Table 1 Ciliopathies, genes and subcellular functions of the proteins

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