Are splicing mutations the most frequent cause of hereditary disease?
Abstract
Disease‐causing point mutations are assumed to act predominantly through subsequent individual changes in the amino acid sequence that impair the normal function of proteins. However, point mutations can have a more dramatic effect by altering the splicing pattern of the gene. Here, we describe an approach to estimate the overall importance of splicing mutations. This approach takes into account the complete set of genes known to be involved in disease and suggest that, contrary to current assumptions, many mutations causing disease may actually be affecting the splicing pattern of the genes.
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One of the main ways genetic variants cause disease is by disrupting splicing.
“One of the main ways genetic variants cause disease is by disrupting splicing15, a process that produces mature RNA sequences by excising introns and ligating exons at splice junctions.”
From Advancing regulatory variant effect prediction with AlphaGenome (2026) · cites this paper as [15]
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“One of the main ways genetic variants cause disease is by disrupting splicing 15 , a process that produces mature RNA sequences by excising”
Defining the regulatory network of the tissue-specific splicing factors Fox-1 and Fox-2
Zhang, C., Zhang, Z., Castle, J., Sun, S., Johnson, J., Krainer, A. R., & Zhang, M. Q. (2008) · Genes & Development · doi:10.1101/gad.1703108 · Cited by 300 · see citing works
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Hiller, M., Huse, K., Szafranski, K., Jahn, N., Hampe, J., Schreiber, S., Backofen, R., & Platzer, M. (2006) · The American Journal of Human Genetics · doi:10.1086/500151 · Cited by 54 · see citing works
A novel LRAT mutation affecting splicing in a family with early onset retinitis pigmentosa
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- Authors
- López-Bigas, N., Audit, B., Ouzounis, C., Parra, G., & Guigó, R.
- Affiliations
- European Bioinformatics Institute (GB)
- Universitat Pompeu Fabra (ES)
- Corresponding author
- López-Bigas, Núria
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2005-03-02
- Volume
- 579
- Issue
- 9
- Pages
- 1900-1903
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W1983924599
- Cited by
- 412
- References
- 0
- Citations by year
- 2026: 12 · 2025: 21 · 2024: 11 · 2023: 33 · 2022: 17 · 2021: 33 · 2020: 16 · 2019: 16 · 2018: 26 · 2017: 22 · 2016: 23 · 2015: 21 · 2014: 25 · 2013: 19 · 2012: 33
- FWCI
- 3.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- splicing mutation, genetic disorders, point mutations, alternative splicing, pathogenic variants, protein function, disease-associated genes
- MeSH terms
- Humans, Models, Genetic, RNA Splicing, Point Mutation, Amino Acid Substitution, Genetic Diseases, Inborn
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