NFATC1

nuclear factor of activated T cells 1, the group of Nuclear factors of activated T-cells |IPT domain containing

Basic information

Region (hg38): 18:79395856-79529325

Links

ENSG00000131196 ∙ NCBI:4772 ∙ OMIM:600489 ∙ HGNC:7775 ∙ Uniprot:O95644 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital heart disease (Disputed Evidence), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NFATC1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NFATC1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				38	20	58
missense			99	21	9	129
nonsense			2			2
start loss					1	1
frameshift						0
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region				4		4
non coding			3	12	3	18
Total	0	0	106	71	33

Variants in NFATC1

This is a list of pathogenic ClinVar variants found in the NFATC1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
18-79396207-C-CCCG		NFATC1-related disorder	Benign (Jun 07, 2019)
18-79396261-C-G		not specified	Uncertain significance (Dec 13, 2022)
18-79396275-G-A			Likely benign (Feb 04, 2023)
18-79396313-C-T			Uncertain significance (Jan 23, 2023)
18-79396326-C-T			Likely benign (Jan 01, 2023)
18-79396328-G-A			Benign (Dec 31, 2019)
18-79396328-GC-AT			Uncertain significance (Jan 29, 2024)
18-79396329-C-T		NFATC1-related disorder	Benign (Dec 31, 2019)
18-79396334-T-C		not specified	Uncertain significance (Apr 14, 2022)
18-79396364-C-T			Likely benign (Oct 24, 2023)
18-79396370-C-G			Likely benign (Aug 10, 2022)
18-79400385-A-ACCCGC		NFATC1-related disorder	Benign (Mar 01, 2019)
18-79400399-G-A		not specified	Uncertain significance (Feb 17, 2022)
18-79400407-G-A		not specified	Uncertain significance (Mar 14, 2023)
18-79400428-T-A		not specified	Uncertain significance (May 21, 2024)
18-79400446-CAGCGCGACG-C		NFATC1-related disorder	Uncertain significance (Jan 30, 2024)
18-79410388-T-G			Likely benign (Jun 06, 2023)
18-79410391-T-A			Likely benign (May 07, 2022)
18-79410424-C-T		not specified	Uncertain significance (Sep 27, 2021)
18-79410428-C-A			Uncertain significance (Mar 04, 2023)
18-79410428-C-T		NFATC1-related disorder	Benign (Jan 06, 2024)
18-79410437-C-T			Likely benign (Oct 13, 2023)
18-79410438-G-T		not specified	Uncertain significance (Jul 21, 2021)
18-79410446-G-A			Likely benign (Sep 29, 2021)
18-79410454-C-T		not specified	Uncertain significance (Nov 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NFATC1	protein_coding	protein_coding	ENST00000329101	10	133470

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.157	0.843	125723	0	24	125747	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.735	590	642	0.918	0.0000462	5928
Missense in Polyphen		177	240.06	0.73732		2188
Synonymous	-1.45	353	320	1.10	0.0000268	2003
Loss of Function	3.96	8	32.3	0.248	0.00000163	356

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000592	0.0000592
Ashkenazi Jewish	0.0000995	0.0000992
East Asian	0.0000572	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000158	0.000141
Middle Eastern	0.0000572	0.0000544
South Asian	0.0000665	0.0000653
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2 or IL-4 gene transcription. Also controls gene expression in embryonic cardiac cells. Could regulate not only the activation and proliferation but also the differentiation and programmed death of T-lymphocytes as well as lymphoid and non-lymphoid cells (PubMed:10358178). Required for osteoclastogenesis and regulates many genes important for osteoclast differentiation and function (By similarity). {ECO:0000250|UniProtKB:O88942, ECO:0000269|PubMed:10358178}.
• Pathway: Oxytocin signaling pathway - Homo sapiens (human);T cell receptor signaling pathway - Homo sapiens (human);B cell receptor signaling pathway - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Inflammatory bowel disease (IBD) - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Tacrolimus/Cyclosporine Pathway, Pharmacodynamics;Heart Development;RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;Ectoderm Differentiation;Initiation of transcription and translation elongation at the HIV-1 LTR;MAPK Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;Wnt Signaling Pathway;T-Cell antigen Receptor (TCR) Signaling Pathway;Signaling by WNT;Signal Transduction;gata3 participate in activating the th2 cytokine genes expression;role of mef2d in t-cell apoptosis;effects of calcineurin in keratinocyte differentiation;nfat and hypertrophy of the heart ;signaling pathway from g-protein families;t cell receptor signaling pathway;bcr signaling pathway;Calcineurin activates NFAT;Signaling by the B Cell Receptor (BCR);CLEC7A (Dectin-1) induces NFAT activation;CLEC7A (Dectin-1) signaling;C-type lectin receptors (CLRs);FCERI mediated Ca+2 mobilization;Fc epsilon receptor (FCERI) signaling;TCR;Innate Immune System;Immune System;Adaptive Immune System;Downstream signaling events of B Cell Receptor (BCR);Glucocorticoid receptor regulatory network;Ca2+ pathway;Beta-catenin independent WNT signaling;fmlp induced chemokine gene expression in hmc-1 cells;BCR signaling pathway;RANKL;Downstream signaling in naïve CD8+ T cells;Calcineurin-regulated NFAT-dependent transcription in lymphocytes;AP-1 transcription factor network;Role of Calcineurin-dependent NFAT signaling in lymphocytes;Validated transcriptional targets of AP1 family members Fra1 and Fra2;Calcium signaling in the CD4+ TCR pathway (Consensus)

Recessive Scores

• pRec: 0.659

Intolerance Scores

• loftool: 0.322
• rvis_EVS: -1.85
• rvis_percentile_EVS: 2.05

Haploinsufficiency Scores

• pHI: 0.267
• hipred: Y
• hipred_score: 0.825
• ghis: 0.553

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.768

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Nfatc1
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; craniofacial phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); embryo phenotype; respiratory system phenotype; liver/biliary system phenotype; immune system phenotype; skeleton phenotype; limbs/digits/tail phenotype; digestive/alimentary phenotype

Gene ontology

• Biological process: cytokine production;transcription by RNA polymerase II;Wnt signaling pathway, calcium modulating pathway;negative regulation of Wnt signaling pathway;calcineurin-NFAT signaling cascade;intracellular signal transduction;Fc-epsilon receptor signaling pathway;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;negative regulation of vascular smooth muscle cell differentiation
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;transcription factor complex;cytoplasm;cytosol;nuclear body;nuclear transcription factor complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II transcription factor binding;RNA polymerase II transcription coactivator binding;DNA-binding transcription activator activity, RNA polymerase II-specific;chromatin binding;DNA-binding transcription factor activity;protein binding;FK506 binding;transcription factor binding;mitogen-activated protein kinase p38 binding