Mendeliome
Gene: RNU6ATAC Green List (high evidence)Green List (high evidence)
PMID 40975062 reports 1 individual from with biallelic RNU6ATAC variants causing childhood‑onset growth restriction, microcephaly, epilepsy, intellectual disability and ataxia. PMID 41808409 reports 3 unrelated families (3 individuals) with biallelic loss‑of‑function RNU6ATAC variants presenting with short stature, neurodevelopmental delay, epilepsy, immunodeficiency, skeletal dysplasia and other multisystem features; RNA‑seq shows marked excess of minor intron retention, confirming spliceosome dysfunction.
However, note overlap in authors between the two papers ?double-counting.
PMID 41864208 -- published version of the preprint referenced in previous reviews. 7 individuals from 4 families with early-onset diabetes (diagnosed aged <5 years) and immune dysregulatory features caused by bi-allelic variants in RNU6ATAC.
Genotype-phenotype correlation unclear at this stage but note that of the three individuals reported in 41808409, one did not have ID/neurological features but all had immunological involvement.Created: 27 Mar 2026, 2:11 p.m. | Last Modified: 27 Mar 2026, 2:11 p.m.
Panel Version: 1.4645
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Syndromic disease, MONDO:0002254
Publications
I don't know
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 5th Feb 2026).
Note gene is not protein coding.Created: 5 Feb 2026, 1:10 p.m. | Last Modified: 5 Feb 2026, 1:10 p.m.
Panel Version: 1.4241
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
neonatal diabetes; humoral immunue defect; microcephaly; developmental delay.
Red List (low evidence)
PMID: 40975062 1 patient compound heterozygous for n.36T>G and n.28C>T. Has short stature, microcephaly, hypotonia, neurodevelopmental delay, ID, seizures, ataxia, ventriculomegaly, syndactyly, nystagmus and oculomotor apraxia. Identified in a cohort of individuals with an excess of significant intron retention outliers in minor intron containing genes which are usually removed by the minor spliceosome of which RNU6ATAC is a part (as is RNU4ATAC). Proband had no candidate variants in RNU4ATAC or RNU12. Both RNU6ATAC variants are in a highly conserved 39bp region, and affect nucleotides predicted to be important for binding to U4ATAC.
Sources: LiteratureCreated: 10 Oct 2025, 1:53 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related
Publications
Phenotypes for gene: RNU6ATAC were changed from Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related; neonatal diabetes to Syndromic disease, MONDO:0002254, RNU6ATAC-related
Publications for gene: RNU6ATAC were set to 40975062
Gene: rnu6atac has been classified as Green List (High Evidence).
Tag non-coding gene tag was added to gene: RNU6ATAC.
Phenotypes for gene: RNU6ATAC were changed from Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related to Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related; neonatal diabetes
Gene: rnu6atac has been classified as Amber List (Moderate Evidence).
Gene: rnu6atac has been classified as Red List (Low Evidence).
Gene: rnu6atac has been classified as Red List (Low Evidence).
gene: RNU6ATAC was added gene: RNU6ATAC was added to Mendeliome. Sources: Literature Mode of inheritance for gene: RNU6ATAC was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNU6ATAC were set to 40975062 Phenotypes for gene: RNU6ATAC were set to Neurodevelopmental disorder (MONDO:0700092), RNU6ATAC-related Review for gene: RNU6ATAC was set to RED
If promoting or demoting a gene, please provide comments to justify a decision to move it.
Genes included in a Genomics England gene panel for a rare disease category (green list) should fit the criteria A-E outlined below.
These guidelines were developed as a combination of the ClinGen DEFINITIVE evidence for a causal role of the gene in the disease(a), and the Developmental Disorder Genotype-Phenotype (DDG2P) CONFIRMED DD Gene evidence level(b) (please see the original references provided below for full details). These help provide a guideline for expert reviewers when assessing whether a gene should be on the green or the red list of a panel.
A. There are plausible disease-causing mutations(i) within, affecting or encompassing an interpretable functional region(ii) of this gene identified in multiple (>3) unrelated cases/families with the phenotype(iii).
