RPF1

Chr 1ADSomatic

ribosome production factor 1 homolog

Also known as: BXDC5

NCBI Gene: 80135 ENSG00000117133 UniProt: Q9H9Y2 OMIM: 609062

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables RNA binding activity. Predicted to be involved in maturation of 5.8S rRNA and maturation of LSU-rRNA. Located in nucleolus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Wilms tumor susceptibility-5}MIM #601583

ADSomatic

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.19

LOEUF

Mechanism· predicted

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 OE?0.76 (0.50–1.19)

0≤0.351.4

Missense OE?0.96 (0.85–1.08)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 14 / 18.4Missense obs/exp: 187 / 194.7Syn Z: -0.14

Background carrier burden — how many people carry a rare variant somewhere in RPF1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 78

468 rare PASS variants

Rare truncating (LoF)

1 in 830

130 rare PASS variants

Rare synonymous (reference)

1 in 280

147 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RPF1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 98	1 in 810
South Asian	~43k	1 in 110	1 in 1,100
Remaining (unassigned)	~30k	1 in 73	1 in 1,100
European (Finnish)	~27k	1 in 180	1 in 2,000
Admixed American	~22k	1 in 71	1 in 630
African / African American	~21k	1 in 77	1 in 800
East Asian	~20k	1 in 98	1 in 780
Ashkenazi Jewish	~13k	1 in 200	1 in 1,700
Middle Eastern	~2,884	1 in 110	1 in 570

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 9 coding exons well covered in gnomAD exomes; exons 2, 3, 4, 6 marginal. Genomes: all 9.? see exons ↓