Related Experiment Video
Updated: Jan 13, 2026
13:19
Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
Published on: November 2, 2013
17.1K
In Silico Characterization of Pathogenic ESR2 Coding and UTR Variants as Oncogenic Potential Biomarkers in
Hakeemah Al-Nakhle1,2, Zainab Almoerifi1, Layan Alharbi1
1Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taibah University, Madinah 42353, Saudi Arabia.
Genes
|October 29, 2025
Summary
Investigating Estrogen Receptor-β1 (ERβ1) gene variants reveals numerous deleterious mutations impacting ERβ1 stability and function. These ESR2 variants show tumor-type-specific clinical effects, highlighting their potential as biomarkers.
Area of Science:
- Genetics and Genomics
- Molecular Biology
- Cancer Research
Background:
- The ESR2 gene encodes Estrogen Receptor-β1 (ERβ1), a key player in hormone-dependent cancers.
- The functional impact of ESR2 genetic variants, including nonsynonymous SNPs (nsSNPs) and untranslated-region (UTR) variants, is not well understood.
Purpose of the Study:
- To conduct an in silico assessment of ESR2 variants to predict their pathogenicity, oncogenicity, and impact on ERβ1 structure and function.
- To evaluate the clinical relevance of ESR2 variants in breast (BRCA), endometrial (UCEC), and ovarian (OV) cancers.
Main Methods:
- Utilized Ensembl for variant retrieval and multiple bioinformatics tools (PredictSNP, I-Mutant, MUpro, HOPE, MutPred2, CScape) for pathogenicity and stability predictions.
- Employed STRING, KEGG, and GO for pathway analysis; RegulomeDB and polymiRTS for regulatory effects; and cBioPortal for pan-cancer survival analysis.
- Assessed the impact of nsSNPs on ERβ1 domains, co-factor recruitment, and post-transcriptional regulation, including miRNA binding.
Main Results:
- Identified 93 consistently deleterious missense nsSNPs, with several predicted to destabilize ERβ1, particularly in ligand-binding (LBD) and DNA-binding (DBD) domains.
- Found potential oncogenic drivers (R198P, D154N) with low population frequencies and predicted disruption of coactivator binding and transcriptional interactions.
- Observed tumor-type-specific clinical associations: worse overall survival (OS) in BRCA but better OS in UCEC and OV for ESR2-Altered cases.
Conclusions:
- This integrative analysis prioritizes high-impact ESR2 variants affecting ERβ1 structure and function.
- ESR2 variants exhibit context-dependent clinical effects, with potential implications for biomarker development.
- Further validation is needed to link specific variant classes to ERβ expression and survival outcomes for therapeutic applications.
