NPHP1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005198 structural molecule activity	NAS PMID:12006559 Nephrocystin-conserved domains involved in targeting to epit...	REMOVE	Summary: Curator statement that nephrocystin has structural molecule activity, based on a domain-deletion study that described it as a docking protein at cell-cell junctions. Reason: The cited paper concludes that nephrocystin is a docking (adaptor) protein that organizes a complex at cell-cell adhesion sites. It does not show that NPHP1 is a structural constituent of any assembly. GO:0005198 is a generic placeholder that adds no information. A more specific activity, proline-rich region binding by the SH3 domain, is captured from other papers. No replacement is proposed for this NAS row because the paper itself does not define a specific activity. Supporting Evidence: PMID:12006559 These findings support a functional role for nephrocystin as a docking protein involved in organizing a protein complex to regulate the actin cytoskeleton at sites of epithelial cell-cell adhesion
GO:0005515 protein binding	IPI PMID:12244321 The gene mutated in juvenile nephronophthisis type 4 encodes...	REMOVE	Summary: Reported physical association of NPHP1 with NPHP4 (nephrocystin-4). Reason: GO:0005515 protein binding is uninformative about the molecular activity of NPHP1. The interaction itself is not disputed. NPHP1 and NPHP4 are core partners in the NPHP1-4-8 module. This is better represented by the NPHP complex (GO:1990957) annotation and by transition-zone localization.
GO:0005515 protein binding	IPI PMID:12872122 Mutations in a novel gene, NPHP3, cause adolescent nephronop...	REMOVE	Summary: Reported physical association of NPHP1 with NPHP3. Reason: GO:0005515 protein binding is uninformative about the molecular activity of NPHP1. The interaction itself is not disputed. The NPHP1-NPHP3 association reported in the NPHP3 gene identification paper has no assigned activity beyond binding.
GO:0005515 protein binding	IPI PMID:15661758 Characterization of the nephrocystin/nephrocystin-4 complex ...	REMOVE	Summary: Reported physical association of NPHP1 with NPHP4. Reason: GO:0005515 protein binding is uninformative about the molecular activity of NPHP1. The interaction itself is not disputed. Duplicate NPHP1-NPHP4 association, mapped by domain analysis. It is captured by the NPHP complex annotation.
GO:0005515 protein binding	IPI PMID:16374509 Identification of preferred protein interactions by phage-di...	MODIFY	Summary: SH3 phage-display screening identified nephrocystin as a strong SH3 partner of the proline-rich cytoplasmic tail of ADAM15. Reason: NPHP1 has a single SH3 domain. Its partners ADAM15, ADAM12 and polycystin-1 bind it through proline-rich motifs. The informative activity is therefore proline-rich region binding (GO:0070064), not generic protein binding. The cached abstract of PMID:16374509 is general, but the follow-up full-text paper PMID:25825872 confirms nephrocystin as an avid ADAM15 SH3 partner. Proposed replacements: proline-rich region binding Supporting Evidence: PMID:25825872 nephrocystin, another SH3-protein previously reported as an avid ADAM15 interacting protein PMID:25825872 a preference for canonical motifs typical for SFK was shared by many SH3 domains, such as nephrocystin, AHI1, OSTF1, intersectin1(III), and Grb2(II)
GO:0005515 protein binding	IPI PMID:18633336 Jouberin localizes to collecting ducts and interacts with ne...	REMOVE	Summary: Reported physical association of NPHP1 with AHI1 (jouberin). Reason: GO:0005515 protein binding is uninformative about the molecular activity of NPHP1. The interaction itself is not disputed. AHI1 is a JBTS protein of the ciliary base and cell junctions. Binding was shown by yeast two-hybrid and co-immunoprecipitation, but no NPHP1 activity is defined by it.
GO:0005515 protein binding	IPI PMID:20664800 Interaction of ciliary disease protein retinitis pigmentosa ...	REMOVE	Summary: Reported physical association of NPHP1 with RPGR. Reason: GO:0005515 protein binding is uninformative about the molecular activity of NPHP1. The interaction itself is not disputed. RPGR was co-immunoprecipitated with NPHP1 and NPHP4 from ciliary preparations. The interaction places NPHP1 in the photoreceptor connecting-cilium network but defines no specific activity.
