Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
Symbol NFATC1 contributors: mct/pgu - updated : 04-08-2018
HGNC name nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
HGNC id 7775
Type widely
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly
Endocrineparathyroid   highly
Lymphoid/Immunelymph node   highly
 spleen   highly
 thymus   highly
Reproductivemale systemprostate   
Skin/Tegumentskin appendageshair   
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Epithelialbarrier liningendocardium  
SystemCellPubmedSpeciesStageRna symbol
Cardiovascularendothelial cell
Lymphoid/ImmuneT cell Homo sapiens
Skin/Tegumenthair follicle cell
cell lineage
cell lines
physiological period embryo
  • calcineurin binding motif (targeting motif, PxIxIT) near at the N-terminus of the regulatory domain
  • a nuclear localization signal (NLS)
  • a serine-rich region
  • three SP motifs
  • a second calcineurin binding domain
  • a central Rel-like DNA-binding domain
  • a C-terminal transactivation domain
  • conjugated PhosphoP
    interspecies homolog to murine Nfatc1 (86.9 pc)
    intraspecies homolog to NFKB/REL proteins
  • REL/DORSAL family
  • CATEGORY immunity/defense , regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies
  • translocated to nucleus after activation controlled by calcineurin-mediated dephosphorylation
  • cytoplasmic phosphorylated form
  • cytosolic in cerebellar granules in the presence of growth factors and KCl
  • basic FUNCTION
  • acting as a putative regulator of gene expression in T cells and immature thymocytes and positive regulator of IL-2 and IL-4 gene transcription
  • playing a critical role in the initiation of epithelial- mesenchymal transformation
  • may be having a major role in fiber type specification in skeletal muscle
  • playing a crucial role for the differentiation of bone-resorbing osteoclasts
  • regulating the beta3 integrin promoter
  • different isoforms of this protein may regulate inducible expression of different cytokine genes
  • controlling gene expression in embryonic cardiac cells
  • may regulate differentiation and programmed death of T-lymphocytes as well as lymphoid and non-lymphoid cells
  • transcription factor required for development of cardiac valves
  • activating the expression of endogenous RCAN1 in the endocardium
  • being required for TGF beta-mediated transcriptional regulation of fibronectin
  • regulating bulge stem cell quiescence, and repressing the expression of CDK4 in hair follicle stem cells
  • required for endocardial expression of TNFSF11 and CTSK during valve formation
  • playing a necessary role for remodeling endocardial cushions into mature heart valve leaflets and being also an essential effector of receptor activator of NFkappaB ligand (RANKL) signaling required for transcriptional activation of bone matrix remodeling enzymes during osteoclast differentiation
  • regulating CTSK promoter activity, after its activation by TNFSF11 via the Ca2+/calmodulin/calcineurin pathway
  • specific determinant of slow muscle gene expression
  • function cooperatively with MITF and MEF2A to transactivate the ATP6V0D2 promoter during RANKL-induced osteoclastogenesis
  • functions as the key regulator of osteoclast differentiation by inducing fusogenic genes such as TM7SF4
  • NFATC1 and NFATC2 are expressed in T cells at various stages of development and states of activation and have been implicated in several essential regulatory mechanisms that exhibit a cell type specificity
  • key transcription factor, playing a role in regulating expression of osteoclast-specific downstream target genes such as ACP5 and OSCAR
  • is an important regulator of cytotoxic T lymphocyte effector functions
  • controls the cytotoxicity and metabolic switching of activated CD8+ T cells required for optimal response to bacteria and tumor cells
  • NFATC1 plays an important role in controlling plasmablast/plasma cell formation
  • transcription factor activated by T-cell receptor (TCR) and Ca2+ signaling that affects T-cell activation and effector function
  • is indispensable in the immune system and the morphogenesis of cardiac valves and septa and is also vital in osteoclasts and atherosclerotic calcification
  • CELLULAR PROCESS nucleotide, transcription, regulation
  • intracellular signaling cascade
  • EDF1/CALM1/PPP3CA/NFATC1 pathway
  • a component
  • component of nuclear factor activated T cells
  • forming cooperative complexes with FOS and JUN on DNA, in expression of cytokine genes collectively coordinating immune response
  • binding to promoters of cytokine genes
  • binding as a monomer
  • RNA
    small molecule
  • cytosolic calcium binds to calmodulin and subsequently activates calcineurin, leading to NFATC1 activation, a master transcription factor required for osteoclast differentiation
  • protein
  • interacting with SOX9 in the differentiation of endocardial cushion cells
  • interacting with SP7 to control osteoblastic bone formation
