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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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EBF2
EBF transcription factor 2
Chromosome 8 · 8p21.2
NCBI Gene: 64641Ensembl: ENSG00000221818.10HGNC: HGNC:19090UniProt: B2RNT0
28PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingregulation of transcription by RNA polymerase IIDNA-binding transcription factor activity, RNA polymerase II-specificRNA polymerase II cis-regulatory region sequence-specific DNA bindingneurodegenerative diseasehypertensionDupuytren Contracturediabetes mellitus
✦AI Summary

EBF2 is a transcription factor that regulates adipocyte development and thermogenesis through multiple mechanisms. In brown adipose tissue (BAT), EBF2 functions as part of the core thermogenic gene activation machinery 1, working cooperatively with other transcriptional regulators to control uncoupling protein 1 (UCP1)-dependent thermogenesis 2. EBF2 stability is regulated by the deubiquitinating enzyme USP2; USP2-mediated EBF2 stabilization promotes BAT thermogenesis and protects against obesity 3. Beyond adipose tissue, EBF2 acts as a transcriptional co-regulator with histone methyltransferase KMT2D to suppress pancreatic cancer progression by upregulating the tumor suppressor KLLN 4. Genetically, EBF2 variants are associated with epicardial and pericardial adiposity, contributing to cardiovascular disease risk 5, and EBF2 polymorphisms show significant association with Kawasaki disease in Korean populations 6. In osteosarcoma, miR-204-5p suppresses the oncogenic effects of EBF2 by targeting its mRNA stability, with EBF2 promoting cancer cell migration and survival 7. EBF2 variants also associate with diabetic nephropathy susceptibility 8. Thus, EBF2 has pleiotropic functions spanning metabolic, immune, and oncogenic pathways.

Sources cited
1
USP2 deubiquitinase stabilizes EBF2 to promote BAT thermogenesis and protect against high-fat diet-induced obesity
PMID: 40189098
2
EBF2 is part of the core transcriptional machinery required for thermogenic gene activation in brown and beige adipocytes
PMID: 29704660
3
EBF2 mediates UCP1 gene activation in beige adipocytes through cooperation with thyroid hormone and ZFP423 pathways
PMID: 39580797
4
EBF2 cooperates with KMT2D-mediated H3K4me1 to upregulate KLLN and suppress pancreatic ductal adenocarcinoma progression
PMID: 38015024
5
EBF2 genetic variants are identified in GWAS of epicardial and pericardial adiposity, associated with cardiovascular disease risk
PMID: 38477908
6
EBF2 gene polymorphisms show significant association with Kawasaki disease in Korean populations
PMID: 29749135
7
miR-204-5p suppresses osteosarcoma by targeting EBF2 mRNA stability; EBF2 promotes osteosarcoma cell survival and migration
PMID: 30529043
8
EBF2 variants are identified as novel diabetic nephropathy susceptibility genes through GWAS meta-analysis
PMID: 29147756
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.54Moderate
hypertensionOpen Targets
0.54Moderate
Dupuytren ContractureOpen Targets
0.51Moderate
diabetes mellitusOpen Targets
0.50Moderate
prostate carcinomaOpen Targets
0.50Moderate
type 2 diabetes mellitusOpen Targets
0.49Moderate
Abnormality of the skeletal systemOpen Targets
0.48Moderate
Inguinal herniaOpen Targets
0.47Moderate
Increased blood pressureOpen Targets
0.45Moderate
essential hypertensionOpen Targets
0.44Moderate
cardiovascular diseaseOpen Targets
0.44Moderate
Palmar FibromatosisOpen Targets
0.42Moderate
HerniaOpen Targets
0.41Moderate
Umbilical herniaOpen Targets
0.40Weak
Hernia of the abdominal wallOpen Targets
0.40Weak
fibroblastic disorderOpen Targets
0.39Weak
response to xenobiotic stimulusOpen Targets
0.34Weak
metabolic syndromeOpen Targets
0.33Weak
lumbar disc herniationOpen Targets
0.33Weak
ovarian dysfunctionOpen Targets
0.33Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PLAC8Shared pathway100%PPARGProtein interaction100%TMTC1Protein interaction85%PRDM16Protein interaction79%ZNF423Protein interaction79%PEMTShared pathway50%
Tissue Expression6 tissues
Brain
100%
Heart
49%
Lung
2%
Ovary
1%
Liver
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
EBF2PLAC8PPARGTMTC1PRDM16ZNF423PEMT
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9HAK2
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.39Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.26 [0.18–0.39]
RankingsWhere EBF2 stands among ~20K protein-coding genes
  • #12,342of 20,598
    Most Researched28
  • #1,945of 17,882
    Most Constrained (LOEUF)0.39 · top quartile
Genes detectedEBF2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Cardiovascular Significance and Genetics of Epicardial and Pericardial Adiposity.
PMID: 38477908
JAMA Cardiol · 2024
1.00
2
EBF2 Links KMT2D-Mediated H3K4me1 to Suppress Pancreatic Cancer Progression via Upregulating KLLN.
PMID: 38015024
Adv Sci (Weinh) · 2024
0.90
3
Deubiquitinating enzyme USP2 regulates brown adipose tissue thermogenesis via controlling EBF2 stabilization.
PMID: 40189098
Mol Metab · 2025
0.80
4
Genetic and epigenetic control of adipose development.
PMID: 29704660
Biochim Biophys Acta Mol Cell Biol Lipids · 2019
0.70
5
Thyroid hormones are required for thermogenesis of beige adipocytes induced by Zfp423 inactivation.
PMID: 39580797
Cell Rep · 2024
0.60