NFATC3
protein-codingnuclear factor of activated T cells 3, the group of Nuclear factors of activated T-cells |IPT domain containing
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~144.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NFATC3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_173165.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 1 | 5 | |||
| missense | 155 | 6 | 1 | 162 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 156 | 10 | 2 | 168 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_775188.1 | 10 | MANE Select | |
| Ensembl | ENSP00000300659.5 | 10 | MANE Select | |
| RefSeq | NP_004546.1 | 10 | Standard | |
| RefSeq | NP_775186.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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)
- HTLV-I infection - Homo sapiens (human)
Biological Process
- cytokine production
- regulation of transcription by RNA polymerase II
- transcription by RNA polymerase II
- inflammatory response
- calcineurin-NFAT signaling cascade
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
- chromatin binding
Cellular Component
- nucleus
- nucleoplasm
- transcription factor complex
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000346183
- Coding exons
- 10
- Length
- 144509
- Individuals with no LoFs
- 125736
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 12
- Defined
- 125748
- p
- 0.0000477
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.494 | 524 | 557 | 0.941 | 0.0000276 | 6886 |
| Missense (PolyPhen) | 170 | 212.42 | 0.8003 | 2608 | ||
| Synonymous | 0.424 | 196 | 204 | 0.962 | 0.0000102 | 2269 |
| Loss of Function | 5.37 | 6 | 44.8 | 0.134 | 0.00000266 | 524 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- 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. {ECO:0000269|PubMed:18815128}.;
Recessive Scores
- pRec
- 0.163
Intolerance Scores
- LoFtool
- 0.512
- RVIS EVS
- 0.16
- RVIS percentile EVS
- 64.96
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.988
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |