Joubert syndrome (WP4656)

Homo sapiens

Joubert syndrome (JS) is a rare hereditary disorder that is classified as a ciliopathy, and is caused by mutations occurring in genes essential for the development and proper functioning of primary cellular cilia. These hair-like structures located on the cell membrane are responsible for detecting and relaying external signals to the interior of the cell. The defining JS feature is the molar tooth sign (MTS), which is the particular manner in which a characteristic malformation of midbrain appears in radiological imaging, and which causes delays in both intellectual and motor development. A visual representation of the pathways underlying JS pathogenesis was synthesized, which might provide a more complete understanding of the disease, possibly aiding in better diagnosis and more successful treatment. Data collection on the genes, pathways and interactions involved was done through a literature search in combination supported by online databases such as OMIM, STRING and GeneMANIA. The pathway was created using PathVisio version 3.3.0. Nodes were annotated using the appropriate Ensembl, ChEBI, or Uniprot-TrEMBL identifiers and standardized MIM notation was used to visualize the interactions between them. A final pathway containing 88 unique nodes and 71 interactions was created. The pathway highlights three functional or structural areas of the primary cilium that appear to play important roles in JS pathogenesis, namely the basal body or centriole, the transition zone and ciliary trafficking. Furthermore, two specific complexes seem to be of particular interest; the B9 ciliary complex and the centriolar satellite contain eight and three JS-associated protein respectively. Lastly, the ARL13B-PDE6D-INPP5E signaling network ensures the proper functioning of INPP5E, and enzyme that converts lipid ciliary membrane components. All three proteins have been found to be mutated in JS patients.


