ZC3HAV1
protein-codingzinc finger CCCH-type containing, antiviral 1, the group of Zinc fingers CCCH-type|Poly(ADP-ribose) polymerases
Gene summary
This gene encodes a CCCH-type zinc finger protein. This antiviral protein inhibits viral replication by recruiting cellular RNA degradation machineries to degrade viral mRNAs. The encoded protein plays an important role in the innate immune response against multiple DNA and RNA viruses, including Ebola virus, HIV and SARS-CoV-2 (which causes COVID-19). [provided by RefSeq, Sep 2021]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~88.6 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 ZC3HAV1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020119.4. 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 | 3 | 2 | 2 | 7 | ||
| missense | 107 | 18 | 125 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 114 | 20 | 2 | 136 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_064504.2 | 13 | MANE Select | |
| Ensembl | ENSP00000242351.5 | 13 | MANE Select | |
| RefSeq | NP_001350420.1 | 13 | Standard | |
| RefSeq | NP_078901.3 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Disease
- Signaling by BRAF and RAF fusions
- Oncogenic MAPK signaling
- Diseases of signal transduction
Biological Process
- response to virus
- negative regulation of viral genome replication
- innate immune response
- defense response to virus
- positive regulation of mRNA catabolic process
Molecular Function
- RNA binding
- NAD+ ADP-ribosyltransferase activity
- protein binding
- cadherin binding
- metal ion binding
Cellular Component
- nucleus
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000242351
- Coding exons
- 13
- Length
- 66200
- Individuals with no LoFs
- 125729
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 19
- Defined
- 125748
- p
- 0.0000756
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.56 | 419 | 519 | 0.807 | 0.0000292 | 5912 |
| Missense (PolyPhen) | 114 | 185.23 | 0.61545 | 2169 | ||
| Synonymous | 0.238 | 200 | 204 | 0.979 | 0.0000123 | 1739 |
| Loss of Function | 3.58 | 15 | 39.2 | 0.383 | 0.00000192 | 482 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000063 | 0.000062 | rare |
| Latino/Admixed American | 0.000097 | 0.000087 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000090 | 0.000088 | rare |
| South Asian | 0.00010 | 0.000098 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Antiviral protein which inhibits the replication of viruses by recruiting the cellular RNA degradation machineries to degrade the viral mRNAs. Binds to a ZAP-responsive element (ZRE) present in the target viral mRNA, recruits cellular poly(A)- specific ribonuclease PARN to remove the poly(A) tail, and the 3'- 5' exoribonuclease complex exosome to degrade the RNA body from the 3'-end. It also recruits the decapping complex DCP1-DCP2 through RNA helicase p72 (DDX17) to remove the cap structure of the viral mRNA to initiate its degradation from the 5'-end. Its target viruses belong to families which include retroviridae: human immunodeficiency virus type 1 (HIV-1), moloney and murine leukemia virus (MoMLV) and xenotropic MuLV-related virus (XMRV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), togaviridae: sindbis virus (SINV) and Ross river virus (RRV). Specifically targets the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation. Isoform 1 is a more potent viral inhibitor than isoform 2. Isoform 2 acts as a positive regulator of DDX58/RIG-I signaling resulting in activation of the downstream effector IRF3 leading to the expression of type I IFNs and IFN stimulated genes (ISGs). {ECO:0000269|PubMed:18225958, ECO:0000269|PubMed:21102435, ECO:0000269|PubMed:21876179, ECO:0000269|PubMed:22720057}.;
Recessive Scores
- pRec
- 0.0809
Intolerance Scores
- LoFtool
- 0.537
- RVIS EVS
- 0.72
- RVIS percentile EVS
- 85.85
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.588
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |