Mutations in ANKS6 cause a nephronophthisis-like phenotype with ESRD

J Am Soc Nephrol. 2014 Aug;25(8):1653-61. doi: 10.1681/ASN.2013060646. Epub 2014 Mar 7.


Nephronophthisis (NPHP) is one of the most common genetic causes of CKD; however, the underlying genetic abnormalities have been established in <50% of patients. We performed genome-wide analysis followed by targeted resequencing in a Turkish consanguineous multiplex family and identified a canonic splice site mutation in ANKS6 associated with an NPHP-like phenotype. Furthermore, we identified four additional ANKS6 variants in a cohort of 56 unrelated patients diagnosed with CKD due to nephronophthisis, chronic GN, interstitial nephritis, or unknown etiology. Immunohistochemistry in human embryonic kidney tissue demonstrated that the expression patterns of ANKS6 change substantially during development. Furthermore, we detected increased levels of both total and active β-catenin in precystic tubuli in Han:SPRD Cy/+ rats. Overall, these data indicate the importance of ANKS6 in human kidney development and suggest a mechanism by which mutations in ANKS6 may contribute to an NPHP-like phenotype in humans.

Keywords: chronic renal failure; end stage kidney disease; end stage renal disease; familial nephropathy; genetic renal disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Cohort Studies
  • Female
  • Humans
  • Infant
  • Kidney Diseases, Cystic / complications
  • Kidney Diseases, Cystic / genetics*
  • Kidney Diseases, Cystic / pathology
  • Kidney Failure, Chronic / genetics*
  • Kidney Failure, Chronic / pathology*
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Nuclear Proteins / genetics*
  • Pedigree
  • Phenotype*
  • Turkey


  • ANKS6 protein, human
  • Nuclear Proteins