ZC3HAV1 Gene: Role in Antiviral Immunity and Disease
ZC3HAV1 encodes a zinc-finger antiviral protein that restricts viral replication and modulates immune responses, with implications in infection, cancer, and inflammatory diseases.
Gene Information Card
| Symbol | ZC3HAV1 |
|---|---|
| Full Name | Zinc Finger CCCH-Type, Antiviral 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q34 (GRCh38: chr7:138,876,950-138,936,938, minus strand) |
| NCBI Gene ID | 56829 ncbi.nlm.nih.gov/gene/56829 |
| Ensembl ID | ENSG00000105974 |
| UniProt ID | Q7Z2W4 |
| OMIM ID | 607312 |
| HGNC ID | 23721 |
| Aliases | ZAP, PARP13, FLB6421, ZC3HDC2, DKFZp686K23100 |
Description
ZC3HAV1 (Zinc Finger CCCH-Type, Antiviral 1) encodes a zinc-finger antiviral protein (ZAP) that functions as a host restriction factor against a broad range of RNA and DNA viruses. ZAP binds to CpG-rich viral RNA sequences, promoting their degradation and inhibiting viral translation. It also participates in innate immune signaling, stress granule formation, and regulation of cellular mRNA stability. Alternative splicing produces isoforms with distinct functions. ZC3HAV1 is implicated in antiviral defense, cancer progression, and inflammatory diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Viral infections (e.g., HIV-1, influenza, SARS-CoV-2) | ZAP binds CpG dinucleotides in viral RNA, recruiting RNA exosome and decapping enzymes to degrade viral RNA, thereby restricting viral replication. | Multiple studies in cell culture and animal models; clinical correlation studies. |
| Hepatocellular carcinoma | ZAP expression is downregulated in HCC tissues; loss of ZAP promotes cell proliferation and metastasis, possibly via altered mRNA stability of oncogenes. | Immunohistochemistry and functional assays in HCC cell lines. |
| Prostate cancer | ZAP expression is reduced in prostate cancer; overexpression inhibits cell growth and induces apoptosis, suggesting tumor suppressor role. | In vitro and xenograft studies. |
| Inflammatory bowel disease (IBD) | ZAP modulates inflammatory responses; polymorphisms in ZC3HAV1 may affect susceptibility to IBD. | Genetic association studies. |
| Systemic lupus erythematosus (SLE) | ZAP is involved in type I interferon regulation; altered expression may contribute to autoimmune pathogenesis. | Gene expression profiling in patient samples. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.4 | Medium |
| Spleen | 11.8 | Medium |
| Bone marrow | 10.2 | Medium |
| Lung | 8.5 | Low |
| Liver | 6.3 | Low |
| Brain | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical carcinoma) | 15.2 | High expression; used in antiviral studies. |
| HepG2 (hepatocellular carcinoma) | 8.7 | Moderate expression; downregulated in HCC. |
| A549 (lung carcinoma) | 7.9 | Moderate expression; responsive to interferon. |
| MCF7 (breast carcinoma) | 5.4 | Low expression. |
| Jurkat (T-cell leukemia) | 12.0 | High expression; relevant to immune function. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs3738579 (intronic variant) | SNV | Allele frequency ~0.3 (1000 Genomes) | Associated with altered ZAP expression and susceptibility to viral infections. |
| rs2074560 (missense, p.Pro427Ser) | SNV | Allele frequency ~0.1 | May affect RNA binding affinity; clinical significance uncertain. |
| Copy number loss in 7q34 | CNV | Rare in general population | Observed in some cancers; may reduce ZAP expression. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., frameshift, nonsense) are rare but lead to reduced antiviral activity, increasing susceptibility to viral infections. In cancer, loss of ZAP expression is associated with poor prognosis.
Gain of Function (GOF)
No clear gain-of-function mutations reported. Overexpression of wild-type ZAP enhances antiviral activity and tumor suppression.
Dominant Negative (DN)
Dominant-negative effects are not well-documented; however, certain splice variants may interfere with full-length ZAP function.
View complete mutation data：
Gene Ontology (GO)
| • RNA binding (GO:0003723) | • Zinc ion binding (GO:0008270) |
| • Poly(A) RNA binding (GO:0044822) | • Protein homodimerization activity (GO:0042803) |
| • Cytoplasm (GO:0005737) | • P-body (GO:0000932) |
| • Stress granule (GO:0010494) | • Negative regulation of viral genome replication (GO:0045071) |
| • Defense response to virus (GO:0051607) | • mRNA catabolic process (GO:0006402) |
Pathways
• RIG-I-like receptor signaling pathway (KEGG: hsa04622)
• Cytosolic DNA-sensing pathway (KEGG: hsa04623)
• Innate Immune System (Reactome: R-HSA-168249)
• Antiviral mechanism by IFN-stimulated genes (Reactome: R-HSA-1169408)
Protein Summary
The ZAP protein (UniProt Q7Z2W4) is a 902-amino acid protein with N-terminal zinc-finger domains that specifically recognize CpG dinucleotides in RNA. It recruits RNA-degrading enzymes (e.g., exosome, DCP2) to promote viral RNA decay. ZAP also contains a PARP-like domain (inactive) and a WWE domain. It is predominantly cytoplasmic, localizing to P-bodies and stress granules. Post-translational modifications include phosphorylation and ubiquitination, regulating its stability and function. ZAP is constitutively expressed in many tissues and is induced by interferon.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ZC3HAV1 Knockout HEK293 Cell Line | EDJ-KQ2855 | Human | 56829 | Details Get a Quote |
| ZC3HAV1L Knockout HEK293 Cell Line | EDJ-KQ10832 | Human | 92092 | Details Get a Quote |
| ZC3HAV1 Knockout A-549 Cell Line | EDJ-KQ23868 | Human | 56829 | Details Get a Quote |
| ZC3HAV1 Knockout HCT 116 Cell Line | EDJ-KQ23869 | Human | 56829 | Details Get a Quote |
| ZC3HAV1 Knockout HeLa Cell Line | EDJ-KQ23870 | Human | 56829 | Details Get a Quote |
| ZC3HAV1L Knockout A-549 Cell Line | EDJ-KQ38483 | Human | 92092 | Details Get a Quote |
| ZC3HAV1L Knockout HCT 116 Cell Line | EDJ-KQ38484 | Human | 92092 | Details Get a Quote |
| ZC3HAV1L Knockout HeLa Cell Line | EDJ-KQ38485 | Human | 92092 | Details Get a Quote |
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