| Written | 2002-03 | Brigitte 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 |
| Identity |
| Alias (NCBI) | KIAA1385 | GPHRYN |
| HGNC (Hugo) | GPHN |
| HGNC Alias symb | KIAA1385 |
| LocusID (NCBI) | 10243 |
| Atlas_Id | 317 |
| Location | 14q23.3 [Link to chromosome band 14q23] |
| Location_base_pair | Starts at 66508147 and ends at 67181800 bp from pter ( according to GRCh38/hg38-Dec_2013) [Mapping GPHN.png] |
| 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 ] |
| Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ] |
|
11q23 rearrangements (KMT2A) in leukaemia
t(11;14)(q23;q24) 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 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Fri Feb 19 17:51:45 CET 2021 |
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