ArticleNature medicine2009
A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans.
Article in Nature medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 167 papers.
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Who cites it
167 citing papers in PubMed, 331 citations in OpenAlex.
- Human CalDAG-GEFI gene (RASGRP2) mutation affects platelet function and causes severe bleeding.The Journal of experimental medicine · 2014Trial
- Regulation of cell adhesion and migration by Kindlin-3 cleavage by calpain.The Journal of biological chemistry · 2012Trial
- CRISPR/Cas9-mediated loss of FERMT3 reveals kindlin-3-independent neutrophil activity in LAD-III.Journal of human immunity · 2026Article
- Beyond Integrin Activation: Kindlin-3 as an Organiser of Immune Receptor Signalling.International journal of molecular sciences · 2026Review
- Structural basis of kindlin-3 in leukocyte adhesion deficiency III.Journal of thrombosis and haemostasis : JTH · 2026Article
- Kindlin-2 Deletion in Mural Cells Leads to Vascular Instability.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Mechanisms and consequences of myeloid adhesome dysfunction in atherogenesis.Cardiovascular research · 2025Article
- Kindlin-3 phosphorylation is crucial for thrombosis and hemostasisResearch and practice in thrombosis and haemostasis · 2025Article
- Nanoscopy reveals integrin clustering reliant on kindlin-3 but not talin-1.Cell communication and signaling : CCS · 2025Article
- Myosin light chain 6 (Myl6) interacts with kindlin-3 and is required to support integrin αJournal of thrombosis and haemostasis : JTH · 2024Article
- A novel leukocyte adhesion deficiency type III mutation manifests functional importance of the compact FERM domain in kindlin-3.Journal of thrombosis and haemostasis : JTH · 2024Article
- Identification biomarkers in disease progression of obstructive sleep apnea from children serum based on WGCNA and Mfuzz.Frontiers in neurology · 2024Article
- SKAP2 acts downstream of CD11b/CD18 and regulates neutrophil effector function.Frontiers in immunology · 2024Article
- Clinical and Osteopetrosis-Like Radiological Findings in Patients with Leukocyte Adhesion Deficiency Type III.Journal of clinical immunology · 2023Article
- Kindlin-3 deficiency leads to impaired erythropoiesis and erythrocyte cytoskeleton.Blood advances · 2023Article
- Roles of focal adhesion proteins in skeleton and diseases.Acta pharmaceutica Sinica. B · 2023Review
- Structure, signal transduction, activation, and inhibition of integrin αIIbβ3.Thrombosis journal · 2023Review
- Delayed cortical development in mice with a neural specific deletion of β1 integrin.Frontiers in neuroscience · 2023Article
- The critical role of Rap1-GAPs Rasa3 and Sipa1 in T cells for pulmonary transit and egress from the lymph nodes.Frontiers in immunology · 2023Article
- A novel compound heterozygous mutation of theFrontiers in pediatrics · 2023Article
107 more citing papers are in PubMed but not listed here.
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13 authors at 5 institutions in 1 country.
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Abstract
Monogenic deficiency diseases provide unique opportunities to define the contributions of individual molecules to human physiology and to identify pathologies arising from their dysfunction. Here we describe a deficiency disease in two human siblings that presented with severe bleeding, frequent infections and osteopetrosis at an early age. These symptoms are consistent with but more severe than those reported for people with leukocyte adhesion deficiency III (LAD-III). Mechanistically, these symptoms arose from an inability to activate the integrins expressed on hematopoietic cells, including platelets and leukocytes. Immortalized lymphocyte cell lines isolated from the two individuals showed integrin activation defects. Several proteins previously implicated in integrin activation, including Ras-associated protein-1 (RAP1) and calcium and diacylglycerol-regulated guanine nucleotide exchange factor-1 (CALDAG-GEF1), were present and functional in these cell lines. The genetic basis for this disease was traced to a point mutation in the coding region of the KINDLIN3 (official gene symbol FERMT3) gene. When wild-type KINDLIN-3 was expressed in the immortalized lymphocytes, their integrins became responsive to activation signals. These results identify a genetic disease that severely compromises the health of the affected individuals and establish an essential role of KINDLIN-3 in integrin activation in humans. Furthermore, allogeneic bone marrow transplantation was shown to alleviate the symptoms of the disease.
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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.