NFATC4

nuclear factor of activated T cells 4, the group of Nuclear factors of activated T-cells |IPT domain containing

Basic information

Region (hg38): 14:24365672-24379604

Links

ENSG00000100968 ∙ NCBI:4776 ∙ OMIM:602699 ∙ HGNC:7778 ∙ Uniprot:Q14934 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NFATC4 gene.

• Inborn genetic diseases (42 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NFATC4 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				1	1	2
missense			40			40
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			2			2
Total	0	0	42	1	1

Variants in NFATC4

This is a list of pathogenic ClinVar variants found in the NFATC4 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-24368413-C-G		not specified	Uncertain significance (Mar 01, 2023)
14-24368417-T-C		not specified	Uncertain significance (Feb 03, 2022)
14-24368417-T-G		not specified	Uncertain significance (Jul 06, 2021)
14-24368423-C-G		not specified	Uncertain significance (Feb 03, 2022)
14-24369532-G-A		not specified	Uncertain significance (Apr 13, 2022)
14-24369532-G-T		not specified	Uncertain significance (Jun 02, 2023)
14-24369570-C-A		not specified	Uncertain significance (Aug 01, 2022)
14-24369609-A-G		not specified	Uncertain significance (Feb 23, 2023)
14-24369642-C-T		not specified	Uncertain significance (Jul 19, 2023)
14-24369666-G-T		not specified	Uncertain significance (Jul 14, 2022)
14-24369722-C-T			Benign (Jun 14, 2018)
14-24369729-C-T		not specified	Uncertain significance (Dec 28, 2022)
14-24369732-G-C		not specified	Uncertain significance (Nov 17, 2022)
14-24369734-G-A			Likely benign (May 31, 2018)
14-24369772-C-T		not specified	Uncertain significance (Jan 26, 2023)
14-24369777-C-A		not specified	Uncertain significance (Jun 28, 2022)
14-24369816-G-T		not specified	Uncertain significance (Aug 08, 2022)
14-24369856-G-C		not specified	Uncertain significance (Dec 13, 2023)
14-24369885-G-T		not specified	Uncertain significance (Oct 03, 2023)
14-24369912-G-T		not specified	Uncertain significance (Nov 10, 2022)
14-24370113-G-A		not specified	Uncertain significance (May 31, 2023)
14-24370177-C-A		not specified	Uncertain significance (Nov 17, 2022)
14-24370177-C-T		not specified	Uncertain significance (Aug 06, 2021)
14-24370290-C-T		not specified	Uncertain significance (Dec 05, 2022)
14-24370339-C-G		not specified	Uncertain significance (Dec 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NFATC4	protein_coding	protein_coding	ENST00000413692	10	13932

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.868	0.132	125735	0	13	125748	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.44	489	587	0.832	0.0000361	6046
Missense in Polyphen		156	244.9	0.63698		2419
Synonymous	0.0969	247	249	0.992	0.0000154	2186
Loss of Function	4.36	6	33.0	0.182	0.00000184	367

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000138	0.000126
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000365	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000695	0.0000653
Other	0.000167	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 and IL- 4. Transcriptionally repressed by estrogen receptors; this inhibition is further enhanced by estrogen. Increases the transcriptional activity of PPARG and has a direct role in adipocyte differentiation. May play an important role in myotube differentiation. May play a critical role in cardiac development and hypertrophy. May play a role in deafferentation-induced apoptosis of sensory neurons. {ECO:0000269|PubMed:11997522, ECO:0000269|PubMed:17213202, ECO:0000269|PubMed:18668201, ECO:0000269|PubMed:7749981}.
• Pathway: Oxytocin signaling pathway - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Axon guidance - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Hepatitis B - 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;Physiological and Pathological Hypertrophy of the Heart;MicroRNAs in cardiomyocyte hypertrophy;Heart Development;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Initiation of transcription and translation elongation at the HIV-1 LTR;Wnt Signaling Pathway;ErbB2/ErbB3 signaling events (Consensus)

Recessive Scores

• pRec: 0.173

Intolerance Scores

• loftool: 0.484
• rvis_EVS: 0.25
• rvis_percentile_EVS: 69.66

Haploinsufficiency Scores

• pHI: 0.839
• hipred: Y
• hipred_score: 0.742
• ghis: 0.463

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.971

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nfatc4
• Phenotype: cellular phenotype; muscle phenotype; craniofacial phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; digestive/alimentary 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); 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); hematopoietic system 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); embryo phenotype

Gene ontology

• Biological process: branching involved in blood vessel morphogenesis;cytokine production;transcription by RNA polymerase II;inflammatory response;heart development;intrinsic apoptotic signaling pathway in response to DNA damage;negative regulation of Wnt signaling pathway;negative regulation of protein binding;positive regulation of tumor necrosis factor production;calcineurin-NFAT signaling cascade;cellular response to UV;negative regulation of chromatin binding;cellular respiration;positive regulation of transcription by RNA polymerase II;regulation of synaptic plasticity;negative regulation of dendrite morphogenesis;smooth muscle cell differentiation;muscle cell development;cellular response to lithium ion;negative regulation of pri-miRNA transcription by RNA polymerase II;cellular response to ionomycin;negative regulation of synapse maturation;positive regulation of apoptotic signaling pathway
• Cellular component: nucleus;transcription factor complex;cytosol;nuclear speck;nuclear transcription factor 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;chromatin binding;DNA-binding transcription factor activity;transcription coactivator activity;protein binding;transcription factor binding;peroxisome proliferator activated receptor binding