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9.B.77 The Meckel Syndrome Protein (Meckelin) Family

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. MKS is genetically heterogeneous, with three loci mapped: MKS1, 17q21-24; MKS2, 11q13 and MKS3. MKS3 is syntenic to the Wpk locus in rat, which is a model for polycystic kidney disease, agenesis of the corpus callosum and hydrocephalus. Positional cloning of the Wpk gene suggested a MKS3 candidate gene, TMEM67, for which pathogenic mutations for five MKS3-linked consanguineous families have been identified (Smith et al., 2006). 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 protein of unknown function (Smith et al., 2006).

MKS3 domains show sequence similarity to zinc finger domains, insect antifreeze domains, neurohypophysial hormones, Bowman-Birk serine proteases, and Leishmanolysin family proteins. These proteins are found in eukaryotes and may prove to be receptors. Their topology resembles one-half of RND transporters.

References associated with 9.B.77 family:

Dawe, H.R., U.M. Smith, A.R. Cullinane, D. Gerrelli, P. Cox, J.L. Badano, S. Blair-Reid, N. Sriram, N. Katsanis, T. Attie-Bitach, S.C. Afford, A.J. Copp, D.A. Kelly, K. Gull, and C.A. Johnson. (2007). The Meckel-Gruber Syndrome proteins MKS1 and meckelin interact and are required for primary cilium formation. Hum Mol Genet 16: 173-186. 17185389
Smith U.M., 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. Malik Sharif, P.A. Batman, C.P. Bennett, C.G. Woods, C. McKeown, M. Bucourt, C.A. Miller, P. Cox, L. Algazali,R.C. Trembath, V.E. Torres, T. Attie-Bitach, D.A. Kelly, E.R. Maher, V.H. Gattone 2nd, P.C. Harris, C.A. Johnson. (2006). The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat. Nat. Genet. 38: 191-196. 16415887
Tkemaladze, T., G. Melikishvili, V. Kherkheulidze, A. Melikishvili, and T. Davitaia. (2017). EXPANDED PHENOTYPE OF TMEM67 GENE MUTATION (CASE REPORT). Georgian Med News 100-103. 28726664