NSUN5
Chr 7NOP2/Sun RNA methyltransferase 5
Also known as: NOL1, NOL1R, NSUN5A, WBSCR20, WBSCR20A, p120, p120(NOL1)
This protein is a methyltransferase that specifically methylates cytosine in 28S ribosomal RNA to promote protein translation and is required for corpus callosum and cerebral cortex development. Biallelic mutations cause autosomal recessive intellectual disability with corpus callosum abnormalities and cortical malformations. The gene is extremely intolerant to loss-of-function variants (pLI near 1), indicating that heterozygous loss alone is likely damaging, though disease manifestation requires biallelic variants.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
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
232 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 | 122 | 0 | 122 |
Likely Pathogenic | 0 | 0 | 6 | 0 | 6 |
VUS | 0 | 75 | 8 | 0 | 83 |
Likely Benign | 0 | 13 | 0 | 1 | 14 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 0 | 88 | 137 | 1 | 226 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NSUN5 · 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