NRXN1 Gene: Neurexin 1 – Synaptic Organizer and Neurodevelopmental Disorder Gene
Comprehensive resource on NRXN1: genomic structure, expression, disease associations, mutations, and functional classification.
Gene Information Card
| Symbol | NRXN1 |
|---|---|
| Full Name | Neurexin 1 |
| Gene Type | protein coding |
| Chromosomal Location | 2p16.3 |
| NCBI Gene ID | 9378 ncbi.nlm.nih.gov/gene/9378 |
| Ensembl ID | ENSG00000121671 |
| UniProt ID | P58400 |
| OMIM ID | 600565 |
| HGNC ID | 7998 |
| Aliases | neurexin I; NRXN1-alpha; PTHSL2; SCZD17 |
Description
NRXN1 encodes neurexin 1, a presynaptic cell adhesion molecule that plays a critical role in synapse formation and function. It is involved in neurotransmitter release and synaptic specificity. Mutations and copy number variations in NRXN1 are associated with a range of neurodevelopmental and psychiatric disorders, including autism spectrum disorder, schizophrenia, and intellectual disability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schizophrenia | Rare copy number variants (CNVs) in NRXN1, particularly deletions, disrupt synaptic function and increase disease risk. | ClinVar; PMID: 25056061 |
| Autism Spectrum Disorder | Deletions and point mutations in NRXN1 impair neurexin function, affecting synaptic connectivity and contributing to ASD. | ClinVar; PMID: 18500341 |
| Intellectual Disability | NRXN1 deletions or mutations lead to synaptic dysfunction, resulting in cognitive impairment. | ClinVar; PMID: 20468064 |
| Epilepsy | NRXN1 variants may alter synaptic transmission, increasing seizure susceptibility. | ClinVar; PMID: 23403945 |
| Pitt-Hopkins-like Syndrome 2 | Biallelic or monoallelic NRXN1 mutations cause a syndromic form of intellectual disability with features resembling Pitt-Hopkins syndrome. | OMIM; PMID: 18500341 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.4 | High |
| Adrenal Gland | 3.2 | Low |
| Testis | 1.8 | Low |
| Lung | 0.9 | Not detected |
| Liver | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 8.5 | Neuronal-like expression |
| U-87 MG (glioblastoma) | 6.2 | Moderate expression |
| HeLa (cervical carcinoma) | 0.3 | Very low |
| A549 (lung carcinoma) | 0.2 | Very low |
| MCF7 (breast carcinoma) | 0.1 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Ter) | Nonsense | Rare | Loss of function; premature truncation |
| c.2345_2349del (p.Leu782fs) | Frameshift | Rare | Loss of function; altered reading frame |
| c.3456G>A (p.Trp1152Ter) | Nonsense | Rare | Loss of function; premature truncation |
| Whole gene deletion | CNV | 0.1-0.5% in schizophrenia | Haploinsufficiency; reduced neurexin dosage |
| c.4567A>G (p.Ile1523Val) | Missense | Rare | Uncertain; potential functional impact |
Mutation functional classification
Loss of Function (LOF)
Most NRXN1 mutations are loss-of-function, including nonsense, frameshift, and deletions, leading to haploinsufficiency or complete loss of neurexin 1 protein, disrupting synaptic adhesion and signaling.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported for NRXN1; the gene primarily acts in a dosage-sensitive manner.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with neurexin binding partners, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • synaptic cell adhesion | • calcium ion binding |
| • protein binding | • cell adhesion |
| • neuron projection | • synapse |
| • presynaptic membrane | • axon guidance |
| • neurotransmitter secretion |
Pathways
• Neurexin-neuroligin signaling
• Synaptic vesicle cycle
• Cell adhesion molecules (CAMs)
• Neuroactive ligand-receptor interaction
Protein Summary
Neurexin 1 is a single-pass type I membrane protein localized to the presynaptic membrane. It binds to neuroligins on the postsynaptic membrane, forming trans-synaptic complexes that are essential for synapse maturation and function. Alternative splicing generates multiple isoforms that determine binding specificity. The protein contains extracellular domains (LNS and EGF-like) and a cytoplasmic tail that interacts with PDZ-domain proteins, linking to the synaptic vesicle release machinery.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NRXN1 Knockout HEK293 Cell Line | EDJ-KQ5905 | Human | 9378 | Details Get a Quote |
| NRXN1 Knockout HeLa Cell Line | EDJ-KQ55146 | Human | 9378 | Details Get a Quote |
| NRXN1 Knockout A-549 Cell Line | EDJ-KQ63626 | Human | 9378 | Details Get a Quote |
| NRXN1 Knockout HCT 116 Cell Line | EDJ-KQ72090 | Human | 9378 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
