Retinal disorders
Gene: RNU4-2EnsemblGeneIds (GRCh38): ENSG00000202538
EnsemblGeneIds (GRCh37): ENSG00000202538
RNU4-2 is in 6 panels
1 review
Ida Ertmanska (Genomics England Curator)
Comment on list classification: Recurrent RNU4-2 variants (n.56T>C & n.18_19insA) were detected in 41 patients from 15 unrelated families with retinitis pigmentosa - 1 case de novo. 78% of the individuals presented with first 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, RNU4-2 should be promoted to Green for Retinal disorders at the next GMS update.Created: 21 Nov 2025, 11:13 a.m. | Last Modified: 21 Nov 2025, 11:13 a.m.
Panel Version: 8.66
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.
Recurrent variants in RNU4-2 were identified in 41 affected individuals from 15 families - 1 case de novo; incomplete penetrance was observed for nine obligate carriers, without visual symptoms. Range of ethnicities: Spanish, German, Polish, USA, Indian Jewish, Afro-carribean, Belgian.
Recurrent variants: n.56T>C, n.18_19insA - not reported in gnomAD v4.1.0.
Family M1-A - 7 siblings and father affected - het for RNU4-2 NR_003137.2:n.18_19insA. Method: genome sequencing.
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, 10:46 a.m. | Last Modified: 21 Nov 2025, 11:47 a.m.
Panel Version: 8.72
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 RNU4-2
- Penetrance
- None
- Publications
- Panels with this gene
History Filter Activity
Added Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag gene-checked tag was added to gene: RNU4-2.
Removed Tag, Added Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag Q4_25_promote_green was removed from gene: RNU4-2. Tag Q3_25_promote_green tag was added to gene: RNU4-2.
Added Tag
Ida Ertmanska (Genomics England Curator)Tag locus-type-rna-small-nuclear tag was added to gene: RNU4-2.
Added Tag
Ida Ertmanska (Genomics England Curator)Tag Q4_25_promote_green tag was added to gene: RNU4-2.
Entity classified by Genomics England curator
Ida Ertmanska (Genomics England Curator)Gene: rnu4-2 has been classified as Amber List (Moderate Evidence).
Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes
Ida Ertmanska (Genomics England Curator)gene: RNU4-2 was added gene: RNU4-2 was added to Retinal disorders. Sources: Literature Mode of inheritance for gene: RNU4-2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: RNU4-2 were set to 39830270 Phenotypes for gene: RNU4-2 were set to retinitis pigmentosa, MONDO:0019200 Review for gene: RNU4-2 was set to GREEN