nphp-4

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0090090 negative regulation of canonical Wnt signaling pathway	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: IBA annotation inferred from phylogeny. Human NPHP4 has been implicated in Wnt signaling regulation, and the mammalian TZ has roles in compartmentalizing signaling molecules. However, direct evidence for NPHP-4 involvement in Wnt signaling in C. elegans is limited. Reason: While human NPHP4 has been linked to Wnt signaling regulation and TZ proteins can modulate ciliary signaling, the core function of C. elegans NPHP-4 is in TZ structure and ciliary gating rather than specific signaling pathway regulation. This may represent a conserved but secondary function. Supporting Evidence: file:worm/nphp-4/nphp-4-deep-research-falcon.md model: Edison Scientific Literature
GO:0035869 ciliary transition zone	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation supported by extensive experimental evidence. NPHP-4 localizes specifically to the TZ in C. elegans sensory neurons (PMID:21422230, PMID:18316409, PMID:21689635). Reason: Core localization supported by multiple IDA studies. The TZ is the primary site of NPHP-4 function. Supporting Evidence: PMID:21422230 MKS/MKSR and NPHP proteins localize specifically to the ciliary TZ PMID:18316409 NPHP-1 and NPHP-4 localize to TZs of male-specific CEM cilia
GO:0097730 non-motile cilium	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation supported by experimental evidence. C. elegans sensory cilia are non-motile primary cilia, and NPHP-4 localizes to these structures (PMID:15817158, PMID:18316409). Reason: Accurate cellular component annotation. NPHP-4 is present in sensory cilia of C. elegans, which are non-motile. This is broader than TZ localization and captures the overall ciliary context. Supporting Evidence: PMID:15817158 GFP-tagged NPHP-1 and NPHP-4 proteins localize to ciliated sensory endings of dendrites
GO:0036064 ciliary basal body	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation. NPHP-4 localizes primarily to the TZ, which is adjacent to but distinct from the basal body. Some studies describe TZ proteins as "basal body" associated due to co-isolation (PMID:21422230). Reason: The TZ is often co-isolated with the basal body, and NPHP-4 is found at the proximal ciliary region. While TZ is the more precise localization, basal body is not incorrect given the structural continuity. Supported by IDA evidence from PMID:27623382 and PMID:18316409. Supporting Evidence: PMID:21422230 The TZ is an underappreciated ciliary subcompartment, often incorrectly presumed to be one and the same with the adjacent BB
GO:0097546 ciliary base	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation. Ciliary base encompasses the TZ and basal body region. NPHP-4 localizes to this region (PMID:18316409, PMID:21422230). Reason: Appropriate broader CC term that accurately captures NPHP-4 localization at the proximal ciliary region.
GO:1904491 protein localization to ciliary transition zone	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation supported by experimental evidence. NPHP-4 functions with MKS-5 to localize other TZ proteins (PMID:21422230). Reason: Core function of NPHP-4 as part of the NPHP module. NPHP-4 is involved in establishing the TZ protein complex and recruiting/localizing other proteins to the TZ. Supported by IGI evidence from PMID:21422230. Supporting Evidence: PMID:21422230 MKS-5 is a central component required for docking/anchoring MKS and NPHP protein modules
GO:0005856 cytoskeleton	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: IEA annotation from InterPro. Cilia are microtubule-based structures, and TZ proteins interact with the axonemal cytoskeleton. Reason: While technically not wrong (cilia are cytoskeletal structures), this is too broad and uninformative. The more specific ciliary component annotations are preferred.
GO:0090090 negative regulation of canonical Wnt signaling pathway	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: IEA annotation from InterPro, duplicate of IBA annotation. Limited direct evidence in C. elegans. Reason: Duplicate annotation by different method. The Wnt signaling role is likely secondary to core ciliary gating function.
GO:0097730 non-motile cilium	IEA GO_REF:0000002	ACCEPT	Summary: IEA annotation from InterPro. Supported by experimental IDA evidence. Reason: Valid broader annotation consistent with more specific experimental evidence.
