NRXN3: Neurexin 3 Gene in Synaptic Function and Neurodevelopmental Disorders
Comprehensive genomic and proteomic overview of NRXN3, a presynaptic cell-adhesion molecule implicated in autism, schizophrenia, and addiction
Gene Information Card
| Symbol | NRXN3 |
|---|---|
| Full Name | Neurexin 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q31.1 |
| NCBI Gene ID | 9369 ncbi.nlm.nih.gov/gene/9369 |
| Ensembl ID | ENSG00000121680 |
| UniProt ID | Q9HDB5 |
| OMIM ID | 600567 |
| HGNC ID | 8012 |
| Aliases | KIAA0743, neurexin III-alpha, neurexin III-beta |
Description
NRXN3 encodes neurexin 3, a member of the neurexin family of presynaptic cell-adhesion molecules. Neurexins bind to postsynaptic neuroligins to form trans-synaptic complexes essential for synaptic specification and neurotransmitter release. NRXN3 undergoes extensive alternative splicing, generating alpha- and beta-neurexin isoforms that differ in extracellular domain composition. The gene is highly expressed in the brain and has been associated with autism spectrum disorder, schizophrenia, nicotine dependence, and alcohol use disorder through rare copy-number variants and common polymorphisms.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autism spectrum disorder | Rare CNVs (deletions/duplications) at 14q31.1 disrupt synaptic adhesion | PMID: 21658581, ClinVar |
| Schizophrenia | Rare NRXN3 deletions impair glutamatergic synapse function | PMID: 21926972, ClinVar |
| Nicotine dependence | Intronic SNP rs760288 (A>G) associated with altered expression | PMID: 21107309 |
| Alcohol use disorder | Common variants in NRXN3 linked to alcohol consumption | PMID: 22534719 |
| Epilepsy | Rare missense variants in NRXN3 found in focal epilepsy | PMID: 28708303 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 28.5 | High |
| Brain (cerebellum) | 22.1 | High |
| Brain (hippocampus) | 25.3 | High |
| Testis | 4.2 | Low |
| Heart | 1.8 | Not detected |
| Liver | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 12.4 | Neuronal model |
| U-87 MG (glioblastoma) | 8.7 | Glial expression |
| HEK293 (embryonic kidney) | 0.3 | No endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.01% | Loss of function – premature truncation |
| c.1567G>A (p.Gly523Arg) | Missense | <0.01% | Altered neuroligin binding |
| 14q31.1 deletion (1.2 Mb) | CNV | Rare | Haploinsufficiency – neurodevelopmental phenotype |
| rs760288 (intronic) | SNP | 30% (MAF) | Associated with nicotine dependence |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift variants leading to nonsense-mediated decay or truncated protein; large deletions causing haploinsufficiency.
Gain of Function (GOF)
Not reported for NRXN3.
Dominant Negative (DN)
Missense variants in the extracellular domain may interfere with neurexin-neuroligin complex formation.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Neurexin-neuroligin signaling pathway (Reactome: R-HSA-6794362)
• Synaptic adhesion-like molecules (SALM) pathway
• Glutamatergic synapse (KEGG: hsa04724)
Protein Summary
Neurexin 3 is a single-pass type I membrane protein localized to the presynaptic membrane. The alpha isoform contains six LNS (laminin-neurexin-sex hormone-binding globulin) domains and three EGF-like repeats, while the beta isoform has a single LNS domain. The protein interacts with postsynaptic neuroligins (NLGN1, NLGN2, NLGN3, NLGN4X) and dystroglycan. Alternative splicing at five canonical splice sites (SS1–SS5) generates thousands of isoforms that determine binding specificity. NRXN3 is essential for proper synapse formation, maintenance, and neurotransmitter release.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NRXN3 Knockout HEK293 Cell Line | EDJ-KQ2602 | Human | 9369 | Details Get a Quote |
| NRXN3 Knockout HeLa Cell Line | EDJ-KQ55142 | Human | 9369 | Details Get a Quote |
| NRXN3 Knockout A-549 Cell Line | EDJ-KQ63621 | Human | 9369 | Details Get a Quote |
| NRXN3 Knockout HCT 116 Cell Line | EDJ-KQ72086 | Human | 9369 | Details Get a Quote |
