NOP58

Chr 2

NOP58 ribonucleoprotein

Also known as: HSPC120, NOP5, NOP5/NOP58

The NOP58 protein is a core component of box C/D small nucleolar ribonucleoprotein complexes that is required for ribosome biogenesis and methylation of ribosomal and messenger RNAs. Mutations cause Bowen-Conradi syndrome, an autosomal recessive disorder characterized by severe growth restriction, microcephaly, and early lethality typically within the first year of life. This gene is highly constrained against loss-of-function variants in the general population.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.55
Clinical SummaryNOP58
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

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 OE0.33 (0.200.55)
00.351.4
Missense OE0.74 (0.660.83)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 10 / 30.6Missense obs/exp: 202 / 274.1Syn Z: -0.33
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NOP58 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

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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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC