RGD Reference Report - The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat. - Rat Genome Database

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

Authors: Smith, UM  Consugar, M  Tee, LJ  McKee, BM  Maina, EN  Whelan, S  Morgan, NV  Goranson, E  Gissen, P  Lilliquist, S  Aligianis, IA  Ward, CJ  Pasha, S  Punyashthiti, R  Malik Sharif, S  Batman, PA  Bennett, CP  Woods, CG  McKeown, C  Bucourt, M  Miller, CA  Cox, P  Algazali, L  Trembath, RC  Torres, VE  Attie-Bitach, T  Kelly, DA  Maher, ER  Gattone VH, 2ND  Harris, PC  Johnson, CA 
Citation: Smith UM, etal., Nat Genet. 2006 Feb;38(2):191-6. Epub 2006 Jan 15.
RGD ID: 11535082
Pubmed: PMID:16415887   (View Abstract at PubMed)
DOI: DOI:10.1038/ng1713   (Journal Full-text)

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 (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. 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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TMEM67HumanMeckel syndrome 3  ISOTmem67 (Rattus norvegicus)DNA:missense mutation:exon:p.P394L (rat)RGD 
TMEM67HumanMeckel syndrome 3  IAGP DNA:deletions more ...RGD 
Tmem67MouseMeckel syndrome 3  ISOTmem67 (Rattus norvegicus)DNA:missense mutation:exon:p.P394L (rat)RGD 
Tmem67MouseMeckel syndrome 3  ISOTMEM67 (Homo sapiens)DNA:deletions more ...RGD 
Tmem67RatMeckel syndrome 3  ISOTMEM67 (Homo sapiens)DNA:deletions more ...RGD 
Tmem67RatMeckel syndrome 3  IAGP DNA:missense mutation:exon:p.P394L (rat)RGD 
Tmem67wpkRatMeckel syndrome 3  IAGP  RGD 
Wpk +/-RatMeckel syndrome 3  IAGP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tmem67  (transmembrane protein 67)
Tmem67wpk  (transmembrane protein 67; wpk mutant)

Genes (Mus musculus)
Tmem67  (transmembrane protein 67)

Genes (Homo sapiens)
TMEM67  (transmembrane protein 67)

Strains
Wpk +/-  (Wpk heterozygous rat)

Objects referenced in this article
Strain Wpk Wistar polycystic kidney rat Rattus norvegicus

Additional Information