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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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ZNF74
zinc finger protein 74
Chromosome 22 · 22q11.21
NCBI Gene: 7625Ensembl: ENSG00000185252.20HGNC: HGNC:13144UniProt: A8K5P3
22PubMed Papers
17Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleoplasmDNA-binding transcription factor activity, RNA polymerase II-specificregulation of transcription by RNA polymerase IInucleussmall intestine carcinomaAbnormality of the skeletal systemopen-angle glaucomaneoplasm
✦AI Summary

ZNF74 is a zinc finger protein that functions as a multifunctional regulator of both transcription and RNA metabolism. The protein exists in multiple isoforms generated through alternative promoter usage and splicing, with ZNF74-II containing an intact KRAB domain showing strong transcriptional repressor activity, while ZNF74-I lacks transcriptional activity 1. ZNF74 demonstrates RNA-binding specificity for poly(U) and poly(G) homopolymers and associates tightly with the nuclear matrix, suggesting a role in RNA processing 2. The protein exhibits distinct subcellular localization patterns depending on the isoform: ZNF74-I colocalizes with splicing factors in nuclear speckles, while the transcriptionally active ZNF74-II shows diffuse nuclear distribution 1. ZNF74 is hemizygously deleted in DiGeorge syndrome patients and shows restricted developmental expression in neural crest-derived tissues and foregut endoderm epithelia, particularly in cardiovascular structures affected in this disorder 34. The gene has clinical relevance beyond developmental disorders, as polymorphisms are associated with age-at-onset in schizophrenia 5, and altered expression occurs in familial prostate cancers 6. These findings establish ZNF74 as a critical developmental regulator linking transcriptional control with RNA metabolism.

Sources cited
1
ZNF74 exists in multiple isoforms with different transcriptional activities and subcellular localizations
PMID: 11313019
2
ZNF74 binds specifically to poly(U) and poly(G) RNA and associates with the nuclear matrix
PMID: 8663113
3
ZNF74 shows restricted expression in neural crest-derived tissues and cardiovascular structures
PMID: 10585771
4
ZNF74 is hemizygously deleted in DiGeorge syndrome patients
PMID: 8268910
5
ZNF74 polymorphisms are associated with age-at-onset in schizophrenia
PMID: 11705709
6
ZNF74 expression is altered in familial prostate cancers
PMID: 36520140
Disease Associationsⓘ17
small intestine carcinomaOpen Targets
0.09Suggestive
Abnormality of the skeletal systemOpen Targets
0.06Suggestive
open-angle glaucomaOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.01Suggestive
schizophreniaOpen Targets
0.01Suggestive
22q11.2 deletion syndromeOpen Targets
0.01Suggestive
lung carcinomaOpen Targets
0.00Suggestive
attention deficit hyperactivity disorderOpen Targets
0.00Suggestive
type 2 diabetes mellitusOpen Targets
0.00Suggestive
Alzheimer diseaseOpen Targets
0.00Suggestive
congenital heart diseaseOpen Targets
0.00Suggestive
cervical cancerOpen Targets
0.00Suggestive
clear cell renal carcinomaOpen Targets
0.00Suggestive
gastric cancerOpen Targets
0.00Suggestive
ovarian serous cystadenocarcinomaOpen Targets
0.00Suggestive
sarcomaOpen Targets
0.00Suggestive
squamous cell lung carcinomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MED15Protein interaction85%TRIM28Protein interaction85%DGCR6Protein interaction85%HIRAProtein interaction84%DGCR6LProtein interaction84%DGCR2Protein interaction84%
Tissue Expression6 tissues
Ovary
100%
Brain
96%
Liver
55%
Heart
50%
Lung
46%
Bone Marrow
37%
Gene Interaction Network
Click a node to explore
ZNF74MED15TRIM28DGCR6HIRADGCR6LDGCR2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q05BG0
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.18LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.72 [0.45–1.18]
RankingsWhere ZNF74 stands among ~20K protein-coding genes
  • #13,811of 20,598
    Most Researched22
  • #12,430of 17,882
    Most Constrained (LOEUF)1.18
Genes detectedZNF74
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
ZNF74, a gene deleted in DiGeorge syndrome, is expressed in human neural crest-derived tissues and foregut endoderm epithelia.
PMID: 10585771
Genomics · 1999
1.00
2
Alternative promoter usage and splicing of ZNF74 multifinger gene produce protein isoforms with a different repressor activity and nuclear partitioning.
PMID: 11313019
DNA Cell Biol · 2001
0.90
3
Association of ZNF74 gene genotypes with age-at-onset of schizophrenia.
PMID: 11705709
Schizophr Res · 2001
0.80
4
Identification of a novel recurrent EEF2 gene amplification in familial prostate tumors.
PMID: 36520140
Genes Chromosomes Cancer · 2023
0.70
5
The KRAB zinc finger gene ZNF74 encodes an RNA-binding protein tightly associated with the nuclear matrix.
PMID: 8663113
J Biol Chem · 1996
0.60