Early onset or syndromic epilepsy

Gene: RNU6ATAC

I don't know

Comment on list classification: There are 2 individuals reported with seizures / epilepsy and biallelic RNU6ATAC variants. Hence, this gene can only be rated Amber for Early onset or syndromic epilepsy until more evidence emerges.

Created: 14 Apr 2026, 2:33 p.m. | Last Modified: 14 Apr 2026, 2:33 p.m.

Panel Version: 8.180

PMID: 41808409 Mendez et al., 2026
Individual A1 - 14-year-old female with intrauterine growth restriction, microcephaly (Z = -2.05 at 13 yrs), refractory epilepsy, cerebral structural anomalies, ataxia, autism, severe intellectual disability, and marked peripheral eosinophilia. Compound het RNU6ATAC variants: n.28C>T & n.36T>G.

Individual B1 - 30-year-old male with immune dysfunction, endocrinopathy, and ectodermal abnormalities (ichthyosis, dystrophic nails, dental anomalies, and alopecia universalis), primary hypothyroidism, failure to thrive, bronchiectasis, chronic inflammatory demyelinating polyneuropathy, and combined variable immunodeficiency (CVID), without neurodevelopmental involvement. Compound het RNU6ATAC variants: n.30C>T & n.64C>G.

Individual C1 - 17-year-old male who presents with microcephaly (no severity stated), growth failure, ID / global developmental delay, immunodeficiency, diabetes mellitus (diagnosed at 9 months), hypothyroidism, and severe skeletal dysplasia. Homozygous for n.43G>A. Parents are first cousins.

PMID: 41864208 Johnson et al., 2026
Identified 19 individuals with early-onset diabetes (diagnosed <5 years) and additional clinical features who had biallelic pathogenic variants in the novel disease gene RNU6ATAC (n=7) or in RNU4ATAC (n=12).

6/7 individuals had variable additional features of immune dysregulation: sepsis, atopic dermatitis, B cell lymphopenia, low IgA, low IgG, B cell lymphopenia, hypothyroidism (2 sibs), agammaglobulinemia, hypoagammaglobulinemia, immunodeficiency, thyroiditis (2 unrelated patients), alopecia (2 unrelated patients), vitiligo. No microcephaly or developmental delay reported. 3/7 individuals died in early infancy.

Among the 4 families with biallelic RNU6ATAC variants, the variants reported were: n.4T>C, n.6G>A, n.43G>A, n.68C>A, n.71C>T (homozygous or compound het).

PMID: 40975062 Arriaga et al., 2025
Individual D1 - comp het for RNU6ATAC variants: n.36T>G and n.28C>T. The individual presented with microcephaly, short stature, hypotonia, ID/DD, seizures, ataxia, ventriculomegaly, syndactyly, nystagmus, and oculomotor apraxia. Patient D1 did not have diabetes, hypothyroidism, or immunodeficiency. RNA analysis demonstrated excess minor intron retention.

RNU6ATAC has not yet been linked to any phenotypes in OMIM (accessed 31st Mar 2026).
Sources: Literature

Created: 14 Apr 2026, 2:26 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neurodevelopmental disorder, MONDO:0700092; Immune dysregulation, HP:0002958; neonatal diabetes mellitus, MONDO:0016391

Publications

• 40975062
• 41864208
• 41808409