ADTKD MUC1

An inherited disorder that causes a gradual loss of kidney function, caused by a mutation in the MUC1 gene that leads to production of an abnormal mucin 1 protein, which deposits in the kidney and leads to slow loss of kidney function¹.

Prevalence

2.5 1,000,000

Disease is affected 1-4/1,000,000 (likely an underestimate due to unremarkable findings); repeat expansion responsibile for 95% of disease²

Age of Onset Details

Age of onset for end-stage renal disease (the only systemic manifestation) ranges from 18³-70².

Locus

hg19

chr1:155160981-155162030

hg38

chr1:155188505-155192239

t2t

chr1:154328121-154330802

Details

Disease is caused by the single base expansion of a heptanucleotide (7) cytosine homopolymer tract within one copy of a coding VNTR, resulting in a frameshift mutation. This VNTR has a 60 bp motif, varying in length and sequence composition. This motif ranges in copy number from 20-125 (~1.5-5 kb) and is GC-rich (>80%). The specific copy of the VNTR motif involved varies by family but is consistent within a family⁴. This locus is particularly difficult to genotype^5,3. Gamaarachchi et al. observed 20 unique VNTR haplotypes which ranged in size from 40–83 copies, with no unrelated individuals sharing the same haplotype. Unique haplotypes implied frequent independent origins of the dupC variant.

Mechanism

GoF

Toxic protein product accumulates in kidneys²

Year

2013⁵

Location in Gene

Exon 2

Gene Strand

Alleles

Ref. Motif

GGCTNNGGGNGCGGTGGAGCCCGGGGCNGGNCTGNTNTCCGGGGCCGAGGTGACANCNTG

Benign (ref.)

GCCCACGGTGTCACCTCGGCCCCGGACACCAGGCCGGCCCCGGGCTCCACCGCCCCCCCA

Benign (gene)

GCCCACGGTGTCACCTCGGCCCCGGACACCAGGCCGGCCCCGGGCTCCACCGCCCCCCCA

Pathogenic (ref.)

GCCCACGGTGTCACCTCGGCCCCGGACACCAGGCCGGCCCCGGGCTCCACCGCCCCCCCCA

Pathogenic (gene)

GCCCACGGTGTCACCTCGGCCCCGGACACCAGGCCGGCCCCGGGCTCCACCGCCCCCCCCA

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0020726

Autosomal Dominant Tubulointerstitial Kidney Disease – MUC1

Anthony J.,Bleyer, Martina,Živná, Kendrah,Kidd, Stanislav,Kmoch

GeneReviews® · 1993-01-01

genereviews:NBK153723

Jeff,Granhøj, Dorte L,Lildballe, Katja V,Pedersen, Birgitte G,Tougaard, Martin,Sokol, Mads M,Aagaard, Annabeth H,Petersen, Tilde,Kristensen, Malene,Djursby, Henrik,Birn, Maria,Rasmussen

Clinical kidney journal · 2024-11-18

pmid:39781475

Resources for Genetics Professionals — Genetic Disorders Caused by Nucleotide Repeat Expansions and Contractions

Stephanie E.,Wallace, Lora JH,Bean

GeneReviews® [Internet] · 2022-10-20

genereviews:NBK535148

Mutations causing medullary cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing.

Andrew,Kirby, Andreas,Gnirke, David B,Jaffe, Veronika,Barešová, Nathalie,Pochet, Brendan,Blumenstiel, Chun,Ye, Daniel,Aird, Christine,Stevens, James T,Robinson, Moran N,Cabili, Irit,Gat-Viks, Edward,Kelliher, Riza,Daza, Matthew,DeFelice, Helena,Hůlková, Jana,Sovová, Petr,Vylet'al, Corinne,Antignac, Mitchell,Guttman, Robert E,Handsaker, Danielle,Perrin, Scott,Steelman, Snaevar,Sigurdsson, Steven J,Scheinman, Carrie,Sougnez, Kristian,Cibulskis, Melissa,Parkin, Todd,Green, Elizabeth,Rossin, Michael C,Zody, Ramnik J,Xavier, Martin R,Pollak, Seth L,Alper, Kerstin,Lindblad-Toh, Stacey,Gabriel, P Suzanne,Hart, Aviv,Regev, Chad,Nusbaum, Stanislav,Kmoch, Anthony J,Bleyer, Eric S,Lander, Mark J,Daly

Nature genetics · 2013-02-10

pmid:23396133

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

pmid:40244446

Phenotypic Heterogeneity of ADTKD-MUC1 Diagnosed Using VNtyper, a Novel Genetic Technique.

Jessica,Kachmar, Hassan,Saei, Vincent,Morinière, Laurence,Heidet, Bertrand,Knebelmann, Olivier,Gribouval, Manon,Mautret-Godefroy, Stéphane,Burtey, Vincent,Vuiblet, Asma,Alla, Axel,Ibalanky, Olivier,Moranne, Mathilde,Nizon, Benjamin,Savenkoff, Patrick,Nitschké, Corinne,Antignac, Guillaume,Dorval

American journal of kidney diseases : the official journal of the National Kidney Foundation · 2025-01-22

pmid:39848530

Unraveling

Amanda,Helms, Vincent,Chang, Stacy A,Malaker, Jennifer S,Brodbelt

Analytical chemistry · 2024-11-22

pmid:39576755

Systematic Screening of Autosomal Dominant Tubulointerstitial Kidney Disease- MUC1 27dupC Pathogenic Variant through Exome Sequencing.

Ilias,Bensouna, Thomas,Robert, Xavier,Vanhoye, Marine,Dancer, Laure,Raymond, Pierre,Delaugère, Pascale,Hilbert, Hugues,Richard, Laurent,Mesnard

Journal of the American Society of Nephrology : JASN · 2024-09-26

pmid:39325540

Erik P,Lillehoj, Yafan,Yu, Avelino C,Verceles, Akihiro,Imamura, Hideharu,Ishida, Kurt H,Piepenbrink, Simeon E,Goldblum

iScience · 2024-08-31

pmid:39314239

Analysis of Molecular Genetic Variants of Lgals4 in Esophageal Cancer: A Preliminary Report.

Surmeet,Kaur, Rajiv,Devgan, Jagdeep,Singh, Namarta,Kalia, Jatinder,Singh, Manpreet,Kaur

Biochemical genetics · 2024-04-12

pmid:38605207

Structural and molecular insight into antibody recognition of dynamic neoepitopes in membrane tethered MUC1 of pancreatic cancer cells and secreted exosomes.

Hajime,Wakui, Yasuhiro,Yokoi, Chieko,Horidome, Toyoyuki,Ose, Min,Yao, Yoshikazu,Tanaka, Hiroshi,Hinou, Shin-Ichiro,Nishimura

RSC chemical biology · 2023-05-24

pmid:37547453

VNtyper enables accurate alignment-free genotyping of

Hassan,Saei, Vincent,Morinière, Laurence,Heidet, Olivier,Gribouval, Said,Lebbah, Frederic,Tores, Manon,Mautret-Godefroy, Bertrand,Knebelmann, Stéphane,Burtey, Vincent,Vuiblet, Corinne,Antignac, Patrick,Nitschké, Guillaume,Dorval

iScience · 2023-06-17

pmid:37456840

Hypoxia controls expression of kidney-pathogenic

Stephanie,Naas, René,Krüger, Karl Xaver,Knaup, Julia,Naas, Steffen,Grampp, Mario,Schiffer, Michael,Wiesener, Johannes,Schödel

Life science alliance · 2023-06-14

pmid:37316299