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| Primary immunodeficiency or monogenic inflammatory bowel disease v8.99 | RNU4ATAC |
Ida Ertmanska changed review comment from: PMID: 26522830 Merico et al., 2015 6 cases with Roifman syndrome from 4 unrelated families (English, Italian, Lebanese, Albanian). All 6 had history of repeat infections. PMID: 28623346 Bogaert et al., 2017 Report of two siblings that presented with a phenotype resembling early-onset common variable immunodeficiency - extra-immunological characteristics were not apparent at that time. Additional features were diagnosed later, including skeletal and organ anomalies and mild facial dysmorphism. Whole exome sequencing revealed c.13 C > T and c.116 A > T RNU4ATAC variants, which is consistent with diagnosis of Roifman syndrome. PMID: 29391254 Heremans et al., 2018 3 patients from 2 unrelated kindreds harboring compound heterozygous or homozygous stem II variants in RNU4ATAC. All patients have a common phenotype of moderate psychomotor delay and autism spectrum disorder, retinal dystrophy with hypovascularization, severe growth retardation, spondyloepiphysial dysplasia with irregularly shaped vertebral bodies with platyspondyly and flattened proximal femoral epiphyses, pruritic ichthyosis-like skin rash, brachydactyly, hyperlaxity, hypotonia, and hepatosplenomegaly. All 3 patients have hypogammaglobulinemia and B-cell lymphopenia, and they experience recurrent viral infections, necessitating immunoglobulin substitution therapy. P2 had mucocutaneous Herpes simplex infection, and P3 presented a pneumococcal sepsis on discontinuation of therapy. Study showed abnormal differentiation of B cells and megakaryocytes in the patients. PMID: 33059947 Hagiwara et al., 2020 18-year-old woman exhibiting congenital dwarfism and microcephaly with structural brain anomaly. She suffered human herpesvirus 6 (HHV-6)-associated acute necrotizing encephalopathy at age one, resulting in severe psychomotor disabilities. Genetic analysis revealed comp het variants in RNU4ATAC (NR_023343.1:n.[50G > A];[55G > A]). Immunological findings showed decreases in total lymphocytes, CD4+ T cells, and T cell regenerative activity, and little response to vaccinations. 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. RNU4ATAC is associated with multiple AR conditions in OMIM: Lowry-Wood syndrome, MIM:226960; Microcephalic osteodysplastic primordial dwarfism, type I, MIM:210710; Roifman syndrome, OMIM:616651. Only Roifman syndrome features immunodeficiency.; to: PMID: 26522830 Merico et al., 2015 6 cases with Roifman syndrome from 4 unrelated families (English, Italian, Lebanese, Albanian). All 6 had history of repeat infections. PMID: 28623346 Bogaert et al., 2017 Report of two siblings that presented with a phenotype resembling early-onset common variable immunodeficiency - extra-immunological characteristics were not apparent at that time. Additional features were diagnosed later, including skeletal and organ anomalies and mild facial dysmorphism. Whole exome sequencing revealed c.13 C > T and c.116 A > T RNU4ATAC variants, which is consistent with diagnosis of Roifman syndrome. PMID: 29391254 Heremans et al., 2018 3 patients from 2 unrelated kindreds harboring compound heterozygous or homozygous stem II variants in RNU4ATAC. All patients have a common phenotype of moderate psychomotor delay and autism spectrum disorder, retinal dystrophy with hypovascularization, severe growth retardation, spondyloepiphysial dysplasia with irregularly shaped vertebral bodies with platyspondyly and flattened proximal femoral epiphyses, pruritic ichthyosis-like skin rash, brachydactyly, hyperlaxity, hypotonia, and hepatosplenomegaly. All 3 patients have hypogammaglobulinemia and B-cell lymphopenia, and they experience recurrent viral infections, necessitating immunoglobulin substitution therapy. P2 had mucocutaneous Herpes simplex infection, and P3 presented a pneumococcal sepsis on discontinuation of therapy. Study showed abnormal differentiation of B cells and megakaryocytes in the patients. PMID: 33059947 Hagiwara et al., 2020 18-year-old woman exhibiting congenital dwarfism and microcephaly with structural brain anomaly. She suffered human herpesvirus 6 (HHV-6)-associated acute necrotizing encephalopathy at age one, resulting in severe delay in psychomotor disabilities. Genetic analysis revealed comp het variants in RNU4ATAC (NR_023343.1:n.[50G > A];[55G > A]). Immunological findings showed decreases in total lymphocytes, CD4+ T cells, and T cell regenerative activity, and little response to vaccinations. 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. RNU4ATAC is associated with multiple AR conditions in OMIM: Lowry-Wood syndrome, MIM:226960; Microcephalic osteodysplastic primordial dwarfism, type I, MIM:210710; Roifman syndrome, OMIM:616651. Only Roifman syndrome features immunodeficiency. |