GO:0005515 protein binding	IPI PMID:20856870 Nephrocystin-1 forms a complex with polycystin-1 via a polyp...	MODIFY	Summary: The NPHP1 SH3 domain binds a polyproline motif in the polycystin-1 C-terminal tail. Reason: This paper maps the interaction to the polycystin-1 polyproline motif and the NPHP1 SH3 domain. That supports the more informative term proline-rich region binding (GO:0070064) in place of protein binding. Proposed replacements: proline-rich region binding Supporting Evidence: PMID:20856870 the C-terminus of PC-1 contains at least one polyproline domain that is able to mediate an interaction with Src-homology 3 domains (SH3) PMID:20856870 Nephrocystin-1 forms a complex with polycystin-1 via a polyproline motif/SH3 domain interaction
GO:0005515 protein binding	IPI PMID:21357692 Nephrocystin-4 regulates Pyk2-induced tyrosine phosphorylati...	REMOVE	Summary: Reported physical association of NPHP1 with NPHP4. Reason: GO:0005515 protein binding is uninformative about the molecular activity of NPHP1. The interaction itself is not disputed. NPHP4 regulates the NPHP1-PYK2 interaction. NPHP1-NPHP4 association is captured by the NPHP complex term.
GO:0005515 protein binding	IPI PMID:21357692 Nephrocystin-4 regulates Pyk2-induced tyrosine phosphorylati...	REMOVE	Summary: NPHP1 binds the tyrosine kinase PTK2B/PYK2, which phosphorylates NPHP1. NPHP4 modulates this. Reason: GO:0005515 protein binding is uninformative about the molecular activity of NPHP1. The interaction itself is not disputed. This interaction makes NPHP1 a PYK2 substrate and partner. It does not establish a kinase-binding activity separate from the substrate relationship, and GO has no informative term that fits better. Supporting Evidence: PMID:21357692 NPHP4 negatively regulates Pyk2-induced tyrosine phosphorylation of NPHP1 by controlling the NPHP1/Pyk2 interaction
GO:0005515 protein binding	IPI PMID:21565611 Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy...	REMOVE	Summary: Reported physical association of NPHP1 with NPHP4. Reason: GO:0005515 protein binding is uninformative about the molecular activity of NPHP1. The interaction itself is not disputed. The LAP-tag proteomics in this paper defines the NPHP1-4-8 module. This is captured by the NPHP complex (GO:1990957) term.
GO:0005515 protein binding	IPI PMID:21565611 Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy...	REMOVE	Summary: Reported physical association of NPHP1 with IQCB1 (NPHP5). Reason: GO:0005515 protein binding is uninformative about the molecular activity of NPHP1. The interaction itself is not disputed. IQCB1 belongs to the separate NPHP5-6 module. UniProt notes that this interaction probably requires additional interactors.
GO:0005515 protein binding	IPI PMID:21565611 Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy...	REMOVE	Summary: Reported physical association of NPHP1 with INVS (inversin/NPHP2). Reason: GO:0005515 protein binding is uninformative about the molecular activity of NPHP1. The interaction itself is not disputed. This is an inter-module association within the NPHP network. No specific activity is defined.
GO:0005515 protein binding	IPI PMID:21633164 Mutations in KIF7 link Joubert syndrome with Sonic Hedgehog ...	REMOVE	Summary: Reported physical association of NPHP1 with KIF7. Reason: GO:0005515 protein binding is uninformative about the molecular activity of NPHP1. The interaction itself is not disputed. KIF7 co-precipitated with nephrocystin-1 in a JBTS gene-identification paper. The functional meaning of the interaction is not established.
GO:0005515 protein binding	IPI PMID:23532844 The Joubert syndrome-associated missense mutation (V443D) in...	REMOVE	Summary: Reported physical association of NPHP1 with AHI1 (jouberin). Reason: GO:0005515 protein binding is uninformative about the molecular activity of NPHP1. The interaction itself is not disputed. This is a further study of the AHI1-NPHP1 interaction and of a JBTS missense variant in AHI1. It defines no NPHP1 activity.
GO:0005515 protein binding	IPI PMID:25825872 Preferred SH3 domain partners of ADAM metalloproteases inclu...	MODIFY	Summary: Systematic SH3-ligand profiling of ADAM metalloproteases found nephrocystin to be a dominant SH3 partner of ADAM12, ADAM15 and ADAM19. Reason: The interaction is mediated by the NPHP1 SH3 domain and canonical proline-rich motifs in the ADAM cytoplasmic tails. This supports GO:0070064 proline-rich region binding in place of generic protein binding. Proposed replacements: proline-rich region binding Supporting Evidence: PMID:25825872 nephrocystin, another SH3-protein previously reported as an avid ADAM15 interacting protein PMID:25825872 a preference for canonical motifs typical for SFK was shared by many SH3 domains, such as nephrocystin, AHI1, OSTF1, intersectin1(III), and Grb2(II)
GO:0005515 protein binding	IPI PMID:26638075 A Dynamic Protein Interaction Landscape of the Human Centros...	REMOVE	Summary: Reported physical association of NPHP1 with NPHP4. Reason: GO:0005515 protein binding is uninformative about the molecular activity of NPHP1. The interaction itself is not disputed. This is a proximity-labelling (BioID) interaction at the centrosome-cilium interface, and it is captured by the NPHP complex term.
GO:0005515 protein binding	IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis...	REMOVE	Summary: Reported physical association of NPHP1 with NPHP4. Reason: GO:0005515 protein binding is uninformative about the molecular activity of NPHP1. The interaction itself is not disputed. This is a ciliary affinity-proteomics interaction. It duplicates the NPHP complex term.
GO:0005515 protein binding	IPI PMID:29959317 Targeted deletion of the AAA-ATPase Ruvbl1 in mice disrupts ...	REMOVE	Summary: Reported physical association of NPHP1 with RUVBL1. Reason: GO:0005515 protein binding is uninformative about the molecular activity of NPHP1. The interaction itself is not disputed. NPHP1 was used as a tagged interaction partner in a study of RUVBL1 and ciliary integrity. No NPHP1 activity is defined.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: Reported physical association of NPHP1 with NPHP4. Reason: GO:0005515 protein binding is uninformative about the molecular activity of NPHP1. The interaction itself is not disputed. This is a proteome-scale binary interaction map (HuRI-type). It duplicates the NPHP complex term.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: Reported physical association of NPHP1 with RPGR. Reason: GO:0005515 protein binding is uninformative about the molecular activity of NPHP1. The interaction itself is not disputed. This is a proteome-scale interaction map. The RPGR association is already noted above.
GO:0005515 protein binding	IPI PMID:40739040 Multi-proteomic profiling of the varicella-zoster virus-host...	REMOVE	Summary: Reported physical association of NPHP1 with NPHP4. Reason: GO:0005515 protein binding is uninformative about the molecular activity of NPHP1. The interaction itself is not disputed. This is a virus-host multi-proteomics study in which NPHP1-NPHP4 was recovered as a host interaction. It duplicates the NPHP complex term.
GO:0005737 cytoplasm	IEA GO_REF:0000117	ACCEPT	Summary: NPHP1 is a soluble cytoplasmic protein. It is diffuse in the cytoplasm before ciliogenesis and concentrates at the ciliary transition zone and cell junctions. Reason: This broad term is correct. NPHP1 has no signal peptide or transmembrane segment, and it is cytoplasmic before it is recruited to the transition zone and junctions. Supporting Evidence: PMID:16885411 nephrocystin can be detected first with a diffuse cytoplasmic localization as soon as cell polarization starts, and translocates to the transition zone when cilia are formed
GO:0005829 cytosol	TAS Reactome:R-HSA-5617816	KEEP AS NON CORE	Summary: Reactome places NPHP1 in the cytosol in the ciliary-vesicle and RAB8A activation steps of ciliogenesis. Reason: NPHP1 does have a diffuse cytosolic pool before ciliogenesis. However, its functional site is the transition zone, so cytosol is kept as a non-core location. Supporting Evidence: PMID:16885411 nephrocystin can be detected first with a diffuse cytoplasmic localization as soon as cell polarization starts, and translocates to the transition zone when cilia are formed
GO:0005829 cytosol	TAS Reactome:R-HSA-5626681	KEEP AS NON CORE	Summary: Reactome places NPHP1 in the cytosol for the 'Recruitment of transition zone proteins' event. Reason: This describes the cytosolic pool that is recruited to the transition zone. It is correct but non-core. Supporting Evidence: PMID:16885411 nephrocystin can be detected first with a diffuse cytoplasmic localization as soon as cell polarization starts, and translocates to the transition zone when cilia are formed
GO:0005829 cytosol	TAS Reactome:R-HSA-5638009	KEEP AS NON CORE	Summary: Reactome places NPHP1 in the cytosol for the CEP164-dependent recruitment of RAB3IP vesicles to the basal body. Reason: This is a correct cytosolic pool but not the functional site of NPHP1. It is kept as non-core. Supporting Evidence: PMID:16885411 nephrocystin can be detected first with a diffuse cytoplasmic localization as soon as cell polarization starts, and translocates to the transition zone when cilia are formed
GO:0005911 cell-cell junction	IDA PMID:21565611 Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy...	ACCEPT	Summary: NPHP1, NPHP4 and RPGRIP1L (NPHP8) accumulate at cell-cell contacts of polarized renal epithelial cells. Reason: This is direct localization evidence from LAP-tagged and endogenous protein in polarized kidney cells. It agrees with the earlier junction-targeting activity of the nephrocystin homology domain. Supporting Evidence: PMID:21565611 as cells approach confluence and develop into polarized epithelial monolayers, these NPHP proteins accumulate to cell-cell contacts, mostly basolateral of tight junctions PMID:12006559 This analysis revealed previously unrecognized functional attributes of the NHD, including abilities to promote both self-association and epithelial cell-cell junctional targeting
GO:0005912 adherens junction	IEA GO_REF:0000044	ACCEPT	Summary: NPHP1 colocalizes with E-cadherin and BCAR1 at or near adherens junctions (UniProt, by similarity to mouse). Reason: This is consistent with the cell-cell junction localization shown for human NPHP1. Adherens junction is a reasonable specific subtype. Supporting Evidence: PMID:21565611 as cells approach confluence and develop into polarized epithelial monolayers, these NPHP proteins accumulate to cell-cell contacts, mostly basolateral of tight junctions
GO:0005923 bicellular tight junction	IEA GO_REF:0000044	ACCEPT	Summary: NPHP1 accumulates near basolateral tight junctions as renal cells approach confluence. Reason: NPHP1-4-8 accumulate at cell-cell contacts mostly basolateral of tight junctions, and NPHP1 is required for timely tight-junction formation. The mapping is acceptable. Supporting Evidence: PMID:21565611 as cells approach confluence and develop into polarized epithelial monolayers, these NPHP proteins accumulate to cell-cell contacts, mostly basolateral of tight junctions PMID:19755384 these results indicate that nephrocystins-1 and -4 are required for the proper timing of tight junctional establishment necessary for the formation of a fully polarized epithelial monolayer
GO:0005929 cilium	IEA GO_REF:0000120	ACCEPT	Summary: NPHP1 is a ciliary protein found at the transition zone of primary, motile and photoreceptor connecting cilia. Reason: This is correct but general. The more specific transition-zone term is also annotated. Supporting Evidence: PMID:16885411 nephrocystin specifically localizes at the ciliary base to the transition zone of renal and respiratory cilia and to photoreceptor connecting cilia
GO:0005930 axoneme	IEA GO_REF:0000044	ACCEPT	Summary: NPHP1 is tightly attached to the axonemal structure within the transition zone of respiratory cilia (UniProt cilium axoneme). Reason: The axoneme annotation reflects the tight attachment of NPHP1 to the axonemal microtubules at the transition zone. The protein is not distributed along the distal axoneme, so the transition zone is the more precise location. Supporting Evidence: PMID:16885411 nephrocystin is attached tightly to the axonemal structure of the transition zone at a region that contains the calcium-sensitive cilia autotomy site
GO:0007165 signal transduction	NAS PMID:12244321 The gene mutated in juvenile nephronophthisis type 4 encodes...	MARK AS OVER ANNOTATED	Summary: A curator statement from the NPHP4 identification paper, which proposed that nephrocystin and nephrocystin-4 participate in a common signaling pathway. Reason: The paper only shows an NPHP1-NPHP4 interaction and speculates about a shared signaling pathway. No signal transduction role was demonstrated, and GO:0007165 is too broad to be informative. Supporting Evidence: PMID:12244321 We demonstrated the interaction of nephrocystin-4 with nephrocystin suggesting that these two proteins participate in a common signaling pathway.
