2026-10-13T17:44:05Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34017076 2026-09-28T17:39:49Z category_7 category_8 category_13 category_24 category_272 category_39 category_734 category_811 category_132 category_134 category_135 portal_5 item_type_3 month_year_09_2026

<p>Suppl data ADPLD.</p> Santosh Varughese (8674614) Mary Huang (12504152) Judy Savige (4245745) Medicine Microbiology Genetics Evolutionary Biology Environmental Sciences not elsewhere classified Ecology Biological Sciences not elsewhere classified Mathematical Sciences not elsewhere classified Infectious Diseases Virology Computational Biology milder clinical phenotype indeed cystic kidneys damaging missense changes 91 ), finnish rarely kidney failure additional causative genes 7 genes (< predicted pathogenic variants div >< p 91 people using adpld variants result commonest affected genes 1 variants assessed pathogenic variants kidney panels likely pathogenic adpld genes 1 variants study determined sec63 </ sec61b )</ population frequency lrp5 </ liver cysts incomplete penetrance general population function structural conserved residue commonly results also included also estimated admixed american 187 ). 0001 compared <div><p>Autosomal dominant polycystic liver disease (ADPLD) commonly results from pathogenic variants in one of 7 genes (<i>GANAB, ALG8, ALG9, PRKCSH, SEC63</i> and possibly <i>LRP5</i> and <i>SEC61B)</i>. These genes are also included in kidney panels because pathogenic variants cause kidney cysts but rarely kidney failure. This study determined the population frequency of predicted pathogenic variants in the ADPLD genes in the general population. Variants for each gene were downloaded from gnomADv.2.1.1 and annotated with ANNOVAR. The population frequencies were calculated from the number of people with ‘predicted pathogenic’ variants in gnomAD: loss-of-function structural and copy number; null; and rare, computationally-damaging missense changes that affected a conserved residue. Frequencies were also estimated from the number of gnomADv.4.1 variants assessed as Pathogenic or Likely pathogenic in ClinVar. Predicted pathogenic variants affected one in 91 people using our strategy and gnomAD v.2.1.1, and one in 130 with ClinVar assessments of gnomAD v.4.1 variants. <i>LRP5</i> and <i>ALG8</i> which are associated with a milder clinical phenotype, were the commonest affected genes with both strategies. Predicted pathogenic variants in ADPLD appear more frequent in admixed American (one in 91), Finnish (one in 110) and African/African American (one in 43) people (p all < 0.0001 compared with Europeans (one in 187). Predicted pathogenic variants for ADPLD may be even more common with the finding of additional causative genes. Assessments will become more accurate too. However not all ADPLD variants result in liver cysts, nor indeed cystic kidneys, because of incomplete penetrance and variable expressivity.</p></div> 2026-09-28T17:39:47Z Dataset Dataset 10.1371/journal.pone.0348109.s001 https://figshare.com/articles/dataset/_p_Suppl_data_ADPLD_p_/34017076 CC BY 4.0