Table 1 Ciliopathies, genes and subcellular functions of the proteins
From: A systems-biology approach to understanding the ciliopathy disorders
| Disorders | Symptoms | Inheritance | Causative genes | Putative protein functions |
|---|---|---|---|---|
| Primary ciliary dyskinesia (PCD)/Kartagener syndrome (KS) | Chronic sinusitis, bronchiectasis and infertility with situs inversus (KS only) and occasional hydrocephalus (PCD) | Autosomal recessive | DNAH5 | Cilia motility |
| DNAH11 | Cilia motility | |||
| DNAl1 | Cilia motility | |||
| DNAl2 | Cilia motility | |||
| TXNDC3 | Unknown | |||
| KTU | Dynein arm preassembly, Cilia motility | |||
| RSPH9 | Central pair/motility | |||
| RSPH4A | Central pair/motility | |||
| LRRC50 | Cilia motility | |||
| Leber congenital amaurosis (LCA) | Retinal dystrophy, blindness or severe visual impairment such as sensory nystagmus, amaurotic pupils and absent electroretinogram signal | Autosomal recessive | CEP290;NPHP6* | RPGR complex, trafficking |
| LCA5 | RPGR complex, trafficking | |||
| TULP1 | Rhodopsin trafficking | |||
| RPGRIP1 | RPGR complex | |||
| Polycystic kidney disease (PKD): dominant (ADPKD), recessive (ARPKD) | Hepatic cysts, pancreatic cysts (10%), cysts in the nephron (ADPKD only) and hepatic fibrosis, cysts in collecting ducts (ARPKD only) | Autosomal dominant, Autosomal recessive | PKD1 | Mechanosensation, cell-cell or cell-matrix interactions |
| PKD2 | Probable calcium channel protein | |||
| PKHD1 | Probable receptor protein, PC2 modulation | |||
| Jeune asphyxiating thoracic dystrophy (JATD) | Postaxial polydactyly, short limbs, short and slender ribs, small ilia, irregular acetabulum and cystic kidney | Autosomal recessive | ATD1 | Role in Shh signaling |
| Ellis-van Creveld syndrome (EVC) | Polydactyly, short ribs, dysplastic fingernails/teeth and cardiac defects | Autosomal recessive | EVC1 | Unknown |
| EVC2 | Unknown | |||
| Oral-facial-digital syndrome type I (OFD1) | Craniofacial malformations, postaxial polydactyly, central nervous system defects and cystic kidney (~15%) | X-linked dominant | OFD1* | Ciliogenesis, Wnt/PCP signaling, association with LCA5 and SDCCAG8 |
| Nephronophthisis (NPHP) | Triad of tubular basement membrane disruption, tubulointerstitial nephropathy, corticomedullary cysts. Pancreatic/hepatic fibrosis, situs inversus, retinitis pigmentosa, cerebellar vermis hypoplasia, oculomotor apraxia and mental retardation (~10%) | Autosomal recessive | NPHP1 * | Cilia structure, cell-cell adhesion |
| NPHP2;INVS | Wnt/PCP, cell cycle control | |||
| NPHP3 | Wnt/PCP pathway | |||
| NPHP4 | Cilia structure, IFT | |||
| NPHP5;IQCB1 | RPGR/Calmodulin complex | |||
| NPHP6;CEP290* | RPGR complex, trafficking | |||
| NPHP7;CLIS2 | Transcription factor, Wnt | |||
| NPHP8;RPGRIP1L* | Shh signaling | |||
| NPHP9;NEK8 | Modulation of PC1 and PC2 | |||
| NPHP10;SDCCAG8 | Association with OFD1 | |||
| NPHP11;TMEM67* | Ciliogenesis | |||
| NPHPL1;XPNPEP3 | Unknown | |||
| Joubert syndrome (JBTS)/JBTS-related disorder (JSRD) | Hypotonia, ataxia, psychomotor delay, oculomotor apraxia, retinal degeneration and mental retardation. Occipital encephalocele, polymicrogyria, cystic kidney, hepatic fibrosis and polydactyly (JSRD) | Autosomal recessive | JBTS1;INPP5E | Cilia stability, phosphatidylinositol signaling |
| JBTS2;TMEM216* | Ciliogenesis, centrosomal docking, PCP signaling | |||
| JBTS3;AHI1 | Wnt signaling | |||
| JBTS4;NPHP1* | Cilia structure, cell-cell adhesion | |||
| JBTS5;CEP290* | RPGR complex, trafficking | |||
| JBTS6;TMEM67* | Ciliogenesis | |||
| JBTS7;RPGRIP1L* | Shh signaling | |||
| JBTS8;ARL13B | Cilia structure, IFT | |||
| JBTS9;CC2D2A* | Association with CEP290 | |||
| JBTS10;OFD1* | Ciliogenesis, Wnt/PCP, association with LCA5 and SDCCAG8 | |||
| JBTS11;TTC21B | Ciliogenesis | |||
| JBTS12;KIF7 | Shh signaling, microtubule dynamics | |||
| JBTS13;TCTN1 | Transition zone complex regulation | |||
| Bardet-Biedl syndrome (BBS) | Obesity, diabetes, polydactyly, mental retardation, cystic kidney, retinitis pigmentosa, hypogenitalism and situs inversus | Autosomal recessive | BBS1 | BBSome, Wnt/PCP, IFT/trafficking |
| BBS2 | BBSome, IFT/trafficking | |||
| BBS3;ARL6 | Vesicle trafficking | |||
| BBS4 | BBSome, IFT/trafficking, microtubule anchoring, cell cycle control | |||
| BBS5 | BBSome, IFT/trafficking, ciliogenesis | |||
| BBS6;MKKS | IFT/trafficking, Wnt/PCP, cytokinesis, chaperonin | |||
| BBS7 | BBSome, IFT/trafficking | |||
| BBS8;TTC8 | BBSome, IFT/trafficking | |||
| BBS9;PTHB1 | BBSome | |||
| BBS10 | Ciliogenesis, Wnt, chaperonin | |||
| BBS11;TRIM32 | E3 ubiquitin-protein ligase | |||
| BBS12 | Ciliogenesis, Wnt, chaperonin | |||
| Alström syndrome (ALMS) | Cone-rod retinal dystrophy, hearing defects, cardiomyopathy, early-onset obesity, renal failure and hepatic dysfunction | Autosomal recessive | ALMS1 | Cilia maintenance |
| Meckel-Gruber syndrome (MKS) | Renal cysts, hepatic fibrosis, central nervous system malformations, polydactyly, liver malformations, laterality defects, cardiac defects | Autosomal recessive | MKS1 | Ciliogenesis |
| MKS2;TMEM216* | Ciliogenesis, centrosomal docking, PCP signaling | |||
| MKS3;TMEM67* | Ciliogenesis | |||
| MKS4;CEP290* | RPGR complex, trafficking | |||
| MKS5;RPGRIP1L* | Shh signaling | |||
| MKS6;CC2D2A* | Association with CEP290 |