NFATC1 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the NFATC1 gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | NFATC1 |
|---|---|
| Full Name | Nuclear factor of activated T cells 1 |
| Gene Type | protein coding |
| Chromosomal Location | 18q23 |
| NCBI Gene ID | 4772 ncbi.nlm.nih.gov/gene/4772 |
| Ensembl ID | ENSG00000131196 |
| UniProt ID | O95644 |
| OMIM ID | 600489 |
| HGNC ID | 7775 |
| Aliases | NFAT2, NF-ATc, NFATc1, NFAT transcription complex |
Description
The NFATC1 gene encodes a transcription factor belonging to the nuclear factor of activated T cells (NFAT) family. It plays a critical role in immune response, particularly in T cell activation, by translocating to the nucleus upon dephosphorylation by calcineurin. NFATC1 also regulates gene expression in various other cell types, including osteoclasts, cardiac myocytes, and endothelial cells. Its activity is essential for development and differentiation processes, and dysregulation is implicated in several diseases, including cancers and autoimmune disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| B-cell acute lymphoblastic leukemia (B-ALL) | NFATC1 is constitutively active in B-ALL cells, promoting survival and proliferation through target gene upregulation. | COSMIC; PMID: 28202488 |
| Diffuse large B-cell lymphoma (DLBCL) | NFATC1 overexpression and nuclear localization contribute to oncogenic signaling in DLBCL. | COSMIC; PMID: 23263627 |
| Rheumatoid arthritis | NFATC1 is a master regulator of osteoclast differentiation, and its upregulation in synovial tissue promotes bone erosion. | OMIM; PMID: 15143267 |
| Cardiac valve defects | NFATC1 is required for embryonic cardiac valve formation; mutations or altered expression lead to valve malformations. | OMIM; PMID: 15601660 |
| Severe combined immunodeficiency (SCID) (rare) | Loss-of-function mutations in NFATC1 impair T cell activation and immune response. | ClinVar; PMID: 27418646 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.4 | Medium |
| Spleen | 11.8 | Medium |
| Bone marrow | 9.2 | Low |
| Thymus | 8.5 | Low |
| Heart | 6.1 | Low |
| Lung | 4.3 | Low |
| Kidney | 3.2 | Low |
| Liver | 1.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.3 | High expression; NFATC1 is constitutively active in this cell line. |
| HeLa (cervical cancer) | 8.7 | Moderate expression; NFATC1 may contribute to proliferation. |
| MCF7 (breast cancer) | 6.4 | Low expression; role in estrogen signaling. |
| A549 (lung cancer) | 5.2 | Low expression; NFATC1 may be induced by inflammatory stimuli. |
| HepG2 (liver cancer) | 2.1 | Very low expression; not a major regulator in hepatocytes. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1003C>T (p.Arg335Ter) | Nonsense | Rare (0.01%) | Truncated protein lacking DNA-binding domain; loss of function. |
| c.1246G>A (p.Gly416Ser) | Missense | 0.05% (COSMIC) | Altered DNA-binding affinity; potential gain-of-function in cancer. |
| c.1570C>T (p.Pro524Ser) | Missense | 0.02% (ClinVar) | Unknown significance; may affect nuclear localization. |
| c.1780_1781insA (p.Thr594AsnfsTer12) | Frameshift | Rare | Loss of function; associated with SCID. |
Mutation functional classification
Loss of Function (LOF)
Mutations that truncate the protein or disrupt the DNA-binding domain lead to loss of transcriptional activity, impairing immune responses and causing immunodeficiency.
Gain of Function (GOF)
Missense mutations that enhance DNA-binding or nuclear localization can increase NFATC1 activity, promoting oncogenic gene expression in cancers.
Dominant Negative (DN)
Some mutations may produce a truncated protein that interferes with wild-type NFATC1 function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • protein binding | • calcium-dependent protein binding |
| • nucleus | • cytoplasm |
| • regulation of transcription by RNA polymerase II | • calcineurin-mediated signaling |
| • T cell activation | • osteoclast differentiation |
Pathways
• Calcineurin/NFAT signaling pathway
• T cell receptor signaling pathway
• Osteoclast differentiation pathway
• Cardiac valve development pathway
• IL-4 signaling pathway
Protein Summary
The NFATC1 protein is a 716-amino acid transcription factor with a conserved Rel homology domain (RHD) that mediates DNA binding and dimerization. It contains a regulatory domain with multiple serine residues that are phosphorylated in the cytoplasm. Upon calcium signaling, calcineurin dephosphorylates these residues, causing NFATC1 to translocate to the nucleus and activate target genes. NFATC1 can form homo- or heterodimers with other NFAT family members or with AP-1 (Fos/Jun) to regulate gene expression. It is essential for T cell anergy, osteoclast differentiation, and cardiac valve morphogenesis. Alternative splicing generates multiple isoforms with distinct functions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NFATC1 Knockout HEK293 Cell Line | EDJ-KQ208 | Human | 4772 | Details Get a Quote |
| NFATC1 Knockout A-549 Cell Line | EDJ-KQ19321 | Human | 4772 | Details Get a Quote |
| NFATC1 Knockout HCT 116 Cell Line | EDJ-KQ19323 | Human | 4772 | Details Get a Quote |
| NFATC1 Knockout HeLa Cell Line | EDJ-KQ19324 | Human | 4772 | Details Get a Quote |
| NFATC1 Overexpression HEK293 Stable Cell Line | EDC01720 | Human | 4772 | Details Get a Quote |
| OPN4 and NFATC1 Overexpression HEK293 Stable Cell Line | EDC90142 | Human | 94233 & 4772 | Details Get a Quote |
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