NOL9

Chr 1

nucleolar protein 9

Also known as: Grc3, NET6

NOL9 encodes a polynucleotide kinase that phosphorylates 5'-hydroxyl groups of RNA and DNA substrates and is essential for ribosomal RNA processing, specifically converting 32S precursor rRNA into mature 5.8S and 28S rRNAs. Mutations cause autosomal recessive intellectual developmental disorder with microcephaly, seizures, and spasticity. The gene is highly constrained against loss-of-function variants (LOEUF 0.549), consistent with its essential role in ribosome biogenesis.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
51
P/LP submissions
0%
P/LP missense
0.55
LOEUF
Mechanism
Clinical SummaryNOL9
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
51 unique Pathogenic / Likely Pathogenic· 100 VUS of 184 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.55LOEUF
pLI 0.009
Z-score 3.40
OE 0.31 (0.190.55)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.55Z-score
OE missense 0.77 (0.700.85)
283 obs / 366.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.31 (0.190.55)
00.351.4
Missense OE0.77 (0.700.85)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 9 / 28.6Missense obs/exp: 283 / 366.3Syn Z: -0.71

ClinVar Variant Classifications

184 submitted variants in ClinVar

Classification Summary

Pathogenic50
Likely Pathogenic1
VUS100
Likely Benign8
Benign1
50
Pathogenic
1
Likely Pathogenic
100
VUS
8
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
50
0
50
Likely Pathogenic
0
0
1
0
1
VUS
0
94
6
0
100
Likely Benign
0
8
0
0
8
Benign
0
0
1
0
1
Total0102580160

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NOL9 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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