Integrating Artificial Intelligence and Bioinformatics Methods to Identify Disruptive STAT1 Variants Impacting Protein Stability and Function

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Abstract

The Signal Transducer and Activator of Transcription 1 (STAT1) gene is an essential component of the JAK-STAT signalling pathway. This pathway has a pivotal role in regulating different cellular processes, including immune responses, cell growth, and apoptosis. Mutations in the STAT1 gene contribute to various body pathologies [OMIM #600555], including immune system dysfunction. In the current study, we used eighteen online computational approaches. Six pathogenic variants (R602W, I648T, V642D, L600P, I578N, and W504C) were predicted to significantly disrupt protein stability and function. These findings highlight the potential of approaches to pinpoint pathogenic single nucleotide polymorphisms, providing a time and cost effective alternative to experimental approaches. Up to the best of our knowledge, this is the original inclusive study, where we analyze STAT1 gene variants using both bioinformatics and artificial intelligence based model tools.
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Abstract The Signal Transducer and Activator of Transcription 1 (STAT1) gene is an essential component of the JAK-STAT signalling pathway. This pathway has a pivotal role in regulating different cellular processes, including immune responses, cell growth, and apoptosis. Mutations in the STAT1 gene contribute to various body pathologies [OMIM #600555], including immune system dysfunction. In the current study, we used eighteen online computational approaches. Six pathogenic variants (R602W, I648T, V642D, L600P, I578N, and W504C) were predicted to significantly disrupt protein stability and function. These findings highlight the potential of approaches to pinpoint pathogenic single nucleotide polymorphisms, providing a time and cost effective alternative to experimental approaches. Up to the best of our knowledge, this is the original inclusive study, where we analyze STAT1 gene variants using both bioinformatics and artificial intelligence based model tools. Competing Interest Statement The authors have declared no competing interest. Footnotes (lkaddam{at}kau.edu.sa) (ma.ahmed{at}psau.edu.sa) (a.alabdulkarim{at}psau.edu.sa)

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last seen: 2026-05-20T01:45:00.602351+00:00