Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: RNU6ATAC

Green List (high evidence)

Comment on list classification: There are 6 individuals reported in literature with biallelic RNU6ATAC variants and immune dysregulation features, including low immunoglobulins, hypothyroidism / thyroiditis, hypoagammaglobulinemia, immunodeficiency, and more. Based on available evidence, this gene should be promoted to Green at the next update.

Created: 31 Mar 2026, 4:14 p.m. | Last Modified: 31 Mar 2026, 4:14 p.m.

Panel Version: 8.93

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: 31 Mar 2026, 4:10 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
hypothyroidism, MONDO:0005420; Immune dysregulation, HP:0002958; thyroiditis, MONDO:0004126; alopecia, MONDO:0004907

Publications

• 40975062
• 41864208