NLGN2
Chr 17neuroligin 2
This gene encodes neuroligin-2, a transmembrane scaffolding protein that clusters postsynaptic GABA receptors and modulates inhibitory synaptic signaling. Mutations cause autism spectrum disorder and intellectual disability with autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants, indicating that complete loss of neuroligin-2 function has severe developmental consequences.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
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
300 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 | 0 | 0 | 24 | 0 | 24 |
Likely Pathogenic | 0 | 1 | 3 | 0 | 4 |
VUS | 10 | 146 | 10 | 1 | 167 |
Likely Benign | 0 | 3 | 9 | 63 | 75 |
Benign | 0 | 1 | 4 | 13 | 18 |
Conflicting | — | 1 | |||
| Total | 10 | 151 | 50 | 77 | 289 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NLGN2 · 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
Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight
RECRUITINGExercise to Fight Obesity
RECRUITINGExternal Resources
Links to major genomics databases and tools