Anna De Brouwer , Egon Willighagen , Friederike Ehrhart , and Eric Weitz


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Homo sapiens


Rare Diseases


Pathway Ontology

disease pathway signaling pathway

Disease Ontology

Joubert syndrome


Label Type Compact URI Comment
GDP Metabolite chebi:17552
PtdIns4P Metabolite chebi:17526
NBS Metabolite chebi:53174
GDP Metabolite chebi:17552
GDP Metabolite chebi:17552
PtdIns(3,4,5)P3 Metabolite chebi:16618
GMP Metabolite chebi:16356
PtdIns(4,5)P2 Metabolite chebi:18348
PtdIns(3,4)P2 Metabolite chebi:84247
cGMP Metabolite chebi:16356
GTP Metabolite chebi:37565
Calmodulin Metabolite chebi:3324
GTP Metabolite chebi:37565
GTP Metabolite chebi:37565
GTP Metabolite chebi:37565
TMEM17 GeneProduct ensembl:ENSG00000186889
TMEM67 GeneProduct ensembl:ENSG00000164953
TMEM216 GeneProduct ensembl:ENSG00000187049
KIAA0586 GeneProduct ensembl:ENSG00000100578
DVL3 GeneProduct ensembl:ENSG00000161202
RAB3IP GeneProduct ensembl:ENSG00000127328
SUFU GeneProduct ensembl:ENSG00000107882
ATF4 GeneProduct ensembl:ENSG00000128272
CEP97 GeneProduct ensembl:ENSG00000182504
MYO5A GeneProduct ensembl:ENSG00000197535
RHOA GeneProduct ensembl:ENSG00000067560
MYO6 GeneProduct ensembl:ENSG00000196586
ARR3 GeneProduct ensembl:ENSG00000120500
FLNA GeneProduct ensembl:ENSG00000196924
PIBF1 GeneProduct ensembl:ENSG00000083535
BBS4 GeneProduct ensembl:ENSG00000140463
TCTN3 GeneProduct ensembl:ENSG00000119977
ARL2 GeneProduct ensembl:ENSG00000213465
TMEM138 GeneProduct ensembl:ENSG00000149483
KAT5 GeneProduct ensembl:ENSG00000172977
PARP1 GeneProduct ensembl:ENSG00000143799
PCM1 GeneProduct ensembl:ENSG00000078674 Component of the centriolar satellite.
CEP120 GeneProduct ensembl:ENSG00000168944
RP2 GeneProduct ensembl:ENSG00000102218
PDE6B GeneProduct ensembl:ENSG00000133256
BBS9 GeneProduct ensembl:ENSG00000122507
ATM GeneProduct ensembl:ENSG00000149311
RHEB GeneProduct ensembl:ENSG00000106615
DVL1 GeneProduct ensembl:ENSG00000107404
BBS5 GeneProduct ensembl:ENSG00000163093
BBS7 GeneProduct ensembl:ENSG00000138686
UNC119 GeneProduct ensembl:ENSG00000109103
NPHP4 GeneProduct ensembl:ENSG00000131697
SHH GeneProduct ensembl:ENSG00000164690
TCTN1 GeneProduct ensembl:ENSG00000204852
CPLANE1 GeneProduct ensembl:ENSG00000197603
ANKS6 GeneProduct ensembl:ENSG00000165138
NPHP3 GeneProduct ensembl:ENSG00000113971
MTOR GeneProduct ensembl:ENSG00000198793
TTC8 GeneProduct ensembl:ENSG00000165533
CSPP1 GeneProduct ensembl:ENSG00000104218
TMEM231 GeneProduct ensembl:ENSG00000205084
ARMC9 GeneProduct ensembl:ENSG00000135931
ARL13B GeneProduct ensembl:ENSG00000169379
INVS GeneProduct ensembl:ENSG00000119509
CCP110 GeneProduct ensembl:ENSG00000103540
CEP104 GeneProduct ensembl:ENSG00000116198
PDE6A GeneProduct ensembl:ENSG00000132915
ZNF423 GeneProduct ensembl:ENSG00000102935
NEK8 GeneProduct ensembl:ENSG00000160602
BBS1 GeneProduct ensembl:ENSG00000174483
TMEM237 GeneProduct ensembl:ENSG00000155755
MRE11 GeneProduct ensembl:ENSG00000020922
BBS2 GeneProduct ensembl:ENSG00000125124
PDE6G GeneProduct ensembl:ENSG00000185527
TCTN2 GeneProduct ensembl:ENSG00000168778
B9D1 GeneProduct ensembl:ENSG00000108641
RAD50 GeneProduct ensembl:ENSG00000113522
OFD1 GeneProduct ensembl:ENSG00000046651 Component of the centriolar satellite.
INPP5E GeneProduct ensembl:ENSG00000148384
CEP41 GeneProduct ensembl:ENSG00000106477
NPHP1 GeneProduct ensembl:ENSG00000144061
AHI1 GeneProduct ensembl:ENSG00000135541
INPP5E GeneProduct ensembl:ENSG00000148384
PDE6D GeneProduct ensembl:ENSG00000156973
ARL13B GeneProduct ensembl:ENSG00000169379
B9D2 GeneProduct ensembl:ENSG00000123810
CC2D2A GeneProduct ensembl:ENSG00000048342
MKS1 GeneProduct ensembl:ENSG00000011143
PDE6D GeneProduct ensembl:ENSG00000156973
RHEB GeneProduct ensembl:ENSG00000106615
PDE6D GeneProduct ensembl:ENSG00000156973
ARL3 GeneProduct ensembl:ENSG00000138175
UNC119 GeneProduct ensembl:ENSG00000109103
ZNF423 GeneProduct ensembl:ENSG00000102935
PDE6D GeneProduct ensembl:ENSG00000156973
RAB8A GeneProduct ensembl:ENSG00000167461
CEP290 GeneProduct ensembl:ENSG00000198707 Component of the centriolar satellite.
CEP164 GeneProduct ensembl:ENSG00000110274
DVL1 GeneProduct ensembl:ENSG00000107404
CEP290 GeneProduct ensembl:ENSG00000198707
ARL3 GeneProduct ensembl:ENSG00000138175
CEP164 GeneProduct ensembl:ENSG00000110274
OFD1 GeneProduct ensembl:ENSG00000046651
RAB8A GeneProduct ensembl:ENSG00000167461
RPGRIP1L GeneProduct ensembl:ENSG00000103494
PCNT Protein uniprot:O95613
NIN Protein uniprot:C9J066
CETN1 Protein uniprot:Q12798
CETN2 Protein uniprot:P41208


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