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| Primary immunodeficiency or monogenic inflammatory bowel disease v8.92 | RNU6ATAC |
Ida Ertmanska gene: RNU6ATAC was added gene: RNU6ATAC was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature Q1_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 Phenotypes for gene: RNU6ATAC were set to hypothyroidism, MONDO:0005420; Immune dysregulation, HP:0002958; thyroiditis, MONDO:0004126; alopecia, MONDO:0004907 Review for gene: RNU6ATAC was set to GREEN Added comment: 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 |
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| Primary immunodeficiency or monogenic inflammatory bowel disease v8.84 | RNU4ATAC |
Ida Ertmanska changed review comment from: PMID: 26522830 Merico et al., 2015 6 cases with Roifman syndrome from 4 unrelated families (English, Italian, Lebanese, Albanian). All 6 had history of repeat infections. PMID: 28623346 Bogaert et al., 2017 Report of two siblings that presented with a phenotype resembling early-onset common variable immunodeficiency - extra-immunological characteristics were not apparent at that time. Additional features were diagnosed later, including skeletal and organ anomalies and mild facial dysmorphism. Whole exome sequencing revealed c.13 C > T and c.116 A > T RNU4ATAC variants, which is consistent with diagnosis of Roifman syndrome. PMID: 29391254 Heremans et al., 2018 3 patients from 2 unrelated kindreds harboring compound heterozygous or homozygous stem II variants in RNU4ATAC. All patients have a common phenotype of moderate psychomotor delay and autism spectrum disorder, retinal dystrophy with hypovascularization, severe growth retardation, spondyloepiphysial dysplasia with irregularly shaped vertebral bodies with platyspondyly and flattened proximal femoral epiphyses, pruritic ichthyosis-like skin rash, brachydactyly, hyperlaxity, hypotonia, and hepatosplenomegaly. All 3 patients have hypogammaglobulinemia and B-cell lymphopenia, and they experience recurrent viral infections, necessitating immunoglobulin substitution therapy. P2 had mucocutaneous Herpes simplex infection, and P3 presented a pneumococcal sepsis on discontinuation of therapy. Study showed abnormal differentiation of B cells and megakaryocytes in the patients. PMID: 33059947 Hagiwara et al., 2020 18-year-old woman exhibiting congenital dwarfism and microcephaly with structural brain anomaly. She suffered human herpesvirus 6 (HHV-6)-associated acute necrotizing encephalopathy at age one, resulting in severe psychomotor disabilities. Genetic analysis revealed comp het variants in RNU4ATAC (NR_023343.1:n.[50G > A];[55G > A]). Immunological findings showed decreases in total lymphocytes, CD4+ T cells, and T cell regenerative activity, and little response to vaccinations. RNU4ATAC is associated with multiple AR conditions in OMIM: Lowry-Wood syndrome, MIM:226960; Microcephalic osteodysplastic primordial dwarfism, type I, MIM:210710; Roifman syndrome, OMIM:616651. Only Roifman syndrome features immunodeficiency.; to: PMID: 26522830 Merico et al., 2015 6 cases with Roifman syndrome from 4 unrelated families (English, Italian, Lebanese, Albanian). All 6 had history of repeat infections. PMID: 28623346 Bogaert et al., 2017 Report of two siblings that presented with a phenotype resembling early-onset common variable immunodeficiency - extra-immunological characteristics were not apparent at that time. Additional features were diagnosed later, including skeletal and organ anomalies and mild facial dysmorphism. Whole exome sequencing revealed c.13 C > T and c.116 A > T RNU4ATAC variants, which is consistent with diagnosis of Roifman syndrome. PMID: 29391254 Heremans et al., 2018 3 patients from 2 unrelated kindreds harboring compound heterozygous or homozygous stem II variants in RNU4ATAC. All patients have a common phenotype of moderate psychomotor delay and autism spectrum disorder, retinal dystrophy with hypovascularization, severe growth retardation, spondyloepiphysial dysplasia with irregularly shaped vertebral bodies with platyspondyly and flattened proximal femoral epiphyses, pruritic ichthyosis-like skin rash, brachydactyly, hyperlaxity, hypotonia, and hepatosplenomegaly. All 3 patients have hypogammaglobulinemia and B-cell lymphopenia, and they experience recurrent viral infections, necessitating immunoglobulin substitution therapy. P2 had mucocutaneous Herpes simplex infection, and P3 presented a pneumococcal sepsis on discontinuation of therapy. Study showed abnormal differentiation of B cells and megakaryocytes in the patients. PMID: 33059947 Hagiwara et al., 2020 18-year-old woman exhibiting congenital dwarfism and microcephaly with structural brain anomaly. She suffered human herpesvirus 6 (HHV-6)-associated acute necrotizing encephalopathy at age one, resulting in severe psychomotor disabilities. Genetic analysis revealed comp het variants in RNU4ATAC (NR_023343.1:n.[50G > A];[55G > A]). Immunological findings showed decreases in total lymphocytes, CD4+ T cells, and T cell regenerative activity, and little response to vaccinations. 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. RNU4ATAC is associated with multiple AR conditions in OMIM: Lowry-Wood syndrome, MIM:226960; Microcephalic osteodysplastic primordial dwarfism, type I, MIM:210710; Roifman syndrome, OMIM:616651. Only Roifman syndrome features immunodeficiency. |
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| Primary immunodeficiency or monogenic inflammatory bowel disease v8.84 | RNU4ATAC | Ida Ertmanska Publications for gene: RNU4ATAC were set to 26522830; 32086639; 21474760; 32048120 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v8.83 | RNU4ATAC | Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: RNU4ATAC. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v8.83 | RNU4ATAC | Ida Ertmanska Classified gene: RNU4ATAC as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v8.83 | RNU4ATAC | Ida Ertmanska Added comment: Comment on list classification: Immunodeficiency is a consistent finding in RNU4ATAC-related Roifman syndrome. In some cases, it may be the sole presenting feature, as other characteristics become apparent later. There are more than 3 unrelated cases reported in literature with biallelic RNU4ATAC variants and syndromic immunodeficiency, Hence, this gene should be promoted to Green at the next GMS update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v8.83 | RNU4ATAC | Ida Ertmanska Gene: rnu4atac has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v8.82 | RNU4ATAC | Ida Ertmanska reviewed gene: RNU4ATAC: Rating: GREEN; Mode of pathogenicity: None; Publications: 26522830, 28623346, 29391254, 33059947; Phenotypes: Roifman syndrome, OMIM:616651; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v5.10 | RNU4ATAC | Sarah Leigh Tag locus-type-rna-small-nuclear tag was added to gene: RNU4ATAC. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v4.202 | RNU4ATAC | Arina Puzriakova Phenotypes for gene: RNU4ATAC were changed from Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly, short stature; Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly; Combined immunodeficiencies with associated or syndromic features to Roifman syndrome, OMIM:616651; Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v2.209 | RNU4ATAC |
Eleanor Williams Source Other was added to RNU4ATAC. Publications for gene RNU4ATAC were updated from 32048120; 32086639 to 26522830; 32086639; 21474760; 32048120 |
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| Primary immunodeficiency or monogenic inflammatory bowel disease v2.208 | RNU4ATAC | Eleanor Williams reviewed gene: RNU4ATAC: Rating: ; Mode of pathogenicity: ; Publications: 21474760, 26522830; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease v2.34 | RNU4ATAC |
Louise Daugherty Source IUIS Classification December 2019 was added to RNU4ATAC. Mode of inheritance for gene RNU4ATAC was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Recurrent bacterial infections, lymphadenopathy, Spondyloepiphyseal dysplasia, extreme intrauterine growth retardation, retinal dystrophy, facial dysmorphism, may present with microcephaly, short stature for gene: RNU4ATAC Publications for gene RNU4ATAC were updated from to 32048120; 32086639 |
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| Primary immunodeficiency or monogenic inflammatory bowel disease | RNU4ATAC | Louise Daugherty commented on gene: RNU4ATAC | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease | RNU4ATAC | Louise Daugherty reviewed gene: RNU4ATAC | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary immunodeficiency or monogenic inflammatory bowel disease | RNU4ATAC | Louise Daugherty Added gene to panel | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||