NOL12
Chr 22nucleolar protein 12
Also known as: Nop25, VITO, dJ37E16.7
NOL12 encodes a multifunctional RNA binding protein that regulates nucleolar organization and size, participates in DNA stress response and genome integrity maintenance, and controls levels of key ribosomal proteins fibrillarin and nucleolin. Mutations cause autosomal recessive developmental delay with seizures and microcephaly. The gene shows tolerance to loss-of-function variants (pLI 0.001, LOEUF 1.13), consistent with the recessive inheritance pattern observed clinically.
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
77 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 | 18 | 0 | 18 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 41 | 2 | 0 | 43 |
Likely Benign | 0 | 2 | 0 | 0 | 2 |
Benign | 0 | 1 | 0 | 0 | 1 |
Conflicting | — | 1 | |||
| Total | 0 | 44 | 21 | 0 | 66 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NOL12 · 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