UTP3

Chr 4

UTP3 small subunit processome component

Also known as: CRL1, CRLZ1, SAS10

NCBI Gene: 57050 ENSG00000132467 UniProt: Q9NQZ2 OMIM: 611614

UTP3 encodes a protein essential for ribosomal small subunit biogenesis in the nucleolus and plays a role in gene silencing through chromatin structure regulation. Mutations cause autosomal recessive intellectual disability with microcephaly and growth retardation, typically manifesting in early childhood. The gene shows minimal constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected individuals.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA binding activity. Involved in ribosomal small subunit biogenesis. Located in nucleolus. Part of small-subunit processome. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.00

Clinical Summary— UTP3

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

42 VUS of 45 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?

1.00LOEUF

pLI 0.000

Z-score 1.56

OE 0.59 (0.36–1.00)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.15Z-score

OE missense 0.80 (0.71–0.90)

203 obs / 254.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.59 (0.36–1.00)

0≤0.351.4

Missense OE?0.80 (0.71–0.90)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 10 / 16.9Missense obs/exp: 203 / 254.9Syn Z: -0.43

This gene — mechanism propensity

0.6936th %ile

GOF

0.3689th %ile

LOF

0.3355th %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

45 submitted variants in ClinVar

ClinVar

Classification Summary

VUS42

Benign3

VUS

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	42	0	42
Likely Benign	0	0	0
Benign	2	1	3
Total	44	1	45

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap UTP3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →