Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Prediction the Functional Impacts of Highly Deleterious Non-Synonymous Variants of Tsga10 Gene Publisher



Jamali Z1 ; Zargar M1 ; Modarressi MH1
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Molecular Biology Research Communications Published:2025


Abstract

Testis specific gene antigen 10 (TSGA10) is a protein which has roles in spermatogenesis and cancers so that deletion or mutation in the TSGA10 gene resulted in non-obstructive infertility and aberrant expression of this protein, was detected in solid tumors and leukemia. Despite the crucial roles of TSGA10 in tumorigenesis and infertility, yet it is not obvious how various nsSNPs of its gene impress the structure and function of the TSGA10. Therefore, it is worthwhile to investigate the potential highly deleterious nsSNPs by several in-silico tools before launching costly experimental approaches. In the current study, we employed several different machine learning algorithms in a two-step screening procedure to analyze single nucleotide substitutions of TSGA10 gene. Prediction tools were included SIFT, PROVEAN, PolyPhen-2, SNAP2, SNPs & GO, PhD-SNP for the first step and the second step included predictive tools such as I-mutant 3.0, MUpro, SNPeffect 4.0 (LIMBO, WALTZ, TANGO, FoldX), MutationTaster and CADD. Also, the 3D models of significantly damaging variants were built by Phyre2. The results elucidated 15 amino acid alterations as the most deleterious ones. Among these S563P, E578K, Q580P, R638L, R638C, R638G, R638S, L648R, R649C, R649H were located in a domain which is approved to has interaction with the HIF1-A protein and D62Y, R105G, D106V and D111Y were located on phosphodiesterase domain. In sum, these predicted mutations significantly influence the function of TSGA10 and they could be used for precise study of this protein in infertility and cancer experimental investigations. © (2025), (Shiraz University). All rights reserved.
Related Docs
View other Related Docs
1. Anti-Angiogenic Effects of Testis-Specific Gene Antigen 10 on Primary Endothelial Cells, Gene (2020)
2. Identification and Expression Analysis of Zebrafitestis-Specific Gene 10 (Tsga10), International Journal of Developmental Biology (2019)
3. New Function of Tsga10 Gene in Angiogenesis and Tumor Metastasis: A Response to a Challengeable Paradox, Human Molecular Genetics (2016)
4. An Introduction to Expression and Regulation of Testicular Cancer Antigens: Review Article, Tehran University Medical Journal (2018)
5. Tsga10 Overexpression Inhibits Angiogenesis of Huvecs: A Hif-2Α Biased Perspective, Microvascular Research (2020)
6. Tsga10, As a Cancer/Testis Gene: Review Article, Tehran University Medical Journal (2015)
7. Identification of Tsga10 and Ggnbp2 Splicing Variants in 5′ Untranslated Region With Distinct Expression Profiles in Brain Tumor Samples, Frontiers in Oncology (2023)
8. The Genetic Perspective of Familial Glucocorticoid Deficiency: In Silico Analysis of Two Novel Variants, International Journal of Endocrinology (2020)
Experts (# of related papers)
View all Related Experts
Mohammad Hossein Modarressi (10)
Ali Reza Tavasoli (5)
Other Related Docs
9. A Novel Pathogenic Variant in the Fzd6 Gene Causes Recessive Nail Dysplasia in a Large Iranian Kindred, Journal of Dermatological Science (2017)
10. Tsga10 Expression Correlates With Sperm Profiles in the Adult Formalin-Exposed Mice, Andrologia (2016)
11. Genotype, Phenotype and in Silico Pathogenicity Analysis of Hexb Mutations: Panel Based Sequencing for Differential Diagnosis of Gangliosidosis, Clinical Neurology and Neurosurgery (2018)
12. Testicular Mirnas in Relation to Spermatogenesis, Spermatogonial Stem Cells and Cancer/Testis Genes, Scientific African (2019)
13. Crystallographic Modeling of the Pnpt1:C.1453A>G Variant As a Cause of Mitochondrial Dysfunction and Autosomal Recessive Deafness; Expanding the Neuroimaging and Clinical Features, Mitochondrion (2021)
14. Genotypes of European and Iranian Patients With Type 3 Von Willebrand Disease Enrolled in 3Winters-Ips, Blood Advances (2021)
15. Catecholaminergic Polymorphic Ventricular Tachycardia (And Seizure) Caused by a Novel Homozygous Likely Pathogenic Variant in Casq2 Gene, Gene (2024)
16. Certain Tsga10 Polymorphisms Are Not Associated With Male Infertility in Iranian Population, Gene Reports (2019)
17. Identification of a Novel Homozygous Gls Gene Variant Associated With Developmental and Epileptic Encephalopathy (Dee) Type 71, Neurogenetics (2024)
18. Whole-Exome Sequencing Uncovers Novel Causative Variants and Additional Findings in Three Patients Affected by Glycogen Storage Disease Type Vi and Fanconi−Bickel Syndrome, Frontiers in Genetics (2021)
19. Genetic Testing of Leukodystrophies Unraveling Extensive Heterogeneity in a Large Cohort and Report of Five Common Diseases and 38 Novel Variants, Scientific Reports (2021)
20. Identification of New Tsga10 Transcript Variants in Human Testis With Conserved Regulatory Rna Elements in 5'Untranslated Region and Distinct Expression in Breast Cancer, Biochimica et Biophysica Acta - Gene Regulatory Mechanisms (2017)
21. Use of Expanded Carrier Screening for Retrospective Diagnosis of Two Deceased Siblings With Van Maldergem Syndrome 2: Case Report, Asian Biomedicine (2022)
22. A Homozygous Truncating Mutation in Nalcn Causing Ihprf1: Detailed Clinical Manifestations and a Review of Literature, Application of Clinical Genetics (2020)
23. Clinical and Genetic Spectrum of a Large Cohort of Patients With Δ-Sarcoglycan Muscular Dystrophy, Brain (2022)
24. Two Novel and Five Rare Mutations in the Non Coding Regions of the Β-Globin Gene in the Iranian Population, Hemoglobin (2020)
25. Brown-Vialetto-Van Laere Syndrome and Fazio-Londe Syndrome: A Novel Mutation and in Silico Analyses, Journal of Clinical Neuroscience (2020)
26. Expanding the Clinical and Neuroimaging Features of Nkx6-2-Related Hereditary Spastic Ataxia Type 8, European Journal of Medical Genetics (2020)
27. Adult-Onset Very-Long-Chain Acyl-Coa Dehydrogenase Deficiency (Vlcadd), European Journal of Neurology (2020)
28. Genotype-Phenotype Correlation and Description of Two Novel Mutations in Iranian Patients With Glycogen Storage Disease 1B (Gsd1b), Orphanet Journal of Rare Diseases (2020)
29. Cancer-Testis Antigens: A Novel Group of Tumor Biomarkers in Ovarian Cancers, International Journal of Cancer Management (2016)
30. Expression Analysis of Tsga10 During in Vitro Differentiation of Germ Cells From Mouse Embryonic Stem Cell, Tehran University Medical Journal (2015)