GO:0036064 ciliary basal body	IDA PMID:27623382 A Conserved Role for Girdin in Basal Body Positioning and Ci...	ACCEPT	Summary: IDA annotation from a study on Girdin's role in basal body positioning. NPHP-4 was used as a marker/reference for basal body/TZ localization. Reason: Direct experimental observation of NPHP-4 at basal body region. Consistent with other IDA annotations. Supporting Evidence: PMID:27623382 Girdin localizes to the proximal regions of centrioles and regulates BB positioning and ciliogenesis
GO:0016358 dendrite development	IGI PMID:26595381 TMEM107 recruits ciliopathy proteins to subdomains of the ci...	KEEP AS NON CORE	Summary: IGI annotation with TMEM-107 (H2L2K0). TMEM-107 functions redundantly with NPHP-4, and double mutants show defects in dendrite structure in addition to ciliary defects. Reason: The primary function is in cilia, but dendrite development is affected in double mutants with MKS module genes, likely as a secondary consequence of TZ/ciliary defects. This is consistent with the functional redundancy between NPHP and MKS modules. Supporting Evidence: PMID:26595381 TMEM-107 controls ciliary composition and functions redundantly with NPHP-4 to regulate cilium integrity, TZ docking and assembly of membrane to microtubule Y-link connectors
GO:1905515 non-motile cilium assembly	IMP PMID:26595381 TMEM107 recruits ciliopathy proteins to subdomains of the ci...	ACCEPT	Summary: IMP annotation. Loss of function results in ciliary assembly defects, particularly when combined with MKS module mutations. Reason: Core function of NPHP-4. The NPHP module works with the MKS module to establish the TZ and enable ciliogenesis. Supporting Evidence: PMID:26595381 TMEM-107 controls ciliary composition and functions redundantly with NPHP-4 to regulate cilium integrity
GO:1905515 non-motile cilium assembly	IGI PMID:26595381 TMEM107 recruits ciliopathy proteins to subdomains of the ci...	ACCEPT	Summary: IGI annotation with TMEM-107 (H2L2K0). nphp-4;tmem-107 double mutants have severe ciliary assembly defects. Reason: Strong genetic interaction evidence supporting NPHP-4's role in cilium assembly. Supporting Evidence: PMID:26595381 Mechanistic studies in Caenorhabditis elegans showed that TMEM-107 controls ciliary composition and functions redundantly with NPHP-4 to regulate cilium integrity, TZ docking and assembly of membrane to microtubule Y-link connectors
GO:1905515 non-motile cilium assembly	IGI PMID:26863025 A Screen for Modifiers of Cilia Phenotypes Reveals Novel MKS...	ACCEPT	Summary: IGI annotation with OSM-3 (C8JQP7). The osm-3(yhw66);nphp-4(tm925) double mutant shows synthetic dye-filling defects and loss of distal ciliary segments. Reason: Important genetic interaction demonstrating NPHP-4's role in regulating OSM-3 function and ciliary distal segment formation. Supporting Evidence: PMID:26863025 nphp-4(tm925);osm-3(yhw66) double mutants lack distal segments and are dye-filling (Dyf) and osmotic avoidance (Osm) defective PMID:26863025 in addition to regulating cilia protein entry or exit, NPHP-4 influences localization and function of a distal ciliary kinesin
GO:1905515 non-motile cilium assembly	IGI PMID:26982032 MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Tr...	ACCEPT	Summary: IGI annotation from MKS5/CEP290 transition zone assembly study. nphp-4 interacts genetically with cep-290 and mks module genes. Reason: Supports NPHP-4's role in TZ assembly pathway, working in parallel with the CEP290-dependent MKS module assembly. Supporting Evidence: PMID:26982032 cep-290;nphp-4 animals fail to uptake the lipophilic dye DiI, a phenotype rescued by low-level expression of the CEP-290::GFP construct
GO:1905515 non-motile cilium assembly	IGI PMID:22152675 TMEM237 is mutated in individuals with a Joubert syndrome re...	ACCEPT	Summary: IGI annotation with JBTS-14/TMEM237. jbts-14;nphp-4 double mutants have ciliary defects consistent with functional redundancy. Reason: Part of the extensive genetic interaction network between NPHP and MKS module proteins in controlling TZ function and ciliogenesis. Supporting Evidence: PMID:22152675 Caenorhabditis elegans jbts-14 genetically interacts with nphp-4, encoding another TZ protein, to control basal body-TZ anchoring to the membrane and ciliogenesis
