NOP58

Chr 2

NOP58 ribonucleoprotein

Also known as: HSPC120, NOP5, NOP5/NOP58

NCBI Gene: 51602 ENSG00000055044 UniProt: Q9Y2X3 OMIM: 616742

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.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.55

Clinical Summary— NOP58

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 55 VUS of 82 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.55LOEUF

pLI 0.004

Z-score 3.46

OE 0.33 (0.20–0.55)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.55Z-score

OE missense 0.74 (0.66–0.83)

202 obs / 274.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.33 (0.20–0.55)

0≤0.351.4

Missense OE?0.74 (0.66–0.83)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 10 / 30.6Missense obs/exp: 202 / 274.1Syn Z: -0.33

This gene — mechanism propensity

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

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic1

VUS55

Pathogenic

Likely Pathogenic

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	1	1
Likely Pathogenic	0	1	1
VUS	55	0	55
Likely Benign	0	0	0
Benign	0	0	0
Total	55	2	57

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 →