TABLE 1.

Localization of NPH proteins and associated phenotypes.

Ciliary localization Function	Gene	Locus	Extraciliary localization/function	NPH subtype(s)	Extrarenal features (Halbritter et al., 2013b; Braun and Hildebrandt, 2017; König et al., 2017; Luo and Tao, 2018)	References
Transition zone (TZ)	NPHP1	NPHP1	Cell junctions	Juvenile, adult	Retinitis pigmentosa, neurologic symptoms, liver disease	Hildebrandt et al. (1997); Saunier et al. (1997)
	NPHP4	NPHP4	Cell junctions Hippo signaling	Juvenile, adult	Retinitis pigmentosa, neurologic symptoms, congenital heart disease, liver disease (all infrequent)	Mollet et al. (2002); Otto et al. (2002)
	IQCB1	NPHP5	–	Juvenile, adult	Retinitis pigmentosa (in all patients), leber congenital amaurosis, neurologic symptoms	Otto et al. (2005); Estrada-Cuzcano et al. (2011)
	CEP290	NPHP6	DDR signaling	Infantile, juvenile, adult	Retinitis pigmentosa, leber congenital amaurosis, neurologic symptoms, liver disease	Sayer et al. (2006); Valente et al. (2006); Helou et al. (2007); Tory et al. (2007)
	RPGRIP1L	NPHP8	–	Infantile, juvenile, adult	Retinitis pigmentosa, neurologic symptoms, liver disease, polydactyly	Arts et al. (2007); Delous et al. (2007); Wolf et al. (2007)
	TMEM67	NPHP11	–	Infantile, juvenile, adult	Retinitis pigmentosa, neurologic symptoms, liver disease, polydactyly	Smith U. M. et al. (2006)
Intraflagellar transport complex IFT-B	IFT172	NPHP17	–	Infantile, juvenile, adult	Retinitis pigmentosa, neurologic symptoms, liver disease, skeletal anomalies, polydactyly	Halbritter et al. (2013a)
	TRAF3IP1/IFT54	SLNS9	Microtubule dynamics	Infantile, Juvenile	Retinitis pigmentosa, hepatic fibrosis, skeletal anomalies, obesity	Bizet et al. (2015)
Intraflagellar transport complex IFT-A	TTC21B/IFT139	NPHP12	Microtubule dynamics	Infantile, juvenile	Neurologic symptoms, situs inversus, liver disease, skeletal anomalies	Davis et al. (2011); Cong et al. (2014)
	WDR19/IFT144	NPHP13	–	Infantile, juvenile	Retinitis pigmentosa, liver disease (especially Caroli disease), pancreas anomalies, skeletal anomalies	Bredrup et al. (2011)
Inversin compartment	INVS	NPHP2	Cell junctions; mitotic spindle poles, midbody	Infantile, juvenile	Retinitis pigmentosa, neurologic symptoms, situs inversus, congenital heart disease, liver disease	Otto et al. (2003); O’Toole et al. (2006); Tory et al. (2009)
	NPHP3	NPHP3	–	Infantile, juvenile, adult	Retinitis pigmentosa, neurologic symptoms, situs inversus, congenital heart defect, liver disease	Omran et al. (2000); Olbrich et al. (2003); Bergmann et al. (2008); Tory et al. (2009)
	NEK8	NPHP9	DDR and Hippo signaling	Infantile, juvenile	Situs inversus, congenital heart disease, liver disease, pancreas anomalies	Otto et al. (2008); Grampa et al. (2016)
	ANKS6	NPHP16	–	Infantile, juvenile, adult	Neurologic symptoms, situs inversus, congenital heart disease, liver disease	Hoff et al. (2013); Taskiran et al. (2014)
Basal body	SDCCAG8	NPHP10	DDR signaling	Infantile, juvenile, adult	Retinitis pigmentosa, neurologic symptoms, obesity, hypogenitalism	Otto et al. (2010); Watanabe et al. (2019)
	CEP164	NPHP15	DDR signaling	Juvenile	Retinitis pigmentosa, Leber congenital amaurosis, neurologic symptoms, liver disease, polydactyly	Chaki et al. (2012)
	CEP83	NPHP18	–	Infantile, juvenile	Retinitis pigmentosa, neurologic symptoms, liver disease	Failler et al. (2014)
Near basal body	ADAMTS9	NPHP21	Metalloproteinase function, protein trafficking	Infantile, juvenile	Deafness, short stature, developmental delay	Choi et al. (2019); Nandadasa et al. (2019)
Ciliary axoneme	GLIS2	NPHP7	Nucleus, role in transcription	Juvenile	–	Attanasio et al. (2007)
	DCDC2	NPHP19	Microtubule dynamics, Wnt signaling	Juvenile	Liver disease, deafness	Schueler et al. (2015)
No ciliary localization	ZNF423	NPHP14	DDR signaling and transcription	Infantile	Neurologic symptoms, situs inversus	Chaki et al. (2012)
	MAPKBP1	NPHP20	DDR and JNK signaling; Mitotic spindle poles during mitosis	Juvenile, adult	Scoliosis, facial dysmorphisms1	Macia et al. (2017)

Presence and severity of extrarenal features varies between patients. ¹Tentative association in one and two families, respectively.