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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
    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)
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    29 - 5024 134 1241 - 2009 19470472
    Type restricted
       expressed in (based on citations)
    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
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell Homo sapiens
    Endocrineislet cell (alpha,beta...) Homo sapiens
    cell lineage
    cell lines
    at STAGE
    physiological period embryo
  • kidney
  • expressed in the epicardium and coronary vessels during embryonic development
  • 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
    interspecies homolog to rattus Nphs1 (82.3 pc)
    homolog to murine Nphs1 (82.6 pc)
  • immunoglobulin superfamily
  • CATEGORY adhesion , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
  • 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
    text urologic
    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
    small molecule
  • 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
    activated by activation of PPARA in embryonic kidney epithelial cells and podocytes by a dual mechanism
    repressed by
  • phosphorylated on tyrosine residues
    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
    Therapy target
    murine Nphs1, expressed in kidney, brain, pancreas, knockout leading to massive proteinuria and neonatal death