IFITM3: Interferon-Induced Transmembrane Protein 3
A key antiviral restriction factor and regulator of immune signaling, implicated in viral infections and cancer.
Gene Information Card
| Symbol | IFITM3 |
|---|---|
| Full Name | Interferon induced transmembrane protein 3 |
| Gene Type | protein coding |
| Chromosomal Location | 11p15.5 |
| NCBI Gene ID | 10410 ncbi.nlm.nih.gov/gene/10410 |
| Ensembl ID | ENSG00000142089 |
| UniProt ID | Q01628 |
| OMIM ID | 605579 |
| HGNC ID | 5412 |
| Aliases | 1-8U, DSPA2b, IP15, Mil-1, STAG2 |
Description
IFITM3 encodes an interferon-induced transmembrane protein that plays a critical role in the innate immune response to viral infections. It restricts the entry of a broad range of enveloped viruses, including influenza A virus, dengue virus, and SARS-CoV-2, by preventing viral membrane fusion with host cell endosomal membranes. Beyond its antiviral function, IFITM3 is involved in cell proliferation, differentiation, and immune signaling, and has been implicated in various cancers and inflammatory conditions. Its expression is induced by interferons and other cytokines, and it is localized to endosomes, lysosomes, and the plasma membrane.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Influenza A virus infection | IFITM3 restricts viral entry by blocking membrane fusion in endosomes; loss-of-function variants increase susceptibility to severe influenza. | ClinVar, PMID: 23274685 |
| COVID-19 (SARS-CoV-2 infection) | IFITM3 inhibits SARS-CoV-2 entry; certain variants (e.g., rs12252) are associated with severe disease outcomes. | ClinVar, PMID: 32514174 |
| West Nile virus infection | IFITM3 restricts West Nile virus replication; overexpression reduces viral titers in vitro. | PMID: 19828672 |
| Hepatitis C virus infection | IFITM3 modulates HCV entry and replication; expression levels correlate with treatment response. | PMID: 23152536 |
| Colorectal cancer | IFITM3 is overexpressed in colorectal cancer and promotes tumor cell proliferation and migration; associated with poor prognosis. | PMID: 28622328 |
| Breast cancer | IFITM3 expression is elevated in breast cancer and correlates with aggressive features; may promote epithelial-mesenchymal transition. | PMID: 29408879 |
| Gastric cancer | IFITM3 overexpression in gastric cancer is associated with lymph node metastasis and poor survival. | PMID: 27662648 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.3 | Medium |
| Spleen | 10.1 | Medium |
| Liver | 8.5 | Low |
| Kidney | 7.2 | Low |
| Small intestine | 6.8 | Low |
| Bone marrow | 5.4 | Low |
| Brain | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung carcinoma) | 18.5 | High expression; used in influenza studies |
| HepG2 (hepatocellular carcinoma) | 12.3 | Moderate expression; HCV studies |
| MCF7 (breast adenocarcinoma) | 9.8 | Moderate expression; cancer studies |
| THP-1 (monocytic leukemia) | 15.2 | High expression; immune response studies |
| HeLa (cervical carcinoma) | 7.4 | Low expression; baseline |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs12252 (c.183C>T, p.Ser61Ser) | SNP | ~30% in East Asian populations; rare in Europeans | Splice variant leading to truncated protein; associated with severe influenza and COVID-19 |
| rs34481144 (c.42A>G, p.Glu14Gly) | SNP | ~10% in Europeans | Alters IFITM3 expression; associated with severe influenza |
| p.Leu80Pro | Missense | Rare | Impairs antiviral activity; found in patients with severe influenza |
| p.Arg87Gln | Missense | Rare | Reduced membrane localization; loss of restriction function |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., rs12252 splice variant) result in a truncated protein lacking the transmembrane domain, leading to reduced antiviral activity and increased susceptibility to viral infections.
Gain of Function (GOF)
Gain-of-function mutations are not well characterized; however, overexpression of wild-type IFITM3 can enhance antiviral restriction, but no specific gain-of-function mutations have been reported.
Dominant Negative (DN)
Some variants may act in a dominant-negative manner by interfering with the function of the wild-type protein, but evidence is limited; further studies are needed.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Innate Immune System (Reactome: R-HSA-168249)
• Interferon Signaling (Reactome: R-HSA-913531)
• Antiviral mechanism by IFN-stimulated genes (Reactome: R-HSA-1169408)
• Vesicle-mediated transport (Reactome: R-HSA-5653656)
Protein Summary
IFITM3 is a small (133 amino acids) transmembrane protein with two hydrophobic domains and a conserved CD225 domain. It localizes to endosomal and lysosomal membranes, where it blocks viral membrane fusion by altering membrane fluidity and curvature. It is post-translationally modified by palmitoylation and ubiquitination, which regulate its stability and trafficking. IFITM3 also interacts with other proteins such as VAPA and VAPB to modulate cholesterol homeostasis and immune signaling. Its expression is tightly regulated by interferons and inflammatory cytokines.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IFITM3 Knockout HEK293 Cell Line | EDJ-KQ50966 | Human | 10410 | Details Get a Quote |
| IFITM3 Knockout HeLa Cell Line | EDJ-KQ55403 | Human | 10410 | Details Get a Quote |
| IFITM3 Knockout A-549 Cell Line | EDJ-KQ63882 | Human | 10410 | Details Get a Quote |
| IFITM3 Knockout HCT 116 Cell Line | EDJ-KQ72341 | Human | 10410 | Details Get a Quote |
