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FLASH GENE
Symbol NPHS1 contributors: mct/pgu - updated : 20-11-2015
HGNC name nephrosis 1, congenital, Finnish type (nephrin)
HGNC id 7908
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrinepancreasislet of Langerhans  highly Homo sapiens
Lymphoid/Immunethymus   moderately Homo sapiens
Urinarykidneynephronrenal capsuleglomerulushighly Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Cardiovascularendothelial cell Homo sapiens
Endocrineislet cell (alpha,beta...) Homo sapiens
Urinarypodocyte
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period embryo
Text
  • kidney
  • expressed in the epicardium and coronary vessels during embryonic development
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • eight Ig-like C2-type motifs
  • a fibronectin type III-like motif
  • a transmembrane segment
  • a intracellular domain connected indirectly to the actin cytoskeleton
  • a C-terminal short 154 AA cytoplasmic tail containing eight tyrosines , with a class 1 PDZ-binding motif, important for XPR1/KIRREL functions, having several putative tyrosine phosphorylation sites that can be phosphorylated by the Src kinase FYN
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to rattus Nphs1 (82.3 pc)
    homolog to murine Nphs1 (82.6 pc)
    Homologene
    FAMILY
  • immunoglobulin superfamily
  • CATEGORY adhesion , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text
  • single-pass type I membrane protein
  • specifically located at the split membrane extending between foot processes of the podocytes
  • basic FUNCTION
  • signaling cell-cell adhesion protein
  • mediating filtration through the podocyte filter which sits at the interface of the capillary and the nephron
  • playing a role in the development or function of the kidney glomerular filtration barrier
  • may anchor the podocyte slit diaphragm to the actin cytoskeleton
  • cooperates with KIRREL to transduce a signal that induces actin polymerization
  • plays a role in organizing the surface expression of ion channel proteins in podocytes and may play a role in outside-in signaling to allow podocytes to adapt to mechanical or neurohumoral stimuli originating in neighboring cells
  • playing a role in vesicular docking and insulin responsiveness of podocytes
  • may be playing a role in secondary fusion of myoblasts into nascent myotubes
  • transduces a phosphotyrosine signal through its cytoplasmic domain, which contains several putative tyrosine phosphorylation sites for Src-family kinases such as FYN
  • with KIRREL2 could interact homophilically and heterophilically, suggesting that NPHS1 and KIRREL2 might regulate certain developmental aspects of PTF1A-positive neurons as homo- or heterooligomers
  • nephrin and KIRREL are essential components of the slit diaphragm
  • nephrin and KIRREL or KIRREL2 trans-interactions promote cell-contact formation, suggesting that they may also function together in slit diaphragm assembly
  • KIRREL and NPHS1 organize a signaling complex at the podocyte cell membrane that forms the structural framework for a functional glomerular filtration barrier
  • not only has a function in kidney podocytes, but is also required for cardiovascular development
  • serves a crucial function in cardiac vessel development
  • NPHS1 and NGFR share a partial overlapping expression pattern in the epicardium and subepicardial coronary vessels
  • not only initiates actin polymerization but also assembles a protein complex that is necessary to regulate the architecture of the generated actin filament network and focal adhesion dynamics
  • key component of the kidney slit diaphragm that contributes to the morphology of podocyte foot processes through signaling to the underlying actin cytoskeleton
  • dynamic molecular link between nephrin signaling and the canonical Hippo pathway in podocytes, which may facilitate the conversion of mechanical cues to biochemical signals promoting podocyte viability
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS excretion
    text urologic
    PATHWAY
    metabolism
    signaling
    JNK cascade
    a component
  • complexing with NPHS2
  • major component of the slit membrane of the glomerular podocytes
  • part of a complex network of proteins that are necessary for the structural and signaling integrity of the podocyte slit diaphragm
  • KIRREL2 homodimerizes and heterodimerizes with nephrin and KIRREL
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with CD2AP C-terminal domain
  • interacting with IQGAP1
  • interacting with podocin/NPHS2 and KIRREL
  • interacting with NPHP1 and PARD3 (interaction mediated through the PDZ domain of PARD3 and conserved carboxyl terminal residues in NPHP1 and NPHS1, essential for establishing the three-dimensional architecture of podocytes at the kidney filtration barrier)
  • binds to the C-terminus of a large-conductance Ca2+-activated K+ channel isoform (KCNMA1) and regulates its expression on the cell surface
  • PTF1A directly controls expression of immunoglobulin superfamily molecules NPHS1, and KIRREL2 in the developing central nervous system
  • interaction between KIRREL, KIRREL3 and NPHS1
  • PRKCA and PICK1 are NPHS1-binding proteins
  • directly interacts with NGFR and reveal an important role for nephrin in murine cardiac development by permitting survival of cardiovascular progenitor cells
  • similarly to KIRREL, MYO1C also binds NPHS1 and reduces its localization at the podocyte cell membrane
  • recruits and regulates a protein complex that includes INPPL1, FLNA and RAPH1, proteins important in regulation of actin and focal adhesion dynamics, as well as lamellipodia formation
  • SIRPA interacts with NPHS1 at the slit diaphragm, and its phosphorylation is dynamically regulated in proteinuric states
  • SEPT7 associates with CD2AP and NPHS1, both essential for glomerular ultrafiltration
  • NCK1 directly modulates NPHS1 phosphorylation through formation of a signaling complex with the Src family kinase FYN
  • NCK1 integrates NPHS1 with the Hippo kinase cascade through association with the adaptor protein WTIP
  • cell & other
    REGULATION
    activated by activation of PPARA in embryonic kidney epithelial cells and podocytes by a dual mechanism
    repressed by
  • phosphorylated on tyrosine residues
  • ASSOCIATED DISORDERS
    corresponding disease(s) NPHS1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    downregulated in patients with proteinuric glomerular diseases
    Susceptibility to minimal change nephrotic syndrome
    Variant & Polymorphism other variants C265R and V822M associated to minimal change nephrotic syndrome
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    murine Nphs1, expressed in kidney, brain, pancreas, knockout leading to massive proteinuria and neonatal death