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9 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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ZCCHC17
zinc finger CCHC-type containing 17
Chromosome 1 · 1p35.2
NCBI Gene: 51538Ensembl: ENSG00000121766.16HGNC: HGNC:30246UniProt: A0A087WXF8
73PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
identical protein bindingprotein bindingRNA bindingRNA stabilizationAlzheimer diseasehepatocellular carcinomaneoplasmThrombocytopenia
✦AI Summary

ZCCHC17 is a master regulator of neuronal RNA processing and synaptic gene expression 1. The protein contains a CCHC-type zinc finger domain and functions as an RNA-binding protein that interacts with splicing machinery 23. ZCCHC17 binding partners are enriched for RNA splicing proteins, and its knockdown causes widespread alterations in neuronal mRNA splicing patterns, particularly affecting synaptic genes 34. In Alzheimer's disease (AD) pathogenesis, ZCCHC17 plays a critical protective role. ZCCHC17 protein levels decline early in AD brain tissue, preceding neuronal loss 31. Loss of ZCCHC17 results in reduced expression of synaptic proteins and disrupts the excitation/inhibition balance of neuronal activity, phenocopying AD-related hyperexcitability 5. ZCCHC17 expression correlates with cognitive resilience in AD patients and shows APOE4-dependent negative correlation with tau pathology burden 34. The overlapping splicing changes between ZCCHC17 knockdown and tau overexpression suggest mechanistic links to tau-related pathology 4. Maintenance of ZCCHC17 function is proposed as a therapeutic strategy for preserving cognitive function in AD 3.

Sources cited
1
ZCCHC17 is a master regulator of synaptic gene expression and is reduced early in AD pathology
PMID: 29028963
2
ZCCHC17 modulates neuronal RNA splicing, correlates with cognitive resilience, and shows APOE4-dependent correlation with tangle burden in AD
PMID: 36993746
3
ZCCHC17 knockdown phenocopies AD-related loss of synaptic proteins and hyperexcitability through disruption of excitation/inhibition balance
PMID: 38630575
4
ZCCHC17 interacts with RNA-splicing proteins and overlaps with tau-related splicing changes
PMID: 38050142
5
ZCCHC17 contains a CCHC-type zinc finger domain and ribosomal protein S1 RNA binding region
PMID: 12893261
6
ZCCHC17 is implicated in late-onset Alzheimer's disease with predicted links to calcium signaling
PMID: 26202100
7
ZCCHC17 is a cross-species DTU gene involved in RNA and cell-cycle control mechanisms
PMID: 37995439
Disease Associationsⓘ20
Alzheimer diseaseOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.06Suggestive
ThrombocytopeniaOpen Targets
0.06Suggestive
Beta-thalassemia - X-linked thrombocytopeniaOpen Targets
0.05Suggestive
beta-thalassemia-X-linked thrombocytopenia syndromeOpen Targets
0.05Suggestive
autosomal dominant macrothrombocytopeniaOpen Targets
0.05Suggestive
thrombocytopenia 4Open Targets
0.05Suggestive
dominant beta-thalassemiaOpen Targets
0.04Suggestive
macrothrombocytopenia, isolated, 2, autosomal dominantOpen Targets
0.04Suggestive
Hemoglobin C - beta-thalassemiaOpen Targets
0.04Suggestive
hemoglobin C-beta-thalassemia syndromeOpen Targets
0.04Suggestive
hemoglobin H diseaseOpen Targets
0.04Suggestive
acute erythroleukemiaOpen Targets
0.04Suggestive
erythroleukemia, familial, susceptibility toOpen Targets
0.04Suggestive
platelet-type bleeding disorder 15Open Targets
0.04Suggestive
essential thrombocythemiaOpen Targets
0.04Suggestive
hemoglobin D diseaseOpen Targets
0.04Suggestive
thrombocythemia 1Open Targets
0.04Suggestive
bleeding disorder, platelet-type, 24Open Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PHAXShared pathway100%PNNProtein interaction76%METTL4Shared pathway25%IGF2BP2Shared pathway17%NAF1Shared pathway14%METTL3Shared pathway5%
Tissue Expression6 tissues
Brain
100%
Heart
75%
Bone Marrow
39%
Ovary
33%
Lung
31%
Liver
25%
Gene Interaction Network
Click a node to explore
ZCCHC17PHAXPNNMETTL4IGF2BP2NAF1METTL3
PROTEIN STRUCTURE
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PDB2CQO · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.85LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.56 [0.38–0.85]
RankingsWhere ZCCHC17 stands among ~20K protein-coding genes
  • #6,524of 20,598
    Most Researched73
  • #7,374of 17,882
    Most Constrained (LOEUF)0.85
Genes detectedZCCHC17
Sources retrieved9 papers
Response time—
📄 Sources
9▼
1
ZCCHC17 knockdown phenocopies Alzheimer's disease-related loss of synaptic proteins and hyperexcitability.
PMID: 38630575
J Neuropathol Exp Neurol · 2024
1.00
2
Integrated genomic approaches identify major pathways and upstream regulators in late onset Alzheimer's disease.
PMID: 26202100
Sci Rep · 2015
0.89
3
ZCCHC17 modulates neuronal RNA splicing and supports cognitive resilience in Alzheimer's disease.
PMID: 36993746
bioRxiv · 2023
0.78
4
Differential transcript usage across mammalian oocytes at the germinal vesicle and metaphase II stages.
PMID: 37995439
Theriogenology · 2024
0.67
5
Molecular characterization of a novel nucleolar protein, pNO40.
PMID: 12893261
Biochem Biophys Res Commun · 2003
0.56