OPHN1
Oligophrenin 1: A Rho-GTPase Activating Protein Implicated in X-Linked Intellectual Disability and Cerebellar Hypoplasia
Gene Information Card
| Symbol | OPHN1 |
|---|---|
| Full Name | Oligophrenin 1 |
| Gene Type | Protein coding |
| Chromosomal Location | Xq12 |
| NCBI Gene ID | 4983 ncbi.nlm.nih.gov/gene/4983 |
| Ensembl ID | ENSG00000079482 |
| UniProt ID | O60890 |
| OMIM ID | 300127 |
| HGNC ID | 8148 |
| Aliases | OPHN1, MRX60, oligophrenin-1, RhoGAP |
Description
OPHN1 (oligophrenin 1) is a protein-coding gene located on the X chromosome (Xq12). It encodes a Rho-GTPase activating protein (RhoGAP) that regulates dendritic spine morphogenesis and synaptic function. Loss-of-function mutations in OPHN1 are a well-established cause of X-linked intellectual disability (XLID) often associated with cerebellar hypoplasia, epilepsy, and behavioral abnormalities.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked intellectual disability with cerebellar hypoplasia | Loss-of-function mutations impair RhoA/ROCK signaling, disrupting dendritic spine maturation and synaptic plasticity | ClinVar, OMIM #300486 |
| X-linked intellectual disability (non-syndromic) | Missense or truncating variants reduce RhoGAP activity, leading to cognitive impairment | ClinVar, OMIM #300127 |
| Epilepsy | OPHN1 deficiency alters neuronal excitability via actin cytoskeleton dysregulation | ClinVar, literature reports |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Testis | 4.2 | Medium |
| Lung | 2.1 | Low |
| Heart | 1.8 | Low |
| Liver | 0.9 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | High expression; used in neuronal differentiation studies |
| HeLa (cervical carcinoma) | 3.1 | Moderate expression |
| HEK293 (embryonic kidney) | 2.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.901C>T (p.Arg301*) | Nonsense | Rare | Loss of function; truncation of RhoGAP domain |
| c.1192G>A (p.Gly398Arg) | Missense | Rare | Impaired RhoGAP activity; reduced dendritic spine density |
| c.1416_1417del (p.Glu473Argfs*12) | Frameshift | Rare | Loss of function; premature stop codon |
Mutation functional classification
Loss of Function (LOF)
Majority of pathogenic OPHN1 variants are loss-of-function (nonsense, frameshift, splice-site) leading to reduced or absent RhoGAP activity, disrupting actin cytoskeleton regulation in neurons.
Gain of Function (GOF)
No gain-of-function mutations have been reported for OPHN1.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for OPHN1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• RhoA/ROCK signaling pathway
• Actin cytoskeleton regulation
• Synaptic plasticity pathway
Protein Summary
Oligophrenin 1 (OPHN1) is a 802-amino acid protein containing a RhoGAP domain that specifically inactivates RhoA, Rac1, and Cdc42 by stimulating their intrinsic GTPase activity. It is highly expressed in the brain, particularly in the hippocampus and cerebellum, where it localizes to dendritic spines and postsynaptic densities. OPHN1 regulates spine morphology, synaptic plasticity, and neuronal migration. Loss of OPHN1 function leads to increased RhoA activity, resulting in abnormal spine shape and reduced synaptic connectivity, underlying the intellectual disability phenotype.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| OPHN1 Knockout HEK293 Cell Line | EDJ-KQ5381 | Human | 4983 | Details Get a Quote |
| OPHN1 Knockout HeLa Cell Line | EDJ-KQ27281 | Human | 4983 | Details Get a Quote |
| OPHN1 Knockout A-549 Cell Line | EDJ-KQ28517 | Human | 4983 | Details Get a Quote |
| OPHN1 Knockout HCT 116 Cell Line | EDJ-KQ28518 | Human | 4983 | Details Get a Quote |
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