GO:0007632 visual behavior	NAS PMID:12205563 A gene mutated in nephronophthisis and retinitis pigmentosa ...	REMOVE	Summary: A curator statement linking NPHP1 to visual behavior, drawn from an NPHP4 disease-gene paper that reported retinitis pigmentosa in Senior-Loken syndrome. Reason: Retinal degeneration in nephronophthisis patients arises from photoreceptor connecting-cilium dysfunction. It does not show that NPHP1 takes part in visual behavior, an organism-level behavioral process. The cited paper concerns NPHP4. A cilium or retina-related term (photoreceptor connecting cilium, retina development) better reflects the biology and is already present. Supporting Evidence: PMID:12205563 Thus, we have identified a novel gene with critical roles in renal tissue architecture and ophthalmic function.
GO:0008104 intracellular protein localization	IBA GO_REF:0000033	ACCEPT	Summary: The PAINT inference that the nephrocystin family acts in intracellular protein localization. Reason: This is consistent with the transition-zone role of NPHP1. NPHP-module proteins help confine ciliary membrane and soluble proteins at the transition zone, and NPHP1 influences IFT protein movement in photoreceptor cilia. The term is broad but correct. The more specific protein localization to ciliary transition zone is also annotated. Supporting Evidence: PMID:28401750 However, combining the disruption of a MKS complex component with the disruption of NPHP1 or NPHP4 severely disrupted ciliogenesis, and ciliary functions
GO:0016020 membrane	NAS PMID:10665934 Nephrocystin: gene expression and sequence conservation betw...	MARK AS OVER ANNOTATED	Summary: A curator statement placing nephrocystin in membrane, citing an expression and sequence-conservation paper. Reason: The cited abstract reports expression and domain conservation, not membrane localization. NPHP1 is a soluble cytoplasmic protein with no transmembrane segment. It may associate with membranes at the transition zone and junctions through partners, but a generic membrane annotation overstates the evidence. Supporting Evidence: PMID:10665934 Its gene product, nephrocystin, is a novel protein of unknown function, which contains a src-homology 3 domain.
GO:0030030 cell projection organization	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Transfer from mouse Nphp1 of a role in cell projection organization, reflecting ciliary phenotypes in photoreceptors and sperm. Reason: The term is very general. NPHP1 is not strictly required for ciliogenesis on its own, but it contributes to cilium structure and function, especially together with MKS-module genes. It is kept as non-core. Supporting Evidence: PMID:16885411 Cilia formation is not altered in primary nephrocystin-deficient respiratory cells PMID:28401750 However, combining the disruption of a MKS complex component with the disruption of NPHP1 or NPHP4 severely disrupted ciliogenesis, and ciliary functions
GO:0030036 actin cytoskeleton organization	NAS PMID:12006559 Nephrocystin-conserved domains involved in targeting to epit...	KEEP AS NON CORE	Summary: A curator statement that nephrocystin organizes the actin cytoskeleton at cell-cell adhesion sites, through filamin binding by its nephrocystin homology domain. Reason: The paper proposes, from interaction and deletion data, that nephrocystin docks a complex that regulates actin at junctions. This is plausible but indirect, and it is secondary to the transition-zone role. Supporting Evidence: PMID:12006559 These findings support a functional role for nephrocystin as a docking protein involved in organizing a protein complex to regulate the actin cytoskeleton at sites of epithelial cell-cell adhesion
GO:0031514 motile cilium	IDA PMID:16885411 Nephrocystin specifically localizes to the transition zone o...	ACCEPT	Summary: Nephrocystin localizes to the transition zone of motile respiratory cilia in human epithelial cells. Reason: This is direct immunolocalization in primary human respiratory epithelium. The protein is restricted to the transition zone within the motile cilium. Supporting Evidence: PMID:16885411 nephrocystin specifically localizes at the ciliary base to the transition zone of renal and respiratory cilia and to photoreceptor connecting cilia
