The product of this gene is a member of the nuclear factors 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. Other members of this family participate to form this complex also. The ... See more...

Aliases for NFATC3 Gene

Aliases for NFATC3 Gene

  • Nuclear Factor Of Activated T Cells 3 2 3 5
  • Nuclear Factor Of Activated T-Cells, Cytoplasmic, Calcineurin-Dependent 3 2 3
  • Nuclear Factor Of Activated T-Cells, Cytoplasmic 3 3 4
  • NF-AT4c 3 4
  • NF-ATc3 3 4
  • NFAT4 3 4
  • Nuclear Factor Of Activated T-Cells C3 Isoform IE-Xa 3
  • Nuclear Factor Of Activated T-Cells 3 2
  • T Cell Transcription Factor NFAT4 3
  • T-Cell Transcription Factor NFAT4 4
  • NF-AT4 4
  • NFATc3 4
  • NFATX 3
  • NFATx 4

External Ids for NFATC3 Gene

Previous GeneCards Identifiers for NFATC3 Gene

  • GC16P058814
  • GC16P068497
  • GC16P067854
  • GC16P067895
  • GC16P066676
  • GC16P053992

Summaries for NFATC3 Gene

Entrez Gene Summary for NFATC3 Gene

  • The product of this gene is a member of the nuclear factors 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. Other members of this family participate to form this complex also. The product of this gene plays a role in the regulation of gene expression in T cells and immature thymocytes. Several transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Nov 2010]

GeneCards Summary for NFATC3 Gene

NFATC3 (Nuclear Factor Of Activated T Cells 3) is a Protein Coding gene. Diseases associated with NFATC3 include Crouzon Syndrome With Acanthosis Nigricans and Leukostasis. Among its related pathways are Oxytocin signaling pathway and Human cytomegalovirus infection. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and RNA polymerase II proximal promoter sequence-specific DNA binding. An important paralog of this gene is NFATC4.

UniProtKB/Swiss-Prot Summary for NFATC3 Gene

  • Acts as a regulator of transcriptional activation. Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2 (PubMed:18815128). Along with NFATC4, involved in embryonic heart development (By similarity).

Tocris Summary for NFATC3 Gene

  • NFAT (Nuclear Factor of Activated T-Cells) proteins are transcription factors that are integral for the development and function of the immune system. Five NFAT isoforms have been identified to date, NFATC1-C4 and NFAT5.

Gene Wiki entry for NFATC3 Gene

Additional gene information for NFATC3 Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NFATC3 Gene

Genomics for NFATC3 Gene

GeneHancer (GH) Regulatory Elements for NFATC3 Gene

Promoters and enhancers for NFATC3 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NFATC3 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NFATC3

Top Transcription factor binding sites by QIAGEN in the NFATC3 gene promoter:
  • AREB6
  • ATF-2
  • E47
  • GR
  • GR-alpha
  • Hand1
  • RORalpha1

Genomic Locations for NFATC3 Gene

Genomic Locations for NFATC3 Gene
chr16:68,084,751-68,229,259
(GRCh38/hg38)
Size:
144,509 bases
Orientation:
Plus strand
chr16:68,118,654-68,263,162
(GRCh37/hg19)
Size:
144,509 bases
Orientation:
Plus strand

Genomic View for NFATC3 Gene

Genes around NFATC3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NFATC3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NFATC3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NFATC3 Gene

Proteins for NFATC3 Gene

  • Protein details for NFATC3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q12968-NFAC3_HUMAN
    Recommended name:
    Nuclear factor of activated T-cells, cytoplasmic 3
    Protein Accession:
    Q12968
    Secondary Accessions:
    • O75211
    • Q14516
    • Q99840
    • Q99841
    • Q99842

    Protein attributes for NFATC3 Gene

    Size:
    1075 amino acids
    Molecular mass:
    115594 Da
    Quaternary structure:
    • Member of the multicomponent NFATC transcription complex that consists of at least two components, a pre-existing cytoplasmic component NFATC2 and an inducible nuclear component NFATC1. Other members such as NFATC4, or members of the activating protein-1 family, MAF, GATA4 and Cbp/p300 can also bind the complex. NFATC proteins bind to DNA as monomers.

