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FLASH GENE
Symbol NPHS1 contributors: mct/pgu - updated : 20-11-2014
HGNC name nephrosis 1, congenital, Finnish type (nephrin)
HGNC id 7908
Corresponding disease
NPHS1 nephrotic 1, congenital, Finnish type
Location 19q13.12      Physical location : 36.316.273 - 36.342.895
Synonym name
  • nephrin
  • renal glomerulus-specific cell adhesion receptor
  • Synonym symbol(s) CNF, NPHN
    DNA
    TYPE functioning gene
    STRUCTURE 26.47 kb     29 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    LOC388533 19 similar to KIPV467 ZD52F10 19q13.13 hypothetical gene ZD52F10 UNQ698 19q13.13 HLAR698 GAPDS 19q13.1 glyceraldehyde-3-phosphate dehydrogenase, testis-specific NIFIE14 19q13.1 seven transmembrane domain protein ATP4A 19q13.1 ATPase, H+/K+ exchanging, alpha polypeptide KIAA0841 19q13.13 KIAA0841 MGC10433 19q13.13 hypothetical protein MGC10433 LOC339321 19q13.13 hypothetical protein LOC339321 COX6B 19q13.1 cytochrome c oxidase subunit VIb UPK1A 19q12-q13.1 uroplakin 1A TZFP 19q13.1 uroplakin 1A MLL4 19q13.1 myeloid/lymphoid or mixed-lineage leukemia 4 FLJ22573 19q13.13 hypothetical protein FLJ22573 U2AF1L3 19q13.13 U2(RNU2) small nuclear RNA auxiliary factor 1-like 3 PEN2 19q13.13 presenilin enhancer 2 F25965 19q13.1 protein F25965 FLJ32389 19q13.13 hypothetical protein FLJ32389 LOC148137 19q13.13 hypothetical protein BC017947 SNX26 19q13.13 sorting nexin 26 PRODH2 19q13.1 proline dehydrogenase (oxidase) 2 NPHS1 19q13.1 nephrosis 1, congenital, Finnish type (nephrin) KIRREL2 19q13.13 kin of IRRE like 2 (Drosophila) APLP1 19q13.1-q13.2 amyloid beta (A4) precursor-like protein 1 TA-NFKBH 19q13.13 T-cell activation NFKB-like protein HCST 19q13.1 hematopoietic cell signal transducer TYROBP 19q13.1 TYRO protein tyrosine kinase binding protein MGC2656 FLJ36445 19q13.13 hypothetical protein FLJ36445 MGC15677 19q13.13 hypothetical protein MGC15677 CLIPR-59 19q13.13 CLIP-170-related protein THAP8 19q13.13 THAP domain containing 8 FLJ33298 19q13.13 hypothetical protein FLJ33298 DKFZP434J046 LOC390925 POLR2I 19q12 polymerase (RNA) II (DNA directed) polypeptide I, 14.5kDa CKAP1 19q13.11-q13.12 cytoskeleton-associated protein 1 CAPNS1 19q13.13 calpain, small subunit 1 COX7A1 19q13.1 cytochrome c oxidase subunit VIIa polypeptide 1 (muscle)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    29 - 5024 134 1241 - 2009 19470472
    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