NFATC1 Gene

HGNC Family	Nuclear factors of activated T-cells (NFAT)
Name	nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
Description	The product of this gene is a component of the nuclear factor of activated T cells DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor (TCR) stimulation, and an inducible nuclear component. Proteins belonging to this family of transcription factors play a central role in inducible gene transcription during immune response. The product of this gene is an inducible nuclear component. It functions as a major molecular target for the immunosuppressive drugs such as cyclosporin A. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. Different isoforms of this protein may regulate inducible expression of different cytokine genes. [provided by RefSeq, Jul 2013]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNFATc1 serves as a master regulator in bone homeostasis by orchestrating osteoclast differentiation and function. In response to RANKL stimulation, NFATc1 cooperates with factors such as PU.1, MITF, and microphthalmia transcription factor to stimulate expression of key osteoclast‐specific genes—including cathepsin K, β3 integrin, and OSCAR—and to promote cell fusion during osteoclast formation. Its activity and stability are finely tuned by post‐translational modifications such as acetylation via p300/PCAF, phosphorylation by kinases like DYRK1A, and regulation by negative modulators such as JMJD5, with immunosuppressive agents (e.g. tacrolimus) also exerting inhibitory effects. These regulatory events help ensure that osteoclast differentiation proceeds in a timely and controlled fashion, though aberrations in NFATc1 regulation can alter bone resorption processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn oncogenic contexts, NFATc1 contributes to tumor progression by modulating critical growth‐promoting genes. In pancreatic carcinomas, for instance, ectopic NFATc1 upregulates c‑myc transcription to enhance cell proliferation and malignant potential. Similarly, in colon cancer cells, NFATc1 supports COX‑2 expression, while in prostate cancer and diffuse large B‑cell lymphoma its transcriptional activity aids in driving tumorigenic gene programs. Collectively, these studies highlight NFATc1’s role as an oncogenic transcription factor whose deregulation can confer a growth advantage."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nNFATc1 also plays pivotal roles within the immune and vascular systems. In T lymphocytes, it is induced upon antigen receptor stimulation and sustains its own expression through positive autoregulation to help determine cell fate. In endothelial cells, NFATc1 activation by VEGF or thrombin leads to robust nuclear translocation, which in turn drives the transcription of genes such as ICAM‑1, CXCR7, and RND1; these events are essential for endothelial proliferation, cardiac valve maintenance, and lymphatic patterning. Moreover, its nuclear localization and transcriptional potency are further modulated by upstream kinases (for example, via PKA phosphorylation) and by reversible post‑translational modifications."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nUpstream signaling events further diversify NFATc1 function. Activation via Ca²⁺/calcineurin driven by receptors such as P2X7 and polycystin‑1 links extracellular cues to NFATc1 nuclear translocation and subsequent transcriptional responses that promote cell survival and proliferation. In addition, particular NFATc1 isoforms undergo modifications like sumoylation that convert the factor from an activator into a context‑dependent repressor, thereby adding an extra layer of control over its downstream genetic programs."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "22", "end_ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Masahito Matsumoto, Masakazu Kogawa, Seiki Wada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Essential role of p38 mitogen-activated protein kinase in cathepsin K gene expression during osteoclastogenesis through association of NFATc1 and PU.1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M408795200"}], "href": "https://doi.org/10.1074/jbc.M408795200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15304486"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15304486"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kabsun Kim, Jung Ha Kim, Junwon Lee, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "PU.1 and NFATc1 mediate osteoclastic induction of the mouse beta3 integrin promoter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.21344"}], "href": "https://doi.org/10.1002/jcp.21344"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18288635"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18288635"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Youngkyun Lee, Jeongim Ha, Hyung Joon Kim, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Expression of the P2X7 receptor increases the Ca2+ content of the endoplasmic reticulum, activates NFATc1, and protects from apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M805805200"}], "href": "https://doi.org/10.1074/jbc.M805805200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19204004"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19204004"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Arnab Nayak, Judith Glöckner-Pagel, Martin Vaeth, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sumoylation of the transcription factor NFATc1 leads to its subnuclear relocalization and interleukin-2 repression by histone deacetylase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M900465200"}], "href": "https://doi.org/10.1074/jbc.M900465200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19218564"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19218564"}]}]}]}
Synonyms	NF-ATC, NFATC, NF-ATC1.2, NFAT2
Proteins	NFAC1_HUMAN
NCBI Gene ID	4772
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

NFATC1 has 9,542 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 136 datasets.

Click the + buttons to view associations for NFATC1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

NFATC1 Gene

Functional Associations

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	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of NFATC1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of NFATC1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of NFATC1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of NFATC1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of NFATC1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of NFATC1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving NFATC1 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of NFATC1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of NFATC1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of NFATC1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of NFATC1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of NFATC1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of NFATC1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with NFATC1 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with NFATC1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with NFATC1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of NFATC1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of NFATC1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of NFATC1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing NFATC1 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of NFATC1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing NFATC1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing NFATC1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with NFATC1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with NFATC1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of NFATC1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with NFATC1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with NFATC1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with NFATC1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with NFATC1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of NFATC1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by NFATC1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with NFATC1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with NFATC1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with NFATC1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with NFATC1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with NFATC1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for NFATC1 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at NFATC1 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of NFATC1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.