    Three dimensional structures from OCA and Proteopedia for NFATC3 Gene

    Alternative splice isoforms for NFATC3 Gene

neXtProt entry for NFATC3 Gene

Post-translational modifications for NFATC3 Gene

  • Phosphorylated by NFATC-kinase; dephosphorylated by calcineurin.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Antibody Products

No data available for DME Specific Peptides for NFATC3 Gene

Domains & Families for NFATC3 Gene

Gene Families for NFATC3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for NFATC3 Gene

Blocks:
  • Cell surface receptor IPT/TIG
  • Nuclear factor of activated T cells (NFAT) signature
  • Rel homology
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for NFATC3 Gene

GenScript: Design optimal peptide antigens:
  • Nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3, isoform CRA_a (B5B2S0_HUMAN)
  • Nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3, isoform CRA_b (B5B2S1_HUMAN)
  • Nuclear factor of activated T-cells c3 isoform IB-IX (B5B2S2_HUMAN)
  • Nuclear factor of activated T-cells c3 isoform IF-deltaXa (B5B2S4_HUMAN)
  • Nuclear factor of activated T-cells c3 isoform IF-IX (B5B2S5_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q12968

UniProtKB/Swiss-Prot:

NFAC3_HUMAN :
  • Rel Similarity Domain (RSD) allows DNA-binding and cooperative interactions with AP1 factors.
Domain:
  • Rel Similarity Domain (RSD) allows DNA-binding and cooperative interactions with AP1 factors.
genes like me logo Genes that share domains with NFATC3: view

Function for NFATC3 Gene

Molecular function for NFATC3 Gene

UniProtKB/Swiss-Prot Function:
Acts as a regulator of transcriptional activation. Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2 (PubMed:18815128). Along with NFATC4, involved in embryonic heart development (By similarity).

Phenotypes From GWAS Catalog for NFATC3 Gene

Gene Ontology (GO) - Molecular Function for NFATC3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IDA 15173172
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific NAS 19274049
GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific IGI 23543060
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific IMP 15173172
GO:0003677 DNA binding IEA --
genes like me logo Genes that share ontologies with NFATC3: view
genes like me logo Genes that share phenotypes with NFATC3: view

Animal Models for NFATC3 Gene

MGI Knock Outs for NFATC3:

Animal Model Products

CRISPR Products

Transcription Factor Targets for NFATC3 Gene

Selected GeneGlobe predicted Target genes for NFATC3

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology and HOMER Transcription for NFATC3 Gene

Localization for NFATC3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NFATC3 Gene

Cytoplasm. Nucleus. Note=Cytoplasmic for the phosphorylated form and nuclear after activation that is controlled by calcineurin-mediated dephosphorylation. Rapid nuclear exit of NFATC is thought to be one mechanism by which cells distinguish between sustained and transient calcium signals. The subcellular localization of NFATC plays a key role in the regulation of gene transcription.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NFATC3 gene
Compartment Confidence
nucleus 5
cytosol 5
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 2
peroxisome 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for NFATC3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin ISA --
GO:0005634 nucleus IBA,IDA 12370307
GO:0005654 nucleoplasm IDA,TAS --
GO:0005667 transcription factor complex IBA 21873635
GO:0005737 cytoplasm IDA,IEA 18815128
genes like me logo Genes that share ontologies with NFATC3: view

Pathways & Interactions for NFATC3 Gene

PathCards logo

SuperPathways for NFATC3 Gene

SuperPathway Contained pathways
1 Activation of cAMP-Dependent PKA
.77
.77
.71
.56
2 TCR Signaling (Qiagen)
.68
.68
.54
.49
3 Human cytomegalovirus infection
4 RANK Signaling in Osteoclasts
.92
.92
.45
5 IL-2 Pathway
.48
.43
.35
genes like me logo Genes that share pathways with NFATC3: view

