NLGN2
Neuroligin 2: A Key Synaptic Adhesion Molecule in GABAergic Synapse Organization
Gene Information Card
| Symbol | NLGN2 |
|---|---|
| Full Name | neuroligin 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 17p13.1 |
| NCBI Gene ID | 57555 ncbi.nlm.nih.gov/gene/57555 |
| Ensembl ID | ENSG00000169992 |
| UniProt ID | Q8NFZ4 |
| OMIM ID | 606479 |
| HGNC ID | 14291 |
| Aliases | KIAA1366, NL2 |
Description
NLGN2 encodes neuroligin 2, a member of the neuroligin family of postsynaptic cell adhesion molecules. Neuroligin 2 is specifically localized at inhibitory GABAergic synapses, where it interacts with presynaptic neurexins to mediate synapse formation, maturation, and function. It plays a critical role in balancing excitatory and inhibitory neurotransmission. Mutations in NLGN2 have been associated with neurodevelopmental disorders including autism spectrum disorder and schizophrenia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autism Spectrum Disorder | Missense and frameshift mutations disrupt neuroligin 2 function, impairing GABAergic synapse formation and leading to altered excitatory/inhibitory balance. | PMID: 19012874, PMID: 23352160 |
| Schizophrenia | Rare variants in NLGN2 may contribute to synaptic dysfunction and altered GABAergic signaling implicated in schizophrenia pathophysiology. | PMID: 21424692, PMID: 24814143 |
| Intellectual Disability | Deleterious mutations in NLGN2 are associated with cognitive impairment, likely due to disrupted inhibitory synaptic transmission. | PMID: 23352160 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Cerebral cortex | 15.3 | High |
| Cerebellum | 8.7 | Medium |
| Heart | 1.2 | Low |
| Liver | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 10.1 | Neuronal model |
| U-87 MG (glioblastoma) | 6.8 | Glial model |
| HEK 293 (embryonic kidney) | 0.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.103C>T (p.Arg35Cys) | Missense | Rare | Reduced binding to neurexin; associated with autism |
| c.1378G>A (p.Gly460Arg) | Missense | Rare | Impaired trafficking to synapse; associated with schizophrenia |
| c.1681delG (p.Ala561Profs*13) | Frameshift | Very rare | Loss of function; truncation of C-terminal domain |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations lead to truncated protein lacking transmembrane and intracellular domains, resulting in complete loss of function.
Gain of Function (GOF)
No gain-of-function mutations have been reported for NLGN2.
Dominant Negative (DN)
Missense mutations such as p.Arg35Cys may exert dominant-negative effects by interfering with wild-type neuroligin 2 function at the synapse.
View complete mutation data：
Gene Ontology (GO)
| • synaptic membrane adhesion | • cell adhesion |
| • protein binding | • neurexin binding |
| • postsynaptic membrane | • GABAergic synapse |
| • chemical synaptic transmission |
Pathways
• Neurexin-neuroligin signaling
• Synaptic adhesion molecules
• GABAergic synapse
Protein Summary
Neuroligin 2 is a 835-amino acid type I transmembrane protein with an extracellular N-terminal domain containing an acetylcholinesterase-like domain that mediates neurexin binding, a single transmembrane domain, and a C-terminal intracellular domain with a PDZ-binding motif. It is specifically enriched at inhibitory postsynaptic sites, where it clusters GABA_A receptors and gephyrin. The protein is essential for proper inhibitory synapse function and neural circuit balance.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NLGN2 Knockout HEK293 Cell Line | EDJ-KQ13687 | Human | 57555 | Details Get a Quote |
| NLGN2 Knockout A-549 Cell Line | EDJ-KQ44649 | Human | 57555 | Details Get a Quote |
| NLGN2 Knockout HCT 116 Cell Line | EDJ-KQ44651 | Human | 57555 | Details Get a Quote |
| NLGN2 Knockout HeLa Cell Line | EDJ-KQ44652 | Human | 57555 | Details Get a Quote |