GO:0032391 photoreceptor connecting cilium	ISS GO_REF:0000024	ACCEPT	Summary: NPHP1 localizes to the photoreceptor connecting cilium, which is the elongated photoreceptor transition zone. Reason: This is supported by direct human and mouse localization data. Supporting Evidence: PMID:16885411 nephrocystin specifically localizes at the ciliary base to the transition zone of renal and respiratory cilia and to photoreceptor connecting cilia
GO:0035869 ciliary transition zone	IBA GO_REF:0000033	ACCEPT	Summary: The PAINT inference that NPHP1 acts at the ciliary transition zone. Reason: This is the core location of NPHP1. It is supported directly in human cells and in C. elegans, where NPHP-1 is part of the NPHP transition-zone module. Supporting Evidence: PMID:16885411 nephrocystin specifically localizes at the ciliary base to the transition zone of renal and respiratory cilia and to photoreceptor connecting cilia PMID:21422230 MKS-5/RPGRIP1L interacts with two distinct TZ functional modules, MKS/MKSR and NPHP, consisting of MKS-1/MKSR-1/MKSR-2/MKS-3/MKS-6 and NPHP-1/NPHP-4 proteins, respectively
GO:0035869 ciliary transition zone	NAS PMID:28401750 The Ciliary Transition Zone: Finding the Pieces and Assembli...	ACCEPT	Summary: A transition-zone review places NPHP1 in the NPHP module at the transition zone. Reason: This is consistent with direct localization data. Supporting Evidence: PMID:28401750 the NPHP complex (NPHP1, NPHP4) presented very mild or no ciliary phenotypes PMID:16885411 nephrocystin specifically localizes at the ciliary base to the transition zone of renal and respiratory cilia and to photoreceptor connecting cilia
GO:0048515 spermatid differentiation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Transfer from mouse, where Nphp1 loss causes male infertility with defects in spermatid differentiation. Reason: Testis expression is high and the mouse phenotype is reported. This is a tissue-specific downstream consequence of ciliary or flagellar dysfunction, so it is non-core. Supporting Evidence: PMID:10665934 In the adult mouse there is strong expression in testis.
GO:0060041 retina development in camera-type eye	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Transfer from mouse of a role in retina development, reflecting photoreceptor degeneration in Nphp1 mutants. Reason: This is a downstream tissue-level consequence of connecting-cilium dysfunction. It is kept as non-core. Supporting Evidence: PMID:16885411 nephrocystin specifically localizes at the ciliary base to the transition zone of renal and respiratory cilia and to photoreceptor connecting cilia
GO:0070161 anchoring junction	IEA GO_REF:0000120	ACCEPT	Summary: NPHP1 localizes to cell-cell and cell-matrix adhesion sites (anchoring junctions). Reason: This is a correct general parent of the cell-cell junction location. Supporting Evidence: PMID:21565611 as cells approach confluence and develop into polarized epithelial monolayers, these NPHP proteins accumulate to cell-cell contacts, mostly basolateral of tight junctions
GO:0070161 anchoring junction	ISS GO_REF:0000024	ACCEPT	Summary: Transfer from mouse of anchoring-junction localization. Reason: This is correct and consistent with the human data. Supporting Evidence: PMID:21565611 as cells approach confluence and develop into polarized epithelial monolayers, these NPHP proteins accumulate to cell-cell contacts, mostly basolateral of tight junctions
GO:0097546 ciliary base	IBA GO_REF:0000033	ACCEPT	Summary: The PAINT inference that NPHP1 acts at the ciliary base. Reason: This is correct. The transition zone is part of the ciliary base. Supporting Evidence: PMID:16885411 nephrocystin specifically localizes at the ciliary base to the transition zone of renal and respiratory cilia and to photoreceptor connecting cilia
