Systematic in Silico Assessment of Potentially Deleterious BMPR2 Variants Associated with Pulmonary Arterial Hypertension

Melih Günay; Meliha Merve Hız

doi:10.28979/jarnas.1858081

Systematic in Silico Assessment of Potentially Deleterious BMPR2 Variants Associated with Pulmonary Arterial Hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a fatal vasculopathy in which germline variation in Bone Morphogenetic Protein Receptor Type II (BMPR2) is considered a major genetic factor for disease susceptibility. This study systematically screened BMPR2 single nucleotide variants using a multi-step in silico pipeline that combined functional annotation, pathogenicity prediction, structural stability assessment, evolutionary conservation, post-translational modification mapping, and protein-protein interaction analysis. From 1569 variants retrieved from gnomAD and annotated with the Variant Effect Predictor, missense substitutions were prioritized and evaluated with multiple classifiers (PredictSNP, PolyPhen-2, SIFT, SNAP), while MuPro and I-Mutant 3.0 estimated effects on protein stability. ConSurf was used to map residue conservation, MusiteDeep to predict post-translational modification sites, and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) to interrogate the BMPR2 interaction network. Most selected missense variants yielded negative ΔΔG values, consistent with predicted reductions in protein structure stability; substitutions such as G68D, G210D and D344Y were predicted to alter polarity, hydrogen bonding and steric constraints. Approximately 92% of prioritized variants were located to highly conserved residues within extracellular cysteine-rich and intracellular kinase domains, often near phosphorylation or glycosylation clusters. Taken together, these in silico findings prioritize several BMPR2 missense variants as candidates for future functional investigation and provide a framework for targeted experimental validation and improved genetic interpretation in PAH.

Keywords

References

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Details

Primary Language

English

Subjects

Bioinformatics and Computational Biology (Other)

Journal Section

Research Article

Authors

Melih Günay ^*
0000-0003-0336-3010
Türkiye

Meliha Merve Hız
0000-0003-4303-9717
Türkiye

Publication Date

March 30, 2026

Submission Date

January 6, 2026

Acceptance Date

March 20, 2026

Published in Issue

Year 2026 Volume: 12 Number: 1

DOI

https://doi.org/10.28979/jarnas.1858081

IZ

https://izlik.org/JA84MS34PF

Cite

RIS / Bibtex

APA

Günay, M., & Hız, M. M. (2026). Systematic in Silico Assessment of Potentially Deleterious BMPR2 Variants Associated with Pulmonary Arterial Hypertension. Journal of Advanced Research in Natural and Applied Sciences, 12(1), 1-14. https://doi.org/10.28979/jarnas.1858081

AMA

1.Günay M, Hız MM. Systematic in Silico Assessment of Potentially Deleterious BMPR2 Variants Associated with Pulmonary Arterial Hypertension. JARNAS. 2026;12(1):1-14. doi:10.28979/jarnas.1858081

Chicago

Günay, Melih, and Meliha Merve Hız. 2026. “Systematic in Silico Assessment of Potentially Deleterious BMPR2 Variants Associated With Pulmonary Arterial Hypertension”. Journal of Advanced Research in Natural and Applied Sciences 12 (1): 1-14. https://doi.org/10.28979/jarnas.1858081.

EndNote

Günay M, Hız MM (March 1, 2026) Systematic in Silico Assessment of Potentially Deleterious BMPR2 Variants Associated with Pulmonary Arterial Hypertension. Journal of Advanced Research in Natural and Applied Sciences 12 1 1–14.

IEEE

[1]M. Günay and M. M. Hız, “Systematic in Silico Assessment of Potentially Deleterious BMPR2 Variants Associated with Pulmonary Arterial Hypertension”, JARNAS, vol. 12, no. 1, pp. 1–14, Mar. 2026, doi: 10.28979/jarnas.1858081.

ISNAD

Günay, Melih - Hız, Meliha Merve. “Systematic in Silico Assessment of Potentially Deleterious BMPR2 Variants Associated With Pulmonary Arterial Hypertension”. Journal of Advanced Research in Natural and Applied Sciences 12/1 (March 1, 2026): 1-14. https://doi.org/10.28979/jarnas.1858081.

JAMA

1.Günay M, Hız MM. Systematic in Silico Assessment of Potentially Deleterious BMPR2 Variants Associated with Pulmonary Arterial Hypertension. JARNAS. 2026;12:1–14.

MLA

Günay, Melih, and Meliha Merve Hız. “Systematic in Silico Assessment of Potentially Deleterious BMPR2 Variants Associated With Pulmonary Arterial Hypertension”. Journal of Advanced Research in Natural and Applied Sciences, vol. 12, no. 1, Mar. 2026, pp. 1-14, doi:10.28979/jarnas.1858081.

Vancouver

1.Melih Günay, Meliha Merve Hız. Systematic in Silico Assessment of Potentially Deleterious BMPR2 Variants Associated with Pulmonary Arterial Hypertension. JARNAS. 2026 Mar. 1;12(1):1-14. doi:10.28979/jarnas.1858081

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