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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ZC3H14
zinc finger CCCH-type containing 14
Chromosome 14 · 14q31.3
NCBI Gene: 79882Ensembl: ENSG00000100722.20HGNC: HGNC:20509UniProt: G3V256
109PubMed Papers
21Diseases
0Drugs
0Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
RNA bindingmRNA 3'-UTR bindingprotein bindingspliceosome-depend formation of circular RNAintellectual disability, autosomal recessive 56autosomal recessive non-syndromic intellectual disabilityAlzheimer diseaseamyotrophic lateral sclerosis
✦AI Summary

ZC3H14 is a conserved CCCH-type zinc finger RNA-binding protein with primary roles in circular RNA (circRNA) biogenesis and poly(A) tail regulation. ZC3H14 binds to exon-intron boundaries and 3'-UTRs of pre-mRNAs to promote circRNA biogenesis through spliceosome association and protein dimerization 1. The protein exists as multiple nuclear and cytoplasmic isoforms generated by alternative splicing, with nuclear isoforms localizing to splicing speckles 2. Beyond circRNA regulation, ZC3H14 controls mRNA poly(A) tail length in neuronal cells and interacts with the THO complex to regulate processing of neuronal transcripts like ATP5MC1 and PSD95 3. ZC3H14 functions antagonistically to PABPN1 in nuclear RNA surveillance, controlling lncRNA turnover and export 4. Clinically, ZC3H14 mutations cause autosomal recessive intellectual developmental disorder 56, with disease mechanisms potentially involving defective axon projection and neuronal mRNA processing 5, 6. ZC3H14 acts as a tumor suppressor; its downregulation through chromosome 14 deletion promotes hepatocellular carcinoma progression 7, while CDK13-mediated ZC3H14 phosphorylation is required for nuclear RNA surveillance and its disruption drives melanoma 8. ZC3H14 is required for male fertility through circRNA-dependent spermatogenesis 1.

Sources cited
1
ZC3H14 binds exon-intron boundaries and 3'-UTRs to promote circRNA biogenesis; required for spermatogenesis
PMID: 39461343
2
ZC3H14 generates multiple splice variants producing nuclear and cytoplasmic isoforms; nuclear forms localize to splicing speckles
PMID: 19303045
3
ZC3H14 interacts with THO complex and regulates poly(A) tail length and processing of neuronal transcripts
PMID: 29912477
4
ZC3H14 functions antagonistically to PABPN1 in nuclear RNA surveillance controlling lncRNA decay and export
PMID: 39898550
5
ZC3H14 orthologs required for axon projection and branching in neurons; conserved role in neuronal development
PMID: 25980665
6
ZC3H14 acts as cytoplasmic regulator of neuronal mRNAs; its loss underlies brain-specific defects in intellectual disability patients
PMID: 28793261
7
ZC3H14 downregulation via 14q31 deletion promotes hepatocellular carcinoma progression; acts as tumor suppressor
PMID: 30371740
8
CDK13-mediated ZC3H14 phosphorylation required for nuclear RNA surveillance; disruption drives melanoma through aberrant RNA stabilization
PMID: 37079685
Disease Associationsⓘ21
intellectual disability, autosomal recessive 56Open Targets
0.44Moderate
autosomal recessive non-syndromic intellectual disabilityOpen Targets
0.37Weak
Alzheimer diseaseOpen Targets
0.30Weak
amyotrophic lateral sclerosisOpen Targets
0.28Weak
placenta praeviaOpen Targets
0.27Weak
Intellectual disabilityOpen Targets
0.22Weak
Fuchs endothelial corneal dystrophyOpen Targets
0.07Suggestive
X-linked endothelial corneal dystrophyOpen Targets
0.06Suggestive
tauopathyOpen Targets
0.06Suggestive
granular corneal dystrophy type IOpen Targets
0.05Suggestive
congenital hereditary endothelial dystrophy of corneaOpen Targets
0.05Suggestive
Familial ocular anterior segment mesenchymal dysgenesisOpen Targets
0.05Suggestive
lattice corneal dystrophy type IOpen Targets
0.05Suggestive
Cataract-microcornea syndromeOpen Targets
0.05Suggestive
posterior polymorphous corneal dystrophyOpen Targets
0.05Suggestive
Lisch epithelial corneal dystrophyOpen Targets
0.05Suggestive
X-linked corneal dermoidOpen Targets
0.05Suggestive
spinocerebellar ataxia type 32Open Targets
0.05Suggestive
respiratory tract infectious disorderOpen Targets
0.05Suggestive
Schnyder corneal dystrophyOpen Targets
0.05Suggestive
Intellectual developmental disorder, autosomal recessive 56UniProt
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NCBP2Protein interaction99%EIF4A3Protein interaction96%MSI2Protein interaction91%PABPN1Protein interaction90%HOOK2Protein interaction89%ALYREFProtein interaction88%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
86%
Ovary
78%
Brain
73%
Heart
63%
Lung
47%
Gene Interaction Network
Click a node to explore
ZC3H14NCBP2EIF4A3MSI2PABPN1HOOK2ALYREF
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q6PJT7
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.45Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.33 [0.24–0.45]
RankingsWhere ZC3H14 stands among ~20K protein-coding genes
  • #4,388of 20,598
    Most Researched109 · top quartile
  • #2,471of 17,882
    Most Constrained (LOEUF)0.45 · top quartile
Genes detectedZC3H14
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Oncogenic
PMID: 37079685
Science · 2023
1.00
2
ZC3H14 facilitates backsplicing by binding to exon-intron boundary and 3' UTR.
PMID: 39461343
Mol Cell · 2024
0.90
3
Splice variants of the human ZC3H14 gene generate multiple isoforms of a zinc finger polyadenosine RNA binding protein.
PMID: 19303045
Gene · 2009
0.80
4
Antagonistic roles by the conserved nuclear poly(A)-binding proteins PABPN1 and ZC3H14 in nuclear RNA surveillance.
PMID: 39898550
Nucleic Acids Res · 2025
0.70
5
The polyadenosine RNA-binding protein ZC3H14 interacts with the THO complex and coordinately regulates the processing of neuronal transcripts.
PMID: 29912477
Nucleic Acids Res · 2018
0.60