NFATC2

nuclear factor of activated T cells 2, the group of Nuclear factors of activated T-cells |IPT domain containing|MicroRNA protein coding host genes

Basic information

Region (hg38): 20:51386957-51562831

Links

ENSG00000101096 ∙ NCBI:4773 ∙ OMIM:600490 ∙ HGNC:7776 ∙ Uniprot:Q13469 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• joint contractures, osteochondromas, and B-cell lymphoma (Limited), mode of inheritance: Unknown
• congenital heart disease (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Joint contractures, osteochondromas, and B-cell lymphoma	AR	Oncologic	The condition can involve risk of hematologic malignancy, and awareness may allow early identification and management	Musculoskeletal; Oncologic	35789258

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NFATC2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NFATC2 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				5	3	8
missense			52	4	2	58
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	52	9	6

Variants in NFATC2

This is a list of pathogenic ClinVar variants found in the NFATC2 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-51391400-G-A		not specified	Uncertain significance (Aug 02, 2022)
20-51391425-A-C		Dilated cardiomyopathy 1A	Likely pathogenic (-)
20-51391439-A-G		not specified	Uncertain significance (Oct 27, 2022)
20-51391444-T-C			Likely benign (Sep 01, 2022)
20-51391469-A-AG			Benign (Dec 30, 2023)
20-51432151-G-C		not specified	Uncertain significance (Jun 11, 2021)
20-51432153-G-A		not specified	Uncertain significance (Jan 26, 2022)
20-51432158-G-A			Benign (Nov 09, 2018)
20-51432246-G-A			Likely benign (Apr 06, 2018)
20-51432252-G-A		not specified	Uncertain significance (Aug 17, 2021)
20-51432277-C-G		not specified	Uncertain significance (Aug 09, 2021)
20-51432289-A-G		not specified	Uncertain significance (Aug 08, 2023)
20-51432327-C-T		not specified	Uncertain significance (May 06, 2024)
20-51432351-T-C		not specified	Uncertain significance (Aug 02, 2022)
20-51432376-G-T		not specified	Uncertain significance (Aug 08, 2023)
20-51432415-C-T		not specified	Uncertain significance (Dec 22, 2023)
20-51432505-G-C		not specified	Uncertain significance (Aug 01, 2022)
20-51432541-C-T		not specified	Uncertain significance (May 03, 2023)
20-51432542-G-A			Benign (Dec 31, 2019)
20-51432546-G-A		not specified	Uncertain significance (Mar 20, 2024)
20-51432568-G-C		not specified	Uncertain significance (Aug 02, 2021)
20-51432571-C-T		not specified	Uncertain significance (Oct 22, 2021)
20-51432609-G-A		not specified	Uncertain significance (Mar 02, 2023)
20-51432616-T-C		not specified	Uncertain significance (Oct 10, 2023)
20-51432625-C-G		not specified	Uncertain significance (Apr 07, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NFATC2	protein_coding	protein_coding	ENST00000396009	10	175877

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000480	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.64	485	598	0.811	0.0000395	5938
Missense in Polyphen		120	215.48	0.55689		2116
Synonymous	-0.451	287	277	1.03	0.0000215	1947
Loss of Function	5.53	3	41.4	0.0725	0.00000255	393

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000454	0.0000439
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.00	0.00

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, IL-3, IL-4, TNF-alpha or GM-CSF. Promotes invasive migration through the activation of GPC6 expression and WNT5A signaling pathway. {ECO:0000269|PubMed:15790681, ECO:0000269|PubMed:21871017}.
• 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);VEGF signaling pathway - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Axon guidance - 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);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;B Cell Receptor Signaling Pathway;T-Cell Receptor and Co-stimulatory Signaling;Cardiac Hypertrophic Response;Hematopoietic Stem Cell Differentiation;Vitamin D Receptor Pathway;Initiation of transcription and translation elongation at the HIV-1 LTR;Wnt Signaling Pathway;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;VEGFA-VEGFR2 Signaling Pathway;Wnt Signaling Pathway;T-Cell antigen Receptor (TCR) Signaling Pathway;Gene expression (Transcription);Generic Transcription 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);RNA Polymerase II Transcription;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);BCR;Noncanonical Wnt signaling pathway;Wnt;RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs);Transcriptional regulation by RUNX1;Downstream signaling in naïve CD8+ T cells;Fc-epsilon receptor I signaling in mast 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: 0.429

Intolerance Scores

• loftool: 0.238
• rvis_EVS: -1.57
• rvis_percentile_EVS: 3.18

Haploinsufficiency Scores

• pHI: 0.926
• hipred: Y
• hipred_score: 0.806
• ghis: 0.512

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.672

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nfatc2
• Phenotype: respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; hematopoietic system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; cellular phenotype; immune system phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; craniofacial phenotype; muscle phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;cytokine production;regulation of transcription, DNA-templated;cellular response to DNA damage stimulus;myotube cell development;cell migration;positive regulation of B cell proliferation;calcineurin-NFAT signaling cascade;Fc-epsilon receptor signaling pathway;response to drug;regulation of regulatory T cell differentiation;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;B cell receptor signaling pathway;positive regulation of myoblast fusion;negative regulation of vascular smooth muscle cell differentiation
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;transcription factor complex;cytoplasm;cytosol;nuclear transcription factor complex;ribonucleoprotein complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;chromatin binding;DNA-binding transcription factor activity;protein binding;transcription factor binding;phosphatase binding