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  3. RNF2
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Early onset or syndromic epilepsy

Gene: RNF2

Amber List (moderate evidence)
RNF2 (ring finger protein 2)
EnsemblGeneIds (GRCh38): ENSG00000121481
EnsemblGeneIds (GRCh37): ENSG00000121481
OMIM: 608985, Gene2Phenotype
RNF2 is in 3 panels

2 reviews

Ida Ertmanska (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There are now 6 unrelated individuals reported in literature with heterozygous variants (mostly de novo missense) and Luo-Schoch-Yamamoto syndrome. Seizures were present in 3/6 patients. Hence, this gene will be recommended for promotion to Green once PMID:40831499 is published.
Created: 14 May 2026, 3:02 p.m. | Last Modified: 14 May 2026, 3:02 p.m.
Panel Version: 9.5
Comment on phenotypes: OMIM phenotype updated 14th May 2026.
Created: 14 May 2026, 2:58 p.m. | Last Modified: 14 May 2026, 2:58 p.m.
Panel Version: 9.4
PMID: 40831499 Ryan et al., 2025 - PRE-PRINT
identified 3 monoallelic RNF2 variants in 4 unrelated individuals: c.245G>T (p.S82I) (in 2 unrelated cases), c.796A>T (p.R266W), and c.472C>T (p.R158*). 3 cases were confirmed to be de novo. Patients were age 21 months - 7 yrs at examination. All 4 patients had prenatal complications (IUGR, oligohydramnios, polyhydramnios), gastrointestinal and feeding difficulties, and dysmorphic features. Cardiovascular anomalies detected in 3/4 individuals, 2 had hearing loss.
Neurological symptoms: hypotonia (3/4), seizures (1/3), spasticity (2/4), developmental delay and intellectual disability (3/4).
Created: 14 May 2026, 2:57 p.m. | Last Modified: 14 May 2026, 3:04 p.m.
Panel Version: 9.5

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Luo-Schoch-Yamamoto syndrome, OMIM:619460; Luo-Schoch-Yamamoto syndrome, MONDO:0859171

Publications

Created: 14 May 2026, 2:57 p.m.
Last Modified: 14 May 2026, 3:04 p.m.
Panel version: 9.1

Eleanor Williams (Genomics England Curator)

I don't know

Comment on list classification: Promoting to amber as there are 2 cases reported
Created: 8 Jul 2021, 3:17 p.m. | Last Modified: 8 Jul 2021, 3:17 p.m.
Panel Version: 2.389
Not associated with any phenotype in OMIM.

PMID:33864376 (Luo et al 2021) report 2 cases of children with de novo missense variants (p.R70H and p.S82R) in RNF2 and a phenotype of intrauterine growth retardation, severe intellectual disabilities, behavioral problems, seizures, feeding difficulties and dysmorphic features. Seizures started in infancy. Both variants are absent from gnomad. Functional studies in Drosophila showed that the disease-linked variants (p.R70H and p.S82R) behave as LoF alleles.
Sources: Literature
Created: 8 Jul 2021, 3:17 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
epilepsy; intellectual disability; intrauterine growth retardation

Publications

Created: 8 Jul 2021, 3:17 p.m.

Panel version: 2.388

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Luo-Schoch-Yamamoto syndrome, OMIM:619460
  • Luo-Schoch-Yamamoto syndrome, MONDO:0859171
OMIM
608985
Clinvar variants
Variants in RNF2
Penetrance
None
Publications
Panels with this gene

History Filter Activity

14 May 2026, Gel status: 2

Entity classified by Genomics England curator

Ida Ertmanska (Genomics England Curator)

Gene: rnf2 has been classified as Amber List (Moderate Evidence).

14 May 2026, Gel status: 2

Set Phenotypes

Ida Ertmanska (Genomics England Curator)

Phenotypes for gene: RNF2 were changed from epilepsy; intellectual disability; intrauterine growth retardation to Luo-Schoch-Yamamoto syndrome, OMIM:619460; Luo-Schoch-Yamamoto syndrome, MONDO:0859171

14 May 2026, Gel status: 2

Set publications

Ida Ertmanska (Genomics England Curator)

Publications for gene: RNF2 were set to 33864376

14 May 2026, Gel status: 2

Set mode of inheritance

Ida Ertmanska (Genomics England Curator)

Mode of inheritance for gene: RNF2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

8 Jul 2021, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: rnf2 has been classified as Amber List (Moderate Evidence).

8 Jul 2021, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Eleanor Williams (Genomics England Curator)

gene: RNF2 was added gene: RNF2 was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: RNF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: RNF2 were set to 33864376 Phenotypes for gene: RNF2 were set to epilepsy; intellectual disability; intrauterine growth retardation Review for gene: RNF2 was set to AMBER