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FLASH GENE
Symbol GPHN contributors: mct/npt/pgu - updated : 09-11-2016
HGNC name gephyrin
HGNC id 15465
Corresponding disease
EEOC2 epileptic encephalopathy, childhood onset 2
MOCODC molybdenum cofactor deficiency, type C
STHE2 Startle disease, hyperekplexia 2
Location 14q23.3      Physical location : 66.974.124 - 67.648.523
Synonym symbol(s) GEPH, GPH, GPHRYN, KIAA1385, HKPX1
EC.number 2.10.1.1/2.7.7.75
DNA
TYPE functioning gene
STRUCTURE 674.40 kb     23 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Physical map
LOC390488 14 similar to 60S ribosomal protein L21 RPL36AP2 14 ribosomal protein L36a pseudogene 2 PTBP1P 14 polypyrimidine tract binding protein 1 pseudogene FUT8 14q24.3 fucosyltransferase 8 (alpha (1,6) fucosyltransferase) RPL21P8 14 ribosomal protein L21 pseudogene 8 NCOA4P 14 nuclear receptor coactivator 4 pseudogene LOC390489 14 similar to Ferritin heavy chain (Ferritin H subunit) NSEP1P 14q23.2 nuclease sensitive element binding protein 1 pseudogene LOC122438 14q23.3 similar to RIKEN cDNA 1110013H04 LOC387993 14 hypothetical gene supported by BC033546 GPHN 14q23.1/14q23,3 gephyrin C14orf54 14 chromosome 14 open reading frame 54 LOC260329 14q23 splicing factor 3b, subunit 4, 49kD pseudogene MPP5 14q23.3 membrane protein, palmitoylated 5 (MAGUK p55 subfamily member 5) ATP6V1D 14q23-q24.2 ATPase, H+ transporting, lysosomal 34kDa, V1 subunit D EIF2S1 14q21.3 eukaryotic translation initiation factor 2, subunit 1 alpha, 35kDa PLEK2 14q23.1-q23.2 pleckstrin 2 FLJ33387 14q24.1 hypothetical protein FLJ33387 PIGH 2p21-p16 phosphatidylinositol glycan, class H LOC390490 14 similar to Ac2-008 ARG2 14q24.1-q24.3 arginase, type II VTI1B 14q23,3 vesicle transport through interaction with t-SNAREs homolog 1B (yeast) COX7A3P 14 cytochrome c oxidase subunit VIIa polypeptide 3 pseudogene RDH11 14q23-q24.3 retinol dehydrogenase 11 (all-trans and 9-cis) RPL21P9 14q23.3 ribosomal protein L21 pseudogene 9 RDH12 14q23.3 retinol dehydrogenase 12 (all-trans and 9-cis)
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
22 - 4219 79.6 736 - 2001 11418245
  • Geph2
  • 23 - 4318 83.3 769 - 2001 11418245
  • GephP1
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon highly
     liver    
    Endocrinethyroid   highly
    Hearing/Equilibriumear   highly
    Nervousbrain    
    Reproductivemale systemprostate   
    Respiratoryrespiratory tractlarynx  highly
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal homologous to the bacterial protein MogA, with conserved N-terminal G- and C-terminal E-domain, connected by the central (C-) domain (
  • a small 15-AAs tubulin-binding domain necessary and sufficient for fusion with MLL in leukemia
  • C terminal domain homolog to the bacterial MoeA believed to activate molybedenum before its incorporation into molybdopterin
  • HOMOLOGY
    interspecies homolog to Drosophila Cinnamon
    Homologene
    FAMILY
  • in the N-terminal section : moaB/mog family
  • in the C-terminal section : moeA family
  • CATEGORY enzyme , structural protein , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytoskeleton
    text
  • mainly expressed in the membrane and cytoplasm of neurons in temporal lobe epileptic foci
  • its presence in a cytosolic 600 kDa protein complex suggests that its metabolic and/or other non-neuronal functions are exerted in the cytoplasm and are not confined to a particular subcellular compartment
  • basic FUNCTION
  • neurotransmitter receptor clustering and anchoring protein to subsynaptic microtubules of inhibitory ion channel receptors
  • third step of molybenum cofactor biosynthesis in non neuronal tissues (insertion of molybdenum into molybdobiopterin)
  • microtubule-associated protein involved in membrane protein-cytoskeleton interactions
  • responsible for molybdenum cofactor synthesis and the clustering of glycine and GABA(A) receptors at inhibitory synapses
  • postsynaptic scaffolding protein participated in clustering GABA(A) receptors at inhibitory synapses
  • major protein determinant for the clustering of inhibitory neurotransmitter receptors
  • major postsynaptic scaffolding protein at inhibitory synapses
  • multimeric scaffolding protein gephyrin forms post-synaptic clusters at inhibitory sites, thereby anchoring inhibitory glycine (GLYR) and subsets of &
  • 947;-aminobutyric acid type A (GABAA) receptors
  • is a scaffold protein essential for the postsynaptic clustering of inhibitory glycine and different subtypes of GABA(A) receptors
  • postsynaptic scaffolding protein, essential for the clustering of glycine and gamma-aminobutyric acid type-A receptors (GABAARs) at inhibitory synapse
  • vital for the organization of proteins at inhibitory receptors, molybdenum cofactor biosynthesis and other diverse functions
  • is a central player at inhibitory postsynapses, directly binds and organizes GABAA and glycine receptors (GABAARs and GlyRs), and is thereby indispensable for normal inhibitory neurotransmission
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS nervous system
    PATHWAY
    metabolism
    signaling neurotransmission
    a component
  • component of the glycine receptor
  • collybistin-gephyrin (ARHGEF9/GPHN)complex has an intimate role in the clustering of GABA(A)Rs containing the alpha2 subunit
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • glycine receptor beta subunit, GABAA receptors tubulin
  • interacts with GABARAP
  • formation of gephyrin scaffolds at inhibitory synapses requires an intact ARHGEF9 PH-domain but is CDC42-independent
  • VPS35 binding to gephyrin
  • interacting with GABRA1, GABRA3
  • GPHN-binding protein AHRGEF9 is involved in regulating the phosphorylation of GPHN
  • ARHGEF9 and CDK5 are involved in regulating the phosphorylation of GPHN at postsynaptic membrane specializations
  • CDK5 plays likely an essential role for the stability of GPHN-dependent GABAA receptor clusters in hippocampal neurons
  • NLGN2 is localized selectively at GABAergic synapses, where it interacts with the scaffolding protein GPHN in the post-synaptic density
  • PIN1-dependent signalling represents a mechanism to modulate GABAergic transmission by regulating NLGN2/GPHN interaction
  • intimate association of GABRA5 with GPHN, resulting in constant synaptic levels of GABRA5 throughout circuit formation that regulates neuronal development
  • GSK3B regulates the sorting of GPHN and NLGN2 complexes in a KIF5A-dependent manner
  • PKC-dependent phosphorylation of GAP43 plays a critical role in regulating postsynaptic GPHN aggregation in developing GABAergic synapses
  • neuron-specific ARHGEF9 interacts with EIF3A, and its binding partner GPHN associates with MTOR
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) MOCODC , STHE2 , EEOC2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    with MLL in t(11;14) (q23;q24) in acute monoblastic leukemia
    constitutional     --low  
    significantly lower in the temporal neocortex of temporal lobe epilepsy patients compared to the controls
    constitutional     --low  
    in Alzheimer Disease
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Gephyrin-deficient (geph(-/-)) mice die after birth due to disinhibition of motor and sensory pathways resulting from a lack of postsynaptic glycine receptor and GABA(A) receptor clusters