Table 1 A summary of the ciliopathies for each inherited disorder

Inherited disorder	Loci	Gene(s)	Location	Protein product	Function and other comments	Interactors	References
PKD (autosomal dominant)
Adult type 1	PKD1	PKD1	16p13.3	PC1	Cell–cell or cell–matrix interactions; interacts with PC-2 to produce calcium-permeable nonselective cation currents	PC-2
Adult type 2	PKD2	PKD2	4q22.1	PC2	Probable channel protein; interacts with PC-1	PC-1
	PKD3?				Further genetic heterogeneity suggested but not proved
PKHD (autosomal recessive)
Infantile type	PKHD1	PKHD1	6p12.2	Fibrocystin, polyductin	Probable receptor protein that acts in collecting duct and biliary differentiation; colocalises with PC-2 at the basal bodies of primary cilia
NPHP, SLS
Juvenile, type 1	NPHP1, SLSN1, JBTS4	NPHP1	2q13	Nephrocystin	Adaptor protein; associates with signalling molecules involved in cell adhesion and actin cytoskeleton organisation, and with β-tubulin, a major component of primary cilia	Nephrocystin-4, p130Cas/BCAR1, signal-rich PTK2B, TNS, β-tubulin	47, 95
Infantile, type 2	NPHP2	INVS	9q31.1	Inversin	Primary cilia function and involvement in the cell cycle; possible molecular switch between different Wnt signalling cascades; left–right axis determination	Nephrocystin, APC2	95–97</citref>
Adolescent, type 3	NPHP3, SLSN3	NPHP3	3q22.1	Nephrocystin-3	With nephrocystin and nephrocytin-4, may mediate a common developmental pathway in the primary cilia of renal epithelial cells	Nephrocystin	98
Juvenile, type 4	NPHP4, SLSN4, JBTS4	NPHP4	1p36	Nephrocystin-4, nephroretinin	Possible 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-4	Nephrocystin, RPGRIP1	47, 64, 95
	SLSN5	IQCB1	3q21.1	IQCB1, nephrocystin-5	IQCB1 and RPGR may participate in a common pathway in connecting cilia of photoreceptors and to primary cilia of renal epithelial cells	RPGR, calmodulin	95
JBTS and related disorders/SLS phenotypes	NPHP6, SLSN6, JBTS5, LCA10, MKS4	CEP290, NPHP6	12q21.3	CEP290	Localised 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 formation	ATF4	34–38
MKS
	MKS1	MKS1, FLJ20345	17q22	MKS1	MKS1 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 meckelin	Meckelin	14, 15
	MKS2		11q13		Causative gene has not been identified		99
	MKS3, JBTS6	MKS3, TMEM67	8q22.1	Meckelin	Meckelin 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 receptors	MKS1	14, 36, 40
Meckel-like cerebro-reno-digital syndrome	MKS4, JBTS5	CEP290, NPHP6	12q21.3	CEP290	See entry above for CEP290; mutations also cause cerebro-reno-digital syndrome, with a phenotype between that of MKS and JBTS		36
CORS, JPTS type B	MKS5, JBTS7, CORS3	RPGRIP1L, KIAA1005	16q12.2	RPGRIP1L	Colocalises 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 signalling	Nephrocystin-4	39, 63, 100
JPTS, CORS
CORS type 1	JBTS1, CORS1		9q34.3		Causative gene has not been identified		28, 29
CORS type 2	JBTS2, CORS2		11p12–q13.3		Causative gene has not been identified		29–31
	JBTS3	AHI1	6q23.3	AAHI1 protein homologue, jouberin	Unknown function; AHI1 expression may contribute to the development of specific types of human leukaemia; may be associated with susceptibility to schizophrenia		32, 101
	JBTS4	NPHP1	2q13	Nephrocystin	See entry above for NPHP1; deletions of the NPHP1 gene are a rare cause of JBTS		33
	JBTS5, MKS4	CEP290, NPHP6	12q21.3	CEP290	See entry above for CEP290		34, 35
	JBTS6, MKS3	MKS3, TMEM67	8q22.1	Meckelin	See entry above for MKS3		36
CORS type 3	JBTS7, CORS3, MKS5	RPGRIP1L, KIAA1005	16q12.2	RPGRIP1L	See entry above for RPGRIP1L		39, 63
LCA
	LCA10	CEP290, NPHP6	12q21.3	CEP290	See entry above for CEP290		37
	LCA5	LCA5, C6orf152	6q14.1	Lebercilin	Localises to the microtubules, centrioles and primary cilia, and to the connecting cilia of photoreceptors	Dynein light chains 1 and 2, p150^glued and p50-dynamitin subunits of dynactin, nucleophosmin, nucleolin, 14-3-3eta, HSP70	13
BBS
Major form (type 1)	BBS1	BBS1, BBS2L2	11q13.1	BBS1	Unknown function; probable role in eye, limb, cardiac and reproductive system development		102
	BBS2	BBS2	16q13	BBS2	Unknown function		103
	BBS3	ARL6	3q11.2	ARL	Member 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 transport		104, 105
	BBS4	BBS4	15q24.1	BBS4	Contains 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 progression	PCM1, p150^glued subunit of dynactin	61, 102
	BBS5	BBS5	2q31.1	BBS5	Localises to basal bodies; in C. elegans it is necessary for the formation of both cilia and flagella		5
MKKS	MKKS, BBS6	MKKS	20p12.2	MKKS/BBS6 putative chaperonin	Group 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 development		62, 106–108</citref>
	BBS7	BBS7, BBS2L1	4q27	BBS7	Unknown function; protein contains a six-bladed β-propeller motif, which shares homology to regions in the BBS1 and BBS2 proteins		79
	BBS8	TTC8	14q31.3	Tetratricopeptide repeat domain 8	Localises 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 complexes	PCM1	50, 109
	BBS9	PTHB1	7p14.3	PTHB1	Unknown function; may be involved in parathyroid hormone action in bones; expressed in ciliated cells in C. elegans		110
	BBS10	BBS10, C12orf58	12q21.2	BBS10	Unknown function; group II chaperonin-like protein		80
	BBS11	TRIM32	9q33.1	tripartite motif-containing 32	Contains a RING finger domain and may be a E3 ubiquitin-protein ligase; possible role in proteasome degradation pathway	HIV-1 Tat protein, TRIM 23 and 27, PDE9A, UBQLN1	111
	BBS12	BBS12, C4orf24	4q27	BBS12	Unknown function; group II chaperonin-like protein; shares distant homology to the BBS6 and BBS10 proteins		112
ALMS
	ALMS1	ALMS1	2p13	ALMS1	Localises 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 trafficking	MEGF10	19–22
OFD syndrome
OFD type 1	OFD1	OFD1, CXorf5	Xp22.2	OFD1	Localises 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 expression		24, 25, 113
ATD, Jeune syndrome
	ATD1	IFT80, WDR56	3q26.1	IFT80	Localises to the basal body and the ciliary axoneme; possible role in Shh signalling	In Chlamydomonas reinhardtii, components of IFT complex B	74, 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.