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FLASH GENE
Symbol NPHP4 contributors: mct/pgu - updated : 05-09-2015
HGNC name nephronophthisis 4
HGNC id 19104
Corresponding disease
NPHP4 nephronophthisis 4
SLSN4 Senior-Loken syndrome 4
Location 1p36.31      Physical location : 5.922.869 - 6.052.531
Synonym name
  • nephrocystin 4
  • nephroretinin
  • Synonym symbol(s) KIAA0673, Q9UFQ2
    DNA
    TYPE functioning gene
    STRUCTURE 129.66 kb     30 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    text multiple alternative transcripts
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    30 - 5020 150 1426 - 2005 15661758
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineneuroendocrinepituitary  highly
    Nervousbrain     Homo sapiens
     nervecranial nerve  highly Homo sapiens
    Reproductivefemale systemovary  moderately
     male systemtestis  highly
    Urinarykidneytubule    Homo sapiens
    Visualeyeretina    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal highly
    Nervouscentral   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text brain
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a proline rich region
  • HOMOLOGY
    interspecies ortholog to murine Nphp4
    Homologene
    FAMILY
  • immunoglobulin superfamily
  • NPHP4 family
  • CATEGORY storage , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,adherens
        intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    text localizes to basal bodies, forming the base of the cilia, and along the axoneme of the cilia
    basic FUNCTION
  • playing a role in cell- cell and cell-matrix signaling
  • may also participate in intraflagellar transport pathways in photoreceptor cells
  • integrating signals related to cell adhesion with those controling cell cycle progression through the cilia sensor thus maintaining the integrity of the renal epithelium
  • may potentially participate in intraflagellar transport (IFT) or sensory signal transduction
  • playing an important role in epithelial cell organization
  • may participate along with the Par polarity complex in microtubule-dependent transport during ciliogenesis
  • role in epithelial polarity and formation of TJs potentially via their association with polarity proteins MPP5 and PARD6A and PARD6B
  • role for NPHP4 in cell adhesion and cytoskeleton modulation
  • necessary for normal photoreceptor ribbon synapse maintenance and outer segment formation, and for sperm development
  • acts upstream of NPHP1 in a common pathway and plays a role in intracellular vesicular transport
  • critical function for NPHP4 and PTK2B in controlling NPHP1 and the NPH protein complex
  • having a role in basal body anchoring and establishing a ciliary gate during ciliogenesis
  • acts as a potent negative regulator of mammalian Hippo signaling
  • NPHP4 and JADE1 additively inhibit canonical WNT signaling
  • NPHP4 exerted pro-proliferative effects through inhibiting hippo signalling
  • NEK8 and NPHP4 co-operated to control TAZ activity
  • CELLULAR PROCESS cell cycle, progression
    PHYSIOLOGICAL PROCESS development
    text renal tubular developement and functin
    PATHWAY
    metabolism
    signaling
    a component
  • forming a complex with nephrocystin NPHP1
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • NPHP1, BCAR1, TNS, FLNA, FLNB, PTK2B
  • interacting with RPGR (RCC1-like domain of RPGR interacts with the N-terminal 316 AAs of NPHP4)
  • NPHP1 and nephrocystin-4 (NPHP4) interact, and NPHP4 negatively regulates tyrosine phosphorylation of NPHP1
  • negatively regulates PTK2B-induced tyrosine phosphorylation of NPHP1 by controlling the NPHP1/PTK2B interaction
  • would be a negative regulator by antagonizing PTK2B-induced phosphorylation and decreasing the interaction of NPHP1/PACS1
  • directly interacted with the kinase LATS1 and inhibited LATS1-mediated phosphorylation of the Yes-associated protein (YAP1) and WWTR1, leading to derepression of these protooncogenic transcriptional regulators
  • NPHP4 acts as a potent negative regulator of mammalian Hippo signalling by interacting with the LATS protein kinase and controlling the phosphorylation of the oncogenic transcriptional activator TAZ
  • NPHP4 enhances the level of nuclear NEK8, thereby promoting the TAZ–NEK8 interaction
  • NPHP4, by inhibiting TAZ phosphorylation at the 14-3-3 binding site, leads to the tandem nuclear accumulation of TAZ and NEK8
  • JADE1 colocalizes with NPHP1 at the transition zone of primary cilia and interacts with NPHP4
  • NUP62 and the C termini of NPHP4 and IQCB1 interact with KIF17 and thus spatially map to the inner region of the ciliary gating zone
  • B9D1, AHI1, and the N termini of NPHP4 and IQCB1 interact with the transmembrane protein SSTR3 and thus spatially map to the outer region of the ciliary gating zone
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) SLSN4 , NPHP4
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    involvement of disrupted interaction with RPGRIP1 in the retinal dystrophy of both SLSN4 and LCA6 patients
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS