GPHN (Gephyrin): Synaptic Scaffold and Molybdenum Cofactor Biosynthesis Gene
A dual-function gene encoding gephyrin, essential for inhibitory synaptic clustering and molybdenum cofactor synthesis; implicated in neurological disorders and cancer.
Gene Information Card
| Symbol | GPHN |
|---|---|
| Full Name | Gephyrin |
| Gene Type | Protein coding |
| Chromosomal Location | 14q23.3 |
| NCBI Gene ID | 10243 ncbi.nlm.nih.gov/gene/10243 |
| Ensembl ID | ENSG00000171723 |
| UniProt ID | Q9NQX3 |
| OMIM ID | 603930 |
| HGNC ID | 15465 |
| Aliases | GPH, gephyrin, MOCS1D, GPHRN |
Description
GPHN encodes gephyrin, a multifunctional protein that acts as a scaffold for inhibitory neurotransmitter receptors (GABA-A and glycine receptors) at postsynaptic sites, and also participates in molybdenum cofactor biosynthesis. Mutations in GPHN are associated with hyperekplexia, epilepsy, and autism spectrum disorders, and altered expression is observed in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hyperekplexia | Loss-of-function mutations impair gephyrin's synaptic clustering function, leading to disrupted glycinergic neurotransmission and exaggerated startle response. | ClinVar, OMIM |
| Epilepsy | Mutations affecting gephyrin function may reduce inhibitory synaptic strength, contributing to neuronal hyperexcitability and seizures. | ClinVar, PubMed |
| Autism spectrum disorder | Rare variants in GPHN have been identified in ASD cohorts, suggesting a role in synaptic dysfunction underlying neurodevelopmental phenotypes. | ClinVar, PubMed |
| Molybdenum cofactor deficiency | GPHN mutations can impair molybdenum cofactor synthesis, leading to severe neurological symptoms due to sulfite oxidase deficiency. | OMIM, PubMed |
| Cancer | Altered GPHN expression is observed in several tumor types, potentially affecting cell adhesion and migration, though mechanistic details are emerging. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | High |
| Adrenal gland | Medium | Medium |
| Kidney | Medium | Medium |
| Liver | Low | Low |
| Heart | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | High | Neuronal-like expression |
| U87MG (glioblastoma) | Medium | Glial expression |
| HepG2 (hepatocellular carcinoma) | Low | Low expression |
| A549 (lung carcinoma) | Low | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1129C>T (p.Arg377Ter) | Nonsense | Rare | Loss of function, associated with hyperekplexia |
| c.491A>G (p.Tyr164Cys) | Missense | Rare | Impaired synaptic clustering, epilepsy |
| c.1045G>A (p.Gly349Ser) | Missense | Rare | Reduced molybdenum cofactor synthesis |
| c.1390C>T (p.Arg464Trp) | Missense | Rare | Dominant negative effect on gephyrin oligomerization |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated gephyrin protein, resulting in loss of synaptic clustering and molybdenum cofactor synthesis.
Gain of Function (GOF)
Not well documented; no clear gain-of-function mutations reported.
Dominant Negative (DN)
Missense mutations in the oligomerization domain can disrupt multimer formation, exerting a dominant-negative effect on wild-type gephyrin.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Molybdenum cofactor biosynthesis
• GABAergic synapse
• Glycinergic synapse
• Postsynaptic density organization
Protein Summary
Gephyrin is a 736-amino acid protein that forms hexameric scaffolds at inhibitory synapses, anchoring glycine and GABA-A receptors via interactions with cytoskeletal elements. It also contains domains for molybdenum cofactor synthesis, with an N-terminal G-domain and C-terminal E-domain that catalyze molybdopterin adenylation and insertion. Alternative splicing generates isoforms with tissue-specific functions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GPHN Knockout HEK293 Cell Line | EDJ-KQ6345 | Human | 10243 | Details Get a Quote |
| GPHN Knockout A-549 Cell Line | EDJ-KQ31672 | Human | 10243 | Details Get a Quote |
| GPHN Knockout HCT 116 Cell Line | EDJ-KQ31673 | Human | 10243 | Details Get a Quote |
| GPHN Knockout HeLa Cell Line | EDJ-KQ31674 | Human | 10243 | Details Get a Quote |
