Leveraging Genomic Databases to Identify Missense Variants and Therapeutic Targets for Atopic Dermatitis
8 affiliations
- 1Faculty of Public Health, Universitas Ahmad Dahlan, Yogyakarta, Indonesia
- 2Faculty of Pharmacy, Universitas Ahmad Dahlan, Yogyakarta, Indonesia
- 3Department of Nursing, Faculty of Nursing and Health Sciences, Universitas Muhammadiyah Semarang, Semarang, Indonesia;
- 4Research Center for Vaccine and Drugs, Research Organization for Health, National Research and Innovation Agency, Cibinong, Indonesia
- 5School of Public Health, Department of Epidemiology and Biostatistics, University of Nevada, Las Vegas, USA
- 6Department of Pharmacy, School of Health Sciences ISFI, Banjarmasin, Indonesia
- 7Department of Clinical Pathology and Laboratory Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
- 8Research Center for Computing, Research Organization for Electronics and Informatics, National Research and Innovation Agency, Cibinong, Indonesia
Abstract
OBJECTIVE Atopic dermatitis (AD) is a complex inflammatory skin disorder with a strong genetic component. Identifying missense variants with functional relevance is essential for understanding disease mechanisms and informing therapeutic development. This study identified functionally relevant SNPs for AD using integrated genomic and bioinformatics analyses. METHODS We screened 180 AD-associated SNPs from the GWAS Catalog and filtered missense variants with genome-wide significance. Functional impact was assessed using PolyPhen-2 and Sorting Intolerant From Tolerant (SIFT). Population allele frequencies were extracted from the 1000 Genomes Project, tissue expression profiles from the GTEx Portal, and drug–gene interactions from DGIdb. RESULTS Two prioritized missense variants were identified: rs2228145 in IL6R, a common benign variant that modulates IL-6 signaling, and rs183884396 in TESPA1, a rare variant predicted to be damaging and enriched in European populations. TESPA1 showed minimal expression in healthy skin but substantial expression in immune-relevant tissues, suggesting an indirect immunoregulatory role in AD. IL6R demonstrated broad immune-tissue expression and multiple interactions with approved anti-inflammatory drugs, underscoring its therapeutic relevance. CONCLUSION By integrating genomic, functional, and pharmacological data, this study highlighted TESPA1 as a biologically plausible yet understudied immunoregulatory gene and IL6R as a clinically actionable target in AD. These computational findings are hypothesis-generating and warrant experimental validation to elucidate variant-specific mechanisms. Importantly, the identification of IL6R-targeting drugs and the ancestry-specific nature of TESPA1 variation provides a foundation for future precisionmedicine approaches in AD.
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BibTeX
@article{santri2026leveraging,
title = {{Leveraging Genomic Databases to Identify Missense Variants and Therapeutic Targets for Atopic Dermatitis}},
author = {Ichtiarini Nurullita Santri and Lalu Muhammad Irham and Satriya Pranata and Firdayani Firdayani and Yohane Vincent Abero Phiri and Riza Alfian and Rahmat Dani Satria and Wirawan Adikusuma},
journal = {Biomedical Sciences and Clinical Medicine},
year = {2026},
month = oct,
doi = {10.12982/bscm.2026.50},
url = {https://doi.org/10.12982/bscm.2026.50},
note = {CC BY},
}
RIS
TY - JOUR
TI - Leveraging Genomic Databases to Identify Missense Variants and Therapeutic Targets for Atopic Dermatitis
AU - Ichtiarini Nurullita Santri
AU - Lalu Muhammad Irham
AU - Satriya Pranata
AU - Firdayani Firdayani
AU - Yohane Vincent Abero Phiri
AU - Riza Alfian
AU - Rahmat Dani Satria
AU - Wirawan Adikusuma
PY - 2026
DA - 2026/10/01
JO - Biomedical Sciences and Clinical Medicine
DO - 10.12982/bscm.2026.50
UR - https://doi.org/10.12982/bscm.2026.50
AB - OBJECTIVE Atopic dermatitis (AD) is a complex inflammatory skin disorder with a strong genetic component. Identifying missense variants with functional relevance is essential for understanding disease mechanisms and informing therapeutic development. This study identified functionally relevant SNPs for AD using integrated genomic and bioinformatics analyses. METHODS We screened 180 AD-associated SNPs from the GWAS Catalog and filtered missense variants with genome-wide significance. Functional impact was assessed using PolyPhen-2 and Sorting Intolerant From Tolerant (SIFT). Population allele frequencies were extracted from the 1000 Genomes Project, tissue expression profiles from the GTEx Portal, and drug–gene interactions from DGIdb. RESULTS Two prioritized missense variants were identified: rs2228145 in IL6R, a common benign variant that modulates IL-6 signaling, and rs183884396 in TESPA1, a rare variant predicted to be damaging and enriched in European populations. TESPA1 showed minimal expression in healthy skin but substantial expression in immune-relevant tissues, suggesting an indirect immunoregulatory role in AD. IL6R demonstrated broad immune-tissue expression and multiple interactions with approved anti-inflammatory drugs, underscoring its therapeutic relevance. CONCLUSION By integrating genomic, functional, and pharmacological data, this study highlighted TESPA1 as a biologically plausible yet understudied immunoregulatory gene and IL6R as a clinically actionable target in AD. These computational findings are hypothesis-generating and warrant experimental validation to elucidate variant-specific mechanisms. Importantly, the identification of IL6R-targeting drugs and the ancestry-specific nature of TESPA1 variation provides a foundation for future precisionmedicine approaches in AD.
SN - 2774-1079
ER -