Computational analysis of functional single nucleotide polymorphisms associated with SLC26A4 gene

Autoři: Mirza Jawad Ul Hasnain aff001;  Muhammad Shoaib aff002;  Salman Qadri aff003;  Bakhtawar Afzal aff004;  Tehreem Anwar aff001;  Syed Hassan Abbas aff001;  Amina Sarwar aff001;  Hafiz Muhammad Talha Malik aff005;  Muhammad Tariq Pervez aff001
Působiště autorů: Department of Bioinformatics, Virtual University of Pakistan, Lahore, Pakistan aff001;  Department of Computer Science and Engineering, UET, Lahore, Pakistan aff002;  Department of CS & IT, The Islamia University of Bahawalpur, Bahawalpur, Pakistan aff003;  Department of Biosciences, COMSATS University, Islamabad, Pakistan aff004;  Alpha Genomics Private Limited, PWD, Islamabad, Pakistan aff005
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225368


Single Nucleotide Polymorphisms (SNPs) are the most common candidate mutations in human beings that play a vital role in the genetic basis of certain diseases. Previous studies revealed that Solute Carrier Family 26 Member 4 (SLC26A4) being an essential gene of the multi-faceted transporter family SLC26 facilitates reflexive movement of Iodide into follicular lumen through apical membrane of thyrocyte. SLC26A4 gene encodes Pendred protein, a membrane glycoprotein, highly hydrophobic in nature, present at the apical membrane of thyrocyte functioning as transporter of iodide for thyroid cells. A minor genetic variation in SLC26A4 can cause Pendred syndrome, a syndrome associated with thyroid glands and deafness. In this study, we performed in-silico analysis of 674 missense SNPs of SLC26A4 using different computational platforms. The bunch of tools including SNPNEXUS, SNAP-2, PhD-SNP, SNPs&GO, I-Mutant, ConSurf, and ModPred were used to predict 23 highly confident damaging and disease causing nsSNPs (G209V, G197R, L458P, S427P, Q101P, W472R, N392Y, V359E, R409C, Q235R, R409P, G139V, G497S, H723R, D87G, Y127H, F667C, G334A, G95R, S427C, R291W, Q383H and E384G) that could potentially alter the SLC26A4 gene. Moreover, protein structure prediction, protein-ligand docking and Molecular Dynamics simulation were performed to confirm the impact of two evident alterations (Y127H and G334A) on the protein structure and function.

Klíčová slova:

Biochemical simulations – Molecular dynamics – Molecular genetics – Mutation – Protein structure – Protein structure comparison – Protein structure prediction – Structural proteins


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