ArticleNAR genomics and bioinformatics2023
Pathogenic signal peptide variants in the human genome.
Article in NAR genomics and bioinformatics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The trial behind it
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Who cites it
23 citing papers in PubMed, 26 citations in OpenAlex.
- Fusion gene heterogeneity and kinase enrichment in high-grade serous carcinomas.Neoplasia (New York, N.Y.) · 2026Article
- Characterization of missense variants in the signal peptide of C1 esterase inhibitor.The Journal of allergy and clinical immunology · 2026Article
- Are Signal Peptides Hidden Regulators of Neurodegenerative Disease?Biomedicines · 2026Review
- Human SRP Subunits Coordinate Protein Targeting and mRNA Quality Control.bioRxiv : the preprint server for biology · 2026Article
- PLA2G2F suppresses ferroptosis through phospholipid remodeling.Nature structural & molecular biology · 2026Article
- Protocol for detecting cytosol-retained proopiomelanocortin by fractionation and co-immunoprecipitation assay.STAR protocols · 2026Article
- Ultra-rare variants in LAMA2 are risk factors for frontotemporal dementia and motor neuron disease.Human molecular genetics · 2026Article
- Improved functional JAG1 and NOTCH2 variant testing in patients with clinical or suspected Alagille syndrome using new low-Notch activity cells.Human genetics · 2026Article
- ZAP targets aberrant mRNA transcripts encoding proteins with defective signal peptides for degradation.The EMBO journal · 2026Article
- Signal recognition particle-dependent secretome in humans.Scientific reports · 2026Article
- A new form of diabetes caused by INS mutations defined by zygosity, stem cell and population data.EMBO molecular medicine · 2026Article
- Multiplex and multimodal mapping of variant effects in secreted proteins via MultiSTEP.Nature structural & molecular biology · 2025Article
- GRIN2B disease-associated mutations disrupt the function of BK channels and NMDA receptor signaling nanodomains.The Journal of general physiology · 2025Article
- A light-resuming strategy as a screening method for selecting Sec61 inhibitors down-modulating PD-L1 expression.Nature communications · 2025Article
- Multiplex, multimodal mapping of variant effects in secreted proteins.bioRxiv : the preprint server for biology · 2025Article
- Molecular puzzle of insulin: structural assembly pathways and their role in diabetes.Frontiers in cell and developmental biology · 2025Review
- Signal Peptides and Their Fragments in Post-Translation: Novel Insights of Signal Peptides.International journal of molecular sciences · 2024Review
- A monoallelic variant in CCN2 causes an autosomal dominant spondyloepimetaphyseal dysplasia with low bone mass.Bone research · 2024Article
- Molecular Origins of the Mendelian Rare Diseases Reviewed by Orpha.net: A Structural Bioinformatics Investigation.International journal of molecular sciences · 2024Article
- A new mRNA structure prediction based approach to identifying improved signal peptides for bone morphogenetic protein 2.BMC biotechnology · 2024Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Secreted and membrane proteins represent a third of all cellular proteins and contain N-terminal signal peptides that are required for protein targeting to endoplasmic reticulum (ER). Mutations in signal peptides affect protein targeting, translocation, processing, and stability, and are associated with human diseases. However, only a few of them have been identified or characterized. In this report, we identified pathogenic signal peptide variants across the human genome using bioinformatic analyses and predicted the molecular mechanisms of their pathology. We recovered more than 65 thousand signal peptide mutations, over 11 thousand we classified as pathogenic, and proposed framework for distinction of their molecular mechanisms. The pathogenic mutations affect over 3.3 thousand genes coding for secreted and membrane proteins. Most pathogenic mutations alter the signal peptide hydrophobic core, a critical recognition region for the signal recognition particle, potentially activating the Regulation of Aberrant Protein Production (RAPP) quality control and specific mRNA degradation. The remaining pathogenic variants (about 25%) alter either the N-terminal region or signal peptidase processing site that can result in translocation deficiencies at the ER membrane or inhibit protein processing. This work provides a conceptual framework for the identification of mutations across the genome and their connection with human disease.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.