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GPHN (Gephyrin)

Written2002-03Brigitte David-Watine
Unité de Biologie Cellulaire du Noyau, CNRS URA 2582, Département de Biologie Cellulaire et Infection, Institut Pasteur, 25, Rue du Docteur Roux, 75724 Paris Cedex 15, France

(Note : for Links provided by Atlas : click)

Identity

Other namesKIAA1385
GPHRYN
HGNC (Hugo) GPHN
LocusID (NCBI) 10243
Atlas_Id 317
Location 14q23.3  [Link to chromosome band 14q23]
Location_base_pair Starts at 66974125 and ends at 67648525 bp from pter ( according to hg19-Feb_2009)  [Mapping GPHN.png]
Local_order The markers associated with the gephyrin sequence correspond to the D14S63-D14S1069 interval.
Fusion genes
(updated 2016)
CDC27 (17q21.32) / GPHN (14q23.3)DNM1L (12p11.21) / GPHN (14q23.3)EIF2S1 (14q23.3) / GPHN (14q23.3)
GPHN (14q23.3) / CCDC12 (3p21.31)GPHN (14q23.3) / KMT2A (11q23.3)KMT2A (11q23.3) / GPHN (14q23.3)
MPP5 (14q23.3) / GPHN (14q23.3)PLEKHH1 (14q24.1) / GPHN (14q23.3)USP6NL (10p14) / GPHN (14q23.3)

DNA/RNA

 
  Exon-intron organization of the human gephyrin gene: Exons coding for the geghyrin are depicted by large traits and roman numerals with the alternative cassettes C1-C7 and exon VIII represented beneath the constant exons (exon VIII is putatively another cassette because one cDNA lacking this exon has been isolated). C1, C6 and C7 were not localized but their site of insertion is indicated by a ? as described . Exons and introns sizes are not drawn to scale. Exon I is telomeric to exon XXVII.
Description 29 exons (30 exons with the putative C1 exon), spanning over 800 kb
Transcription in a telomeric to centromeric direction. The alternative use of different exons, particularly of the exons termed C1 to C7, produces splice variants which are differentially expressed in the central nervous system and other tissues.

Protein

Note Gephyrin is a cytoplasmic, peripheral membrane protein that anchors the GlyR as well as a subset of GABAA receptors to the subsynaptic cytoskeleton in neurons
Description 736-770 amino acids; sizes varying from 93-105 kDa to smaller products 52-60 kDa. The N-terminal domain of gephyrin is homologous to the bacterial protein MogA, and the C-terminal domain is homologous to bacterial MoeA, both proteins being involved in the biosynthesis of Moco.
Expression wide if not ubiquitous, especially in brain, spinal cord, lung, liver and kidney. Precise distribution of expression of the different variants is not known.
Localisation Gephyrin is a cytoplasmic, peripheral membrane protein.
Function anchor inhibitory neuronal receptors (glycine, GABA) to the sub-synaptic cytoskeleton; plays a role in Moco biosynthesis.
Homology bacterial MogA et MoeA, drosophila Cinnamon and Arabidopsis thaliana Cnx1.

Mutations

Note deletion of the exons 2 and 3 resulting into a frameshift after 21codons of the normal coding sequence. No gephyrin detected in the patient's fibroblats.

Implicated in

Note
Entity Molybdenum cofactor (Moco) hereditary deficiency syndrome.
Note Disruption of the gephyrin gene is lethal at birth in the mouse. The mutant phenotype resembles that of humans with hereditary deficiency of molybdenum cofactor and hyperhekplexia, a disease which is associated with defects in glycinergic inhibition in many patients suggesting that gephyrin function may be impaired in patients affected by either of these two diseases.
Prognosis lethal in the three cases described.
  
Entity t(11;14)(q23;q23) in AML --> MLL - GPHN
Abnormal Protein The fusion protein contains the MLL AT hook motifs and a DNA methyl transferase homology domain fused to the C-terminal part of Gephyrin , including a presumed tubulin binding site and a domain homologous to the Escherichia coli molybdenum cofactor biosynthesis protein MoeA.
  

To be noted

High-titer antibodies against gephyrin have been identified in a patient with a mediastinal cancer and clinical features of stiff-man syndrome These findings provided evidence for a link between autoimmunity directed against components of inhibitory synapses and neurologic conditions characterized by chronic rigidity and spams.

