RPF1

Chr 1ADSomatic

ribosome production factor 1 homolog

Also known as: BXDC5

NCBI Gene: 80135ENSG00000117133UniProt: Q9H9Y2

The RPF1 protein enables RNA binding and is involved in ribosome biogenesis, specifically in the maturation of ribosomal RNA components within the nucleolus. Mutations cause Wilms tumor susceptibility-5, inherited in an autosomal dominant pattern, though somatic mutations also occur. The gene shows moderate constraint against loss-of-function variants (LOEUF 1.19), indicating some intolerance to complete protein loss.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

{Wilms tumor susceptibility-5}MIM #601583
ADSomatic
0
Active trials
4
Pubs (1 yr)
16
P/LP submissions
0%
P/LP missense
1.19
LOEUF
DN
Mechanism· predicted
Clinical Summary— RPF1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 unique Pathogenic / Likely Pathogenic· 64 VUS of 101 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
1.19LOEUF
pLI 0.000
Z-score 0.94
OE 0.76 (0.50–1.19)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.20Z-score
OE missense 0.96 (0.85–1.08)
187 obs / 194.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.76 (0.50–1.19)
0≤0.351.4
Missense OE0.96 (0.85–1.08)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 14 / 18.4Missense obs/exp: 187 / 194.7Syn Z: -0.14
DN
0.6162th %ile
GOF
0.4086th %ile
LOF
0.4037th %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

101 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic2
VUS64
Likely Benign4
14
Pathogenic
2
Likely Pathogenic
64
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
2
0
2
VUS
0
61
3
0
64
Likely Benign
0
4
0
0
4
Benign
0
0
0
0
0
Total06519084

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

View in ClinVar →

Protein Context — Lollipop Plot

RPF1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients