NOP53

Chr 19

NOP53 ribosome biogenesis factor

Also known as: GLTSCR2, PICT-1, PICT1

NCBI Gene: 29997 ENSG00000105373 UniProt: Q9NZM5 OMIM: 605691

NOP53 encodes a nucleolar protein that integrates 5S ribosomal RNA into the large ribosomal subunit during ribosome biogenesis and functions as a nucleolar sensor that regulates p53 activation in response to ribosomal stress and DNA damage. Mutations cause autosomal dominant colorectal cancer with chromosomal instability, typically presenting as adult-onset malignancy. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.494), suggesting some tolerance for inactivating mutations.

OMIM ResearchSummary from RefSeq, UniProt

Enables 5S rRNA binding activity; identical protein binding activity; and p53 binding activity. Involved in several processes, including mitotic G2 DNA damage checkpoint signaling; regulation of intracellular signal transduction; and regulation of primary metabolic process. Located in cytosol; nuclear lumen; and rDNA heterochromatin. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.49

Clinical Summary— NOP53

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

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ClinVar Variants

121 VUS of 158 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?

0.49LOEUF

pLI 0.181

Z-score 3.40

OE 0.25 (0.14–0.49)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

-0.65Z-score

OE missense 1.11 (1.01–1.22)

306 obs / 275.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.25 (0.14–0.49)

0≤0.351.4

Missense OE?1.11 (1.01–1.22)

0≤0.61.4

Synonymous OE?1.23

0≤1.21.6

LoF obs/exp: 6 / 24.0Missense obs/exp: 306 / 275.8Syn Z: -1.99

This gene — mechanism propensity

0.6454th %ile

GOF

0.5760th %ile

LOF

0.3259th %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

158 submitted variants in ClinVar

ClinVar

Classification Summary

VUS121

Likely Benign6

Benign3

121

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	121	0	121
Likely Benign	4	2	6
Benign	0	3	3
Total	125	5	130

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap NOP53 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →