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Neonatal diabetes v5.21 RNU6ATAC Ida Ertmanska edited their review of gene: RNU6ATAC: Added comment: 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.; Changed publications to: 40975062, 41864208
Neonatal diabetes v5.21 RNU6ATAC Ida Ertmanska changed review comment from: 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, hypothyroidism 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).; to: 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).
Neonatal diabetes v5.21 RNU6ATAC Ida Ertmanska Publications for gene: RNU6ATAC were set to MedRxiv preprint Johnson et al., 2025 https://doi.org/10.1101/2025.09.12.25335567
Neonatal diabetes v5.20 RNU6ATAC Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: RNU6ATAC.
Neonatal diabetes v5.20 RNU6ATAC Ida Ertmanska changed review comment from: 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.; to: 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.
Neonatal diabetes v5.20 RNU6ATAC Ida Ertmanska edited their review of gene: RNU6ATAC: Changed publications to: 41864208
Neonatal diabetes v5.20 RNU6ATAC Ida Ertmanska commented on gene: RNU6ATAC: 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.
Neonatal diabetes v5.20 RNU6ATAC Ida Ertmanska changed review comment from: 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). 12/19 had additional immune features of immune dysregulation.
Around 60% of patients also had microcephaly and developmental delay.

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).; to: 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, hypothyroidism 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).
Neonatal diabetes v5.20 RNU6ATAC Ida Ertmanska changed review comment from: 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). 12/19 had additional immune features of immune dysregulation.
Around 60% of patients also had microcephaly and developmental delay.

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).; to: 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). 12/19 had additional immune features of immune dysregulation.
Around 60% of patients also had microcephaly and developmental delay.

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).
Neonatal diabetes v5.13 RNU6ATAC Ida Ertmanska Phenotypes for gene: RNU6ATAC were changed from neonatal diabetes; hypothyroidism; humoral immunue defect; hepatic disorder; growth failure; failure to thrive; skeletal abnormalities; atopic dermatitis; vitiligo; alopecia to neonatal diabetes mellitus, MONDO:0016391; hypothyroidism; humoral immunue defect; hepatic disorder; growth failure; failure to thrive; skeletal abnormalities; atopic dermatitis; vitiligo; alopecia
Neonatal diabetes v5.12 RNU6ATAC Ida Ertmanska Classified gene: RNU6ATAC as Amber List (moderate evidence)
Neonatal diabetes v5.12 RNU6ATAC Ida Ertmanska Gene: rnu6atac has been classified as Amber List (Moderate Evidence).
Neonatal diabetes v5.11 RNU6ATAC Ida Ertmanska Tag locus-type-rna-small-nuclear tag was added to gene: RNU6ATAC.
Neonatal diabetes v5.11 RNU6ATAC Ida Ertmanska changed review comment from: 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). 12/19 had additional immune features of immune dysregulation.
Around 60% of patients also had microcephaly and developmental delay.

Among the 4 families with biallelic RNU4ATAC 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).; to: 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). 12/19 had additional immune features of immune dysregulation.
Around 60% of patients also had microcephaly and developmental delay.

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).
Neonatal diabetes v5.11 RNU6ATAC Ida Ertmanska commented on gene: RNU6ATAC: 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.
Neonatal diabetes v5.11 RNU6ATAC Ida Ertmanska edited their review of gene: RNU6ATAC: Changed rating: GREEN
Neonatal diabetes v5.11 RNU6ATAC Ida Ertmanska reviewed gene: RNU6ATAC: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: neonatal diabetes mellitus, MONDO:0016391; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Neonatal diabetes v5.9 RNU6ATAC Anna-Marie Johnson gene: RNU6ATAC was added
gene: RNU6ATAC was added to Neonatal diabetes. Sources: Literature
Mode of inheritance for gene: RNU6ATAC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU6ATAC were set to MedRxiv preprint Johnson et al., 2025 https://doi.org/10.1101/2025.09.12.25335567
Phenotypes for gene: RNU6ATAC were set to neonatal diabetes; hypothyroidism; humoral immunue defect; hepatic disorder; growth failure; failure to thrive; skeletal abnormalities; atopic dermatitis; vitiligo; alopecia
Penetrance for gene: RNU6ATAC were set to Complete
Mode of pathogenicity for gene: RNU6ATAC was set to Other
Review for gene: RNU6ATAC was set to GREEN
Added comment: 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