GO:1904491 protein localization to ciliary transition zone	IGI PMID:21422230 MKS and NPHP modules cooperate to establish basal body/trans...	ACCEPT	Summary: IGI annotation with MKS-5. NPHP-4 is part of the NPHP module that is anchored to the TZ by MKS-5, and functions to localize other proteins. Reason: Key functional role of NPHP-4 in the TZ protein localization hierarchy. Supporting Evidence: PMID:21422230 MKS-5 is a central component required for docking/anchoring MKS and NPHP protein modules
GO:1905515 non-motile cilium assembly	IGI PMID:21422230 MKS and NPHP modules cooperate to establish basal body/trans...	ACCEPT	Summary: IGI annotation based on genetic interactions with multiple MKS module genes (mks-1, mks-2, mks-3, mks-5, mks-6, mksr-1, mksr-2). Double mutants have severe ciliary defects including loss of membrane-TZ attachments and axoneme extension defects. Reason: Comprehensive genetic interaction study establishing the modular organization of TZ proteins and their collective role in ciliogenesis. Supporting Evidence: PMID:21422230 MKS/MKSR and NPHP modules are collectively required for two essential aspects of ciliogenesis, namely membrane anchoring of the BB/TZ and formation of an intact TZ region PMID:21422230 Joint disruption of an MKS/MKSR protein and NPHP-4 results in BB/TZ membrane association defects
GO:0023041 neuronal signal transduction	IC PMID:15817158 Functional characterization of the C. elegans nephrocystins ...	KEEP AS NON CORE	Summary: IC annotation inferred from localization in sensory cilia. nphp-1;nphp-4 double mutant males show sensory behavior defects consistent with impaired signal transduction. Reason: While NPHP-4 is required for sensory neuron function, the primary defect is in ciliary structure/gating rather than direct signal transduction. The behavioral phenotypes are likely secondary to ciliary gating defects that affect signaling molecule compartmentalization. Supporting Evidence: PMID:15817158 We propose that NPHP-1 and NPHP-4 proteins play important and redundant roles in facilitating ciliary sensory signal transduction
GO:0034606 response to hermaphrodite contact	IGI PMID:15817158 Functional characterization of the C. elegans nephrocystins ...	KEEP AS NON CORE	Summary: IGI annotation with NPHP-1. nphp-1;nphp-4 double mutant males are defective in response to hermaphrodite contact during mating. Reason: Behavioral phenotype that reflects ciliary sensory function rather than core molecular function. Important for understanding organismal role but secondary to TZ structural function. Supporting Evidence: PMID:15817158 nphp-1; nphp-4 double, but not single, mutant males are response defective
GO:0034607 turning behavior involved in mating	IGI PMID:15817158 Functional characterization of the C. elegans nephrocystins ...	KEEP AS NON CORE	Summary: IGI annotation with NPHP-1. nphp-1;nphp-4 double mutant males show mating behavior defects. Reason: Male-specific sensory behavior dependent on ciliary function. Secondary phenotype reflecting ciliary gating defects. Supporting Evidence: PMID:15817158 nphp-1; nphp-4 double, but not single, mutant males are response defective
GO:0097730 non-motile cilium	IDA PMID:15817158 Functional characterization of the C. elegans nephrocystins ...	ACCEPT	Summary: IDA showing NPHP-4::GFP localization to sensory cilia. First characterization of C. elegans nephrocystins. Reason: Direct experimental observation of ciliary localization in multiple sensory neuron types. Supporting Evidence: PMID:15817158 GFP-tagged NPHP-1 and NPHP-4 proteins localize to ciliated sensory endings of dendrites and colocalize with PKD-2 in male-specific sensory cilia
GO:0035869 ciliary transition zone	IDA PMID:21689635 Caenorhabditis elegans ciliary protein NPHP-8, the homologue...	ACCEPT	Summary: IDA showing NPHP-4 colocalization with NPHP-8 at the TZ. NPHP-8 depends on NPHP-4 for proper localization. Reason: Direct visualization of TZ localization, consistent with other studies. Supporting Evidence: PMID:21689635 NPHP-8 co-localized with NPHP-4 at the transition zone at the base of cilia
