Intellectual disability
Gene: RNU6ATAC

RNU6ATAC (RNA, U6atac small nuclear (U12-dependent splicing))
EnsemblGeneIds (GRCh38): ENSG00000221676
EnsemblGeneIds (GRCh37): ENSG00000221676
OMIM: 601429, Gene2Phenotype
RNU6ATAC is in 5 panels

1 review

Ida Ertmanska (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There are 3 unrelated individuals with biallelic RNU6ATAC variants and intellectual disability / global developmental delay. Hence, this gene should be promoted to Green at the next update, with MOI BIALLELIC, autosomal or pseudoautosomal.
Created: 14 Apr 2026, 2:23 p.m. | Last Modified: 14 Apr 2026, 2:23 p.m.

Panel Version: 9.380

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, 2:21 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

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

Publications

Created: 14 Apr 2026, 2:21 p.m.

Panel version: 9.379

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Amber
Literature

Phenotypes

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

Tags

Q2_26_promote_green

OMIM

601429

Clinvar variants

Variants in RNU6ATAC

Penetrance

None

Publications

Panels with this gene

History Filter Activity

14 Apr 2026, Gel status: 2

Entity classified by Genomics England curator

Ida Ertmanska (Genomics England Curator)

Gene: rnu6atac has been classified as Amber List (Moderate Evidence).

14 Apr 2026, Gel status: 1

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

Ida Ertmanska (Genomics England Curator)

gene: RNU6ATAC was added gene: RNU6ATAC was added to Intellectual disability. Sources: Literature Q2_26_promote_green tags were added to gene: RNU6ATAC. Mode of inheritance for gene: RNU6ATAC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNU6ATAC were set to 40975062; 41864208; 41808409 Phenotypes for gene: RNU6ATAC were set to neurodevelopmental disorder, MONDO:0700092; Immune dysregulation, HP:0002958; neonatal diabetes mellitus, MONDO:0016391 Review for gene: RNU6ATAC was set to GREEN

Intellectual disability Gene: RNU6ATAC