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GPHN (Gephyrin)

Identity

Other namesKIAA1385
GPHRYN
HGNC (Hugo) GPHN
LocusID (NCBI) 10243
Location 14q23.3
Location_base_pair Starts at 66974125 and ends at 67648525 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order The markers associated with the gephyrin sequence correspond to the D14S63-D14S1069 interval.

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

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 ANLL --> 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.

External links

Nomenclature
HGNC (Hugo)GPHN   15465
Cards
AtlasGPHNID317
Entrez_Gene (NCBI)GPHN  10243  gephyrin
GeneCards (Weizmann)GPHN
Ensembl (Hinxton)ENSG00000171723 [Gene_View]  chr14:66974125-67648525 [Contig_View]  GPHN [Vega]
AceView (NCBI)GPHN
Genatlas (Paris)GPHN
WikiGenes10243
SOURCE (Princeton)NM_001024218 NM_020806
Genomic and cartography
GoldenPath (UCSC)GPHN  -  14q23.3   chr14:66974125-67648525 +  14q23.3   [Description]    (hg19-Feb_2009)
EnsemblGPHN - 14q23.3 [CytoView]
Mapping of homologs : NCBIGPHN [Mapview]
OMIM149400   252150   603930   
Gene and transcription
Genbank (Entrez)AB037806 AF272663 AJ272033 AJ272343 AK025169
RefSeq transcript (Entrez)NM_001024218 NM_020806
RefSeq genomic (Entrez)AC_000146 NC_000014 NC_018925 NG_008875 NT_026437 NW_001838112 NW_004929393
Consensus coding sequences : CCDS (NCBI)GPHN
Cluster EST : UnigeneHs.208765 [ NCBI ]
CGAP (NCI)Hs.208765
Alternative Splicing : Fast-db (Paris)GSHG0008922
Alternative Splicing GalleryENSG00000171723
Gene ExpressionGPHN [ NCBI-GEO ]     GPHN [ SEEK ]   GPHN [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9NQX3 (Uniprot)
NextProtQ9NQX3  [Medical]
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 ]   
Domaine pattern : Prosite (Expaxy)MOCF_BIOSYNTHESIS_1 (PS01078)    MOCF_BIOSYNTHESIS_2 (PS01079)   
Domains : Interpro (EBI)Mo_cofactor_synthesis    MoCF_biosynth_CS    MoeA_C_domain_IV    MoeA_linker/N    Mopterin-bd_dom   
Related proteins : CluSTrQ9NQX3
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)Q9NQX3
PDB (SRS)1JLJ   
PDB (PDBSum)1JLJ   
PDB (IMB)1JLJ   
PDB (RSDB)1JLJ   
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
InParanoidQ9NQX3
Interologous Interaction database Q9NQX3
IntegromeDBGPHN
STRING (EMBL)GPHN
Ontologies - Pathways
Ontology : AmiGOATP binding  cytoplasm  cytoskeleton  plasma membrane  vitamin metabolic process  water-soluble vitamin metabolic process  Mo-molybdopterin cofactor biosynthetic process  establishment of synaptic specificity at neuromuscular junction  transferase activity  cell junction  molybdopterin cofactor biosynthetic process  small molecule metabolic process  postsynaptic membrane  metal ion binding  
Ontology : EGO-EBIATP binding  cytoplasm  cytoskeleton  plasma membrane  vitamin metabolic process  water-soluble vitamin metabolic process  Mo-molybdopterin cofactor biosynthetic process  establishment of synaptic specificity at neuromuscular junction  transferase activity  cell junction  molybdopterin cofactor biosynthetic process  small molecule metabolic process  postsynaptic membrane  metal ion binding  
Pathways : BIOCARTAGamma-aminobutyric Acid Receptor Life Cycle [Genes]   
Pathways : KEGGGABAergic synapse   
REACTOMEGPHN
Protein Interaction DatabaseGPHN
Wikipedia pathwaysGPHN
Gene fusion - rearrangments
Rearrangement : TICdbGPHN [14q23.3]  -  KMT2A [11q23.3]
Rearrangement : TICdbKMT2A [11q23.3]  -  GPHN [14q23.3]
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)GPHN
SNP (GeneSNP Utah)GPHN
SNP : HGBaseGPHN
Genetic variants : HAPMAPGPHN
1000_GenomesGPHN 
ICGC programENSG00000171723 
Cancer Gene: CensusGPHN 
Somatic Mutations in Cancer : COSMICGPHN 
CONAN: Copy Number AnalysisGPHN 
Mutations and Diseases : HGMDGPHN
OMIM149400    252150    603930   
GENETestsGPHN
Disease Genetic AssociationGPHN
Huge Navigator GPHN [HugePedia]  GPHN [HugeCancerGEM]
Genomic VariantsGPHN  GPHN [DGVbeta]
Exome VariantGPHN
dbVarGPHN
ClinVarGPHN
snp3D : Map Gene to Disease10243
General knowledge
Homologs : HomoloGeneGPHN
Homology/Alignments : Family Browser (UCSC)GPHN
Phylogenetic Trees/Animal Genes : TreeFamGPHN
Chemical/Protein Interactions : CTD10243
Chemical/Pharm GKB GenePA28840
Clinical trialGPHN
Cancer Resource (Charite)ENSG00000171723
Other databases
Other databaseKIAA1385 (HUGE)
Probes
Litterature
PubMed56 Pubmed reference(s) in Entrez
CoreMineGPHN
iHOPGPHN

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
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written03-2002Brigitte 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

Citation

This paper should be referenced as such :
David-Watine B . GPHN (Gephyrin). Atlas Genet Cytogenet Oncol Haematol. March 2002 .
URL : http://AtlasGeneticsOncology.org/Genes/GPHNID317.html

The various updated versions of this paper are referenced and archived by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/37862/1/03-2002-GPHNID317.pdf   [ Bibliographic record ]

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indexed on : Fri Apr 18 17:38:27 CEST 2014

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