RPGRIP1L
| RPGRIP1-like | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | RPGRIP1L | ||||||
| Alt. symbols | NPHP8, KIAA1005, CORS3, JBTS7, MKS5, FTM | ||||||
| NCBI gene | 23322 | ||||||
| HGNC | 29168 | ||||||
| OMIM | 610937 | ||||||
| RefSeq | NM_015272 | ||||||
| UniProt | Q68CZ1 | ||||||
| Other data | |||||||
| Locus | Chr. 16 q12.2 | ||||||
| |||||||
Function
[edit]The protein encoded by this gene is localized to primary cilia and centrosomes in ciliated human epithelial kidney cells and retinal pigment epithelial cells . RPGRIP1L colocalized at the basal body-centrosome complex with the proteins NPHP4, NPHP6, and TUBG1.[2][3] Also, it can interact with MyosinVa [4]
Clinical significance
[edit]Mutations in the RPGRIP1L gene are associated with Joubert syndrome and Meckel syndrome which belong to a group of developmental autosomal recessive disorders that are associated with cilium dysfunction.[2] Mutations in this gene are also associated with nephronophthisis.[5] Copy number variation affecting the gene was associated with schizophrenia in one study.[6]
A genetic variation within the RPGRIP1L gene, rs3213758, is associated with increased BMI.[7][8] Genetic variations strongly associated with obesity within the FTO gene have also been implicated in the control of RPGRIP1L expression.[9] Mice with decreased expression of RPGRIP1L are fatter, eat more, have diminished sensitivity to the hormone leptin that normally reduces food intake, and display altered morphology of the brain center that regulates feeding.[10][11][12] Similarly, cells derived from Joubert patients with RPGRIP1L mutations have decreased leptin sensitivity,[10][13] and neurons important for food intake segregating for obesity-risk variations at the FTO locus have decreased RPGRIP1L expression and diminished outgrowth.[12] These studies suggest that RPGRIP1L is a gene important in human obesity.
References
[edit]- ^ Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (February 1999). "Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 6 (1): 63–70. doi:10.1093/dnares/6.1.63. PMID 10231032.
- ^ a b Delous M, Baala L, Salomon R, Laclef C, Vierkotten J, Tory K, Golzio C, Lacoste T, Besse L, Ozilou C, Moutkine I, Hellman NE, Anselme I, Silbermann F, Vesque C, Gerhardt C, Rattenberry E, Wolf MT, Gubler MC, Martinovic J, Encha-Razavi F, Boddaert N, Gonzales M, Macher MA, Nivet H, Champion G, Berthélémé JP, Niaudet P, McDonald F, Hildebrandt F, Johnson CA, Vekemans M, Antignac C, Rüther U, Schneider-Maunoury S, Attié-Bitach T, Saunier S (July 2007). "The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome". Nature Genetics. 39 (7): 875–81. doi:10.1038/ng2039. PMID 17558409. S2CID 6982566.
- ^ Arts HH, Doherty D, van Beersum SE, Parisi MA, Letteboer SJ, Gorden NT, Peters TA, Märker T, Voesenek K, Kartono A, Ozyurek H, Farin FM, Kroes HY, Wolfrum U, Brunner HG, Cremers FP, Glass IA, Knoers NV, Roepman R (July 2007). "Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome". Nature Genetics. 39 (7): 882–8. doi:10.1038/ng2069. PMID 17558407. S2CID 12910768.
- ^ Assis LH, et al. (2017). "The molecular motor Myosin Va interacts with the cilia-centrosomal protein RPGRIP1L". Sci. Rep. 7: 43692. Bibcode:2017NatSR...743692A. doi:10.1038/srep43692. PMC 5339802. PMID 28266547.
- ^ Devuyst O, Arnould VJ (May 2008). "Mutations in RPGRIP1L: extending the clinical spectrum of ciliopathies". Nephrol. Dial. Transplant. 23 (5): 1500–3. doi:10.1093/ndt/gfn033. PMID 18281315.