GO:0035869 ciliary transition zone	IDA PMID:21422230 MKS and NPHP modules cooperate to establish basal body/trans...	ACCEPT	Summary: IDA from comprehensive TZ protein study. High-resolution imaging of NPHP-4 localization at the TZ. Reason: Key study establishing TZ as a distinct compartment and NPHP-4 as a core TZ-localized protein. Supporting Evidence: PMID:21422230 MKS/MKSR and NPHP proteins localize specifically to the ciliary TZ
GO:0008340 determination of adult lifespan	IMP PMID:19208769 Functional interactions between the ciliopathy-associated Me...	KEEP AS NON CORE	Summary: IMP annotation from MKS1-related proteins study. Double mutants of mks/mksr genes (which interact with nphp genes) show increased lifespan due to abnormal insulin-IGF-I signaling. Reason: Pleiotropic phenotype that may result from altered ciliary signaling. Not a core function of NPHP-4 but represents downstream physiological consequence of ciliary dysfunction. Supporting Evidence: PMID:19208769 we find genetic interactions between all double mks/mksr mutant combinations, manifesting as an increased lifespan phenotype, which is due to abnormal insulin-IGF-I signaling
GO:0008104 intracellular protein localization	IGI PMID:18316409 The Caenorhabditis elegans nephrocystins act as global modif...	MODIFY	Summary: IGI annotation with NPHP-1. nphp-1;nphp-4 double mutants show abnormal localization of IFT components including OSM-6 and BBS proteins. Reason: This is too broad. The annotation should more specifically reflect the role in regulating ciliary access and localization of specific IFT components. Proposed replacements: intraciliary transport protein localization to ciliary transition zone Supporting Evidence: PMID:18316409 loss of both NPHP-1 and NPHP-4 but not NPHP-1 alone leads to the abnormal ciliary localization of the IFT-B polypeptide OSM-6, the OSM-3-kinesin, and the BBS proteins BBS-7 and BBS-8
GO:0036064 ciliary basal body	IDA PMID:18316409 The Caenorhabditis elegans nephrocystins act as global modif...	ACCEPT	Summary: IDA from detailed ultrastructural study of nephrocystin function. NPHP-4 localizes to basal body/TZ region. Reason: Comprehensive study with electron microscopy and fluorescence imaging confirming localization at the ciliary base region. Supporting Evidence: PMID:18316409 NPHP-1 and NPHP-4 localize to TZs of male-specific CEM cilia
GO:0097730 non-motile cilium	IDA PMID:18316409 The Caenorhabditis elegans nephrocystins act as global modif...	ACCEPT	Summary: IDA showing localization in sensory cilia across multiple neuron types. Reason: Consistent with other IDA studies showing ciliary localization. Supporting Evidence: PMID:18316409 NPHP-1 and NPHP-4 localize to TZs of male-specific CEM cilia
GO:1905515 non-motile cilium assembly	IMP PMID:18316409 The Caenorhabditis elegans nephrocystins act as global modif...	ACCEPT	Summary: IMP annotation from study showing nphp-4 mutants have ultrastructural defects in ciliary B tubules and IFT transport abnormalities. Reason: Core function demonstrated by loss-of-function analysis with ultrastructural characterization. Supporting Evidence: PMID:18316409 nphp-4 mutants have B tubule defects in amphid channel cilia PMID:18316409 We propose that NPHP-1 and NPHP-4 act globally at the TZ to regulate ciliary access of the IFT machinery, axonemal structural components, and signaling molecules
GO:0035177 larval foraging behavior	IMP PMID:18337471 Functional redundancy of the B9 proteins and nephrocystins i...	KEEP AS NON CORE	Summary: IMP annotation from study on B9 proteins and nephrocystins. nphp-4 mutants with B9 protein mutations have foraging behavior defects. Reason: Behavioral phenotype reflecting sensory function. The foraging defect is likely due to chemosensory impairment from ciliary dysfunction rather than a direct role in behavior per se. Supporting Evidence: PMID:18337471 the B9 proteins function redundantly with the nephrocystins to regulate the formation and/or maintenance of cilia and dendrites in the amphid and phasmid ciliated sensory neurons
GO:0030674 protein-macromolecule adaptor activity	NAS	NEW	Summary: Added to align core_functions with existing annotations. Reason: Core function term not present in existing_annotations.

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

Tags

Deep Research

Falcon

📄 View Raw YAML