The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat.

U M Smith, M Consugar, L J Tee, B M McKee, E N Maina, S Whelan, N V Morgan, E Goranson, P Gissen, S Lilliquist, I A Aligianis, C J Ward, S Pasha, R Punyashthiti, S M Sharif, P A Batman, C P Bennett, C G Woods, C McKeown, M BucourtC A Miller, P Cox, L Algazali, R C Trembath, V E Torres, T Attie-Bitach, D A Kelly, E R Maher, V H Gattone, P C Harris, C A Johnson

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227 Citations (Scopus)


Meckel-Gruber syndrome is a severe autosomal, recessively inherited disorder characterized by bilateral renal cystic dysplasia, developmental defects of the central nervous system ( most commonly occipital encephalocele), hepatic ductal dysplasia and cysts and polydactyly(1-3). MKS is genetically heterogeneous, with three loci mapped: MKS1, 17q21-24 (ref. 4); MKS2, 11q13 ( ref. 5) and MKS3 ( ref. 6). We have refined MKS3 mapping to a 12.67-Mb interval (8q21.13-q22.1) that is syntenic to the Wpk locus in rat, which is a model with polycystic kidney disease, agenesis of the corpus callosum and hydrocephalus(7,8). Positional cloning of the Wpk gene suggested a MKS3 candidate gene, TMEM67, for which we identified pathogenic mutations for five MKS3-linked consanguineous families. MKS3 is a previously uncharacterized, evolutionarily conserved gene that is expressed at moderate levels in fetal brain, liver and kidney but has widespread, low levels of expression. It encodes a 995 - amino acid seven-transmembrane receptor protein of unknown function that we have called meckelin
Original languageEnglish
Pages (from-to)191 - 196
Number of pages6
JournalNature Genetics
Issue number2
Publication statusPublished - Feb 2006


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