GPHN (Gephyrin)

2002-03-01 Brigitte David-Watine Affiliation

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

GPHN

LOCATION

14q23.3

LOCUSID

10243

ALIAS

GEPH,GPH,GPHRYN,HKPX1,MOCODC

FUSION GENES

Show Gene Fusions

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.

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

t(11;14)(q23;q23) in AML --> KMT2A - ARHGAP26

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.

Article Bibliography

Pubmed ID	Last Year	Title	Authors
11418245	2001	The human gephyrin (GPHN) gene: structure, chromosome localization and expression in non-neuronal cells.	David-Watine B et al
11579461	2001	GPHN, a novel partner gene fused to MLL in a leukemia with t(11;14)(q23;q24).	Eguchi M et al
9812897	1998	Dual requirement for gephyrin in glycine receptor clustering and molybdoenzyme activity.	Feng G et al
1319186	1992	Primary structure and alternative splice variants of gephyrin, a putative glycine receptor-tubulin linker protein.	Prior P et al
11095995	2001	A 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 ID	Transcript ID	Uniprot
ENSG00000171723	ENST00000315266	Q9NQX3
ENSG00000171723	ENST00000459628	G3V582
ENSG00000171723	ENST00000478722	Q9NQX3
ENSG00000171723	ENST00000543237	F5H039
ENSG00000171723	ENST00000553936	G3V4D2
ENSG00000171723	ENST00000555456	H0YJ30
ENSG00000171723	ENST00000555503	H0YJR5
ENSG00000171723	ENST00000555668	G3V4R0
ENSG00000171723	ENST00000556240	H0YIY4
ENSG00000171723	ENST00000556633	G3V355
ENSG00000171723	ENST00000557654	G3V4R0

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Folate biosynthesis	KEGG	ko00790
Folate biosynthesis	KEGG	hsa00790
Metabolic pathways	KEGG	hsa01100
GABAergic synapse	KEGG	ko04727
GABAergic synapse	KEGG	hsa04727
Metabolism	REACTOME	R-HSA-1430728
Metabolism of vitamins and cofactors	REACTOME	R-HSA-196854
Metabolism of water-soluble vitamins and cofactors	REACTOME	R-HSA-196849
Molybdenum cofactor biosynthesis	REACTOME	R-HSA-947581

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
35717442	2022	Complex regulation of Gephyrin splicing is a determinant of inhibitory postsynaptic diversity.	6
35717442	2022	Complex regulation of Gephyrin splicing is a determinant of inhibitory postsynaptic diversity.	6
28073605	2017	Comprehensive association analysis of 27 genes from the GABAergic system in Japanese individuals affected with schizophrenia.	6
28883437	2017	Alpha subunit-dependent glycine receptor clustering and regulation of synaptic receptor numbers.	31
28073605	2017	Comprehensive association analysis of 27 genes from the GABAergic system in Japanese individuals affected with schizophrenia.	6
28883437	2017	Alpha subunit-dependent glycine receptor clustering and regulation of synaptic receptor numbers.	31
27002143	2016	IQ Motif and SEC7 Domain-containing Protein 3 (IQSEC3) Interacts with Gephyrin to Promote Inhibitory Synapse Formation.	14
27002143	2016	IQ Motif and SEC7 Domain-containing Protein 3 (IQSEC3) Interacts with Gephyrin to Promote Inhibitory Synapse Formation.	14
25755278	2015	Protein kinase C-dependent growth-associated protein 43 phosphorylation regulates gephyrin aggregation at developing GABAergic synapses.	15
25813846	2015	Human gephyrin is encompassed within giant functional noncoding yin-yang sequences.	5
26613940	2015	Simultaneous impairment of neuronal and metabolic function of mutated gephyrin in a patient with epileptic encephalopathy.	21
25755278	2015	Protein kinase C-dependent growth-associated protein 43 phosphorylation regulates gephyrin aggregation at developing GABAergic synapses.	15
25813846	2015	Human gephyrin is encompassed within giant functional noncoding yin-yang sequences.	5
26613940	2015	Simultaneous impairment of neuronal and metabolic function of mutated gephyrin in a patient with epileptic encephalopathy.	21
24561070	2014	Exonic microdeletions of the gephyrin gene impair GABAergic synaptic inhibition in patients with idiopathic generalized epilepsy.	23

Citation

Brigitte David-Watine

GPHN (Gephyrin)

Atlas Genet Cytogenet Oncol Haematol. 2002-03-01

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