GO:0098609 cell-cell adhesion	NAS PMID:12006559 Nephrocystin-conserved domains involved in targeting to epit...	MARK AS OVER ANNOTATED	Summary: A curator statement that nephrocystin participates in cell-cell adhesion. Reason: The paper shows junctional targeting and a modest effect on tight-junction formation (transepithelial resistance). It does not show a direct role in adhesion between cells. Junction assembly is captured more precisely by the tight-junction assembly annotation. Supporting Evidence: PMID:12006559 This analysis revealed previously unrecognized functional attributes of the NHD, including abilities to promote both self-association and epithelial cell-cell junctional targeting
GO:1903348 positive regulation of bicellular tight junction assembly	IMP PMID:19755384 Nephrocystin-1 and nephrocystin-4 are required for epithelia...	ACCEPT	Summary: NPHP1 knockdown in MDCK cells delays tight-junction formation and disrupts epithelial morphogenesis. NPHP1 associates with PALS1/PATJ and PAR6. Reason: This is experimental evidence in renal epithelial cells, corroborated by 3D spheroid assays. It is one of the two main cellular roles of the NPHP1-4-8 module, alongside its transition-zone role. Supporting Evidence: PMID:19755384 these results indicate that nephrocystins-1 and -4 are required for the proper timing of tight junctional establishment necessary for the formation of a fully polarized epithelial monolayer PMID:21565611 cells depleted of Nphp1, Nphp4, Nphp8 and Nphp2 developed spheroids with irregular lumens, reduced sphericity, fewer ZO1 positive tight junctions
GO:1904491 protein localization to ciliary transition zone	NAS PMID:28401750 The Ciliary Transition Zone: Finding the Pieces and Assembli...	ACCEPT	Summary: NPHP-module proteins contribute to the assembly and composition of the transition zone. Reason: In C. elegans the NPHP module (NPHP-1/NPHP-4) and the MKS module act redundantly to build transition-zone membrane attachments and the ciliary gate. NPHP1 helps localize proteins at the transition zone. This is accepted as core. Supporting Evidence: PMID:28401750 However, combining the disruption of a MKS complex component with the disruption of NPHP1 or NPHP4 severely disrupted ciliogenesis, and ciliary functions PMID:28401750 suggesting that the known TZ modules are assembled, at least in part, prior to their incorporation into the TZ
GO:1905515 non-motile cilium assembly	IBA GO_REF:0000033	ACCEPT	Summary: The PAINT inference that NPHP1 functions in non-motile (primary) cilium assembly. Reason: NPHP1 alone is dispensable for ciliogenesis in human respiratory cells. In C. elegans, however, NPHP-1 loss combined with MKS-module mutations abolishes cilium formation and transition-zone membrane attachment. The function is therefore real but redundant, and the IBA is acceptable. Supporting Evidence: PMID:28401750 However, combining the disruption of a MKS complex component with the disruption of NPHP1 or NPHP4 severely disrupted ciliogenesis, and ciliary functions PMID:16885411 Cilia formation is not altered in primary nephrocystin-deficient respiratory cells
GO:1990957 NPHP complex	NAS PMID:17558407 Mutations in the gene encoding the basal body protein RPGRIP...	ACCEPT	Summary: NPHP1 is part of the NPHP (NPHP1-4-8) complex with NPHP4 and RPGRIP1L. Reason: This is well supported by interaction and LAP-tag proteomics data in human cells. Supporting Evidence: PMID:21565611 Our data show that NPHP-JBTS-MKS proteins form an interaction network that can be classified into three distinct modules PMID:21565611 This NPHP1-4-8 compartment is reminiscent of the ciliary transition zone

Gene Description

Existing Annotations Review

Core Functions

Component of the NPHP (NPHP1-4-8) transition-zone module. It acts redundantly with the MKS module to build transition-zone membrane attachments and the ciliary gate, and to localize proteins at the transition zone. No specific molecular activity has been defined.

At epithelial cell-cell junctions, NPHP1 promotes timely tight-junction formation and apical organization. It acts as an SH3-domain adaptor that binds proline-rich motifs of partners such as polycystin-1 and ADAM metalloproteases.

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