Project leader: Anna Greka, M.D., Ph.D.
Key collaborators:  Eric Lander, Ph.D.

MUC1 kidney disease (MKD, also known as ADTKD-MUC1, and formerly called MCKD1) is a rare disorder characterized by autosomal dominant inheritance of tubulo-interstitial kidney disease. Affected individuals develop a slow deterioration in kidney function usually commencing in the second to third decade of life and resulting in the need for dialysis or kidney transplantation approximately two decades later.

While a genetic association with MKD was mapped more than a decade ago to a 2-Mb region on chromosome 1, extensive automated sequencing did not point to a causative mutation. Detailed investigation led to the conclusion that the causative mutations resided in an extremely long, GC-rich, variable-number-of-tandem-repeats region in the coding sequence of the mucin 1 (MUC1) gene. Genomes from multiple MKD families were studied and found to harbor similar mutations in the MUC1 gene. The insertion causes a frame shift and gives rise to a novel peptide repeat before premature termination. These findings pointed to MUC1 as a key therapeutic target in the treatment of MKD.