Joubert syndrome (Homo sapiens)

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243655292120NodeCiliary traffickingTransition zone35Basal body / centrioleTMEM17553513, 2913, 293253513, 292013, 2913, 2952, 292113, 291432432932232024335152115221, 8172128211718183418, 24155527, 332641241724, 272210716, 3334Nodes6LegendAxonemeTMEM67TMEM216Ciliary membraneWntKIAA0586GDPDVL3RAB3IPSUFUATF4CEP97MYO5ARHOAMYO6ARR3FLNAPIBF1BBS4TCTN3ARL2PtdIns4PNBSTMEM138GDPKAT5PARP1PCM1CEP120PCNTRP2PDE6BBBS9ATMRHEBDVL1BBS5GDPBBS7PtdIns(3,4,5)P3UNC119NPHP4SHHGMPPtdIns(4,5)P2TCTN1PtdIns(3,4)P2CPLANE1ANKS6NPHP3MTORNINTTC8CSPP1TMEM231ARMC9ARL13BINVSCCP110CEP104PDE6AZNF423cGMPNEK8GTPCETN1CETN2BBS1TMEM237MRE11BBS2PDE6GCalmodulinTCTN2B9D1RAD50OFD1INPP5ECEP41NPHP1AHI1INPP5EPDE6DARL13B21B9D2CC2D2AMKS1PDE6DGTPRHEBPDE6D15ARL3UNC119NucleusZNF423PDE6DRAB8AGTPCEP290CEP164DVL1CEP290Non JS-associated gene product or proteinJS-associated gene or gene productMetabolitePathwayMIM-interaction: conversionMIM-interaction: bindingMIM-interaction: activationMIM-interaction: catalysisMIM-interaction: inhibitionLinks two identical nodesEdgesGTPARL3CEP164OFD1WntRAB8ARPGRIP1LNodeNodeNodePhosphoinositides metabolism


Description

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.

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Bibliography

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History

View all...
CompareRevisionActionTimeUserComment
134349view05:34, 21 July 2024EgonwRemoved template comments
125785view09:57, 10 March 2023DeSlConverted NIN-protein ID to reviewed UniProt
125784view09:55, 10 March 2023DeSlAdded PW node to link to more detailed molecular mechanism
125783view09:52, 10 March 2023DeSlChanged DataNodes in Legend to textLabels
120396view08:56, 30 November 2021Fehrhartboxed pathway nodes
117153view09:44, 18 May 2021EweitzModified title
105130view12:27, 9 July 2019Fehrhartconnected unconnected lines
105068view07:38, 4 July 2019EgonwReplaced secondary ChEBI identifiers with a primary identifiers.
105054view13:07, 3 July 2019AnneDBA small adjustmen was made regarding the structural organization of the pathway.
105022view16:47, 28 June 2019AnneDBModified description
104971view13:54, 27 June 2019AnneDBModified description
104969view13:51, 27 June 2019AnneDBModified description
104958view12:34, 27 June 2019AnneDBModified description
104956view11:41, 27 June 2019AnneDBA few corrections were made, in addition to replacements of interactions of unknown nature by MIM notations.
104932view14:14, 25 June 2019AnneDBModified description
104931view14:12, 25 June 2019AnneDBModified description
104922view11:40, 25 June 2019AnneDBOntology Term : 'signaling pathway' added !
104921view11:40, 25 June 2019AnneDBOntology Term : 'disease pathway' added !
104890view13:18, 23 June 2019AnneDBOntology Term : 'Joubert syndrome' added !
104889view13:14, 23 June 2019AnneDBModified description
104888view13:14, 23 June 2019AnneDBModified description
104887view13:08, 23 June 2019AnneDBModified title
104886view13:07, 23 June 2019AnneDBNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AHI1GeneProductENSG00000135541 (Ensembl)
ANKS6GeneProductENSG00000165138 (Ensembl)
ARL13BGeneProductENSG00000169379 (Ensembl)
ARL2GeneProductENSG00000213465 (Ensembl)
ARL3GeneProductENSG00000138175 (Ensembl)
ARMC9GeneProductENSG00000135931 (Ensembl)
ARR3GeneProductENSG00000120500 (Ensembl)
ATF4GeneProductENSG00000128272 (Ensembl)
ATMGeneProductENSG00000149311 (Ensembl)
B9D1GeneProductENSG00000108641 (Ensembl)
B9D2GeneProductENSG00000123810 (Ensembl)
BBS1GeneProductENSG00000174483 (Ensembl)
BBS2GeneProductENSG00000125124 (Ensembl)
BBS4GeneProductENSG00000140463 (Ensembl)
BBS5GeneProductENSG00000163093 (Ensembl)
BBS7GeneProductENSG00000138686 (Ensembl)
BBS9GeneProductENSG00000122507 (Ensembl)
CC2D2AGeneProductENSG00000048342 (Ensembl)
CCP110GeneProductENSG00000103540 (Ensembl)
CEP104GeneProductENSG00000116198 (Ensembl)
CEP120GeneProductENSG00000168944 (Ensembl)
CEP164GeneProductENSG00000110274 (Ensembl)
CEP290GeneProductENSG00000198707 (Ensembl)
CEP41GeneProductENSG00000106477 (Ensembl)
CEP97GeneProductENSG00000182504 (Ensembl)
CETN1ProteinQ12798 (Uniprot-TrEMBL)
CETN2ProteinP41208 (Uniprot-TrEMBL)
CPLANE1GeneProductENSG00000197603 (Ensembl)
CSPP1GeneProductENSG00000104218 (Ensembl)
CalmodulinMetaboliteCHEBI:3324 (ChEBI)
DVL1GeneProductENSG00000107404 (Ensembl)
DVL3GeneProductENSG00000161202 (Ensembl)
FLNAGeneProductENSG00000196924 (Ensembl)
GDPMetaboliteCHEBI:17552 (ChEBI)
GMPMetaboliteCHEBI:16356 (ChEBI)
GTPMetaboliteCHEBI:37565 (ChEBI)
INPP5EGeneProductENSG00000148384 (Ensembl)
INVSGeneProductENSG00000119509 (Ensembl)
KAT5GeneProductENSG00000172977 (Ensembl)
KIAA0586GeneProductENSG00000100578 (Ensembl)
MKS1GeneProductENSG00000011143 (Ensembl)
MRE11GeneProductENSG00000020922 (Ensembl)
MTORGeneProductENSG00000198793 (Ensembl)
MYO5AGeneProductENSG00000197535 (Ensembl)
MYO6GeneProductENSG00000196586 (Ensembl)
NBSMetaboliteCHEBI:53174 (ChEBI)
NEK8GeneProductENSG00000160602 (Ensembl)
NINProteinQ8N4C6 (Uniprot-TrEMBL)
NPHP1GeneProductENSG00000144061 (Ensembl)
NPHP3GeneProductENSG00000113971 (Ensembl)
NPHP4GeneProductENSG00000131697 (Ensembl)
OFD1GeneProductENSG00000046651 (Ensembl)
PARP1GeneProductENSG00000143799 (Ensembl)
PCM1GeneProductENSG00000078674 (Ensembl) Component of the centriolar satellite.
PCNTProteinO95613 (Uniprot-TrEMBL)
PDE6AGeneProductENSG00000132915 (Ensembl)
PDE6BGeneProductENSG00000133256 (Ensembl)
PDE6DGeneProductENSG00000156973 (Ensembl)
PDE6GGeneProductENSG00000185527 (Ensembl)
PIBF1GeneProductENSG00000083535 (Ensembl)
Phosphoinositides metabolismPathwayWP4971 (WikiPathways)
PtdIns(3,4)P2MetaboliteCHEBI:84247 (ChEBI)
PtdIns(3,4,5)P3MetaboliteCHEBI:16618 (ChEBI)
PtdIns(4,5)P2MetaboliteCHEBI:18348 (ChEBI)
PtdIns4PMetaboliteCHEBI:17526 (ChEBI)
RAB3IPGeneProductENSG00000127328 (Ensembl)
RAB8AGeneProductENSG00000167461 (Ensembl)
RAD50GeneProductENSG00000113522 (Ensembl)
RHEBGeneProductENSG00000106615 (Ensembl)
RHOAGeneProductENSG00000067560 (Ensembl)
RP2GeneProductENSG00000102218 (Ensembl)
RPGRIP1LGeneProductENSG00000103494 (Ensembl)
SHHGeneProductENSG00000164690 (Ensembl)
SUFUGeneProductENSG00000107882 (Ensembl)
TCTN1GeneProductENSG00000204852 (Ensembl)
TCTN2GeneProductENSG00000168778 (Ensembl)
TCTN3GeneProductENSG00000119977 (Ensembl)
TMEM138GeneProductENSG00000149483 (Ensembl)
TMEM17GeneProductENSG00000186889 (Ensembl)
TMEM216GeneProductENSG00000187049 (Ensembl)
TMEM231GeneProductENSG00000205084 (Ensembl)
TMEM237GeneProductENSG00000155755 (Ensembl)
TMEM67GeneProductENSG00000164953 (Ensembl)
TTC8GeneProductENSG00000165533 (Ensembl)
UNC119GeneProductENSG00000109103 (Ensembl)
WntPathwayWP428 (WikiPathways)
ZNF423GeneProductENSG00000102935 (Ensembl)
cGMPMetaboliteCHEBI:16356 (ChEBI)

Annotated Interactions

No annotated interactions

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