GPHN (Gephyrin)

2002-03-01   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

HGNC
LOCATION
14q23.3
LOCUSID
ALIAS
GEPH,GPH,GPHRYN,HKPX1,MOCODC
FUSION GENES

DNA/RNA

Atlas Image
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.

Proteins

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 patients fibroblats.

Implicated in

Entity name
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 name
Fusion 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.

Bibliography

Pubmed IDLast YearTitleAuthors
114182452001The human gephyrin (GPHN) gene: structure, chromosome localization and expression in non-neuronal cells.David-Watine B et al
115794612001GPHN, a novel partner gene fused to MLL in a leukemia with t(11;14)(q23;q24).Eguchi M et al
98128971998Dual requirement for gephyrin in glycine receptor clustering and molybdoenzyme activity.Feng G et al
13191861992Primary structure and alternative splice variants of gephyrin, a putative glycine receptor-tubulin linker protein.Prior P et al
110959952001A mutation in the gene for the neurotransmitter receptor-clustering protein gephyrin causes a novel form of molybdenum cofactor deficiency.Reiss J et al

Other Information

Locus ID:

NCBI: 10243
MIM: 603930
HGNC: 15465
Ensembl: ENSG00000171723

Variants:

dbSNP: 10243
ClinVar: 10243
TCGA: ENSG00000171723
COSMIC: GPHN

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000171723ENST00000315266Q9NQX3
ENSG00000171723ENST00000459628G3V582
ENSG00000171723ENST00000478722Q9NQX3
ENSG00000171723ENST00000543237F5H039
ENSG00000171723ENST00000553936G3V4D2
ENSG00000171723ENST00000555456H0YJ30
ENSG00000171723ENST00000555503H0YJR5
ENSG00000171723ENST00000555668G3V4R0
ENSG00000171723ENST00000556240H0YIY4
ENSG00000171723ENST00000556633G3V355
ENSG00000171723ENST00000557654G3V4R0

Expression (GTEx)

0
5
10
15
20
25
30
35
40
45
50

Pathways

PathwaySourceExternal ID
Folate biosynthesisKEGGko00790
Folate biosynthesisKEGGhsa00790
Metabolic pathwaysKEGGhsa01100
GABAergic synapseKEGGko04727
GABAergic synapseKEGGhsa04727
MetabolismREACTOMER-HSA-1430728
Metabolism of vitamins and cofactorsREACTOMER-HSA-196854
Metabolism of water-soluble vitamins and cofactorsREACTOMER-HSA-196849
Molybdenum cofactor biosynthesisREACTOMER-HSA-947581

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
198745742009Genetical genomic determinants of alcohol consumption in rats and humans.93
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
206220202010Complex role of collybistin and gephyrin in GABAA receptor clustering.63
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
233931572013Rare exonic deletions implicate the synaptic organizer Gephyrin (GPHN) in risk for autism, schizophrenia and seizures.46
172933952007Multiple association states between glycine receptors and gephyrin identified by SPT analysis.45
234084242013Extracellular signal-regulated kinase and glycogen synthase kinase 3β regulate gephyrin postsynaptic aggregation and GABAergic synaptic function in a calpain-dependent mechanism.39
126845232003Isoform heterogeneity of the human gephyrin gene (GPHN), binding domains to the glycine receptor, and mutation analysis in hyperekplexia.32
218291702011Regulation of glycine receptor diffusion properties and gephyrin interactions by protein kinase C.32
115547962001Crystal structures of human gephyrin and plant Cnx1 G domains: comparative analysis and functional implications.31

Citation

Brigitte David-Watine

GPHN (Gephyrin)

Atlas Genet Cytogenet Oncol Haematol. 2002-03-01

Online version: http://atlasgeneticsoncology.org/gene/317/gphn