Table 1 A summary of the ciliopathies for each inherited disorder
Inherited disorderLociGene(s)LocationProtein productFunction and other commentsInteractorsReferences
PKD (autosomal dominant)
Adult type 1PKD1PKD116p13.3PC1Cell–cell or cell–matrix interactions; interacts with PC-2 to produce calcium-permeable nonselective cation currentsPC-2
Adult type 2PKD2PKD24q22.1PC2Probable channel protein; interacts with PC-1PC-1
PKD3?Further genetic heterogeneity suggested but not proved
PKHD (autosomal recessive)
Infantile typePKHD1PKHD16p12.2Fibrocystin, polyductinProbable receptor protein that acts in collecting duct and biliary differentiation; colocalises with PC-2 at the basal bodies of primary cilia
Juvenile, type 1NPHP1, SLSN1, JBTS4NPHP12q13NephrocystinAdaptor protein; associates with signalling molecules involved in cell adhesion and actin cytoskeleton organisation, and with β-tubulin, a major component of primary ciliaNephrocystin-4, p130Cas/BCAR1, signal-rich PTK2B, TNS, β-tubulin47, 95
Infantile, type 2NPHP2INVS9q31.1InversinPrimary cilia function and involvement in the cell cycle; possible molecular switch between different Wnt signalling cascades; left–right axis determinationNephrocystin, APC295–97</citref>
Adolescent, type 3NPHP3, SLSN3NPHP33q22.1Nephrocystin-3With nephrocystin and nephrocytin-4, may mediate a common developmental pathway in the primary cilia of renal epithelial cellsNephrocystin98
Juvenile, type 4NPHP4, SLSN4, JBTS4NPHP41p36Nephrocystin-4, nephroretininPossible roles in signal transduction, cell–cell adhesion and actin cytoskeleton organisation and biogenesis; mutations in RPGRIP1 (associated with Leber congenital amaurosis type 6) disrupt the interaction with nephrocystin-4Nephrocystin, RPGRIP147, 64, 95
SLSN5IQCB13q21.1IQCB1, nephrocystin-5IQCB1 and RPGR may participate in a common pathway in connecting cilia of photoreceptors and to primary cilia of renal epithelial cellsRPGR, calmodulin95
JBTS and related disorders/SLS phenotypesNPHP6, SLSN6, JBTS5, LCA10, MKS4CEP290, NPHP612q21.3CEP290Localised at the nuclei of renal epithelial cells in a cell cycle-dependent manner, in connecting cilia of photoreceptors, centrosomes and primary cilia; modulates the activity of ATF4, a transcription factor implicated in cAMP-dependent renal cyst formationATF434–38
MKS1MKS1, FLJ2034517q22MKS1MKS1 is a member of the flagellar apparatus basal body proteome; contains a B9 domain of unknown function; localises to basal bodies and centrosomes, but interacts with meckelinMeckelin14, 15
MKS211q13Causative gene has not been identified99
MKS3, JBTS6MKS3, TMEM678q22.1MeckelinMeckelin localises to the cell surface and primary cilia; putative transmembrane receptor with an extracellular cysteine-rich domain that may have similarities to those in Frizzled-type receptorsMKS114, 36, 40
Meckel-like cerebro-reno-digital syndromeMKS4, JBTS5CEP290, NPHP612q21.3CEP290See entry above for CEP290; mutations also cause cerebro-reno-digital syndrome, with a phenotype between that of MKS and JBTS36
CORS, JPTS type BMKS5, JBTS7, CORS3RPGRIP1L, KIAA100516q12.2RPGRIP1LColocalises at the basal body and centrosomes with CEP290, and interacts with nephrocystin-4; in mice, Ftm/Rpgrip1l is necessary for the establishment of left–right asymmetry and patterning of the neural tube and the limbs; may mediate cilium-related Shh signallingNephrocystin-439, 63, 100
CORS type 1JBTS1, CORS19q34.3Causative gene has not been identified28, 29
CORS type 2JBTS2, CORS211p12–q13.3Causative gene has not been identified29–31
JBTS3AHI16q23.3AAHI1 protein homologue, jouberinUnknown function; AHI1 expression may contribute to the development of specific types of human leukaemia; may be associated with susceptibility to schizophrenia32, 101
JBTS4NPHP12q13NephrocystinSee entry above for NPHP1; deletions of the NPHP1 gene are a rare cause of JBTS33
JBTS5, MKS4CEP290, NPHP612q21.3CEP290See entry above for CEP29034, 35
JBTS6, MKS3MKS3, TMEM678q22.1MeckelinSee entry above for MKS336
CORS type 3JBTS7, CORS3, MKS5RPGRIP1L, KIAA100516q12.2RPGRIP1LSee entry above for RPGRIP1L39, 63
LCA10CEP290, NPHP612q21.3CEP290See entry above for CEP29037
LCA5LCA5, C6orf1526q14.1LebercilinLocalises to the microtubules, centrioles and primary cilia, and to the connecting cilia of photoreceptorsDynein light chains 1 and 2, p150glued and p50-dynamitin subunits of dynactin, nucleophosmin, nucleolin, 14-3-3eta, HSP7013