OR
B. There are plausible disease-causing mutations(i) within, affecting or encompassing cis-regulatory elements convincingly affecting the expression of a single gene identified in multiple (>3) unrelated cases/families with the phenotype(iii).
OR
C. As definitions A or B but in 2 or 3 unrelated cases/families with the phenotype, with the addition of convincing bioinformatic or functional evidence of causation e.g. known inborn error of metabolism with mutation in orthologous gene which is known to have the relevant deficient enzymatic activity in other species; existence of an animal model which recapitulates the human phenotype.
AND
D. Evidence indicates that disease-causing mutations follow a Mendelian pattern of causation appropriate for reporting in a diagnostic setting(iv).
AND
E. No convincing evidence exists or has emerged that contradicts the role of the gene in the specified phenotype.
(i)Plausible disease-causing mutations: Recurrent de novo mutations convincingly affecting gene function. Rare, fully-penetrant mutations - relevant genotype never, or very rarely, seen in controls. (ii) Interpretable functional region: ORF in protein coding genes miRNA stem or loop. (iii) Phenotype: the rare disease category, as described in the eligibility statement. (iv) Intermediate penetrance genes should not be included.
It’s assumed that loss-of-function variants in this gene can cause the disease/phenotype unless an exception to this rule is known. We would like to collect information regarding exceptions. An example exception is the PCSK9 gene, where loss-of-function variants are not relevant for a hypercholesterolemia phenotype as they are associated with increased LDL-cholesterol uptake via LDLR (PMID: 25911073).
If a curated set of known-pathogenic variants is available for this gene-phenotype, please contact us at panelapp@genomicsengland.co.uk
We classify loss-of-function variants as those with the following Sequence Ontology (SO) terms:
Term descriptions can be found on the PanelApp homepage and Ensembl.
If you are submitting this evaluation on behalf of a clinical laboratory please indicate whether you report variants in this gene as part of your current diagnostic practice by checking the box
Standardised terms were used to represent the gene-disease mode of inheritance, and were mapped to commonly used terms from the different sources. Below each of the terms is described, along with the equivalent commonly-used terms.
A variant on one allele of this gene can cause the disease, and imprinting has not been implicated.
A variant on the paternally-inherited allele of this gene can cause the disease, if the alternate allele is imprinted (function muted).
A variant on the maternally-inherited allele of this gene can cause the disease, if the alternate allele is imprinted (function muted).
A variant on one allele of this gene can cause the disease. This is the default used for autosomal dominant mode of inheritance where no knowledge of the imprinting status of the gene required to cause the disease is known. Mapped to the following commonly used terms from different sources: autosomal dominant, dominant, AD, DOMINANT.
A variant on both alleles of this gene is required to cause the disease. Mapped to the following commonly used terms from different sources: autosomal recessive, recessive, AR, RECESSIVE.
The disease can be caused by a variant on one or both alleles of this gene. Mapped to the following commonly used terms from different sources: autosomal recessive or autosomal dominant, recessive or dominant, AR/AD, AD/AR, DOMINANT/RECESSIVE, RECESSIVE/DOMINANT.
A variant on one allele of this gene can cause the disease, however a variant on both alleles of this gene can result in a more severe form of the disease/phenotype.
A variant in this gene can cause the disease in males as they have one X-chromosome allele, whereas a variant on both X-chromosome alleles is required to cause the disease in females. Mapped to the following commonly used term from different sources: X-linked recessive.
A variant in this gene can cause the disease in males as they have one X-chromosome allele. A variant on one allele of this gene may also cause the disease in females, though the disease/phenotype may be less severe and may have a later-onset than is seen in males. X-linked inactivation and mosaicism in different tissues complicate whether a female presents with the disease, and can change over their lifetime. This term is the default setting used for X-linked genes, where it is not known definitately whether females require a variant on each allele of this gene in order to be affected. Mapped to the following commonly used terms from different sources: X-linked dominant, x-linked, X-LINKED, X-linked.
The gene is in the mitochondrial genome and variants within this can cause this disease, maternally inherited. Mapped to the following commonly used term from different sources: Mitochondrial.
Mapped to the following commonly used terms from different sources: Unknown, NA, information not provided.
For example, if the mode of inheritance is digenic, please indicate this in the comments and which other gene is involved.