ArticlePLoS genetics2012
CNOT3 is a modifier of PRPF31 mutations in retinitis pigmentosa with incomplete penetrance.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05573984 (A Natural History and Outcome Measure Discovery Study of PRPF31 Mutation-Associated Retinal Dystrophy), which is not on this map. Cited by 76 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Natural History and Outcome Measure Discovery Study of PRPF31 Mutation-Associated Retinal Dystrophy
Who cites it
76 citing papers in PubMed, 123 citations in OpenAlex.
- Revisiting retinal and macular degeneration in the genomics era.Nature reviews. Genetics · 2026Review
- Nutritional supplements: current evidence for retinitis pigmentosa and Stargardt disease.Current opinion in ophthalmology · 2026Review
- Low population penetrance of variants associated with inherited retinal degenerations.American journal of human genetics · 2026Article
- Decoding retinitis pigmentosa: molecular targets and therapy with focus on pre-mRNA splicing.Cellular and molecular life sciences : CMLS · 2025Review
- History of Finding Genes and Mutations Causing Inherited Retinal Diseases.Cold Spring Harbor perspectives in medicine · 2024Review
- A Precision Therapy Approach for Retinitis Pigmentosa 11 Using Splice-Switching Antisense Oligonucleotides to Restore the Open Reading Frame of PRPF31.International journal of molecular sciences · 2024Article
- PRPF31-retinitis pigmentosa: Challenges and opportunities for clinical translation.Vision research · 2023Review
- Alternative RNA Splicing in the Retina: Insights and Perspectives.Cold Spring Harbor perspectives in medicine · 2023Review
- Disruption of the Mammalian Ccr4-Not Complex Contributes to Transcription-Mediated Genome Instability.Cells · 2023Article
- Natural disease history of a canine model of oligogenic RPGRIP1-cone-rod dystrophy establishes variable effects of previously and newly mapped modifier loci.Human molecular genetics · 2023Article
- Modulating the Kynurenine pathway or sequestering toxic 3-hydroxykynurenine protects the retina from light-induced damage in Drosophila.PLoS genetics · 2023Article
- Article
- The pathogenic c.1171A>G (p.Arg391Gly) and c.2359G>A (p.Val787Ile) ABCC6 variants display incomplete penetrance causing pseudoxanthoma elasticum in a subset of individuals.Human mutation · 2022Article
- A 69 kb Deletion in chr19q13.42 includingJournal of clinical medicine · 2022Article
- Modeling PRPF31 retinitis pigmentosa using retinal pigment epithelium and organoids combined with gene augmentation rescue.NPJ Regenerative medicine · 2022Article
- Article
- Autosomal dominant retinitis pigmentosa with incomplete penetrance due to an intronic mutation of theMolecular vision · 2022Article
- Determinants of Disease Penetrance inGenes · 2021Article
- Observational
- Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heterozygous mutations in the PRPF31 gene cause autosomal dominant retinitis pigmentosa (adRP), a hereditary disorder leading to progressive blindness. In some cases, such mutations display incomplete penetrance, implying that certain carriers develop retinal degeneration while others have no symptoms at all. Asymptomatic carriers are protected from the disease by a higher than average expression of the PRPF31 allele that is not mutated, mainly through the action of an unknown modifier gene mapping to chromosome 19q13.4. We investigated a large family with adRP segregating an 11-bp deletion in PRPF31. The analysis of cell lines derived from asymptomatic and affected individuals revealed that the expression of only one gene among a number of candidates within the 19q13.4 interval significantly correlated with that of PRPF31, both at the mRNA and protein levels, and according to an inverse relationship. This gene was CNOT3, encoding a subunit of the Ccr4-not transcription complex. In cultured cells, siRNA-mediated silencing of CNOT3 provoked an increase in PRPF31 expression, confirming a repressive nature of CNOT3 on PRPF31. Furthermore, chromatin immunoprecipitation revealed that CNOT3 directly binds to a specific PRPF31 promoter sequence, while next-generation sequencing of the CNOT3 genomic region indicated that its variable expression is associated with a common intronic SNP. In conclusion, we identify CNOT3 as the main modifier gene determining penetrance of PRPF31 mutations, via a mechanism of transcriptional repression. In asymptomatic carriers CNOT3 is expressed at low levels, allowing higher amounts of wild-type PRPF31 transcripts to be produced and preventing manifestation of retinal degeneration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.