Neonatal diabetes

Gene: RNU6ATAC

Green List (high evidence)

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.

Created: 31 Mar 2026, 4:11 p.m. | Last Modified: 31 Mar 2026, 4:11 p.m.

Panel Version: 5.21

Comment on list classification: As the article PMID: 41864208 Johnson et al., 2026 is now published, this gene is tagged for promotion to Green at the next GMS update.

Created: 31 Mar 2026, 3:56 p.m. | Last Modified: 31 Mar 2026, 3:56 p.m.

Panel Version: 5.20

Comment on list classification: There are 7 individuals from 4 unrelated families with biallelic RNU6ATAC variants and early-onset diabetes (article not yet peer-reviewed). Hence, this gene will be recommended for promotion to Green on Neonatal diabetes panel once the article is published.

Created: 29 Dec 2025, 5:22 p.m. | Last Modified: 31 Mar 2026, 3:56 p.m.

Panel Version: 5.20

MedRxiv preprint Johnson et al., 2025 doi: https://doi.org/10.1101/2025.09.12.25335567
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).

RNU6ATAC has not yet been linked to any phenotypes in OMIM (accessed 29th Dec 2025).

Created: 29 Dec 2025, 5:21 p.m. | Last Modified: 31 Mar 2026, 3:58 p.m.

Panel Version: 5.21

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neonatal diabetes mellitus, MONDO:0016391

Publications

• 40975062
• 41864208

Green List (high evidence)

RNU6ATAC is a non-protein-coding gene and a component of the minor spliceosome, a protein-RNA complex mediating splicing of ~700 genes containing U12/minor-type introns. Johnson et al report RNU6ATAC as a novel disease gene causing monogenic autoimmune diabetes (median onset: 17 weeks) with additional immune dysregulation; whole genome sequencing of 4 individuals from 4 families identified 4 different biallelic pathogenic variants in the RNU6ATAC gene, all known causes of monogenic diabetes had already been excluded. Sanger sequencing of affected siblings from family A and D confirmed co segregation (1 additional case in family A, 2 in family D). RNA-seq from Family D confirmed intron retention in comparison to controls. Multi-omic analysis of patient samples revealed a profound B cell developmental defect.
Sources: Literature

Created: 11 Dec 2025, 8:31 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neonatal diabetes; hypothyroidism; humoral immunue defect; hepatic disorder; growth failure; failure to thrive; skeletal abnormalities; atopic dermatitis; vitiligo; alopecia

Publications

• MedRxiv preprint Johnson et al., 2025 https://doi.org/10.1101/2025.09.12.25335567

Mode of pathogenicity
Other