THBD was first reported in relation to autosomal dominant atypical hemolytic uremic syndrome (aHUS) in 2009 (Delvaeye et al., PMID: 19625716). Genetic variants in THBD, which encodes thrombomodulin, have been reported to cause aHUS (PMID: 19625716) however, analysis of large aHUS cohorts (PMIDs: 23307876, 37369098, 37567446) and enrichment analysis (PMIDs: 29500241, 30377230) have failed to reproduce these findings. Therefore, none of the genetic variants in THBD identified in patients with aHUS were included in this curation for scoring. Furthermore, the experimental evidence available (PMID: 19625716) has been excluded in light of the evidence disputing this gene-disease relationship. In summary, the evidence supporting the relationship between THBD and autosomal dominant aHUS has been disputed and no valid evidence remains to support the claim. More evidence is needed to either support or entirely refute the role THBD plays in this disease. This classification was approved by the ClinGen Complement-Mediated Kidney Diseases GCEP on the meeting date May 15, 2024 (SOP Version 10).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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