ArticleThe Journal of allergy and clinical immunology2022
Comprehensive analysis of ADA2 genetic variants and estimation of carrier frequency driven by a function-based approach.
Article in The Journal of allergy and clinical immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 54 citations in OpenAlex.
- Advancements in Diagnosis and Care for Immune Dysregulation and Inborn Errors of Immunity in Pediatric Rheumatology: Our 50-Year Journey.Arthritis care & research · 2026Review
- Adenosine deaminase type 2 deficiency: From rare to common.Journal of human immunity · 2026Review
- ADA2 genotype and enzyme activity may predict vasculitic or hematologic DADA2 phenotype.Journal of human immunity · 2026Article
- Immune Dysregulation and Lymphoma Risk in Deficiency of Adenosine Deaminase 2.International journal of rheumatic diseases · 2026Article
- Anifrolumab, a potential treatment for ADA2 deficiency.RMD open · 2026Article
- Decoding variants of uncertain significance in systemic autoinflammatory diseases.Nature reviews. Rheumatology · 2026Review
- Aneurysmal Subarachnoid Hemorrhage in Pediatric DADA2: A Case Report and Literature Review.Cureus · 2026Article
- Diagnostic Implications and Correlates of Plasma Adenosine Deaminase 2 Activity and ADA2 Variants.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Decoding neurovascular signatures: advanced imaging insights in DADA2-Related Cerebral Microangiopathy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- Dominant negative ADA2 mutations cause ADA2 deficiency in heterozygous carriers.The Journal of experimental medicine · 2025Article
- Rheumatologic and Autoimmune Features of Inborn Errors of Immunity: Implications for Diagnosis and Management.Journal of human immunity · 2025Article
- Phenome-wide association study of monogenic inflammatory bowel disease genes in diverse biobanks identifies population-specific and shared Goldilocks alleles: implications for Precision Medicine.Journal of Crohn's & colitis · 2025Article
- Structural basis for the substrate specificity of Helix pomatia AMP deaminase and a chimeric ADGF adenosine deaminase.The Journal of biological chemistry · 2025Article
- The pathogenesis, clinical presentations and treatment of monogenic systemic vasculitis.Nature reviews. Rheumatology · 2025Review
- Getting to know adenosine deaminase 2 deficiency inside and out.The Journal of allergy and clinical immunology · 2025Review
- Deficiency of Adenosine Deaminase 2 Masquerading as Behçet's Disease: Phenotypic Mimicry with HLA-B*51 Positivity.Journal of clinical immunology · 2025Article
- Vasculitis in Children.Turkish archives of pediatrics · 2024Review
- Rare primary vasculitis: update on multiple complex diseases and the new kids on the block.Advances in rheumatology (London, England) · 2024Review
- Human ADA2 Deficiency: Ten Years Later.Current allergy and asthma reports · 2024Review
- Neurological phenotype of adenosine deaminase 2 deficient patients: a cohort study.European journal of neurology · 2024Article
Corrections and comments
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Authors and funding
16 authors at 9 institutions in 4 countries.
Funding
Abstract
backgroundDeficiency of adenosine deaminase 2 (DADA2) is an autoinflammatory disease caused by deleterious ADA2 variants. The frequency of these variants in the general population, and hence the expected disease prevalence, remain unknown.
objectiveWe aimed to characterize the functional impact and carrier frequency of ADA2 variants.
methodsWe performed functional studies and in silico analysis on 163 ADA2 variants, including DADA2-associated variants and population variants identified in the Genome Aggregation Database. We estimated the carrier rate using the aggregate frequency of deleterious variants.
resultsFunctional studies of ADA2 variants revealed that 77 (91%) of 85 of DADA2-associated variants reduced ADA2 enzymatic function by >75%. Analysis of 100 ADA2 variants in the database showed a full spectrum of impact on ADA2 function, rather than a dichotomy of benign versus deleterious variants. We found several in silico algorithms that effectively predicted the impact of ADA2 variants with high sensitivity and specificity, and confirmed a correlation between the residual function of ADA2 variants in vitro and the plasma ADA2 activity of individuals carrying these variants (n = 45; r = 0.649; P < .0001). Using <25% residual enzymatic activity as the cutoff to define potential pathogenicity, integration of our results with the database population data revealed an estimated carrier frequency of at least 1 in 236 individuals, corresponding to an expected DADA2 disease prevalence of ~1 in 222,000 individuals.
conclusionsFunctional annotation guides the interpretation of ADA2 variants to create a framework that enables estimation of DADA2 carrier frequency and disease prevalence.
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