Major form (type 1)BBS1BBS1, BBS2L211q13.1BBS1Unknown function; probable role in eye, limb, cardiac and reproductive system development102
BBS2BBS216q13BBS2Unknown function103
BBS3ARL63q11.2ARLMember of the ARL subgroup of the Ras superfamily; may regulate diverse cellular functions, including regulation of intracellular traffic; in C. elegans ARL6 undergoes intraflagellar transport in the ciliary axoneme, implicating it in ciliary transport104, 105
BBS4BBS415q24.1BBS4Contains tetratricopeptide repeats; localises to the centriolar satellites of centrosomes and basal bodies of primary cilia; adaptor of the p150(glued) subunit of the dynein transport machinery; may be required for microtubule anchoring and cell cycle progressionPCM1, p150glued subunit of dynactin61, 102
BBS5BBS52q31.1BBS5Localises to basal bodies; in C. elegans it is necessary for the formation of both cilia and flagella5
MKKSMKKS, BBS6MKKS20p12.2MKKS/BBS6 putative chaperoninGroup II chaperonin-like protein that localises to pericentriolar material; centrosomal component required for cytokinesis; possible role in protein processing in limb, cardiac and reproductive system development62, 106–108</citref>
BBS7BBS7, BBS2L14q27BBS7Unknown function; protein contains a six-bladed β-propeller motif, which shares homology to regions in the BBS1 and BBS2 proteins79
BBS8TTC814q31.3Tetratricopeptide repeat domain 8Localises to centrosomes and basal bodies; colocalises with γ-tubulin and BBS4 in centrosomes, and interacts with PCM1, a protein probably involved in ciliogenesis; in C. elegans, bbs-8 is required for the stability of intraflagellar transport complexesPCM150, 109
BBS9PTHB17p14.3PTHB1Unknown function; may be involved in parathyroid hormone action in bones; expressed in ciliated cells in C. elegans110
BBS10BBS10, C12orf5812q21.2BBS10Unknown function; group II chaperonin-like protein80
BBS11TRIM329q33.1tripartite motif-containing 32Contains a RING finger domain and may be a E3 ubiquitin-protein ligase; possible role in proteasome degradation pathwayHIV-1 Tat protein, TRIM 23 and 27, PDE9A, UBQLN1111
BBS12BBS12, C4orf244q27BBS12Unknown function; group II chaperonin-like protein; shares distant homology to the BBS6 and BBS10 proteins112
ALMS1ALMS12p13ALMS1Localises to centrosome and basal body; in vivo phenotypes of Alms1 gene-trap mice include a lack of sperm flagella and defective rhodopsin transport through the connecting cilia of photoreceptor cells; possible role in intracellular traffickingMEGF1019–22
OFD syndrome
OFD type 1OFD1OFD1, CXorf5Xp22.2OFD1Localises to centrosomes and basal bodies; defective primary ciliary and left-right asymmetry in Ofd1 knock-out mice, with impaired patterning of the neural tube and altered expression24, 25, 113
ATD, Jeune syndrome
ATD1IFT80, WDR563q26.1IFT80Localises to the basal body and the ciliary axoneme; possible role in Shh signallingIn Chlamydomonas reinhardtii, components of IFT complex B74, 114
  • AHI1, Abelson helper integration site 1; ALMS, Alström syndrome; APC2, anaphase-promoting complex subunit-2; ARL-6, ADP-ribosylation factor-like 6; ATD, asphyxiating thoracic dystrophy; ATF4, activating transcription factor 4; BBS, Bardet–Biedl syndrome; C. elegans, Caenorhabdits elegans; CEP290, Centrosomal protein 290 kDa; CORS, cerebello-oculo-renal syndrome; GTP, guanidine triphosphate; HIV, human immunodeficiency virus; HSP, heat shock protein; IFT80, Intraflagellar transport 80 kDa protein homologue; IQCB1, IQ motif-containing protein B1; JBTS, Joubert syndrome; LCA, Leber congenital amaurosis; MEGF-10 multiple epidermal growth factor-like-domains 10; MKKS, McKusick–Kaufman syndrome; MKS, Meckel–Gruber syndrome; NPHP, nephronophthisis; OFD, orofaciodigital; PC, polycystin; PCM1, Pericentriolar material 1; PDE9A, phosphodiesterase 9A; PKD, polycystic kidney disease; PKHD, polycystic kidney and hepatic disease; PTHB1, Parathyroid hormone-responsive B1; PTK2B, protein tyrosine kinase 2B; Ref., reference; RPGR, retinitis pigmentosa GTPase regulator; RPGRIP1, retinitis pigmentosa GTPase regulator-interacting protein; SLS, Senior–Løken syndrome; TNS, tensin; TRIM, tripartite motif-containing; UBQLN1, ubiquilin 1.