NOP53

Chr 19

NOP53 ribosome biogenesis factor

Also known as: GLTSCR2, PICT-1, PICT1

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.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.49
Clinical SummaryNOP53
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.49LOEUF
pLI 0.181
Z-score 3.40
OE 0.25 (0.140.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-0.65Z-score
OE missense 1.11 (1.011.22)
306 obs / 275.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.25 (0.140.49)
00.351.4
Missense OE1.11 (1.011.22)
00.61.4
Synonymous OE1.23
01.21.6
LoF obs/exp: 6 / 24.0Missense obs/exp: 306 / 275.8Syn Z: -1.99
DN
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NOP53 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →