General Information:

Id: 7,102
Diseases: Nephronophthisis
Mammalia
review
Reference: [PMID: 27625867]

Interaction Information:

Comment The most common genetic cause of NPHP is mutations in NPHP1, which account for around 20% of cases. The most common NPHP1 gene defect is a large homozygous deletion of the whole gene.
Formal Description
Interaction-ID: 69872

gene/protein

NPHP1

affects_activity of

Comment The NPHP genes encoded proteins are almost all (except for XPNPEP3 and SLC41A1) expressed in centrosomes and primary cilia; nephronophthisis is therefore considered to be part of the spectrum of disorders known as ciliopathies, a group of disorders resulting from ciliary disturbances.
Formal Description
Interaction-ID: 69873

cellular component

cilium

affects_activity of

disease

Nephronophthisis

Comment SDCCAG8 was one of the first nephronophthisis-causing genes to be identified using next-generation sequencing approaches. Patients with mutations in this gene were diagnosed with Senior-Loken syndrome (SLSN), but may also have features suggestive of Bardet-Biedl syndrome (BBS) including obesity.
Formal Description
Interaction-ID: 69874

gene/protein

SDCCAG8

affects_activity of

disease

Nephronophthisis

Comment The encoded protein SDCCAG8 localizes to centrioles and directly interacts with the ciliopathy-associated protein OFD1. A murine model of SDCCAG8 has implicated elevated levels of DNA damage response signaling as a potential mechanism of kidney disease.
Formal Description
Interaction-ID: 69875

gene/protein

SDCCAG8

is localized in

cellular component

centriole

Comment The encoded protein SDCCAG8 localizes to centrioles and directly interacts with the ciliopathy-associated protein OFD1. A murine model of SDCCAG8 has implicated elevated levels of DNA damage response signaling as a potential mechanism of kidney disease.
Formal Description
Interaction-ID: 69876

gene/protein

SDCCAG8

interacts (colocalizes) with

gene/protein

OFD1

Comment The encoded protein SDCCAG8 localizes to centrioles and directly interacts with the ciliopathy-associated protein OFD1. A murine model of SDCCAG8 has implicated elevated levels of DNA damage response signaling as a potential mechanism of kidney disease.
Formal Description
Interaction-ID: 69877

gene/protein

SDCCAG8

affects_activity of

Comment TTC21B mutations have been associated with both isolated NPHP and Jeune syndrome.
Formal Description
Interaction-ID: 69878

gene/protein

TTC21B

affects_activity of

Comment TTC21B encodes the retrograde intraflagellar transport (IFT) protein IFT139, which has been shown to regulate Shh signaling.
Formal Description
Interaction-ID: 69879

gene/protein

TTC21B

increases_activity of

Comment TTC21B encodes the retrograde intraflagellar transport (IFT) protein IFT139, which has been shown to regulate Shh signaling.
Formal Description
Interaction-ID: 69880

gene/protein

TTC21B

affects_activity of

Comment WDR19 mutations have been reported in patients with ciliopathy syndromes including Sensenbrenner syndrome, Jeune syndrome, SLSN and isolated NPHP.
Formal Description
Interaction-ID: 69881

gene/protein

WDR19

affects_activity of

Comment WDR19 encodes for IFT144, a protein, which participates in retrograde IFT and is important for ciliogenesis.
Formal Description
Interaction-ID: 69882

gene/protein

WDR19

increases_activity of

Comment WDR19 encodes for IFT144, a protein, which participates in retrograde IFT and is important for ciliogenesis.
Formal Description
Interaction-ID: 69883

gene/protein

WDR19

increases_activity of

process

cilium assembly

Comment ZNF423 mutations have been shown to cause Joubert syndrome with NPHP. The encoded protein ZNF423 interacts with DNA damage response protein PARP1 (poly (ADP-ribose) polymerase 1) and also CEP290.
Formal Description
Interaction-ID: 69884

gene/protein

ZNF423

affects_activity of

Comment ZNF423 mutations have been shown to cause Joubert syndrome with NPHP. The encoded protein ZNF423 interacts with DNA damage response protein PARP1 (poly (ADP-ribose) polymerase 1) and also CEP290.
Formal Description
Interaction-ID: 69885

gene/protein

ZNF423

interacts (colocalizes) with

gene/protein

PARP1

Drugbank entries Show/Hide entries for PARP1
Comment ZNF423 mutations have been shown to cause Joubert syndrome with NPHP. The encoded protein ZNF423 interacts with DNA damage response protein PARP1 (poly (ADP-ribose) polymerase 1) and also CEP290.
Formal Description
Interaction-ID: 69886

gene/protein

ZNF423

interacts (colocalizes) with

gene/protein

CEP290

Comment Mutations in CEP164 may cause NPHP and related ciliopathy syndromes including SLSN. The CEP164 protein is a regulator of ciliogenesis and defines the mature centriole by formation of the distal appendage of the centriole. Loss of CEP164 induces DNA damage.
Formal Description
Interaction-ID: 69887

gene/protein

CEP164

affects_activity of

Comment Mutations in CEP164 may cause NPHP and related ciliopathy syndromes including SLSN. The CEP164 protein is a regulator of ciliogenesis and defines the mature centriole by formation of the distal appendage of the centriole. Loss of CEP164 induces DNA damage.
Formal Description
Interaction-ID: 69888

gene/protein

CEP164

affects_activity of

process

cilium assembly

Comment ANKS6 mutations lead to NPHP. ANKS6 localizes to the proximal cilium and links the NPHP proteins inversin, NPHP3 and NEK8. This functional role of ANKS6 in a NPHP module may explain the phenotypic overlap, i.e. abnormalities in heart and liver, seen in the patients carrying individual mutations in these genes.
Formal Description
Interaction-ID: 69889

gene/protein

ANKS6

affects_activity of

Comment ANKS6 mutations lead to NPHP. ANKS6 localizes to the proximal cilium and links the NPHP proteins inversin, NPHP3 and NEK8. This functional role of ANKS6 in a NPHP module may explain the phenotypic overlap, i.e. abnormalities in heart and liver, seen in the patients carrying individual mutations in these genes.
Formal Description
Interaction-ID: 69890

gene/protein

ANKS6

is localized in

cellular component

cilium

Comment ANKS6 mutations lead to NPHP. ANKS6 localizes to the proximal cilium and links the NPHP proteins inversin, NPHP3 and NEK8. This functional role of ANKS6 in a NPHP module may explain the phenotypic overlap, i.e. abnormalities in heart and liver, seen in the patients carrying individual mutations in these genes.
Formal Description
Interaction-ID: 69891

gene/protein

ANKS6

interacts (colocalizes) with

gene/protein

INVS

Comment ANKS6 mutations lead to NPHP. ANKS6 localizes to the proximal cilium and links the NPHP proteins inversin, NPHP3 and NEK8. This functional role of ANKS6 in a NPHP module may explain the phenotypic overlap, i.e. abnormalities in heart and liver, seen in the patients carrying individual mutations in these genes.
Formal Description
Interaction-ID: 69892

gene/protein

ANKS6

interacts (colocalizes) with

gene/protein

NPHP3

Comment ANKS6 mutations lead to NPHP. ANKS6 localizes to the proximal cilium and links the NPHP proteins inversin, NPHP3 and NEK8. This functional role of ANKS6 in a NPHP module may explain the phenotypic overlap, i.e. abnormalities in heart and liver, seen in the patients carrying individual mutations in these genes.
Formal Description
Interaction-ID: 69893

gene/protein

ANKS6

interacts (colocalizes) with

gene/protein

NEK8

Comment CEP83 mutations have been described to cause infantile NPHP. The CEP83 gene encodes a centriolar distal appendage protein, CEP83. In the seven families so far described, the NPHP phenotype was early-onset and in some was also associated with hydrocephalus and learning difficulties.
Formal Description
Interaction-ID: 69894

gene/protein

CEP83

affects_activity of

Comment The link between NPHP and cilia was first established after the discovery that INVS mutations cause infantile NPHP and that the encoded protein inversin localizes to cilia and interacts with nephrocystin-1 and beta-tubulin.
Formal Description
Interaction-ID: 69895

gene/protein

INVS

affects_activity of

Comment The link between NPHP and cilia was first established after the discovery that INVS mutations cause infantile NPHP and that the encoded protein inversin localizes to cilia and interacts with nephrocystin-1 and beta-tubulin.
Formal Description
Interaction-ID: 69896

gene/protein

INVS

is localized in

cellular component

cilium

Comment The link between NPHP and cilia was first established after the discovery that INVS mutations cause infantile NPHP and that the encoded protein inversin localizes to cilia and interacts with nephrocystin-1 and beta-tubulin.
Formal Description
Interaction-ID: 69897

gene/protein

INVS

interacts (colocalizes) with

gene/protein

NPHP1

Comment The link between NPHP and cilia was first established after the discovery that INVS mutations cause infantile NPHP and that the encoded protein inversin localizes to cilia and interacts with nephrocystin-1 and beta-tubulin.
Formal Description
Interaction-ID: 69898

