NOP58

Chr 2

NOP58 ribonucleoprotein

Also known as: HSPC120, NOP5, NOP5/NOP58

The protein encoded by this gene is a core component of box C/D small nucleolar ribonucleoproteins. Some box C/D small nucleolar RNAs (snoRNAs), such as U3, U8, and U14, are dependent upon the encoded protein for their synthesis. This protein is SUMOylated, which is necessary for high affinity binding to snoRNAs. [provided by RefSeq, Nov 2015]

OMIMResearchGenerating clinical summary…
DNmechanismLOEUF 0.55
Clinical SummaryNOP58
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
2 unique Pathogenic / Likely Pathogenic· 55 VUS of 82 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.55LOEUF
pLI 0.004
Z-score 3.46
OE 0.33 (0.200.55)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
1.55Z-score
OE missense 0.74 (0.660.83)
202 obs / 274.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.33 (0.200.55)
00.351.4
Missense OE?0.74 (0.660.83)
00.61.4
Synonymous OE?1.04
01.21.6
LoF obs/exp: 10 / 30.6Missense obs/exp: 202 / 274.1Syn Z: -0.33

This gene — mechanism propensity

DN
0.74top 25%
GOF
0.4283th %ile
LOF
0.3551th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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

82 submitted variants in ClinVar

Classification Summary

Pathogenic1
Likely Pathogenic1
VUS55
1
Pathogenic
1
Likely Pathogenic
55
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
1
0
1
Likely Pathogenic
0
0
1
0
1
VUS
0
55
0
0
55
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total0552057

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

View in ClinVar →

29 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap NOP58 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

NOP58 · 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 →