NRXN1

Chr 2AR

neurexin 1

Also known as: Hs.22998, PTHSL2, SCZD17

NCBI Gene: 9378 ENSG00000179915 UniProt: P58400 OMIM: 600565

The protein is a presynaptic cell membrane neurexin that binds neuroligins to form calcium-dependent complexes required for efficient neurotransmission and synaptic contact formation. Mutations cause autosomal recessive Pitt-Hopkins-like syndrome 2 and contribute to schizophrenia susceptibility through loss of function mechanisms. The gene is highly intolerant to loss-of-function variants, indicating haploinsufficiency as the likely pathogenic mechanism.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a single-pass type I membrane protein that belongs to the neurexin family. Neurexins are cell-surface receptors that bind neuroligins to form Ca(2+)-dependent neurexin/neuroligin complexes at synapses in the central nervous system. This complex is required for efficient neurotransmission and is involved in the formation of synaptic contacts. Three members of this gene family have been studied in detail and are estimated to generate over 3,000 variants through the use of two alternative promoters (alpha and beta) and extensive alternative splicing in each family member. Recently, a third promoter (gamma) was identified for this gene in the 3' region. Mutations in this gene are associated with Pitt-Hopkins-like syndrome-2 and may contribute to susceptibility to schizophrenia. [provided by RefSeq, Aug 2016]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Schizophrenia, susceptibility to, 17}MIM #621407

Pitt-Hopkins-like syndrome 2MIM #614325

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.25

LOEUF· LoF intol.

LOF

Mechanism· G2P