The RPGRIP1L gene encodes a protein that localizes to the basal body-centrosome complex in ciliated cells. It interacts with the ciliary protein NPHP4 and is responsible for negatively regulating signaling through the G-protein coupled thromboxane A2 receptor (TBXA2R). Based on mouse ortholog studies, the protein is also predicted to play a role in the determination of left/right symmetry, in-utero embryonic development and programmed cell death.
The gene is associated with the overlapping allelic disorders Joubert Syndrome 7 (JBTS7), Meckel Syndrome type 5 (MKS5) and COACH syndrome. Joubert Syndrome 7 is a congenital ciliopathy defined by cerebellar vermis hypoplasia and brainstem malformations that result in a ‘molar tooth sign’ on brain imaging studies. Affected patients also suffer from developmental delay, ataxia, hypotonia, nephronophthisis and ocular anomalies such as oculomotor apraxia and nystagmus. Meckel Syndrome, type 5 is an often fatal, severe disorder characterized by occipital encephalocele, polydactly of the hands and feet, and cystic dysplasia of the kidneys. COACH syndrome is a multisystem disorder characterized by cerebellar vermis hypo/aplasia, oligophrenia, ataxia, ocular coloboma, and hepatic fibrosis.