https://journals.riphah.edu.pk/index.php/rjahs <p>Issues: 2 per year <br />Chief Editor: Prof. Dr. Syed Shakil-ur-Rehman<br />Editor: Dr. Hafiz Ghulam Murtaza Saleem <br />Managing Editor: Dr. Safia Firdous Contact: [email protected] <br />Dr Faqeeha Javed Contact: [email protected]<br />ISSN: 3005-2742 (Print)<br />ISSN: 3005-2750 (Online)<br />Journal Website: https://journals.riphah.edu.pk/index.php/rjahs<br />Affiliation University website: https://www.riphah.edu.pk/<br />Scope and Mission: Riphah Journal of Allied Health Sciences (RJAHS) is new, and primarily focused on bridging clinical and basic research in the area of Allied Health Sciences. Journal accepts articles in all research areas lie under the umbrella of Allied Health Sciences including diagnostics and disease prognosis in areas of Medical Laboratory sciences, Health Biotechnology, Optometry, Food Science and Human Nutrition</p> en-US Wed, 24 Dec 2025 11:24:41 +0000 OJS 3.2.1.4 http://blogs.law.harvard.edu/tech/rss 60 https://journals.riphah.edu.pk/index.php/rjahs/article/view/2871 <p><strong>Background:</strong> The Fas receptor (FAS) and its ligand (FASLG) are key regulators of the extrinsic apoptotic pathway, play essential role in immune homeostasis. Their genetic alterations disrupt apoptotic signaling and contribute to autoimmune disorders, and cancer.<br />Objective: This study was designed to perform a comprehensive in-silico analysis to identify pathogenic missense variants in FAS and FASLG and to evaluate their structure-functional consequences.<br /><strong>Methodology:</strong> 12 different pathogenicity prediction tools were used to screen 392 missense variants of FAS and structural modeling was performed. Interaction analyses was performed with GeneMANIA and COACH.<br /><strong>Results:</strong> We identified G112S (rs2133504146) as the deleterious variant. Consensus filtering initially highlighted 82 risk-associated variants, including C85Y (rs2133502994), C119Y (rs2133513826), and C127G (rs1848386782). Structural modeling confirmed conformational alterations and disulfide bond loss in these variants. Similarly, 258 missense variants in FASLG were analyzed and were narrowed down to 44 high-confidence pathogenic variants. Among these, N184K (rs771262843), N250D (rs1659251672), and N260K (rs761374744) were predicted to abrogate N-glycosylation sites within the TNF homology domain, potentially impairing ligand function. Pathogenic FAS variants were predominantly localized to the extracellular ligand-binding domain, whereas those in FASLG clustered within the TNF homology region.</p> <p><strong>Conclusion:</strong> Collectively, this work delineates key pathogenic variants within the FAS/FASLG axis, provides mechanistic insights into how disrupted apoptosis contributes to immune dysregulation, and sets a foundation for their future experimental validation.<br /><br /></p> Amna Ayub, Khulod Ibraheem , Prof. Dr. Saima Sadaf Copyright (c) 2025 Riphah Journal of Allied Health Sciences https://journals.riphah.edu.pk/index.php/rjahs/article/view/2871 Wed, 24 Dec 2025 00:00:00 +0000