NSG1
Chr 4neuronal vesicle trafficking associated 1
Also known as: D4S234, D4S234E, NEEP21, P21
The NSG1 protein regulates neuronal receptor recycling, particularly AMPA receptors and L1CAM, which is critical for synaptic transmission and plasticity, and also has a role in apoptosis following DNA damage. Mutations cause neurodevelopmental disorders with intellectual disability, though the gene shows relatively low constraint to loss-of-function variants. The inheritance pattern has not been definitively established for NSG1-related disorders.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
111 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | — | — | — | — | 98 |
Likely Pathogenic | — | — | — | — | 4 |
VUS | — | — | — | — | 7 |
Likely Benign | — | — | — | — | 1 |
Benign | — | — | — | — | 0 |
| Total | — | 110 | |||
Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NSG1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools