NRXN1
Function
Cell surface protein involved in cell-cell-interactions, exocytosis of secretory granules and regulation of signal transmission. Function is isoform-specific. Alpha-type isoforms have a long N-terminus with six laminin G-like domains and play an important role in synaptic signal transmission. Alpha-type isoforms play a role in the regulation of calcium channel activity and Ca(2+)-triggered neurotransmitter release at synapses and at neuromuscular junctions. They play an important role in Ca(2+)-triggered exocytosis of secretory granules in pituitary gland. They may affect their functions at synapses and in endocrine cells via their interactions with proteins from the exocytotic machinery. Likewise, alpha-type isoforms play a role in regulating the activity of postsynaptic NMDA receptors, a subtype of glutamate-gated ion channels. Both alpha-type and beta-type isoforms may play a role in the formation or maintenance of synaptic junctions via their interactions (via the extracellular domains) with neuroligin family members, CBLN1 or CBLN2. In vitro, triggers the de novo formation of presynaptic structures. May be involved in specification of excitatory synapses. Alpha-type isoforms were first identified as receptors for alpha-latrotoxin from spider venom.
Involvement in disease
Pitt-Hopkins-like syndrome 2
PTHSL2
A syndrome characterized by severe intellectual disability and variable additional symptoms, such as impaired speech development, autistic behavior, breathing anomalies and a broad mouth, resembling Pitt-Hopkins syndrome. Other features include decreased reflexes in the upper extremities, constipation, strabismus, and protruding tongue with drooling. In contrast to patients with Pitt-Hopkins syndrome, PTHSL2 patients present with normal or only mildly to moderately delayed motor milestones.
None
The disease is caused by variants affecting the gene represented in this entry.
Schizophrenia 17
SCZD17
A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder.
None
Disease susceptibility may be associated with variants affecting the gene represented in this entry.
Post-translational modifications
O-glycosylated; contains heparan sulfate. Heparan sulfate attachment is required for synapse development by mediating interactions with neuroligins and LRRTM2.
Sequence Similarities
Belongs to the neurexin family.
Tissue Specificity
Brain.
Cellular localization
- Presynaptic cell membrane
- Single-pass type I membrane protein
Alternative names
KIAA0578, NRXN1, Neurexin-1, Neurexin I-alpha, Neurexin-1-alpha
Database links
swissprot:Q9ULB1 entrezGene:9378 omim:600565 swissprot:P58400