ArticleEuropean journal of human genetics : EJHG2014
Autosomal recessive mutations in nuclear transport factor KPNA7 are associated with infantile spasms and cerebellar malformation.
Article in European journal of human genetics : EJHG, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Heterozygous Nonsense Mutation in the Nuclear Transport FactorInternational journal of molecular sciences · 2026Article
- Proteome-scale characterisation of motif-based interactome rewiring by disease mutations.Molecular systems biology · 2024Article
- Nuclear localization signal-tagged systems: relevant nuclear import principles in the context of current therapeutic design.Chemical Society reviews · 2024Review
- Review
- Nuclear ERK1/2 signaling potentiation enhances neuroprotection and cognition via Importinα1/KPNA2.EMBO molecular medicine · 2023Article
- Potential Role of Protein Kinase FAM20C on the Brain in Raine Syndrome, an In Silico Analysis.International journal of molecular sciences · 2023Article
- Karyopherin α deficiency contributes to human preimplantation embryo arrest.The Journal of clinical investigation · 2023Article
- NPM2 in malignant peritoneal mesothelioma: from basic tumor biology to clinical medicine.World journal of surgical oncology · 2022Review
- Differential recognition of canonical NF-κB dimers by Importin α3.Nature communications · 2022Article
- Article
- An epilepsy-associated mutation in the nuclear import receptor KPNA7 reduces nuclear localization signal binding.Scientific reports · 2020Article
- Proteomics of nucleocytoplasmic partitioning.Current opinion in chemical biology · 2019Review
- Importin α: functions as a nuclear transport factor and beyond.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2018Review
- Targeted sequencing of 351 candidate genes for epileptic encephalopathy in a large cohort of patients.Molecular genetics & genomic medicine · 2016Article
- Lessons learned from gene identification studies in Mendelian epilepsy disorders.European journal of human genetics : EJHG · 2016Review
- Recessive loss-of-function mutations in AP4S1 cause mild fever-sensitive seizures, developmental delay and spastic paraplegia through loss of AP-4 complex assembly.Human molecular genetics · 2015Article
- Diversification of importin-α isoforms in cellular trafficking and disease states.The Biochemical journal · 2015Review
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Authors and funding
10 authors at 4 institutions in 1 country.
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Abstract
Nuclear import receptors of the KPNA family recognize the nuclear localization signal in proteins and together with importin-β mediate translocation into the nucleus. Accordingly, KPNA family members have a highly conserved architecture with domains that contact the nuclear localization signal and bind to importin-β. Here, we describe autosomal recessive mutations in KPNA7 found by whole exome sequencing in a sibling pair with severe developmental disability, infantile spasms, subsequent intractable epilepsy consistent with Lennox-Gastaut syndrome, partial agenesis of the corpus callosum, and cerebellar vermis hypoplasia. The mutations mapped to exon 7 in KPNA7 result in two amino-acid substitutions, Pro339Ala and Glu344Gln. On the basis of the crystal structure of the paralog KPNA2 bound to a bipartite nuclear localization signal from the retinoblastoma protein, the amino-acid substitutions in the affected subjects were predicted to occur within the seventh armadillo repeat that forms one of the two nuclear localization signal-binding sites in KPNA family members. Glu344 is conserved in all seven KPNA proteins, and we found that the Glu354Gln mutation in KPNA2 is sufficient to reduce binding to the retinoblastoma nuclear localization signal to approximately one-half that of wild-type protein. Our data show that compound heterozygous mutations in KPNA7 are associated with a human neurodevelopmental disease, and provide the first example of a human disease associated with mutation of a nuclear transport receptor.
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