PRPF3

Chr 1AD

pre-mRNA processing factor 3

Also known as: HPRP3, HPRP3P, PRP3, Prp3p, RP18, SNRNP90

NCBI Gene: 9129 ENSG00000117360 UniProt: O43395 OMIM: 607301

This gene encodes a protein that is an essential component of the U4/U6-U5 tri-snRNP complex required for pre-mRNA splicing and spliceosome assembly. Mutations cause autosomal dominant retinitis pigmentosa 18, a progressive retinal degeneration affecting vision. The gene is highly constrained against loss-of-function variants, indicating intolerance to functional disruption.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The removal of introns from nuclear pre-mRNAs occurs on complexes called spliceosomes, which are made up of 4 small nuclear ribonucleoprotein (snRNP) particles and an undefined number of transiently associated splicing factors. This gene product is one of several proteins that associate with U4 and U6 snRNPs. Mutations in this gene are associated with retinitis pigmentosa-18. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Retinitis pigmentosa 18MIM #601414

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · retinitis pigmentosa 18 · AD · ClinGen 2025

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.07

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

📖

GeneReview available — PRPF3

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.07LOEUF

pLI 1.000

Z-score 6.12

OE 0.00 (0.00–0.07)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

3.85Z-score

OE missense 0.44 (0.38–0.50)

160 obs / 367.6 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.07)

0≤0.351.4

Missense OE?0.44 (0.38–0.50)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 0 / 43.6Missense obs/exp: 160 / 367.6Syn Z: 0.57

Background carrier burden — how many people carry a rare variant somewhere in PRPF3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 290

497 rare PASS variants

Rare truncating (LoF)

1 in 4,300

22 rare PASS variants

Rare synonymous (reference)

1 in 160

289 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PRPF3. 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 310	1 in 5,200
South Asian	~43k	1 in 210	1 in 6,200
Remaining (unassigned)	~30k	1 in 230	≈ 1 in 9,900
European (Finnish)	~27k	1 in 1,300	1 in 920
Admixed American	~22k	1 in 320	1 in 970
African / African American	~21k	1 in 320	1 in 3,200
East Asian	~20k	1 in 190	none seen
Ashkenazi Jewish	~13k	1 in 900	≈ 1 in 4,200
Middle Eastern	~2,884	1 in 360	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 15 coding exons well covered in gnomAD exomes and genomes.? see exons ↓