PRPF6
Chr 20ADpre-mRNA processing factor 6
Also known as: ANT-1, ANT1, C20orf14, Prp6, RP60, SNRNP102, TOM, U5-102K
PRPF6 encodes a protein that functions as a component of the U4/U6-U5 tri-snRNP complex in the spliceosome, essential for pre-mRNA splicing, and also enhances steroid hormone receptor transactivation. Mutations cause autosomal dominant retinitis pigmentosa 60, a form of inherited retinal degeneration. The gene is highly constrained against loss-of-function variants (LOEUF 0.44), reflecting its essential role in RNA processing.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Highly missense-constrained (top ~0.1%)
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
200 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 2 | 0 | 2 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 6 | 83 | 8 | 1 | 98 |
Likely Benign | 0 | 0 | 41 | 36 | 77 |
Benign | 0 | 0 | 1 | 2 | 3 |
Conflicting | — | 1 | |||
| Total | 6 | 83 | 53 | 39 | 182 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PRPF6 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools