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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ZNF516
zinc finger protein 516
Chromosome 18 · 18q23
NCBI Gene: 9658Ensembl: ENSG00000101493.12HGNC: HGNC:28990UniProt: Q2YDX2
53PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingpositive regulation of cold-induced thermogenesisnucleusDNA-binding transcription factor activity, RNA polymerase II-specificatrial fibrillationopen-angle glaucomaalcohol drinkingJoint stiffness
✦AI Summary

ZNF516 (zinc finger protein 516) is a transcriptional regulator with tumor suppressor properties that functions primarily through chr18 modification complexes. The protein acts as a transcriptional repressor by physically associating with the CtBP/LSD1/CoREST complex to regulate genes involved in cell proliferation and motility, including EGFR 1. ZNF516 binds directly to gene promoters, such as ABCC5, to repress their transcriptional activation 2. Loss of ZNF516 expression is strongly associated with cervical cancer progression, showing inverse correlation with lesion grade and high-risk HPV infection 3. The ZNF516 promoter undergoes frequent hypermethylation in cervical neoplasia, serving as a biomarker with 90% sensitivity and specificity for cancer detection 4. In breast cancer, low ZNF516 expression correlates with advanced pathological staging and poor survival, while the ZNF516-CtBP/LSD1/CoREST complex suppresses cancer cell proliferation, invasion, and metastasis 1. Additionally, ZNF516 is regulated by miR-371-5p and plays roles in trophoblast cell function during placental development 5. The protein also contributes to drug sensitivity in lung adenocarcinoma by repressing ABCC5 expression 2.

Sources cited
1
ZNF516 is a transcriptional repressor that associates with CtBP/LSD1/CoREST complex and represses EGFR and other genes involved in cell proliferation
PMID: 28947780
2
ZNF516 binds to ABCC5 promoter and represses its transcriptional activation, contributing to drug sensitivity
PMID: 40253507
3
Loss of ZNF516 expression is inversely related to cervical lesion grade and associated with HR-HPV infection
PMID: 30564931
4
ZNF516 promoter methylation serves as biomarker for cervical cancer with 90% sensitivity and specificity
PMID: 24241165
5
ZNF516 is regulated by miR-371-5p and affects trophoblast cell proliferation, migration, and invasion
PMID: 38761180
Disease Associationsⓘ20
atrial fibrillationOpen Targets
0.42Moderate
open-angle glaucomaOpen Targets
0.39Weak
alcohol drinkingOpen Targets
0.39Weak
Joint stiffnessOpen Targets
0.32Weak
breast benign neoplasmOpen Targets
0.32Weak
bile duct disorderOpen Targets
0.31Weak
spinal fractureOpen Targets
0.29Weak
pernicious anemiaOpen Targets
0.26Weak
portal hypertensionOpen Targets
0.26Weak
hair colorOpen Targets
0.24Weak
Abnormal nasolacrimal system morphologyOpen Targets
0.24Weak
mood disorderOpen Targets
0.19Weak
asthmaOpen Targets
0.19Weak
adolescent idiopathic scoliosisOpen Targets
0.18Weak
duodenal ulcerOpen Targets
0.18Weak
depressive disorderOpen Targets
0.18Weak
CachexiaOpen Targets
0.17Weak
schizophreniaOpen Targets
0.16Weak
rectosigmoid junction neoplasmOpen Targets
0.15Weak
bronchopneumoniaOpen Targets
0.11Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
HDAC1Protein interaction100%HDAC2Protein interaction100%KDM1AProtein interaction100%CTBP1Protein interaction95%CTBP2Protein interaction95%RCOR1Protein interaction95%
Tissue Expression6 tissues
Ovary
100%
Bone Marrow
51%
Brain
32%
Lung
31%
Liver
26%
Heart
19%
Gene Interaction Network
Click a node to explore
ZNF516HDAC1HDAC2KDM1ACTBP1CTBP2RCOR1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q2YDX2
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.41Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.28 [0.19–0.41]
RankingsWhere ZNF516 stands among ~20K protein-coding genes
  • #8,518of 20,598
    Most Researched53
  • #2,110of 17,882
    Most Constrained (LOEUF)0.41 · top quartile
Genes detectedZNF516
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Gene-gene interaction between RBMS3 and ZNF516 influences bone mineral density.
PMID: 23045156
J Bone Miner Res · 2013
1.00
2
Hyaluronic acid-modified milk exosomes carrying ZNF516 inhibit ABCC5 and contribute to pemetrexed sensitivity in lung adenocarcinoma.
PMID: 40253507
Hum Cell · 2025
0.90
3
MiR-371-5p regulates trophoblast cell proliferation, migration, and invasion by directly targeting ZNF516.
PMID: 38761180
Aging (Albany NY) · 2024
0.80
4
Loss of ZNF516 protein expression is related with HR-HPV infection and cervical preneoplastic lesions.
PMID: 30564931
Arch Gynecol Obstet · 2019
0.70
5
Machine Learning for Chromatin Regulators in Coronary Artery Disease Diagnosis.
PMID: 39976036
Cardiovasc Hematol Disord Drug Targets · 2025
0.60