RGD Reference Report - Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome. - Rat Genome Database

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Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome.

Authors: Arts, HH  Doherty, D  Van Beersum, SE  Parisi, MA  Letteboer, SJ  Gorden, NT  Peters, TA  Marker, T  Voesenek, K  Kartono, A  Ozyurek, H  Farin, FM  Kroes, HY  Wolfrum, U  Brunner, HG  Cremers, FP  Glass, IA  Knoers, NV  Roepman, R 
Citation: Arts HH, etal., Nat Genet. 2007 Jul;39(7):882-8. Epub 2007 Jun 10.
RGD ID: 11537356
Pubmed: PMID:17558407   (View Abstract at PubMed)
DOI: DOI:10.1038/ng2069   (Journal Full-text)

Protein-protein interaction analyses have uncovered a ciliary and basal body protein network that, when disrupted, can result in nephronophthisis (NPHP), Leber congenital amaurosis, Senior-Loken syndrome (SLSN) or Joubert syndrome (JBTS). However, details of the molecular mechanisms underlying these disorders remain poorly understood. RPGRIP1-like protein (RPGRIP1L) is a homolog of RPGRIP1 (RPGR-interacting protein 1), a ciliary protein defective in Leber congenital amaurosis. We show that RPGRIP1L interacts with nephrocystin-4 and that mutations in the gene encoding nephrocystin-4 (NPHP4) that are known to cause SLSN disrupt this interaction. RPGRIP1L is ubiquitously expressed, and its protein product localizes to basal bodies. Therefore, we analyzed RPGRIP1L as a candidate gene for JBTS and identified loss-of-function mutations in three families with typical JBTS, including the characteristic mid-hindbrain malformation. This work identifies RPGRIP1L as a gene responsible for JBTS and establishes a central role for cilia and basal bodies in the pathophysiology of this disorder.



Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Rpgrip1lRataxonemal microtubule  IDA  RGD 
Cep290Ratciliary basal body  IDA  RGD 
Nphp4Ratciliary basal body  IDA  RGD 
Rpgrip1lRatciliary basal body  IDA  RGD 
Rpgrip1lRatphotoreceptor connecting cilium  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cep290  (centrosomal protein 290)
Nphp4  (nephrocystin 4)
Rpgrip1l  (Rpgrip1-like)


Additional Information