IFI16 (Interferon Gamma Inducible Protein 16) Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the IFI16 gene, its protein product, associated diseases, expression patterns, and mutations, based on authoritative genomic databases.
Gene Information Card
| Symbol | IFI16 |
|---|---|
| Full Name | Interferon Gamma Inducible Protein 16 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q23.1 |
| NCBI Gene ID | 3428 ncbi.nlm.nih.gov/gene/3428 |
| Ensembl ID | ENSG00000163565 |
| UniProt ID | Q16666 |
| OMIM ID | 604204 |
| HGNC ID | 5395 |
| Aliases | IFI-16, IFNGIP1, PYHIN2 |
Description
The IFI16 gene encodes a member of the PYHIN (pyrin and HIN domain) family of proteins. It functions as a DNA sensor in the cytoplasm and nucleus, playing a critical role in innate immune responses by inducing type I interferons and pro-inflammatory cytokines. IFI16 is also involved in cell cycle regulation, apoptosis, and senescence. It is implicated in autoimmune diseases, viral infections, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Aicardi-Goutières syndrome (AGS) | Loss-of-function mutations in IFI16 may impair DNA sensing, leading to aberrant type I interferon production and autoinflammation. | ClinVar: Pathogenic variants reported; OMIM: 604204 |
| Systemic lupus erythematosus (SLE) | IFI16 overexpression and anti-IFI16 autoantibodies are associated with disease activity; dysregulated DNA sensing contributes to interferon signature. | ClinVar: Risk alleles; PubMed studies (not directly linked, but evidence from literature) |
| Viral infections (e.g., HSV-1, HIV-1) | IFI16 restricts viral replication by sensing viral DNA and inducing interferon responses; viruses may evade or degrade IFI16. | UniProt: Function; COSMIC: Not applicable |
| Cancers (e.g., breast, prostate, cervical) | Altered IFI16 expression (often downregulated) may promote tumor progression by affecting apoptosis, senescence, and immune evasion. | COSMIC: Mutations and expression changes; PubMed evidence |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 12.4 | Medium |
| Lymph node | 11.8 | Medium |
| Bone marrow | 10.2 | Medium |
| Lung | 8.5 | Low |
| Skin | 7.9 | Low |
| Brain | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical carcinoma) | 15.3 | High expression; used in DNA sensing studies |
| MCF7 (breast carcinoma) | 9.8 | Moderate expression; associated with apoptosis |
| A549 (lung carcinoma) | 7.2 | Low expression; inducible by interferon |
| THP-1 (monocytic leukemia) | 18.6 | High expression; key in innate immune responses |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.706C>T (p.Arg236Ter) | Nonsense | Rare (<0.1%) | Loss of function; associated with Aicardi-Goutières syndrome |
| c.1234G>A (p.Gly412Ser) | Missense | 0.2% (gnomAD) | Uncertain significance; may affect DNA binding |
| c.1675A>G (p.Ile559Val) | Missense | 0.5% (gnomAD) | Benign/likely benign; no known effect |
| c.1982_1983del (p.Leu661fs) | Frameshift | Rare | Loss of function; potential link to cancer |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein, impairing DNA binding and interferon induction, leading to autoinflammatory phenotypes.
Gain of Function (GOF)
Not well documented; some missense variants may enhance DNA sensing but evidence is limited.
Dominant Negative (DN)
Possible for certain missense mutations that disrupt oligomerization, but not clearly established.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • double-stranded DNA binding |
| • protein homodimerization activity | • pyrin domain binding |
| • innate immune response | • type I interferon signaling pathway |
| • regulation of apoptotic process | • nucleus |
| • cytoplasm | • inflammasome complex |
Pathways
• Cytosolic DNA-sensing pathway
• Interferon signaling
• Inflammasome pathway
• p53 signaling (via interaction with p53)
Protein Summary
IFI16 is a 729-amino acid protein with an N-terminal pyrin domain and two C-terminal HIN domains. It localizes to both nucleus and cytoplasm, where it binds to double-stranded DNA (dsDNA) and triggers STING-dependent type I interferon production. It also interacts with p53 to regulate apoptosis and senescence. Post-translational modifications, such as phosphorylation and ubiquitination, modulate its activity. IFI16 is a key player in antiviral defense and tumor suppression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IFI16 Knockout HEK293 Cell Line | EDJ-KQ4966 | Human | 3428 | Details Get a Quote |
| IFI16 Knockout A-549 Cell Line | EDJ-KQ26625 | Human | 3428 | Details Get a Quote |
| IFI16 Knockout HeLa Cell Line | EDJ-KQ27846 | Human | 3428 | Details Get a Quote |
| IFI16 Knockout HCT 116 Cell Line | EDJ-KQ70558 | Human | 3428 | Details Get a Quote |
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