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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ZNF746
zinc finger protein 746
Chromosome 7 · 7q36.1
NCBI Gene: 155061Ensembl: ENSG00000181220.18HGNC: HGNC:21948UniProt: A0A2R8YDQ5
36PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
transcription cis-regulatory region bindingRNA polymerase II cis-regulatory region sequence-specific DNA bindingDNA-binding transcription repressor activity, RNA polymerase II-specificDNA-binding transcription factor activityneurodegenerative diseasetype 2 diabetes mellitushypertensionovarian dysfunction
✦AI Summary

ZNF746 (zinc finger protein 746) is a transcription repressor that binds to specific DNA consensus sequences and regulates gene expression with significant implications for neurodegeneration and cancer progression. The protein functions primarily as a transcriptional repressor, specifically binding to 5'-TATTTT[T/G]-3' consensus sequences to suppress PGC-1α (PPARGC1A) transcription 1. In Parkinson's disease, ZNF746 accumulates when parkin activity is lost, as parkin normally targets ZNF746 for proteasomal degradation through ubiquitination 12. This accumulation contributes to mitochondrial dysfunction and dopamine neuron death through reactive oxygen species generation and NLRP3 inflammasome activation 1. Beyond neurodegeneration, ZNF746 demonstrates oncogenic properties in multiple cancer types. In colorectal cancer, it enhances c-Myc stability through direct protein binding and modulation of GSK3β and FBW7-mediated degradation pathways, promoting tumor progression 34. Similarly, in breast cancer, ZNF746 promotes M2 macrophage polarization via the Jagged1/Notch pathway, facilitating tumor progression and metastasis 5. The protein also suppresses epithelial-to-mesenchymal transition markers in lung cancer cells 6. These findings establish ZNF746 as a critical regulator linking transcriptional control to both neurodegeneration and cancer pathogenesis.

Sources cited
1
ZNF746 is a parkin substrate that accumulates in Parkinson's disease and contributes to neuronal death through NLRP3 inflammasome activation
PMID: 35654037
2
Parkin normally targets ZNF746 for degradation, and loss of parkin activity leads to ZNF746 accumulation in sporadic Parkinson's disease
PMID: 24029689
3
ZNF746 promotes M2 macrophage polarization and breast cancer progression via the Jagged1/Notch pathway
PMID: 37730102
4
ZNF746 is regulated by miR193a-5p and enhances c-Myc stability in colorectal cancer cells
PMID: 34440834
5
ZNF746 promotes colorectal cancer progression by stabilizing c-Myc through GSK3β and FBW7-mediated mechanisms
PMID: 29628506
6
ZNF746 inhibition suppresses invasion and epithelial-to-mesenchymal transition in lung cancer cells
PMID: 24145959
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.45Moderate
type 2 diabetes mellitusOpen Targets
0.37Weak
hypertensionOpen Targets
0.30Weak
ovarian dysfunctionOpen Targets
0.27Weak
multiple sclerosisOpen Targets
0.26Weak
metabolic syndromeOpen Targets
0.23Weak
diabetes mellitusOpen Targets
0.21Weak
acquired thrombocytopeniaOpen Targets
0.15Weak
Parkinson diseaseOpen Targets
0.10Weak
Alzheimer diseaseOpen Targets
0.06Suggestive
melanomaOpen Targets
0.06Suggestive
colorectal carcinomaOpen Targets
0.03Suggestive
breast cancerOpen Targets
0.03Suggestive
uncombable hair syndromeOpen Targets
0.03Suggestive
Griscelli diseaseOpen Targets
0.03Suggestive
Griscelli disease type 1Open Targets
0.03Suggestive
Griscelli syndrome type 1Open Targets
0.03Suggestive
hepatocellular carcinomaOpen Targets
0.03Suggestive
ovarian neoplasmOpen Targets
0.02Suggestive
non-small cell lung carcinomaOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TRIM28Protein interaction91%ZNF212Protein interaction84%ZNF398Protein interaction84%SGTBShared pathway67%KCTD4Shared pathway50%KCTD18Shared pathway50%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
49%
Brain
43%
Liver
40%
Ovary
37%
Heart
21%
Gene Interaction Network
Click a node to explore
ZNF746TRIM28ZNF212ZNF398SGTBKCTD4KCTD18
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q6NUN9
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.55Moderately Constrained
pLIⓘ
0.87Intermediate
Observed/Expected LoF0.36 [0.24–0.55]
RankingsWhere ZNF746 stands among ~20K protein-coding genes
  • #10,900of 20,598
    Most Researched36
  • #3,532of 17,882
    Most Constrained (LOEUF)0.55 · top quartile
Genes detectedZNF746
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Neuronal NLRP3 is a parkin substrate that drives neurodegeneration in Parkinson's disease.
PMID: 35654037
Neuron · 2022
1.00
2
Parkin plays a role in sporadic Parkinson's disease.
PMID: 24029689
Neurodegener Dis · 2014
0.90
3
ZNF746 promotes M2 macrophage polarisation and favours tumour progression in breast cancer via the Jagged1/Notch pathway.
PMID: 37730102
Cell Signal · 2023
0.80
4
miR193a-5p Mediated ZNF746 and c-Myc Signaling Axis Is Critically Involved in Morusin Induced Apoptosis in Colorectal Cancer Cells.
PMID: 34440834
Cells · 2021
0.70
5
Genome Sequencing Identifies 13 Novel Candidate Risk Genes for Autism Spectrum Disorder in a Qatari Cohort.
PMID: 39519104
Int J Mol Sci · 2024
0.60