Intellectual disability
Gene: RNF2

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

1 review

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. Syndromic GDD / ID was present in 5/6 patients. Hence, this gene will be recommended for promotion to Green once PMID:40831499 is published.
Created: 14 May 2026, 3:15 p.m. | Last Modified: 14 May 2026, 3:15 p.m.

Panel Version: 10.16

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).

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: 14 May 2026, 3:07 p.m.

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, 3:07 p.m.

Panel version: 10.15

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: 1

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

Ida Ertmanska (Genomics England Curator)

gene: RNF2 was added gene: RNF2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: RNF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RNF2 were set to 33864376; 40831499 Phenotypes for gene: RNF2 were set to Luo-Schoch-Yamamoto syndrome, OMIM:619460; Luo-Schoch-Yamamoto syndrome, MONDO:0859171 Review for gene: RNF2 was set to GREEN

Intellectual disability Gene: RNF2