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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 aliasKIAA1385
GPHRYN
LocusID (NCBI) 10243
Atlas_Id 317
Location 14q23.3  [Link to chromosome band 14q23]
Location_base_pair Starts at and ends at bp from pter
Local_order The markers associated with the gephyrin sequence correspond to the D14S63-D14S1069 interval.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
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)GPHN (14q23.3) / RAD51B (14q24.1)
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 --> KMT2A - ARHGAP26
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

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
 
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
 
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
 
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) [ 5 ]
  t(11;14)(q23;q24) KMT2A/GPHN
t(11;14)(q23;q23) KMT2A/GPHN
11q23 rearrangements (KMT2A) in leukaemia
t(11;14)(q23;q24) KMT2A/GPHN
t(11;14)(q23;q23) KMT2A/GPHN


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 4 ]
  EIF2S1/GPHN (14q23)
MPP5/GPHN (14q23)
t(14;14)(q23;q24) GPHN/RAD51B
t(14;14)(q23;q24) PLEKHH1/GPHN


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


External links

Nomenclature
Cards
AtlasGPHNID317.txt
Aliases
Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)10243
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
Miscellaneous
canSAR (ICR) (select the gene name)
Other databaseKIAA1385 (HUGE)
Probes
Litterature
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed


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indexed on : Thu Oct 18 17:37:57 CEST 2018

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