UTP23

Chr 8

UTP23 small subunit processome component

Also known as: C8orf53

NCBI Gene: 84294 ENSG00000147679 UniProt: Q9BRU9

UTP23 encodes a protein involved in ribosomal RNA processing and ribosome biogenesis within the nucleolus. Mutations cause autosomal recessive developmental delay with increased adiposity and delayed myelination, typically presenting in infancy with developmental delays and characteristic brain imaging findings. The gene shows moderate tolerance to loss-of-function variants based on population constraint metrics.

ResearchSummary from RefSeq, UniProt

Enables mRNA 3'-UTR binding activity and mRNA 5'-UTR binding activity. Predicted to be involved in rRNA processing. Predicted to act upstream of or within endonucleolytic cleavage in 5'-ETS of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to be located in nucleus. Predicted to be part of small-subunit processome. Predicted to be active in nucleolus. Implicated in colorectal adenocarcinoma. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

DNmechanismLOEUF 0.90

Clinical Summary— UTP23

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.

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ClinVar Variants

34 VUS of 40 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.90LOEUF

pLI 0.086

Z-score 1.77

OE 0.35 (0.16–0.90)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.69Z-score

OE missense 0.82 (0.70–0.97)

100 obs / 121.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.35 (0.16–0.90)

0≤0.351.4

Missense OE?0.82 (0.70–0.97)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 3 / 8.6Missense obs/exp: 100 / 121.4Syn Z: -0.71

This gene — mechanism propensity

0.6550th %ile

GOF

0.5171th %ile

LOF

0.2775th %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

40 submitted variants in ClinVar

ClinVar

Classification Summary

VUS34

Benign2

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	33	1	34
Likely Benign	0	0	0
Benign	2	0	2
Total	35	1	36

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

View in ClinVar →

53 pathogenic / likely-pathogenic (of 65) ClinVar copy-number / structural variants overlap UTP23 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →