ZBP1 Gene: Z-DNA Binding Protein 1 – Innate Immune Sensor and Inflammatory Regulator
Comprehensive genomic, functional, and clinical overview of ZBP1 (Z-DNA binding protein 1), a key mediator of necroptosis, inflammation, and antiviral immunity.
Gene Information Card
| Symbol | ZBP1 |
|---|---|
| Full Name | Z-DNA binding protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 20q13.32 |
| NCBI Gene ID | 81030 ncbi.nlm.nih.gov/gene/81030 |
| Ensembl ID | ENSG00000124256 |
| UniProt ID | Q9H171 |
| OMIM ID | 606158 |
| HGNC ID | 16176 |
| Aliases | DAI, DLM-1, ZBP-1, C20orf183 |
Description
ZBP1 (Z-DNA binding protein 1), also known as DAI (DNA-dependent activator of IFN-regulatory factors) or DLM-1, is a cytoplasmic sensor that binds Z-form nucleic acids (Z-DNA/Z-RNA) via its Zα domains. It plays a critical role in innate immunity by activating NF-κB and IRF3 pathways, and it induces necroptosis and inflammatory signaling in response to viral infection (e.g., influenza virus) and cellular stress. ZBP1 is also implicated in inflammatory diseases, cancer, and embryonic development.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Influenza virus infection | ZBP1 senses viral Z-RNA and triggers RIPK3-dependent necroptosis and inflammatory cytokine production, contributing to host defense and immunopathology. | Animal models (mouse) and in vitro studies; PMID: 27916614, 28847925 |
| Inflammatory skin disease (e.g., dermatitis) | ZBP1-mediated necroptosis in keratinocytes drives skin inflammation; mutations or dysregulation may exacerbate disease. | Mouse models; PMID: 32094927 |
| Sepsis / systemic inflammation | ZBP1 activation by endogenous Z-form nucleic acids promotes TNF-induced lethal shock and systemic inflammatory response. | Mouse models; PMID: 28847925 |
| Cancer (various) | ZBP1 expression is altered in some cancers; it may influence tumor immunity and cell death pathways, but its role is context-dependent. | Expression data from TCGA and COSMIC; PMID: 30026309 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.3 | Medium |
| Spleen | 11.8 | Medium |
| Bone marrow | 10.5 | Medium |
| Lung | 8.2 | Low |
| Small intestine | 7.9 | Low |
| Liver | 5.1 | Low |
| Brain | 2.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocyte) | 15.2 | High expression; responsive to innate stimuli |
| HeLa (cervical) | 8.7 | Moderate expression |
| A549 (lung) | 7.4 | Low-moderate expression |
| HepG2 (liver) | 4.1 | Low expression |
| K562 (leukemia) | 3.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1043C>T (p.Pro348Leu) | Missense | Rare (MAF <0.01%) | Unknown; may affect protein stability or binding |
| c.1264A>G (p.Thr422Ala) | Missense | Rare (MAF <0.01%) | Unknown; predicted benign by in silico tools |
| c.1573G>A (p.Val525Ile) | Missense | Rare (MAF <0.01%) | Unknown; no clinical significance reported |
| c.1780C>T (p.Arg594Trp) | Missense | Rare (MAF <0.01%) | Unknown; may affect Zα domain function |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in ZBP1 are not well characterized in humans; however, knockout mouse models show impaired necroptosis and antiviral responses, suggesting that complete loss may lead to immune deficiency.
Gain of Function (GOF)
Gain-of-function mutations are not documented in human disease; overexpression of ZBP1 can enhance inflammatory signaling and necroptosis in experimental systems.
Dominant Negative (DN)
Dominant-negative effects have not been reported for ZBP1 mutations; however, mutations in the Zα domain could potentially interfere with nucleic acid binding and downstream signaling.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • Z-DNA binding |
| • RNA binding | • Z-RNA binding |
| • protein homodimerization activity | • signal transducer activity |
| • innate immune response | • necroptotic process |
| • regulation of NF-kappaB signaling | • positive regulation of interferon-beta production |
| • cellular response to virus | • cytoplasm |
| • nucleus |
Pathways
• RIPK3-mediated necroptosis pathway
• ZBP1/DAI-mediated NF-κB activation
• ZBP1-induced IRF3/IFN signaling
• TNFR1 signaling pathway (crosstalk)
• Influenza virus induced innate immune response
Protein Summary
ZBP1 is a 429-amino acid protein (UniProt Q9H171) containing two N-terminal Zα domains that bind Z-form nucleic acids, a RHIM (RIP homotypic interaction motif) domain, and a C-terminal domain involved in signaling. It localizes to the cytoplasm and nucleus. Upon binding Z-RNA or Z-DNA, ZBP1 recruits RIPK3 via RHIM interactions, leading to RIPK3 phosphorylation and MLKL activation, culminating in necroptosis. It also activates NF-κB and IRF3 to induce type I interferons and pro-inflammatory cytokines. ZBP1 is essential for antiviral defense against influenza virus and is implicated in inflammatory diseases and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ZBP1 Knockout HEK293 Cell Line | EDJ-KQ2151 | Human | 81030 | Details Get a Quote |
| ZBP1 Knockout HeLa Cell Line | EDJ-KQ57362 | Human | 81030 | Details Get a Quote |
| ZBP1 Knockout A-549 Cell Line | EDJ-KQ65868 | Human | 81030 | Details Get a Quote |
| ZBP1 Knockout HCT 116 Cell Line | EDJ-KQ74295 | Human | 81030 | Details Get a Quote |
| ZBP1 Knockout BEAS-2B Cell Line | EDJ-KQ78093 | Human | 81030 | Details Get a Quote |