Pathways by source for NFATC3 Gene

5 GeneGo (Thomson Reuters) pathways for NFATC3 Gene
  • Immune response CD28 signaling
  • Immune response NFAT in immune response
  • Immune response T cell receptor signaling pathway
  • Signal transduction Activation of PKC via G-Protein coupled receptor
  • Signal transduction_JNK pathway
29 Qiagen pathways for NFATC3 Gene
  • Activation of cAMP-Dependent PKA
  • Activation of PKA through GPCR
  • APRIL Pathway
  • BAFF in B-Cell Signaling
  • cAMP Pathway
1 Cell Signaling Technology pathway for NFATC3 Gene

SIGNOR curated interactions for NFATC3 Gene

Activates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for NFATC3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001816 cytokine production IBA 21873635
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006357 regulation of transcription by RNA polymerase II TAS 7749981
GO:0006366 transcription by RNA polymerase II TAS 7739550
GO:0006954 inflammatory response TAS 7739550
genes like me logo Genes that share ontologies with NFATC3: view

Drugs & Compounds for NFATC3 Gene

(4) Drugs for NFATC3 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Calcium Approved Nutra 7884
genes like me logo Genes that share compounds with NFATC3: view

Transcripts for NFATC3 Gene

mRNA/cDNA for NFATC3 Gene

4 REFSEQ mRNAs :
33 NCBI additional mRNA sequence :
22 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for NFATC3 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5a · 5b · 5c · 5d ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15
SP1: - - - -
SP2: - - - -
SP3: - - - - -
SP4: - - - - - - - -
SP5: - -
SP6: -
SP7:

Relevant External Links for NFATC3 Gene

GeneLoc Exon Structure for
NFATC3

Expression for NFATC3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NFATC3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for NFATC3 Gene

This gene is overexpressed in Muscle - Skeletal (x4.1).

Protein differential expression in normal tissues from HIPED for NFATC3 Gene

This gene is overexpressed in Breast (39.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for NFATC3 Gene



Protein tissue co-expression partners for NFATC3 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NFATC3

SOURCE GeneReport for Unigene cluster for NFATC3 Gene:

Hs.436585

mRNA Expression by UniProt/SwissProt for NFATC3 Gene:

Q12968-NFAC3_HUMAN
Tissue specificity: Isoform 1 is predominantly expressed in thymus and is also found in peripheral blood leukocytes and kidney. Isoform 2 is predominantly expressed in skeletal muscle and is also found in thymus, kidney, testis, spleen, prostate, ovary, small intestine, heart, placenta and pancreas. Isoform 3 is expressed in thymus and kidney. Isoform 4 is expressed in thymus and skeletal muscle.

Evidence on tissue expression from TISSUES for NFATC3 Gene

  • Muscle(4.6)
  • Blood(4.5)
  • Kidney(4.4)
  • Lung(3.2)
  • Nervous system(3.1)
  • Heart(2.6)
genes like me logo Genes that share expression patterns with NFATC3: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for NFATC3 Gene

Orthologs for NFATC3 Gene

This gene was present in the common ancestor of animals.

Orthologs for NFATC3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NFATC3 31 30
  • 99.6 (n)
OneToOne
dog
(Canis familiaris)
Mammalia NFATC3 31 30
  • 93.27 (n)
OneToOne
cow
(Bos Taurus)
Mammalia NFATC3 31 30
  • 93.2 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Nfatc3 30
  • 90.1 (n)
mouse
(Mus musculus)
Mammalia Nfatc3 17 31 30
  • 89.79 (n)
oppossum
(Monodelphis domestica)
Mammalia NFATC3 31
  • 78 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NFATC3 31
  • 68 (a)
OneToOne
chicken
(Gallus gallus)
Aves NFATC3 31 30
  • 77.04 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia NFATC3 31
  • 71 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia nfatc3 30
  • 65.34 (n)
Str.18348 30
African clawed frog
(Xenopus laevis)
Amphibia nf-at 30
zebrafish
(Danio rerio)
Actinopterygii nfatc3 30
  • 62.48 (n)
NFATC3 31
  • 59 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta NFAT 31
  • 12 (a)
OneToMany
Species where no ortholog for NFATC3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for NFATC3 Gene

