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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ZNF687
zinc finger protein 687
Chromosome 1 · 1q21.3
NCBI Gene: 57592Ensembl: ENSG00000143373.19HGNC: HGNC:29277UniProt: Q8N1G0
82PubMed Papers
21Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTranscription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleoplasmprotein bindingDNA-binding transcription factor activitynucleusosteitis deformansovarian dysfunctionhepatocellular carcinomalung adenocarcinoma
✦AI Summary

ZNF687 is a zinc finger transcription factor with diverse roles in bone development, hematopoiesis, and cancer biology. In bone biology, ZNF687 mutations are associated with Paget disease of bone (PDB), a disorder characterized by increased bone resorption and excessive bone formation 1. ZNF687 is regulated by bone-associated transcription factors including DLX5, NFκB, PU.1, and SOX9, with DNA methylation modulating their activity on ZNF687 promoters 2. Notably, disease-causing variants cluster within ZNF687's nuclear localization signal, suggesting this domain is functionally critical 3. In hematopoiesis, ZNF687 functions as a lineage-preferential transcription factor regulating neutrophil development by recruiting the BRD4-SMRT corepressor complex to negatively regulate gfi1aa 4. Beyond bone, ZNF687 acts as an oncogene in multiple cancers. In hepatocellular carcinoma, elevated ZNF687 confers tyrosine kinase inhibitor resistance and poor prognosis 5. In lung adenocarcinoma, ZNF687 overexpression promotes proliferation and epithelial-mesenchymal transition via PI3K/AKT pathway activation 6. In colorectal cancer, FTO-mediated ZNF687 drives tumor progression through the Wnt/β-catenin pathway 7. ZNF687 dysregulation represents a therapeutic target across multiple disease contexts.

Sources cited
1
ZNF687 mutations associated with Paget's disease of bone; regulation by DLX5, NFκB, PU.1, and SOX9 transcription factors; DNA methylation effects on promoter activity
PMID: 36372390
2
ZNF687 is one of at least two genes with mutations causing Paget's disease of bone, characterized by increased osteoclast-mediated bone resorption and compensatory bone formation
PMID: 30671590
3
ZNF687 is a tyrosine kinase inhibitor-resistant gene in hepatocellular carcinoma; overexpression associated with worse overall survival prognosis
PMID: 39377570
4
ZNF687 is a lineage-preferential transcription factor that recruits BRD4-SMRT complex to negatively regulate gfi1aa during neutrophil development
PMID: 38326409
5
ZNF687 pathogenic variants in Paget's disease cluster in the nuclear localization signal; nuclear localization signal is functionally important
PMID: 37728743
6
ZNF687 overexpression in lung adenocarcinoma promotes cell proliferation, migration, invasion, and epithelial-mesenchymal transition through PI3K/AKT signaling pathway activation
PMID: 36944484
7
FTO-mediated ZNF687 accelerates colorectal cancer tumor growth, metastasis, and angiogenesis through Wnt/β-catenin pathway
PMID: 37983718
8
ZNF687 germline mutations cause giant cell tumor of bone in Paget disease context; ZNF687 encodes transcription factor involved in DNA double-strand break repair repression
PMID: 32502498
Disease Associationsⓘ21
osteitis deformansOpen Targets
0.63Moderate
ovarian dysfunctionOpen Targets
0.17Weak
hepatocellular carcinomaOpen Targets
0.09Suggestive
lung adenocarcinomaOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.06Suggestive
Granular Cell TumorOpen Targets
0.02Suggestive
cancerOpen Targets
0.01Suggestive
colorectal carcinomaOpen Targets
0.01Suggestive
Paget diseaseOpen Targets
0.01Suggestive
giant cell tumorOpen Targets
0.01Suggestive
acute myeloid leukemiaOpen Targets
0.01Suggestive
colorectal cancerOpen Targets
0.01Suggestive
ulcerative colitisOpen Targets
0.01Suggestive
bone giant cell tumorOpen Targets
0.01Suggestive
osteosarcomaOpen Targets
0.00Suggestive
bone neoplasmOpen Targets
0.00Suggestive
CirrhosisOpen Targets
0.00Suggestive
gastric cancerOpen Targets
0.00Suggestive
liver cancerOpen Targets
0.00Suggestive
undifferentiated sarcomaOpen Targets
0.00Suggestive
Paget disease of bone 6UniProt
Pathogenic Variants1
NM_020832.3(ZNF687):c.725G>T (p.Ser242Ile)Pathogenic
Paget disease of bone 6
☆☆☆☆2016→ Residue 242
View on ClinVar ↗
Related Genes
INTS3Protein interaction100%INTS5Protein interaction100%ZNF592Protein interaction99%ZMYND8Protein interaction99%INTS1Protein interaction99%INTS6Protein interaction99%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
44%
Brain
42%
Lung
37%
Heart
32%
Liver
30%
Gene Interaction Network
Click a node to explore
ZNF687INTS3INTS5ZNF592ZMYND8INTS1INTS6
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8N1G0
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.29Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.19 [0.12–0.29]
RankingsWhere ZNF687 stands among ~20K protein-coding genes
  • #5,839of 20,598
    Most Researched82
  • #4,956of 5,498
    Most Pathogenic Variants1
  • #1,085of 17,882
    Most Constrained (LOEUF)0.29 · top 10%
Genes detectedZNF687
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Regulation of human ZNF687, a gene associated with Paget's disease of bone.
PMID: 36372390
Int J Biochem Cell Biol · 2023
1.00
2
Paget's Disease of Bone.
PMID: 30671590
Calcif Tissue Int · 2019
0.90
3
An analysis of the clinical significance of the TKI-resistant gene ZNF687 for hepatocellular carcinoma patients.
PMID: 39377570
Adv Clin Exp Med · 2025
0.80
4
Znf687 recruits Brd4-Smrt complex to regulate gfi1aa during neutrophil development.
PMID: 38326409
Leukemia · 2024
0.70
5
Genetic Screening of ZNF687 and PFN1 in a Paget's Disease of Bone Cohort Indicates an Important Role for the Nuclear Localization Signal of ZNF687.
PMID: 37728743
Calcif Tissue Int · 2023
0.60