{
  "abstract": "Autosomal dominant polycystic liver disease (ADPLD) commonly results from pathogenic variants in one of 7 genes (GANAB, ALG8, ALG9, PRKCSH, SEC63 and possibly LRP5 and SEC61B). 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. LRP5 and ALG8 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.",
  "abstract_shown": true,
  "affiliations": [
    "The University of Melbourne Department of Medicine (Melbourne Health and Northern Health), Royal Melbourne Hospital, Parkville, Victoria, Australia",
    "Department of Nephrology, Christian Medical College, Vellore, Tamil Nadu, India"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Santosh Varughese"
    },
    {
      "affs": [
        1
      ],
      "name": "Mary Huang"
    },
    {
      "name": "Judy Savige"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cepakt36x4mmt.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0348109",
  "fulltext_url": null,
  "id": "cepakt36x4mmt",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0348109",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1311|Genetic and Kidney Cyst Diseases"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Renal system/Kidneys"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Transmembrane transport proteins"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular structures and organelles/Cell membranes/Membrane proteins"
    ],
    [
      "plos",
      "/Biology and life sciences/Computational biology/Genome complexity/Copy number variation"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genomics/Genome complexity/Copy number variation"
    ],
    [
      "plos",
      "/Medicine and health sciences/Anatomy/Renal system/Kidneys"
    ],
    [
      "plos",
      "/Medicine and health sciences/Clinical genetics/Genetic diseases/Autosomal dominant diseases/Polycystic kidney disease"
    ],
    [
      "plos",
      "/Medicine and health sciences/Gastroenterology and hepatology/Liver diseases"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Genetic diseases/Autosomal dominant diseases/Polycystic kidney disease"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogenesis"
    ],
    [
      "plos",
      "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens"
    ]
  ],
  "openalex": "W7214574231",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0348109&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-28",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/cepakt36x4mmt.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:37Z",
      "native_id": "10.1371/journal.pone.0348109",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0348109"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "plos:computational biology",
      "subfield": "bioinformatics"
    },
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
    },
    {
      "field": "medicine",
      "origin": "plos:anatomy",
      "subfield": "physiology"
    }
  ],
  "title": "The population frequency of predicted pathogenic variants in the genes associated with Autosomal Dominant Polycystic Liver Disease (ADPLD) and kidney cysts",
  "title_text": "The population frequency of predicted pathogenic variants in the genes associated with Autosomal Dominant Polycystic Liver Disease (ADPLD) and kidney cysts",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:37Z",
  "url": "https://research.draconitic.com/paper/cepakt36x4mmt",
  "venue": "PLOS One",
  "versions": []
}