAT signaling pathway (Reactome: R-HSA-2871837)
• Cardiac hypertrophy (KEGG: hsa05410)
• T cell receptor signaling pathway (KEGG: hsa04660)
• VEGF signaling pathway (KEGG: hsa04370)
Protein Summary
NFATC4 is a 902-amino acid transcription factor with a conserved Rel homology domain (RHD) for DNA binding and a calcineurin-binding domain. It is predominantly cytoplasmic in resting cells; upon calcium signaling, calcineurin dephosphorylates NFATC4, exposing a nuclear localization signal. In the nucleus, it binds to NFAT response elements in promoters of genes involved in cell cycle, differentiation, and immune function. Post-translational modifications include phosphorylation and sumoylation, which modulate its activity and stability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NFATC4 Knockout HEK293 Cell Line | EDJ-KQ316 | Human | 4776 | Details Get a Quote |
| NFATC4 Knockout HCT 116 Cell Line | EDJ-KQ18460 | Human | 4776 | Details Get a Quote |
| NFATC4 Knockout HeLa Cell Line | EDJ-KQ18461 | Human | 4776 | Details Get a Quote |
| NFATC4 Knockout A-549 Cell Line | EDJ-KQ62479 | Human | 4776 | Details Get a Quote |
