NRXN1
Chr 2ARneurexin 1
Also known as: Hs.22998, PTHSL2, SCZD17
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.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
234 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 3 | 0 | 21 | 0 | 24 |
Likely Pathogenic | 2 | 0 | 3 | 0 | 5 |
VUS | 0 | 82 | 8 | 5 | 95 |
Likely Benign | 0 | 3 | 32 | 59 | 94 |
Benign | 0 | 0 | 3 | 1 | 4 |
Conflicting | — | 12 | |||
| Total | 5 | 85 | 67 | 65 | 234 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NRXN1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools