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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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ZCCHC3
zinc finger CCHC-type containing 3
Chromosome 20 · 20p13
NCBI Gene: 85364Ensembl: ENSG00000247315.4HGNC: HGNC:16230UniProt: Q9NUD5
92PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cellular response to exogenous dsRNAcytoplasmRNA bindingprotein bindingCrigler-Najjar syndrome type 2plasma fibronectin deficiencytransient familial neonatal hyperbilirubinemiagluthathione peroxidase deficiency
✦AI Summary

ZCCHC3 is a nucleic acid-binding protein that serves as a critical regulator of innate immune responses to viral infections. The protein functions as a co-sensor that enhances viral nucleic acid recognition by promoting the activity of key innate immune receptors including RIG-I, MDA5, and cGAS 1. ZCCHC3 employs liquid-liquid phase separation as a unified mechanism, forming condensates with nucleic acids that enrich and activate these immune sensors 2. For RNA virus detection, ZCCHC3 binds double-stranded RNA and facilitates RIG-I and MDA5 binding to viral RNA, while also recruiting TRIM25 to promote K63-linked ubiquitination and activation of these receptors 1. Additionally, ZCCHC3 acts as a co-sensor for cGAS-mediated DNA virus recognition by promoting cGAS oligomerization and activation through DNA-induced condensation 2. The protein demonstrates antiviral activity against influenza H9N2 virus by promoting IFN-β expression and downstream antiviral factor transcription 3. ZCCHC3 also restricts LINE-1 retrotransposition and localizes to stress granules 4. Beyond immune function, ZCCHC3 shows clinical significance as a poor prognostic marker in triple-negative breast cancer and ovarian carcinomas when co-expressed with Efp 567.

Sources cited
1
ZCCHC3 is a positive regulator of RIG-I and MDA5 that binds dsRNA, enhances RLR binding to viral RNA, and facilitates TRIM25-mediated K63-linked ubiquitination
PMID: 30193849
2
ZCCHC3 undergoes liquid phase condensation with nucleic acids to enrich and activate innate immune sensors including RLRs and cGAS
PMID: 39983719
3
ZCCHC3 demonstrates antiviral activity against H9N2 influenza virus by promoting IFN-β expression and downstream antiviral factors
PMID: 35872280
4
ZCCHC3 restricts LINE-1 retrotransposition and localizes to stress granules
PMID: 37405998
5
ZCCHC3 promotes triple-negative breast cancer progression by regulating NCAPH expression in coordination with Efp
PMID: 39276521
6
Combined ZCCHC3 and Efp immunoreactivity serves as a poor prognostic marker in triple-negative breast cancer
PMID: 39936817
7
ZCCHC3 and Efp immunoreactivities are associated with worse prognosis in high-grade serous and clear cell ovarian carcinomas
PMID: 41693303
Disease Associationsⓘ20
Crigler-Najjar syndrome type 2Open Targets
0.06Suggestive
plasma fibronectin deficiencyOpen Targets
0.06Suggestive
transient familial neonatal hyperbilirubinemiaOpen Targets
0.04Suggestive
gluthathione peroxidase deficiencyOpen Targets
0.04Suggestive
Rotor syndromeOpen Targets
0.04Suggestive
Dubin-Johnson syndromeOpen Targets
0.04Suggestive
hypercholanemia, familial, 2Open Targets
0.04Suggestive
hemolytic anemia due to glutathione reductase deficiencyOpen Targets
0.03Suggestive
alcohol drinkingOpen Targets
0.03Suggestive
congenital lethal erythrodermaOpen Targets
0.03Suggestive
cholestasis, progressive familial intrahepatic, 11Open Targets
0.03Suggestive
neonatal intrahepatic cholestasis due to citrin deficiencyOpen Targets
0.03Suggestive
Crigler-Najjar syndrome type 1Open Targets
0.03Suggestive
triple-negative breast cancerOpen Targets
0.03Suggestive
Gilbert syndromeOpen Targets
0.03Suggestive
viral diseaseOpen Targets
0.03Suggestive
severe acute respiratory syndromeOpen Targets
0.02Suggestive
facial painOpen Targets
0.02Suggestive
COVID-19Open Targets
0.02Suggestive
infectionOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
IFIH1Protein interaction96%PAIP1Protein interaction71%PQBP1Shared pathway44%GARIN5AShared pathway33%DDX60Shared pathway33%CGASShared pathway31%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
63%
Heart
63%
Brain
58%
Liver
53%
Lung
38%
Gene Interaction Network
Click a node to explore
ZCCHC3IFIH1PAIP1PQBP1GARIN5ADDX60CGAS
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9NUD5
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.96LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.90 [1.07–1.96]
RankingsWhere ZCCHC3 stands among ~20K protein-coding genes
  • #5,227of 20,598
    Most Researched92
  • #17,762of 17,882
    Most Constrained (LOEUF)1.96
Genes detectedZCCHC3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Nucleic-acid-induced ZCCHC3 condensation promotes broad innate immune responses.
PMID: 39983719
Mol Cell · 2025
1.00
2
ZCCHC3 is a stress granule zinc knuckle protein that strongly suppresses LINE-1 retrotransposition.
PMID: 37405998
PLoS Genet · 2023
0.90
3
Proteomic analysis reveals zinc-finger CCHC-type containing protein 3 as a factor inhibiting virus infection by promoting innate signaling.
PMID: 35872280
Virus Res · 2022
0.80
4
PRRSV GP2a blocks the RLR signaling pathway by targeting RIG-I.
PMID: 41070967
J Virol · 2025
0.70
5
ZCCHC3 and Efp coordinately contribute to the pathophysiology of triple-negative breast cancer by modulating NCAPH.
PMID: 39276521
Biochem Biophys Res Commun · 2024
0.60