ArticleGenome medicine2017
De novo and rare mutations in the HSPA1L heat shock gene associated with inflammatory bowel disease.
Article in Genome medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
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- Automatic Text-Mining Approach to Identify Molecular Target Candidates Associated with Metabolic Processes for Myotonic Dystrophy Type 1.International journal of environmental research and public health · 2023Article
- Integrative genetic, genomic and transcriptomic analysis of heat shock protein and nuclear hormone receptor gene associations with spontaneous preterm birth.Scientific reports · 2021Article
- Spontaneous preterm birth: the underpinnings in the maternal and fetal genomes.NPJ genomic medicine · 2021Review
- Differential mitochondrial proteomic analysis of A549 cells infected with avian influenza virus subtypes H5 and H9.Virology journal · 2021Article
- Effects of vitrification and cryostorage duration on single-cell RNA-Seq profiling of vitrified-thawed human metaphase II oocytes.Frontiers of medicine · 2021Article
- Genetic Sequencing of Pediatric Patients Identifies Mutations in Monogenic Inflammatory Bowel Disease Genes that Translate to Distinct Clinical Phenotypes.Clinical and translational gastroenterology · 2020Observational
- The heat shock protein family genePeerJ · 2020Article
- MAPKAP kinase 2-mediated phosphorylation of HspA1L protects male germ cells from heat stress-induced apoptosis.Cell stress & chaperones · 2019Article
- The Functions and Therapeutic Potential of Heat Shock Proteins in Inflammatory Bowel Disease-An Update.International journal of molecular sciences · 2019Review
- Melatonin Enhances Mitophagy by Upregulating Expression of Heat Shock 70 kDa Protein 1L in Human Mesenchymal Stem Cells under Oxidative Stress.International journal of molecular sciences · 2019Article
- GenePy - a score for estimating gene pathogenicity in individuals using next-generation sequencing data.BMC bioinformatics · 2019Article
- Insights into genetics, human biology and disease gleaned from family based genomic studies.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Review
- Neuroinflammation in preterm babies and autism spectrum disorders.Pediatric research · 2019Review
- Platinum Nanoparticles As A Therapeutic Agent Against Dextran Sodium Sulfate-Induced Colitis In Mice.International journal of nanomedicine · 2019Article
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundInflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disease of the gastrointestinal tract which includes ulcerative colitis and Crohn's disease. Genetic risk factors for IBD are not well understood.
methodsWe performed a family-based whole exome sequencing (WES) analysis on a core family (Family A) to identify potential causal mutations and then analyzed exome data from a Caucasian pediatric cohort (136 patients and 106 controls) to validate the presence of mutations in the candidate gene, heat shock 70 kDa protein 1-like (HSPA1L). Biochemical assays of the de novo and rare (minor allele frequency, MAF < 0.01) mutation variant proteins further validated the predicted deleterious effects of the identified alleles.
resultsIn the proband of Family A, we found a heterozygous de novo mutation (c.830C > T; p.Ser277Leu) in HSPA1L. Through analysis of WES data of 136 patients, we identified five additional rare HSPA1L mutations (p.Gly77Ser, p.Leu172del, p.Thr267Ile, p.Ala268Thr, p.Glu558Asp) in six patients. In contrast, rare HSPA1L mutations were not observed in controls, and were significantly enriched in patients (P = 0.02). Interestingly, we did not find non-synonymous rare mutations in the HSP70 isoforms HSPA1A and HSPA1B. Biochemical assays revealed that all six rare HSPA1L variant proteins showed decreased chaperone activity in vitro. Moreover, three variants demonstrated dominant negative effects on HSPA1L and HSPA1A protein activity.
conclusionsOur results indicate that de novo and rare mutations in HSPA1L are associated with IBD and provide insights into the pathogenesis of IBD, and also expand our understanding of the roles of HSP70s in human disease.
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