ArticlePLoS genetics2008
Disruption of AP1S1, causing a novel neurocutaneous syndrome, perturbs development of the skin and spinal cord.
Article in PLoS genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 170 citations in OpenAlex.
- Copper in Human Health and Disease: Insights from Inherited Disorders.Physiology (Bethesda, Md.) · 2026Review
- Disorders Mimicking Wilson's Disease: Clinical, Biochemical, and Molecular Perspectives for Accurate Differential Diagnosis.Diagnostics (Basel, Switzerland) · 2026Review
- The Golgi apparatus: adaptations to neuronal shape and functions.The EMBO journal · 2026Review
- Feeding-Triggered Seizures in a Newborn withJournal of clinical medicine · 2025Article
- Uncovering cargo clients and accessory factors of AP-1 and AP-4 through vesicle proteomics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Ap1s1 reduction in the aging brain heightens neuronal vulnerability to amyloid-β and oxidative stress in Alzheimer's pathogenesis.Alzheimer's research & therapy · 2025Article
- IDEDNIK syndrome: a newly recognized rare genetic disorder caused byFrontiers in neurology · 2025Review
- Clinical and Genetic Functional Validation of a NovelInternational journal of genomics · 2025Article
- Epidermal lamellar bodies, essential organelles for the skin barrier.Frontiers in cell and developmental biology · 2025Review
- Skin lamellar bodies: a unique set of lysosome-related organelles.Frontiers in cell and developmental biology · 2025Article
- Revising pathogenesis of AP1S1-related MEDNIK syndrome: a missense variant in the AP1S1 gene as a causal genetic lesion.Journal of molecular medicine (Berlin, Germany) · 2024Article
- An AAGAB-to-CCDC32 handover mechanism controls the assembly of the AP2 adaptor complex.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Mapping the global interactome of the ARF family reveals spatial organization in cellular signaling pathways.Journal of cell science · 2024Article
- SpliceProt 2.0: A Sequence Repository of Human, Mouse, and Rat Proteoforms.International journal of molecular sciences · 2024Article
- The genetics of monogenic intestinal epithelial disorders.Human genetics · 2023Review
- Deficiency of AP1 ComplexInternational journal of molecular sciences · 2023Article
- Syndromic ichthyoses.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2023Article
- A neurodevelopmental disorder associated with an activating de novo missense variant in ARF1.Human molecular genetics · 2023Article
- Association between single nucleotide variants and severe chronic pain in older adult patients after lower extremity arthroplasty.Journal of orthopaedic surgery and research · 2023Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adaptor protein (AP) complexes regulate clathrin-coated vesicle assembly, protein cargo sorting, and vesicular trafficking between organelles in eukaryotic cells. Because disruption of the various subunits of the AP complexes is embryonic lethal in the majority of cases, characterization of their function in vivo is still lacking. Here, we describe the first mutation in the human AP1S1 gene, encoding the small subunit sigma1A of the AP-1 complex. This founder splice mutation, which leads to a premature stop codon, was found in four families with a unique syndrome characterized by mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratodermia (MEDNIK). To validate the pathogenic effect of the mutation, we knocked down Ap1s1 expression in zebrafish using selective antisens morpholino oligonucleotides (AMO). The knockdown phenotype consisted of perturbation in skin formation, reduced pigmentation, and severe motility deficits due to impaired neural network development. Both neural and skin defects were rescued by co-injection of AMO with wild-type (WT) human AP1S1 mRNA, but not by co-injecting the truncated form of AP1S1, consistent with a loss-of-function effect of this mutation. Together, these results confirm AP1S1 as the gene responsible for MEDNIK syndrome and demonstrate a critical role of AP1S1 in development of the skin and spinal cord.
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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.