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FLASH GENE
Symbol NDP contributors: shn - updated : 24-05-2017
HGNC name Norrie disease (pseudoglioma)
HGNC id 7678
DNA
TYPE functioning gene
STRUCTURE 24.90 kb     3 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
Map pter - DXS8379 - DXS8035 - NDP - DXS8080 - DXS8054 - cen
Authors Sims et al (02)
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
3 - 2058 12.44 133 - 1999 10023053
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Nervousbrainlimbic systemhippocampus highly
 brainhindbraincerebellumcerebellar nucleihighly
 brainforebraincerebral cortex highly
Olfactory (smell)olfactory bulb   highly
Visualeyeretina  highly Mus musculusFetal
cells
SystemCellPubmedSpeciesStageRna symbol
Visualcone photoreceptor
Visualganglion cell
VisualMuller cell
Visualrod photoreceptor
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal, pregnancy
Text active during eye and brain development, placenta
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • one CTCK (C-terminal cystine knot-like) domain, with three pairs of cysteines that form the highly conserved trio of disulfide bonds necessary for its function
  • a dinucleotide repeat
  • a disulfide-rich motif and prepro-von Willebrand factor promotes interchain disulfide bond formation among polypeptides in which it is found
  • contains separate binding sites for FZD4 and for the Wnt ligand coreceptor LRP5 or LRP6
  • mono polymer dimer , octamer
    HOMOLOGY
    interspecies ortholog to NDP, Pan troglodytes
    ortholog to Ndp, Rattus norvegicus
    ortholog to Ndp, Mus musculus
    Homologene
    FAMILY
    CATEGORY signaling growth factor
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text secreted protein
    basic FUNCTION
  • involved in retinal developmental vasculogenesis
  • could play a critical role in the differentiation or maintenance of the differentiated state of the retina
  • may be involved in a pathway that regulates neural cell differentiation and proliferation
  • a possible role in neuroectodermal cell-cell interaction
  • inducing FZD4-dependent activation of the classical Wnt pathway
  • NDP-FZD4 is a signaling system playing a central role in vascular development in the eye and ear
  • playing a crucial role in hyaloid vessel regression and in sprouting angiogenesis during retinal vascular development, especially in the development of the deep retinal capillary networks
  • forms disulfide-bonded oligomers that are associated with the extracellular matrix upon secretion from cells
  • in the retina, serves as a ligand and binds to FZD4 to activate the Wnt signaling pathway in normal angiogenesis and vascularization
  • is a mitogenic stimulus for cells in the superficial retinal vascular plexus (SRVP)
  • is required downstream of HH activation to induce retinal progenitor proliferation in the retina
  • cell autonomous function for NDP in retinal progenitor proliferation that is independent of its function in the retinal vasculature, which could explain the neural defects associated with ND
  • stimulates cell proliferation in the superficial retinal vascular plexus and is pivotal for the recruitment of mural cells
  • play a crucial role in retinal vascularization
  • cysteine-rich growth factor that is required for angiogenesis in the eye, ear, brain, and female reproductive organs
  • may play a role in the regulation of angiogenesis in the colorectal cancer tumor microenvironment
  • protected blood-brain barrier integrity and improved neurological outcome after subarachnoid hemorrhage, and the action of NDP appeared mediated by FZD4 receptor activation
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling signal transduction , sensory transduction/hearing , sensory transduction/vision
  • RCBTB1 participates in the NDP/FZD4 signaling pathway
  • a component
  • FZD4, LRP5, and TSPAN12 are component of the Norrin-FZD4 complex
  • instead of inducing FZD4 dimerization, NDP induces the formation of a ternary complex with FZD4 and LRP5/6 by binding to their respective extracellular domains
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ligand of FZD4 through the FZD4 N-terminal ligand-binding domain (the "cysteine-rich domain" (CRD)(function as a ligand-receptor pair to control vascular development in the retina and inner ear)
  • ligand of a receptor complex consisting of FZD4, LRP5 and TSPAN12
  • acts on FZD4, participates in angiogenesis in a variety of contexts through the Wnt-signaling pathway
  • is a rare ligand capable of binding three receptors/binding proteins that are important for BMP and Wnt signaling pathways
  • interplay of NDP and WNT7A/WNT7B signaling systems in blood-brain barrier and blood-retina barrier development and maintenance
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) ND , EVR2 , COATS
    related resource Retinal Information Network
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    partly deleted in several typical Norrie Disease patients
    Susceptibility to retinopathy of prematurity (ROP)
    Variant & Polymorphism other deletion within the non-coding region was associated with only mild-regressed ROP (Dickinson 2006)
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • NDP mutant mice develop retrolental structures in the vitreous body and show an overall disorganization of the retinal ganglion cell layer
  • Norrin-/y mice have a leaky and aberrant retinal vasculature