Bibliography

Primary structure and alternative splice variants of gephyrin, a putative glycine receptor-tubulin linker protein.
Prior P, Schmitt B, Grenningloh G, Pribilla I, Multhaup G, Beyreuther K, Maulet Y, Werner P, Langosch D, Kirsch J
Neuron. 1992 ; 8 (6) : 1161-1170.
PMID 1319186
 
Dual requirement for gephyrin in glycine receptor clustering and molybdoenzyme activity.
Feng G, Tintrup H, Kirsch J, Nichol MC, Kuhse J, Betz H, Sanes JR
Science (New York, N.Y.). 1998 ; 282 (5392) : 1321-1324.
PMID 9812897
 
The human gephyrin (GPHN) gene: structure, chromosome localization and expression in non-neuronal cells.
David-Watine B
Gene. 2001 ; 271 (2) : 239-245.
PMID 11418245
 
GPHN, a novel partner gene fused to MLL in a leukemia with t(11;14)(q23;q24).
Eguchi M, Eguchi-Ishimae M, Seto M, Morishita K, Suzuki K, Ueda R, Ueda K, Kamada N, Greaves M
Genes, chromosomes & cancer. 2001 ; 32 (3) : 212-221.
PMID 11579461
 
A mutation in the gene for the neurotransmitter receptor-clustering protein gephyrin causes a novel form of molybdenum cofactor deficiency.
Reiss J, Gross-Hardt S, Christensen E, Schmidt P, Mendel RR, Schwarz G
American journal of human genetics. 2001 ; 68 (1) : 208-213.
PMID 11095995
 

Citation

This paper should be referenced as such :
David-Watine, B
GPHN (gephyrin)
Atlas Genet Cytogenet Oncol Haematol. 2002;6(3):188-189.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/GPHNID317.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ]
  11q23 rearrangements (KMT2A) in leukaemia
t(11;14)(q23;q24) KMT2A/GPHN

Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ]
  Stiff-person syndrome

External links

Nomenclature
HGNC (Hugo)GPHN   15465
Cards
AtlasGPHNID317
Entrez_Gene (NCBI)GPHN  10243  gephyrin
AliasesGEPH; GPH; GPHRYN; HKPX1; 
MOCODC
GeneCards (Weizmann)GPHN
Ensembl hg19 (Hinxton)ENSG00000171723 [Gene_View]  chr14:66974125-67648525 [Contig_View]  GPHN [Vega]
Ensembl hg38 (Hinxton)ENSG00000171723 [Gene_View]  chr14:66974125-67648525 [Contig_View]  GPHN [Vega]
ICGC DataPortalENSG00000171723
TCGA cBioPortalGPHN
AceView (NCBI)GPHN
Genatlas (Paris)GPHN
WikiGenes10243
SOURCE (Princeton)GPHN
Genomic and cartography
GoldenPath hg19 (UCSC)GPHN  -     chr14:66974125-67648525 +  14q23.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)GPHN  -     14q23.3   [Description]    (hg38-Dec_2013)
EnsemblGPHN - 14q23.3 [CytoView hg19]  GPHN - 14q23.3 [CytoView hg38]
Mapping of homologs : NCBIGPHN [Mapview hg19]  GPHN [Mapview hg38]
OMIM149400   603930   615501   
Gene and transcription
Genbank (Entrez)AB037806 AF272663 AJ272033 AJ272343 AK025169
RefSeq transcript (Entrez)NM_001024218 NM_020806
RefSeq genomic (Entrez)NC_000014 NC_018925 NG_008875 NT_026437 NW_004929393
Consensus coding sequences : CCDS (NCBI)GPHN
Cluster EST : UnigeneHs.208765 [ NCBI ]
CGAP (NCI)Hs.208765
Alternative Splicing GalleryENSG00000171723
Gene ExpressionGPHN [ NCBI-GEO ]   GPHN [ EBI - ARRAY_EXPRESS ]   GPHN [ SEEK ]   GPHN [ MEM ]
Gene Expression Viewer (FireBrowse)GPHN [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)10243
GTEX Portal (Tissue expression)GPHN
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9NQX3 (Uniprot)
NextProtQ9NQX3  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9NQX3
Splice isoforms : SwissVarQ9NQX3 (Swissvar)
Catalytic activity : Enzyme2.7.7.75 [ Enzyme-Expasy ]   2.7.7.752.7.7.75 [ IntEnz-EBI ]   2.7.7.75 [ BRENDA ]   2.7.7.75 [ KEGG ]   
PhosPhoSitePlusQ9NQX3
Domaine pattern : Prosite (Expaxy)MOCF_BIOSYNTHESIS_1 (PS01078)    MOCF_BIOSYNTHESIS_2 (PS01079)   
Domains : Interpro (EBI)MoaB/Mog_dom    MoCF_biosynth_CS    MoeA_C_domain_IV    MoeA_linker/N   
Domain families : Pfam (Sanger)MoCF_biosynth (PF00994)    MoeA_C (PF03454)    MoeA_N (PF03453)   
Domain families : Pfam (NCBI)pfam00994    pfam03454    pfam03453   
Domain families : Smart (EMBL)MoCF_biosynth (SM00852)  
DMDM Disease mutations10243
Blocks (Seattle)GPHN
PDB (SRS)1JLJ   
PDB (PDBSum)1JLJ   
PDB (IMB)1JLJ   
PDB (RSDB)1JLJ   
Structural Biology KnowledgeBase1JLJ   
SCOP (Structural Classification of Proteins)1JLJ   
CATH (Classification of proteins structures)1JLJ   
SuperfamilyQ9NQX3
Human Protein AtlasENSG00000171723
Peptide AtlasQ9NQX3
HPRD04893
IPIIPI00016006   IPI00184477   IPI00922682   IPI01010764   IPI01026451   IPI01025137   IPI01024800   IPI01026238   IPI01025919   IPI01026565   IPI01025811   
Protein Interaction databases
DIP (DOE-UCLA)Q9NQX3
IntAct (EBI)Q9NQX3
FunCoupENSG00000171723
BioGRIDGPHN
STRING (EMBL)GPHN
ZODIACGPHN
Ontologies - Pathways
QuickGOQ9NQX3
Ontology : AmiGOprotein binding  ATP binding  cytoplasm  cytoskeleton  plasma membrane  Mo-molybdopterin cofactor biosynthetic process  molybdenum incorporation into molybdenum-molybdopterin complex  cell junction  dendrite  molybdopterin cofactor biosynthetic process  molybdopterin cofactor biosynthetic process  postsynaptic membrane  metal ion binding  molybdopterin adenylyltransferase activity  molybdopterin molybdotransferase activity  molybdopterin molybdotransferase activity  glycine receptor clustering  gamma-aminobutyric acid receptor clustering  
Ontology : EGO-EBIprotein binding  ATP binding  cytoplasm  cytoskeleton  plasma membrane  Mo-molybdopterin cofactor biosynthetic process  molybdenum incorporation into molybdenum-molybdopterin complex  cell junction  dendrite  molybdopterin cofactor biosynthetic process  molybdopterin cofactor biosynthetic process  postsynaptic membrane  metal ion binding  molybdopterin adenylyltransferase activity  molybdopterin molybdotransferase activity  molybdopterin molybdotransferase activity  glycine receptor clustering  gamma-aminobutyric acid receptor clustering  
Pathways : BIOCARTAGamma-aminobutyric Acid Receptor Life Cycle [Genes]   
Pathways : KEGGGABAergic synapse   
REACTOMEQ9NQX3 [protein]
REACTOME PathwaysR-HSA-947581 Molybdenum cofactor biosynthesis [pathway]
NDEx Network
Atlas of Cancer Signalling NetworkGPHN
Wikipedia pathwaysGPHN
Orthology - Evolution
OrthoDB10243
GeneTree (enSembl)ENSG00000171723
Phylogenetic Trees/Animal Genes : TreeFamGPHN
Homologs : HomoloGeneGPHN
Homology/Alignments : Family Browser (UCSC)GPHN
Gene fusions - Rearrangements
Fusion : MitelmanEIF2S1/GPHN [14q23.3/14q23.3]  [t(14;14)(q23;q23)]  
Fusion : MitelmanMPP5/GPHN [14q23.3/14q23.3]  [t(14;14)(q23;q23)]  
Fusion : MitelmanPLEKHH1/GPHN [14q24.1/14q23.3]  [t(14;14)(q23;q24)]  
Fusion : COSMICKMT2A [11q23.3]  -  GPHN [14q23.3]  [fusion_1850]  [fusion_1851]  [fusion_1852]  
Fusion: TCGAEIF2S1 14q23.3 GPHN 14q23.3 BRCA
Fusion: TCGAMPP5 14q23.3 GPHN 14q23.3 BLCA BRCA LUAD
Fusion: TCGAPLEKHH1 14q24.1 GPHN 14q23.3 BLCA
Fusion : TICdbKMT2A [11q23.3]  -  GPHN [14q23.3]
Polymorphisms : SNP, variants
NCBI Variation ViewerGPHN [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)GPHN
dbVarGPHN
ClinVarGPHN
1000_GenomesGPHN 
Exome Variant ServerGPHN
ExAC (Exome Aggregation Consortium)GPHN (select the gene name)
Genetic variants : HAPMAP10243
Genomic Variants (DGV)GPHN [DGVbeta]
Mutations
ICGC Data PortalGPHN 
TCGA Data PortalGPHN 
Broad Tumor PortalGPHN
OASIS PortalGPHN [ Somatic mutations - Copy number]
Cancer Gene: CensusGPHN 
Somatic Mutations in Cancer : COSMICGPHN 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)MSeqDR-LSDB Mitochondrial Disease Locus Specific Database
BioMutasearch GPHN
DgiDB (Drug Gene Interaction Database)GPHN
DoCM (Curated mutations)GPHN (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)GPHN (select a term)
intoGenGPHN
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)14:66974125-67648525  ENSG00000171723
CONAN: Copy Number AnalysisGPHN 
Mutations and Diseases : HGMDGPHN
OMIM149400    603930    615501   
MedgenGPHN
Genetic Testing Registry GPHN
NextProtQ9NQX3 [Medical]
TSGene10243
GENETestsGPHN
Huge Navigator GPHN [HugePedia]
snp3D : Map Gene to Disease10243
BioCentury BCIQGPHN
ClinGenGPHN (curated)
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD10243
Chemical/Pharm GKB GenePA28840
Clinical trialGPHN
Miscellaneous
canSAR (ICR)GPHN (select the gene name)
Other databaseKIAA1385 (HUGE)
Probes
Litterature
PubMed67 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineGPHN
EVEXGPHN
GoPubMedGPHN
iHOPGPHN
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Sat Jun 11 13:07:34 CEST 2016

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