*LRP5 *was first reported in relation to autosomal dominant polycystic liver disease with or without kidney cysts in 2014 (Cnoseen et al., PMID: 24706814). Of note, *LRP5 *is associated with a number of gene-disease relationships in OMIM. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, given differences in phenotype and inheritance patterns, these different clinical entities were split. This curation focuses only on the association between *LRP5 *and autosomal dominant polycystic liver disease with or without kidney cysts. Four variants (all missense) that have been reported in *LRP5 *probands in one publication (PMID: 24706814) are included in this curation. Given this curation focuses on monoallelic disease, publications supporting the role of *LRP5 *in modifying phenotype in patients with an alternate genetic mechanism for their cystic disease were not included in this curation. This gene-disease association is also supported by expression studies that demonstrated *LRP5 *expression in liver tissue (PMID: 24706814) and studies that demonstrate that LRP5 has a role in the WNT-signaling pathway that is associated with polycystic liver disease (PMID: 30361437). In summary, there is limited evidence to support a gene-disease relationship between *LRP5 *and autosomal dominant polycystic liver disease with or without kidney cysts. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Cystic and Ciliopathy Disorders GCEP on 8/12/2020 (SOP Version 7).
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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