- ^ Gene Overview of All Published Schizophrenia-Association Studies for RPGRIP1L Archived 2009-02-21 at the Wayback Machine – SzGene database at Schizophrenia Research Forum.
- ^ Hoffmann, Thomas J; Choquet, Hélène; Yin, Jie; Banda, Yambazi; Kvale, Mark N; Glymour, Maria; Schaefer, Catherine; Risch, Neil; Jorgenson, Eric (2018-10-01). "A Large Multiethnic Genome-Wide Association Study of Adult Body Mass Index Identifies Novel Loci". Genetics. 210 (2): 499–515. doi:10.1534/genetics.118.301479. ISSN 1943-2631. PMC 6216593. PMID 30108127.
- ^ Turcot, Valérie; Lu, Yingchang; Highland, Heather M.; Schurmann, Claudia; Justice, Anne E.; Fine, Rebecca S.; Bradfield, Jonathan P.; Esko, Tõnu; Giri, Ayush; Graff, Mariaelisa; Guo, Xiuqing (January 2018). "Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity". Nature Genetics. 50 (1): 26–41. doi:10.1038/s41588-017-0011-x. ISSN 1546-1718. PMC 5945951. PMID 29273807.
- ^ Stratigopoulos, George; Leibel, Rudolph L. (December 2010). "FTO gains function". Nature Genetics. 42 (12): 1038–1039. doi:10.1038/ng1210-1038. ISSN 1546-1718. PMC 3818900. PMID 21102620.
- ^ a b Stratigopoulos, George; Martin Carli, Jayne F.; O’Day, Diana R.; Wang, Liheng; LeDuc, Charles A.; Lanzano, Patricia; Chung, Wendy K.; Rosenbaum, Michael; Egli, Dieter; Doherty, Daniel A.; Leibel, Rudolph L. (May 2014). "Hypomorphism for RPGRIP1L, a Ciliary Gene Vicinal to the FTO Locus, Causes Increased Adiposity in Mice". Cell Metabolism. 19 (5): 767–779. doi:10.1016/j.cmet.2014.04.009. ISSN 1550-4131. PMC 4131684. PMID 24807221.
- ^ Stratigopoulos, George; Burnett, Lisa Cole; Rausch, Richard; Gill, Richard; Penn, David Barth; Skowronski, Alicja A.; LeDuc, Charles A.; Lanzano, Anthony J.; Zhang, Pumin; Storm, Daniel R.; Egli, Dieter (2016-05-02). "Hypomorphism of Fto and Rpgrip1l causes obesity in mice". The Journal of Clinical Investigation. 126 (5): 1897–1910. doi:10.1172/JCI85526. ISSN 0021-9738. PMC 4855930. PMID 27064284.
- ^ a b Wang, Liheng; Solis, Alain J. De; Goffer, Yossef; Birkenbach, Kathryn E.; Engle, Staci E.; Tanis, Ross; Levenson, Jacob M.; Li, Xueting; Rausch, Richard; Purohit, Manika; Lee, Jen-Yi (2019-02-07). "Ciliary gene RPGRIP1L is required for hypothalamic arcuate neuron development". JCI Insight. 4 (3). doi:10.1172/jci.insight.123337. ISSN 0021-9738. PMC 6413800. PMID 30728336.
- ^ Stratigopoulos, George; LeDuc, Charles A.; Cremona, Maria L.; Chung, Wendy K.; Leibel, Rudolph L. (January 2011). "Cut-like Homeobox 1 (CUX1) Regulates Expression of the Fat Mass and Obesity-associated and Retinitis Pigmentosa GTPase Regulator-interacting Protein-1-like (RPGRIP1L) Genes and Coordinates Leptin Receptor Signaling". Journal of Biological Chemistry. 286 (3): 2155–2170. doi:10.1074/jbc.m110.188482. ISSN 0021-9258. PMC 3023512. PMID 21037323.
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