{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T19:37:09Z","timestamp":1789846629790,"version":"4.0.1"},"reference-count":160,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T00:00:00Z","timestamp":1691020800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>With the increased availability of genomic sequencing technologies, the molecular bases for kidney diseases such as nephronophthisis and mitochondrially inherited and autosomal-dominant tubulointerstitial kidney diseases (ADTKD) has become increasingly apparent. These tubulointerstitial kidney diseases (TKD) are monogenic diseases of the tubulointerstitium and result in interstitial fibrosis and tubular atrophy (IF\/TA). However, monogenic inheritance alone does not adequately explain the highly variable onset of kidney failure and extra-renal manifestations. Phenotypes vary considerably between individuals harbouring the same pathogenic variant in the same putative monogenic gene, even within families sharing common environmental factors. While the extreme end of the disease spectrum may have dramatic syndromic manifestations typically diagnosed in childhood, many patients present a more subtle phenotype with little to differentiate them from many other common forms of non-proteinuric chronic kidney disease (CKD). This review summarises the expanding repertoire of genes underpinning TKD and their known phenotypic manifestations. Furthermore, we collate the growing evidence for a role of modifier genes and discuss the extent to which these data bridge the historical gap between apparently rare monogenic TKD and polygenic non-proteinuric CKD (excluding polycystic kidney disease).<\/jats:p>","DOI":"10.3390\/genes14081582","type":"journal-article","created":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T11:08:43Z","timestamp":1691060923000},"page":"1582","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Role for Genetic Modifiers in Tubulointerstitial Kidney Diseases"],"prefix":"10.3390","volume":"14","author":[{"given":"Gary P.","family":"Leggatt","sequence":"first","affiliation":[{"name":"Human Genetics & Genomic Medicine, University of Southampton, Southampton SO16 6YD, UK"},{"name":"Wessex Kidney Centre, Queen Alexandra Hospital, Portsmouth Hospitals NHS Trust, Portsmouth PO6 3LY, UK"},{"name":"Renal Department, University Hospital Southampton, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6814-8648","authenticated-orcid":false,"given":"Eleanor G.","family":"Seaby","sequence":"additional","affiliation":[{"name":"Human Genetics & Genomic Medicine, University of Southampton, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Veighey","sequence":"additional","affiliation":[{"name":"Human Genetics & Genomic Medicine, University of Southampton, Southampton SO16 6YD, UK"},{"name":"Renal Department, University Hospital Southampton, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Gast","sequence":"additional","affiliation":[{"name":"Human Genetics & Genomic Medicine, University of Southampton, Southampton SO16 6YD, UK"},{"name":"Wessex Kidney Centre, Queen Alexandra Hospital, Portsmouth Hospitals NHS Trust, Portsmouth PO6 3LY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodney D.","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Human Genetics & Genomic Medicine, University of Southampton, Southampton SO16 6YD, UK"},{"name":"Department of Paediatric Nephrology, Southampton Children\u2019s Hospital, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Ennis","sequence":"additional","affiliation":[{"name":"Human Genetics & Genomic Medicine, University of Southampton, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"527","DOI":"10.2215\/CJN.06380613","article-title":"Variable Clinical Presentation of an MUC1 Mutation Causing Medullary Cystic Kidney Disease Type 1","volume":"9","author":"Bleyer","year":"2014","journal-title":"Clin. 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