ENSEMBL:
Gene Tree for NFATC3 (if available)
TreeFam:
Gene Tree for NFATC3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NFATC3: view image

Paralogs for NFATC3 Gene

Paralogs for NFATC3 Gene

(2) SIMAP similar genes for NFATC3 Gene using alignment to 13 proteins:

  • NFAC3_HUMAN
  • B5B2S0_HUMAN
  • B5B2S1_HUMAN
  • B5B2S2_HUMAN
  • B5B2S3_HUMAN
  • B5B2S4_HUMAN
  • B5B2S5_HUMAN
  • F8VPH9_HUMAN
  • H3BR83_HUMAN
  • H3BRM3_HUMAN
  • H3BRS1_HUMAN
  • H3BU30_HUMAN
  • I3L3K7_HUMAN
genes like me logo Genes that share paralogs with NFATC3: view

Variants for NFATC3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NFATC3 Gene

SNP ID Clinical significance and condition Chr 16 pos Variation AA Info Type
707956 Likely Benign: not provided 68,191,402(+) A/C MISSENSE_VARIANT
782312 Benign: not provided 68,122,699(+) G/A SYNONYMOUS_VARIANT
788366 Benign: not provided 68,122,295(+) C/T MISSENSE_VARIANT
788367 Benign: not provided 68,191,498(+) A/G SYNONYMOUS_VARIANT
rs772345934 Uncertain Significance: Keratoconus 68,181,481(+) G/A MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for NFATC3 Gene

Structural Variations from Database of Genomic Variants (DGV) for NFATC3 Gene

Variant ID Type Subtype PubMed ID
dgv2996n100 CNV loss 25217958
esv3638903 CNV loss 21293372
nsv1126432 CNV deletion 24896259
nsv1148964 CNV insertion 26484159
nsv1846 CNV insertion 18451855
nsv977989 CNV duplication 23825009

Variation tolerance for NFATC3 Gene

Residual Variation Intolerance Score: 17% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.92; 59.47% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NFATC3 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
NFATC3

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NFATC3 Gene

Disorders for NFATC3 Gene

MalaCards: The human disease database

(3) MalaCards diseases for NFATC3 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
crouzon syndrome with acanthosis nigricans
  • can
leukostasis
polyomavirus-associated nephropathy
  • polyomavirus associated nephropathy
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for NFATC3

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with NFATC3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for NFATC3 Gene

Publications for NFATC3 Gene

  1. Intramolecular masking of nuclear import signal on NF-AT4 by casein kinase I and MEKK1. (PMID: 9630228) Zhu J … McKeon F (Cell 1998) 3 4 23 54
  2. Carboxyl-terminal 15-amino acid sequence of NFATx1 is possibly created by tissue-specific splicing and is essential for transactivation activity in T cells. (PMID: 9759864) Imamura R … Arai N (Journal of immunology (Baltimore, Md. : 1950) 1998) 3 4 23 54
  3. Isolation of two new members of the NF-AT gene family and functional characterization of the NF-AT proteins. (PMID: 7749981) Hoey T … Xu X (Immunity 1995) 2 3 4 54
  4. NFATx, a novel member of the nuclear factor of activated T cells family that is expressed predominantly in the thymus. (PMID: 7739550) Masuda ES … Arai N (Molecular and cellular biology 1995) 3 4 23 54
  5. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 41 54

Products for NFATC3 Gene