NOP2

Chr 12

NOP2 nucleolar protein

Also known as: NOL1, NOP120, NSUN1, p120

NOP2 encodes a methyltransferase that methylates cytosine residues in 28S rRNA and is required for ribosome biogenesis and 60S ribosomal subunit assembly. The gene is highly constrained against loss-of-function variants (pLI=1.00, LOEUF=0.17), indicating that mutations are likely to cause severe developmental consequences. Pathogenic variants in NOP2 have not yet been definitively associated with a recognized human disease phenotype in the medical literature.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
77
Pubs (1 yr)
44
P/LP submissions
0%
P/LP missense
0.17
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryNOP2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
44 unique Pathogenic / Likely Pathogenic· 125 VUS of 204 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.17LOEUF
pLI 1.000
Z-score 5.38
OE 0.05 (0.020.17)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
0.64Z-score
OE missense 0.92 (0.850.99)
431 obs / 469.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.05 (0.020.17)
00.351.4
Missense OE0.92 (0.850.99)
00.61.4
Synonymous OE0.88
01.21.6
LoF obs/exp: 2 / 37.6Missense obs/exp: 431 / 469.9Syn Z: 1.31
DN
0.3991th %ile
GOF
0.2994th %ile
LOF
0.69top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.17

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

204 submitted variants in ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic2
VUS125
Likely Benign10
Benign7
42
Pathogenic
2
Likely Pathogenic
125
VUS
10
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
42
0
42
Likely Pathogenic
0
0
2
0
2
VUS
0
117
8
0
125
Likely Benign
0
7
0
3
10
Benign
1
4
1
1
7
Total1128534186

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

View in ClinVar →

Protein Context — Lollipop Plot

NOP2 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →