PRPF6

Chr 20AD

pre-mRNA processing factor 6

Involved in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex, one of the building blocks of the spliceosome (PubMed:20118938, PubMed:21549338, PubMed:28781166). Enhances dihydrotestosterone-induced transactivation activity of AR, as well as dexamethasone-induced transactivation activity of NR3C1, but does not affect estrogen-induced transactivation

OMIMResearchGenerating clinical summary…
MultiplemechanismADLOEUF 0.441 OMIM phenotype
Clinical SummaryPRPF6
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Missense constrained — critical functional residues
LoF Constraint?
0.44LOEUF
pLI 0.003
Z-score 4.78
OE 0.29 (0.190.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
4.85Z-score
OE missense 0.43 (0.380.47)
242 obs / 567.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.29 (0.190.44)
00.351.4
Missense OE?0.43 (0.380.47)
00.61.4
Synonymous OE?1.06
01.21.6
LoF obs/exp: 15 / 52.3Missense obs/exp: 242 / 567.1Syn Z: -0.75
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedPRPF6-related retinitis pigmentosaOTHERAD

This gene — mechanism propensity

DN
0.75top 25%
GOF
0.6833th %ile
LOF
0.3455th %ile

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.

DNprediction above median
GOFprediction 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

0 submitted variants 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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