Retinal disorders
Gene: RNU6-8EnsemblGeneIds (GRCh38): ENSG00000202337
EnsemblGeneIds (GRCh37): ENSG00000202337
RNU6-8 is in 1 panel
1 review
Ida Ertmanska (Genomics England Curator)
Comment on list classification: Recurrent RNU6-8 variant n.55_56insG was detected in patients from 12 unrelated diverse families with retinitis pigmentosa - 1 case confirmed de novo, 1 suspected to be de novo. 78% of individuals with U4/U6 changes presented with first RP symptoms during childhood or adolescence. Importantly, 9 obligate carriers from these families had no visual symptoms, hinting at incomplete disease penetrance. Based on the available evidence, RNU6-8 should be promoted to Green for Retinal disorders at the next GMS update.Created: 21 Nov 2025, 11:36 a.m. | Last Modified: 21 Nov 2025, 11:36 a.m.
Panel Version: 8.70
PMID: 39830270 Quinodoz et al., 2025
Large cohort of RP patients screened using Sanger sequencing of genes encoding U4 and U6. Reported 153 individuals across 67 families with retinitis pigmentosa, with monoallelic variants in RNU4-2 and RNU6 paralogs.
n.55_56insG insertion recurred in the RNU6 paralogs (RNU6-1, RNU6-2, RNU6-8, and RNU6-9) - 102 individuals from 47 diverse, unrelated families. Pathogenic variants were NOT detected in RNU6-7. Insertion at the same position, n.55_56insT, is reported in gnomAD in all 5 paralogs (181 alleles total).
Insertion n.56_57insG was detected in RNU6 paralogs in individuals from 6 families.
RNU6-8 specific data: n.55_56insG insertion in RNU6-8 reported in numerous patients from 12 diverse RP families - 1 case confirmed and 1 suspected to be de novo; n.56_57insG not detected in RNU6-8 (based on pre-print supplementary table 2).
Details for patients with U4 and U6 changes:
Age of onset of RP: under 12yo = 42 patients (62%); 13-19 years = 11; 20-30 years = 8; adulthood 30+ = 7 patients.
Phenotype spectrum in addition to classical RP features: ocular edema (56%), non-age-related cataract / lens opacity (24%), vitreoretinal complications (31%).
Functional effect prediction: RP-related variants identified reside in a region that critical for binding of the U4/U6 duplex to the splicing factors PRPF31, PRPF3, and PRPF8 - genes previously linked to AD retinitis pigmentosa.
Sources: LiteratureCreated: 21 Nov 2025, 11:35 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
retinitis pigmentosa, MONDO:0019200
Publications
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
- Sources
-
- Expert Review Amber
- Literature
- Phenotypes
-
- retinitis pigmentosa, MONDO:0019200
- Tags
- Clinvar variants
- Variants in RNU6-8
- Penetrance
- None
- Publications
- Panels with this gene
History Filter Activity
Removed Tag, Added Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag Q4_25_promote_green was removed from gene: RNU6-8. Tag Q3_25_promote_green tag was added to gene: RNU6-8.
Added Tag
Ida Ertmanska (Genomics England Curator)Tag locus-type-rna-small-nuclear tag was added to gene: RNU6-8.
Entity classified by Genomics England curator
Ida Ertmanska (Genomics England Curator)Gene: rnu6-8 has been classified as Amber List (Moderate Evidence).
Created, Added New Source, Added Tag, Set mode of inheritance, Set publications, Set Phenotypes
Ida Ertmanska (Genomics England Curator)gene: RNU6-8 was added gene: RNU6-8 was added to Retinal disorders. Sources: Literature Q4_25_promote_green tags were added to gene: RNU6-8. Mode of inheritance for gene: RNU6-8 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: RNU6-8 were set to 39830270 Phenotypes for gene: RNU6-8 were set to retinitis pigmentosa, MONDO:0019200 Review for gene: RNU6-8 was set to GREEN