NFAT5

nuclear factor of activated T cells 5, the group of Nuclear factors of activated T-cells |IPT domain containing

Basic information

Region (hg38): 16:69565093-69704666

Links

ENSG00000102908 ∙ NCBI:10725 ∙ OMIM:604708 ∙ HGNC:7774 ∙ Uniprot:O94916 ∙ 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 NFAT5 gene.

• Immunodeficiency (534 variants)
• Inborn genetic diseases (41 variants)
• not provided (15 variants)
• not specified (6 variants)
• NFAT5-related condition (6 variants)
• Immunodeficiency and Autoimmune Enterocolopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NFAT5 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			4	152	12	168
missense			305	3	4	312
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel			13	3		16
splice donor/acceptor (+/-2bp)			2			2
splice region			9	10	2	21
non coding				22	19	41
Total	0	0	326	180	35

Variants in NFAT5

This is a list of pathogenic ClinVar variants found in the NFAT5 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-69566340-A-C		NFAT5-related disorder	Likely benign (Aug 16, 2022)
16-69568504-A-G		not specified	Uncertain significance (May 27, 2022)
16-69626426-A-G			Uncertain significance (-)
16-69626496-C-T			Uncertain significance (Jul 15, 2022)
16-69647057-A-G		Immunodeficiency	Uncertain significance (Apr 20, 2019)
16-69647058-T-C		not specified	Uncertain significance (Aug 14, 2023)
16-69647062-C-T		Immunodeficiency	Likely benign (Mar 26, 2023)
16-69647063-G-A		Immunodeficiency	Uncertain significance (Apr 17, 2022)
16-69647068-T-C		Immunodeficiency	Likely benign (Jul 12, 2022)
16-69647099-A-G		Immunodeficiency • not specified	Uncertain significance (Oct 29, 2023)
16-69647100-C-T		Immunodeficiency	Uncertain significance (Jul 05, 2022)
16-69647101-C-T		Immunodeficiency	Likely benign (Oct 23, 2022)
16-69647109-C-G		not specified	Uncertain significance (Jun 22, 2023)
16-69647113-C-T		Immunodeficiency	Likely benign (Dec 23, 2020)
16-69647115-C-T		Immunodeficiency	Uncertain significance (Nov 21, 2023)
16-69647120-A-G		Immunodeficiency	Uncertain significance (Oct 05, 2020)
16-69647122-C-A		Immunodeficiency	Likely benign (Jan 18, 2023)
16-69647123-G-A		Immunodeficiency	Uncertain significance (May 01, 2023)
16-69647125-C-T		Immunodeficiency	Likely benign (Jul 03, 2023)
16-69647135-A-T		Immunodeficiency	Uncertain significance (Oct 21, 2020)
16-69647146-G-C		Immunodeficiency	Uncertain significance (Aug 20, 2021)
16-69647161-C-T		Immunodeficiency	Likely benign (Nov 24, 2023)
16-69647162-G-A		Immunodeficiency	Benign (Sep 23, 2022)
16-69647164-G-T		Immunodeficiency	Likely benign (Jul 03, 2022)
16-69647176-C-G		not specified	Uncertain significance (Mar 16, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NFAT5	protein_coding	protein_coding	ENST00000432919	14	139573

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000192	125718	0	30	125748	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.13	537	784	0.685	0.0000379	10215
Missense in Polyphen		171	324.28	0.52732		4316
Synonymous	1.13	263	287	0.915	0.0000149	2991
Loss of Function	7.15	9	76.4	0.118	0.00000417	804

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000294	0.0000294
Ashkenazi Jewish	0.00	0.00
East Asian	0.000894	0.000870
Finnish	0.0000959	0.0000924
European (Non-Finnish)	0.0000849	0.0000791
Middle Eastern	0.000894	0.000870
South Asian	0.0000368	0.0000327
Other	0.000190	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor involved, among others, in the transcriptional regulation of osmoprotective and inflammatory genes. Mediates the transcriptional response to hypertonicity (PubMed:10051678). Positively regulates the transcription of LCN2 and S100A4 genes; optimal transactivation of these genes requires the presence of DDX5/DDX17 (PubMed:22266867). Binds the DNA consensus sequence 5'- [ACT][AG]TGGAAA[CAT]A[TA][ATC][CA][ATG][GT][GAC][CG][CT]-3' (PubMed:10377394). {ECO:0000269|PubMed:10051678, ECO:0000269|PubMed:10377394, ECO:0000269|PubMed:22266867}.

Recessive Scores

• pRec: 0.302

Intolerance Scores

• loftool: 0.439
• rvis_EVS: -1.37
• rvis_percentile_EVS: 4.45

Haploinsufficiency Scores

• pHI: 0.855
• hipred: Y
• hipred_score: 0.532
• ghis: 0.638

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.514

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nfat5
• Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle 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); immune system phenotype; renal/urinary system phenotype

Zebrafish Information Network

• Gene name: nfat5a
• Affected structure: pericardium
• Phenotype tag: abnormal
• Phenotype quality: edematous

Gene ontology

• Biological process: cytokine production;transcription by RNA polymerase II;signal transduction;excretion;calcineurin-NFAT signaling cascade;positive regulation of transcription by RNA polymerase II;regulation of calcineurin-NFAT signaling cascade;cellular response to cytokine stimulus;positive regulation of NIK/NF-kappaB signaling;positive regulation of leukocyte adhesion to vascular endothelial cell
• Cellular component: nucleus;nucleoplasm;transcription factor complex;cytosol;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 activator activity, RNA polymerase II-specific;chromatin binding;DNA-binding transcription factor activity;protein binding;transcription factor binding