GNL2
Chr 1G protein nucleolar 2
Also known as: HUMAUANTIG, NGP1, Ngp-1, Nog2, Nug2
The protein functions as a GTPase that associates with pre-60S ribosomal subunits in the nucleolus and is required for their nuclear export and maturation. Mutations cause autosomal recessive neurodevelopmental disorder with dysmorphic facies and distal limb anomalies, typically presenting in early childhood with intellectual disability, developmental delays, and characteristic facial features. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
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
134 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 | 4 | 0 | 4 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 101 | 7 | 0 | 108 |
Likely Benign | 0 | 4 | 1 | 1 | 6 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 105 | 13 | 1 | 119 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
GNL2 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools