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10.4103/aja202628
In silico prediction and functional analysis of non-synonymous single-nucleotide polymorphisms (nsSNPs) in human ACTL7A gene associated with spermatogenesis
Yi-Ni Zhang1,2,3,*
Miao Liu4,*
Yi-Si Sun2
Xin-Yue Yang3
Jun-Yan Chen5
Hui-Juan Shi2
Guo-Wu Chen3,
Ai-Jie Xin2,3,6,
1Department of Obstetrics and Gynecology, Reproductive Medicine Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China
2Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies (SIBPT), School of Pharmacy, Fudan University, Shanghai 200032, China
3Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China
4Reproductive Medicine Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China
5School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China
6Center of Reproductive Medicine, Affiliated Hospital of Youjiang Medical College for Nationalities, Baise 533000, China
Correspondence: Dr. AJ Xin (aijie_xin@163.com) or Dr. GW Chen (chengw911@qq.com)
Received: 19 December 2025; Accepted: 11 June 2026; published online: 13 October 2026
| Abstract |
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Actin-like 7A (ACTL7A) is considered to play an important role in acrosome formation, fertilization, and early embryo development. Several single-nucleotide polymorphisms (SNPs) in ACTL7A have been reported to be associated with male infertility. However, the functional consequences of the most non-synonymous SNPs (nsSNPs) in ACTL7A remain largely unclear. Here, a total of 489 nsSNPs in the ACTL7A gene were retrieved from the Database of Single-Nucleotide Polymorphism (dbSNP) and systematically analyzed using a series of computational tools. Among these, 44 nsSNPs were predicted to be potentially deleterious. Further in vitro validation identified eight nsSNPs associated with significantly decreased ACTL7A protein levels, which were therefore considered candidate functional variants, including rs534593253, rs775405375, rs768576884, rs1308056655, rs779034458, rs779515458, rs1827186853, and rs1827186891. In addition, one deletion variant and three nonsense variants were identified. Structural modeling further suggested that these nsSNP-derived variants may induce conformational alterations in the ACTL7A protein. Overall, this study provides a framework for prioritizing functionally relevant ACTL7A nsSNPs for future investigation.
Keywords: ACTL7A; in silico prediction; PolyPhen; SIFT; SNP
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