Identifying six single nucleotide variants in the COL17A1 gene that alter RNA splicing: database analysis and minigene assays

Abstract Collagen type XVII alpha 1 chain (COL17A1) is a protein in the collagen family crucial for maintaining the integrity of skin and epithelial tissues. It is also vital for enamel formation and plays a significant role in the differentiation of ameloblasts. Many studies have indicated that sin...

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Main Authors: Yingfei Shao, Ran Zhang
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-95851-9
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author Yingfei Shao
Ran Zhang
author_facet Yingfei Shao
Ran Zhang
author_sort Yingfei Shao
collection DOAJ
description Abstract Collagen type XVII alpha 1 chain (COL17A1) is a protein in the collagen family crucial for maintaining the integrity of skin and epithelial tissues. It is also vital for enamel formation and plays a significant role in the differentiation of ameloblasts. Many studies have indicated that single nucleotide variants (SNVs) can disrupt normal splicing process of the pre-mRNA by altering various splicing regulatory signals. This study aimed to explore the potential impact of SNVs in COL17A1 geneon splicing events, with the ultimate aim of improving the prediction of disease prognosis. Here, we analyzed 703 SNVs including 446 exonic variants and 257 intronic variants in the COL17A1 gene using bioinformatics tools and identified candidate variants that may induce splicing alterations via minigene assays. Our study identified that, among eight candidate variants, six variants (c.1139 C > T, c.1834G > A, c.3198 C > T, c.202 + 6T > G, c.1222 + 4 A > G, c.3071-5G > A) induced splicing alterations by interfering with the recognition of classical splice sites or disrupting the ratio of exonic splicing enhancers/exonic splicing silencers, or both. This study emphasizes the necessity of assessing the effects of SNVs on at the mRNA level, aiding accurate characterization of COL17A1 variants and enabling the development of personalized treatment options.
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spelling doaj-art-e89b125102504e1ca7d3ce15e841f72e2025-08-20T03:07:41ZengNature PortfolioScientific Reports2045-23222025-04-011511710.1038/s41598-025-95851-9Identifying six single nucleotide variants in the COL17A1 gene that alter RNA splicing: database analysis and minigene assaysYingfei Shao0Ran Zhang1Wenzhou Medical University Renji CollegeDepartment of Nephrology, The Affiliated Qingdao Municipal Hospital of Qingdao UniversityAbstract Collagen type XVII alpha 1 chain (COL17A1) is a protein in the collagen family crucial for maintaining the integrity of skin and epithelial tissues. It is also vital for enamel formation and plays a significant role in the differentiation of ameloblasts. Many studies have indicated that single nucleotide variants (SNVs) can disrupt normal splicing process of the pre-mRNA by altering various splicing regulatory signals. This study aimed to explore the potential impact of SNVs in COL17A1 geneon splicing events, with the ultimate aim of improving the prediction of disease prognosis. Here, we analyzed 703 SNVs including 446 exonic variants and 257 intronic variants in the COL17A1 gene using bioinformatics tools and identified candidate variants that may induce splicing alterations via minigene assays. Our study identified that, among eight candidate variants, six variants (c.1139 C > T, c.1834G > A, c.3198 C > T, c.202 + 6T > G, c.1222 + 4 A > G, c.3071-5G > A) induced splicing alterations by interfering with the recognition of classical splice sites or disrupting the ratio of exonic splicing enhancers/exonic splicing silencers, or both. This study emphasizes the necessity of assessing the effects of SNVs on at the mRNA level, aiding accurate characterization of COL17A1 variants and enabling the development of personalized treatment options.https://doi.org/10.1038/s41598-025-95851-9COL17A1Amelogenesis imperfectaJunctional epidermolysis BullosaMinigene analysisSingle nucleotide variants
spellingShingle Yingfei Shao
Ran Zhang
Identifying six single nucleotide variants in the COL17A1 gene that alter RNA splicing: database analysis and minigene assays
Scientific Reports
COL17A1
Amelogenesis imperfecta
Junctional epidermolysis Bullosa
Minigene analysis
Single nucleotide variants
title Identifying six single nucleotide variants in the COL17A1 gene that alter RNA splicing: database analysis and minigene assays
title_full Identifying six single nucleotide variants in the COL17A1 gene that alter RNA splicing: database analysis and minigene assays
title_fullStr Identifying six single nucleotide variants in the COL17A1 gene that alter RNA splicing: database analysis and minigene assays
title_full_unstemmed Identifying six single nucleotide variants in the COL17A1 gene that alter RNA splicing: database analysis and minigene assays
title_short Identifying six single nucleotide variants in the COL17A1 gene that alter RNA splicing: database analysis and minigene assays
title_sort identifying six single nucleotide variants in the col17a1 gene that alter rna splicing database analysis and minigene assays
topic COL17A1
Amelogenesis imperfecta
Junctional epidermolysis Bullosa
Minigene analysis
Single nucleotide variants
url https://doi.org/10.1038/s41598-025-95851-9
work_keys_str_mv AT yingfeishao identifyingsixsinglenucleotidevariantsinthecol17a1genethatalterrnasplicingdatabaseanalysisandminigeneassays
AT ranzhang identifyingsixsinglenucleotidevariantsinthecol17a1genethatalterrnasplicingdatabaseanalysisandminigeneassays