{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T17:23:06Z","timestamp":1782580986913,"version":"3.54.5"},"reference-count":41,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T00:00:00Z","timestamp":1649635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Human DNA contains several variations, which can affect the structure and normal functioning of a protein. These variations could be single nucleotide polymorphisms (SNPs) or insertion-deletions (InDels). SNPs, as opposed to InDels, are more commonly present in DNA and may cause genetic disorders. In the current study, several bioinformatic tools were used to prioritize the pathogenic variants in the SLITRK1 gene. Out of all of the variants, 16 were commonly predicted to be pathogenic by these tools. All the variants had very low frequency, i.e., &lt;0.0001 in the global population. The secondary structure of all filtered variants was predicted, but no structural change was observed at the site of variation in any variant. Protein stability analysis of these variants was then performed, which determined a decrease in protein stability of 10 of the variants. Amino acid conservation analysis revealed that all the amino acids were highly conserved, indicating their structural and functional importance. Protein 3D structure of wildtype SLITRK1 and all of its variants was predicted using I-TASSER, and the effect of variation on 3D structure of the protein was observed using the Missense3D tool, which presented the probable structural loss in three variants, i.e., Asn529Lys, Leu496Pro and Leu94Phe. The wildtype SLITRK1 protein and these three variants were independently docked with their close interactor protein PTPRD, and remarkable differences were observed in the docking sites of normal and variants, which will ultimately affect the functional activity of the SLITRK1 protein. Previous studies have shown that mutations in SLITRK1 are involved in Tourette syndrome. The present study may assist a molecular geneticist in interpreting the variant pathogenicity in research as well as diagnostic setup.<\/jats:p>","DOI":"10.3390\/genes13040672","type":"journal-article","created":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T00:23:11Z","timestamp":1649722991000},"page":"672","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["In Silico Analysis Identified Putative Pathogenic Missense nsSNPs in Human SLITRK1 Gene"],"prefix":"10.3390","volume":"13","author":[{"given":"Muhammad Zeeshan","family":"Ali","sequence":"first","affiliation":[{"name":"Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29111, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5147-5936","authenticated-orcid":false,"given":"Arshad","family":"Farid","sequence":"additional","affiliation":[{"name":"Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29111, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1149-5665","authenticated-orcid":false,"given":"Safeer","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29111, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Muzammal","sequence":"additional","affiliation":[{"name":"Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29111, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0185-4484","authenticated-orcid":false,"given":"Mohammed Al","family":"Mohaini","sequence":"additional","affiliation":[{"name":"Basic Sciences Department, College of Applied Medical Sciences, King Saud Bin Abdulaziz University for Health Sciences, Al Ahsa 31982, Saudi Arabia"},{"name":"King Abdullah International Medical Research Center, Al Ahsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulkhaliq J.","family":"Alsalman","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2026-0451","authenticated-orcid":false,"given":"Maitham A.","family":"Al Hawaj","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Clinical Pharmacy, King Faisal University, Al Ahsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4435-3003","authenticated-orcid":false,"given":"Yousef N.","family":"Alhashem","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Sciences Department, Mohammed Al-Mana College for Medical Sciences, Dammam 34222, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulmonem A.","family":"Alsaleh","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Sciences Department, Mohammed Al-Mana College for Medical Sciences, Dammam 34222, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman M.","family":"Almusalami","sequence":"additional","affiliation":[{"name":"King\u2019s College London, Strand, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahpara","family":"Maryam","sequence":"additional","affiliation":[{"name":"Department of Zoology, Government College No.1, Dera Ismail Khan 29111, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8591-0377","authenticated-orcid":false,"given":"Muzammil Ahmad","family":"Khan","sequence":"additional","affiliation":[{"name":"Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29111, Pakistan"},{"name":"Department of Human Genetics, Sidra Medical and Research Centre, Doha 26999, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"915","DOI":"10.56899\/149.3A.18","article-title":"Resistance gene analogs of mango: Insights on molecular defenses and evolutionary dynamics","volume":"149","author":"Lantican","year":"2020","journal-title":"Philipp. J. 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