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GeneE
3 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ZBTB26
zinc finger and BTB domain containing 26
Chromosome 9 · 9q33.2
NCBI Gene: 57684Ensembl: ENSG00000171448.10HGNC: HGNC:23383UniProt: Q9HCK0
16PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingidentical protein bindingsequence-specific double-stranded DNA bindingRNA polymerase II cis-regulatory region sequence-specific DNA bindingAbnormality of the skeletal systemdiabetes mellitustype 2 diabetes mellitusmetabolic syndrome
✦AI Summary

ZBTB26 is a zinc finger transcription factor that functions as a transcriptional repressor through its BTB domain-mediated protein interactions. The BTB domains of ZBTB26 and related ZBTB family members form dynamic filaments that promote clustering into nuclear foci, enhancing DNA binding and transcriptional repression activity 1. ZBTB26 is implicated in both cancer and developmental disease. In lung squamous cell carcinoma, ZBTB26 expression is upregulated by the risk variant rs4573350 combined with tobacco smoke exposure through altered FOXA1 transcription factor binding; increased ZBTB26 promotes tumorigenesis by regulating PCNA expression and cell cycle progression 2. In thyroid development, ZBTB26 is essential for proper thyroid genesis, as demonstrated by morpholino knockdown in Xenopus laevis, which reduces thyroid anlagen size and PAX8 expression 3. De novo and inherited ZBTB26 mutations are associated with congenital hypothyroidism characterized by thyroid dysgenesis 3, highlighting its critical role in transcriptional regulation of developmental pathways. These findings establish ZBTB26 as a functionally important transcription factor with disease relevance in both cancer susceptibility and developmental endocrinology.

Sources cited
1
BTB domain filamentation promotes clustering of ZBTB proteins and supports transcriptional repression
PMID: 38996459
2
ZBTB26 expression is regulated by rs4573350 variant and smoking exposure; promotes LUSC tumorigenesis via PCNA regulation
PMID: 40168134
3
ZBTB26 mutations cause congenital hypothyroidism through impaired thyroid development; regulates PAX8 expression
PMID: 34946811
⚠Limited data available — This gene has 3 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.26Weak
diabetes mellitusOpen Targets
0.07Suggestive
type 2 diabetes mellitusOpen Targets
0.06Suggestive
metabolic syndromeOpen Targets
0.06Suggestive
osteoarthritis, kneeOpen Targets
0.06Suggestive
osteoarthritis, hipOpen Targets
0.04Suggestive
kidney failureOpen Targets
0.04Suggestive
amyloidosisOpen Targets
0.02Suggestive
type 2 diabetes nephropathyOpen Targets
0.02Suggestive
colorectal cancerOpen Targets
0.02Suggestive
congenital hypothyroidismOpen Targets
0.01Suggestive
hypothyroidismOpen Targets
0.01Suggestive
Primary hypothyroidismOpen Targets
0.01Suggestive
atrophy of thyroidOpen Targets
0.01Suggestive
Chédiak-Higashi syndromeOpen Targets
0.01Suggestive
atherosclerosisOpen Targets
0.00Suggestive
breast cancerOpen Targets
0.00Suggestive
cancerOpen Targets
0.00Suggestive
kidney cancerOpen Targets
0.00Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ZBTB14Shared pathway100%ZBTB25Shared pathway100%ZNF131Shared pathway100%ZNF134Shared pathway100%ZBTB39Shared pathway100%HIC2Shared pathway100%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
71%
Heart
43%
Brain
39%
Lung
36%
Liver
27%
Gene Interaction Network
Click a node to explore
ZBTB26ZBTB14ZBTB25ZNF131ZNF134ZBTB39HIC2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9HCK0
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.59Moderately Constrained
pLIⓘ
0.76Intermediate
Observed/Expected LoF0.36 [0.23–0.59]
RankingsWhere ZBTB26 stands among ~20K protein-coding genes
  • #15,446of 20,598
    Most Researched16
  • #3,959of 17,882
    Most Constrained (LOEUF)0.59 · top quartile
Genes detectedZBTB26
Sources retrieved3 papers
Response time—
📄 Sources
3
1
Dynamic BTB-domain filaments promote clustering of ZBTB proteins.
PMID: 38996459
Mol Cell · 2024
1.00
2
Genetic susceptibility to lung squamous cell carcinoma: new insights on 9q33.2 variants and tobacco smoking.
PMID: 40168134
Carcinogenesis · 2025
0.67
3
Identification of ZBTB26 as a Novel Risk Factor for Congenital Hypothyroidism.
PMID: 34946811
Genes (Basel) · 2021
0.33