gene/protein

INVS

interacts (colocalizes) with

gene/protein

TUBB

Drugbank entries Show/Hide entries for TUBB
Comment Primary cilia have been shown to play a role in many developmental signaling pathways including the Hedgehog (Hh), Wnt, planar cell polarity, platelet derived growth factor receptor alpha, fibroblast growth factor and Hippo pathways.
Formal Description
Interaction-ID: 69899

cellular component

cilium

affects_activity of

Comment Primary cilia have been shown to play a role in many developmental signaling pathways including the Hedgehog (Hh), Wnt, planar cell polarity, platelet derived growth factor receptor alpha, fibroblast growth factor and Hippo pathways.
Formal Description
Interaction-ID: 69900

cellular component

cilium

affects_activity of

Comment Primary cilia have been shown to play a role in many developmental signaling pathways including the Hedgehog (Hh), Wnt, planar cell polarity, platelet derived growth factor receptor alpha, fibroblast growth factor and Hippo pathways.
Formal Description
Interaction-ID: 69901

cellular component

cilium

affects_activity of

Comment Primary cilia have been shown to play a role in many developmental signaling pathways including the Hedgehog (Hh), Wnt, planar cell polarity, platelet derived growth factor receptor alpha, fibroblast growth factor and Hippo pathways.
Formal Description
Interaction-ID: 69902

cellular component

cilium

affects_activity of

Comment Primary cilia have been shown to play a role in many developmental signaling pathways including the Hedgehog (Hh), Wnt, planar cell polarity, platelet derived growth factor receptor alpha, fibroblast growth factor and Hippo pathways.
Formal Description
Interaction-ID: 69903

cellular component

cilium

affects_activity of

Comment Primary cilia have been shown to play a role in many developmental signaling pathways including the Hedgehog (Hh), Wnt, planar cell polarity, platelet derived growth factor receptor alpha, fibroblast growth factor and Hippo pathways.
Formal Description
Interaction-ID: 69904

cellular component

cilium

affects_activity of

process

hippo signaling

Comment Shh signaling is intimately related to the primary cilium. Shh binds to Patched and regulates the translocation of Smoothened into the primary cilum. Smoothened, when enriched in the primary cilium, activates GLI proteins that in turn regulate gene expression. An intact cilium is important for Hh signaling. The evidence implicating the defects of the Hh signaling in NPHP, renal development and cystogenesis is evolving. Loss of the transcription factor GLIS2, which is related to the GLI protein family, causes NPHP.
Formal Description
Interaction-ID: 69905

gene/protein

SHH

interacts (colocalizes) with

gene/protein

PTCH1

Comment Shh signaling is intimately related to the primary cilium. Shh binds to Patched and regulates the translocation of Smoothened into the primary cilum. Smoothened, when enriched in the primary cilium, activates GLI proteins that in turn regulate gene expression. An intact cilium is important for Hh signaling. The evidence implicating the defects of the Hh signaling in NPHP, renal development and cystogenesis is evolving. Loss of the transcription factor GLIS2, which is related to the GLI protein family, causes NPHP.
Formal Description
Interaction-ID: 69906

gene/protein

SHH

affects transport of

gene/protein

SMO

into primary cilia
Drugbank entries Show/Hide entries for SMO
Comment Shh signaling is intimately related to the primary cilium. Shh binds to Patched and regulates the translocation of Smoothened into the primary cilum. Smoothened, when enriched in the primary cilium, activates GLI proteins that in turn regulate gene expression. An intact cilium is important for Hh signaling. The evidence implicating the defects of the Hh signaling in NPHP, renal development and cystogenesis is evolving. Loss of the transcription factor GLIS2, which is related to the GLI protein family, causes NPHP.
Formal Description
Interaction-ID: 69907

gene/protein

SMO

increases_activity of

gene/protein

GLIS2

Drugbank entries Show/Hide entries for SMO
Comment Shh signaling is intimately related to the primary cilium. Shh binds to Patched and regulates the translocation of Smoothened into the primary cilum. Smoothened, when enriched in the primary cilium, activates GLI proteins that in turn regulate gene expression. An intact cilium is important for Hh signaling. The evidence implicating the defects of the Hh signaling in NPHP, renal development and cystogenesis is evolving. Loss of the transcription factor GLIS2, which is related to the GLI protein family, causes NPHP.
Formal Description
Interaction-ID: 69908

gene/protein

GLIS2

affects_activity of