  • direct transcriptional target of RCAN1 within the endocardium during a critical window of heart valve formation
  • interacting with ATP6V0D2 (NFATC1/ATP6V0D2 and dendritic cell-specific transmembrane protein signaling axis plays a key role in the osteoclast multinucleation process, which is essential for efficient bone resorption)
  • OSCAR is an important costimulatory receptor for osteoclast differentiation through activation of NFATC1
  • demethylation of H3K27me3 in the NFATC1 gene locus by KDM6B plays a critical role in TNFSF11-induced osteoclast differentiation
  • GPC6 is a novel NFATC1, NFATC2, NFATC3, NFATC4 target gene in breast cancer cells that promotes invasive migration through WNT5A signalling
  • both FOXP3 and SIVA1 function as negative regulators of IL2 gene expression in Treg cells, via suppression of NFATC1 by FOXP3 and of NFKB1 by both FOXP3 and SIVA1
  • IL2 upregulates CD86 expression on human CD4(+) and CD8(+) T cells via a receptor-dependent mechanism that involves the NFATC1 and mammalian target of rapamycin pathways
  • AKT2 a negative regulator of NFATC1 activation through its ability to inhibit calcium mobilization from the ER
  • KDM8 is a post-translational co-repressor for NFATC1 that attenuates osteoclastogenesis
  • synthesis of FN1 is mediated by a transcriptional complex consisting of NFATC1, SP7 and FOS
  • upon TNFSF11 activation, HDAC7 suppresses NFATC1 and prevents CTNNB1 down-regulation, thereby blocking osteoclast differentiation
  • SERPINA12 likely downregulates osteoclastogenesis in part by inhibiting expression of the transcription factor NFATC1
  • mediates RHOA-induced FN1 upregulation in glomerular podocytes
  • FAM102A plays a critical role in TNFRSF11A-induced osteoclast differentiation, and its role may be closely related to the induction of NFATC1
  • autocrine/paracrine role for RARRES2 in regulating osteoclast differentiation of hematopoietic stem cell (HSC) through modulating intracellular calcium and NFATC1 expression/activation
  • NFATC1 sequestering the SMAD3 prevents the proteasome mediated degradation of SKIL and SKIL has a role on the regulation of MMP2, MMP9 activity
  • ASIC1-mediated calcium entry plays a critical role in osteoclastogenesis by regulating activation of the NFATC1
  • ETS1 promotes the expression of IL2 by modulating the activity of NFATC1
  • NFATC1-mediated transcription regulates UTRN expression and FHL1 which promotes muscle hypertrophy, is a transcriptional activator of NFATC1
  • GRK5-mediated pathological cardiac hypertrophy involves the activation of NFATC1 because GRK5 causes enhancement of NFATC1-mediated hypertrophic gene transcription
  • BSG plays a critical role in the differentiation and function of osteoclasts by upregulating NFATC1 through the autoamplification of its expression in osteoclastogenesis
  • TNFSF11-induced LDHA, LDHB activation stimulates glycolytic and mitochondrial respiratory metabolism, facilitating mature osteoclast formation via osteoclast precursor fusion and NFATC1 signaling
  • IKBKE promotes NFATC1 phosphorylation and inhibits T cell responses, identifying IKBKE as a crucial negative regulator of T cell activation
  • DYRK1A is a positive kinase in regulation of NFATC1
  • biphasic roles of MTOR in osteoclastogenesis, dosage-dependent effects of rapamycin on bone, and a calcineurin-MTOR-NFATC1 phosphorylation-regulatory signaling cascade
  • STAT3 could drive the transcription of NFATC1 by binding to its promoter
  • DYRK1A activates NFATC1 to increase glioblastoma migration
  • GAP43 attenuated podocyte injury by inhibiting calcineurin/NFATC1 signaling
  • likely ESR1 interacts with NFATC1 to repress WNT5B protein expression
  • activation of NFATC1 represses osteoblastogenesis by activating WNT5B expression
  • cell & other
    activated by calcineurin
    both Ca2+ oscillation/calcineurin-dependent and independent signal pathways and the Ca2+ oscillation-independent pathway depends completely on osteoblasts and is not activated during RANKL/M-CSF-induced osteoclastogenesis
    induced by insulin and activation of ATP6V0D2 and NFATC1 is involved in regulation of osteoclast differentiation and fusion through ERK1/2
    inhibited by cyclosporin A,FK506
    CDK1, a novel NFAT protein kinase that inhibits NFATC1 activation by direct phosphorylation of the NFATC1 S263 residue
    Other calcineurin dependent
    corresponding disease(s)
    Variant & Polymorphism other
  • SNP rs2887571 is a binding site for ESR1 and NFATC1 and they regulate the expression of WNT5B
  • Candidate gene potential VSD-susceptibility gene
    Therapy target
    FHL1-NFATC1-UTRN signaling axis that can functionally compensate for dystrophin and treat DMD
    targeting NFATC1 SUMOylation presents a novel and promising strategy to treat T cell-mediated inflammatory diseases
    critical participant in antitumor immune responses in patients with NSCLC
  • mice with NFATc1-deficient T cells are defective in controlling Listeria infection