IFIT3
protein-codinginterferon induced protein with tetratricopeptide repeats 3, the group of Tetratricopeptide repeat domain containing
Gene summary
Enables identical protein binding activity. Involved in antiviral innate immune response; negative regulation of apoptotic process; and negative regulation of cell population proliferation. Located in cytosol and mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]
- IFIT4
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~50.2 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 IFIT3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001549.6. 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 | 1 | 1 | ||||
| missense | 58 | 3 | 1 | 62 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 58 | 3 | 2 | 63 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001540.2 | 2 | MANE Select | |
| Ensembl | ENSP00000360883.4 | 2 | MANE Select | |
| RefSeq | NP_001026853.1 | 2 | Standard | |
| RefSeq | NP_001276687.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- The human immune response to tuberculosis
- Cytokine Signaling in Immune system
- Immune System
- Interferon alpha/beta signaling
- Interferon Signaling
Biological Process
- negative regulation of cell population proliferation
- response to virus
- cellular response to interferon-alpha
- negative regulation of apoptotic process
- defense response to virus
Molecular Function
- molecular_function
- protein binding
- identical protein binding
Cellular Component
- cytoplasm
- mitochondrion
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000371818
- Coding exons
- 2
- Length
- 13078
- Individuals with no LoFs
- 125650
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 125659
- p
- 0.0000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.797 | 215 | 251 | 0.858 | 0.0000124 | 3234 |
| Missense (PolyPhen) | 46 | 59.322 | 0.77543 | 832 | ||
| Synonymous | 0.607 | 91 | 98.7 | 0.922 | 0.00000496 | 898 |
| Loss of Function | 1.32 | 2 | 5.28 | 0.379 | 2.27e-7 | 66 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: IFN-induced antiviral protein which acts as an inhibitor of cellular as well as viral processes, cell migration, proliferation, signaling, and viral replication. Enhances MAVS- mediated host antiviral responses by serving as an adapter bridging TBK1 to MAVS which leads to the activation of TBK1 and phosphorylation of IRF3 and phosphorylated IRF3 translocates into nucleus to promote antiviral gene transcription. Exihibits an antiproliferative activity via the up-regulation of cell cycle negative regulators CDKN1A/p21 and CDKN1B/p27. Normally, CDKN1B/p27 turnover is regulated by COPS5, which binds CDKN1B/p27 in the nucleus and exports it to the cytoplasm for ubiquitin- dependent degradation. IFIT3 sequesters COPS5 in the cytoplasm, thereby increasing nuclear CDKN1B/p27 protein levels. Upregulates CDKN1A/p21 by downregulating MYC, a repressor of CDKN1A/p21. Can negatively regulate the apoptotic effects of IFIT2. {ECO:0000269|PubMed:17050680, ECO:0000269|PubMed:20686046, ECO:0000269|PubMed:21190939, ECO:0000269|PubMed:21642987, ECO:0000269|PubMed:21813773}.;
Recessive Scores
- pRec
- 0.127
Intolerance Scores
- LoFtool
- 0.705
- RVIS EVS
- 0.11
- RVIS percentile EVS
- 61.91
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.915
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |