ReviewCurrent opinion in immunology2015
Immunological loss-of-function due to genetic gain-of-function in humans: autosomal dominance of the third kind.
Review in Current opinion in immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 76 citations in OpenAlex.
- Human immunity to fungal infections.The Journal of experimental medicine · 2025Review
- Functionally constrained human proteins are less prone to mutational instability from single amino acid substitutions.Nature communications · 2025Article
- IKK2 controls the inflammatory potential of tissue-resident regulatory T cells in a murine gain of function model.Nature communications · 2024Article
- Signal Transducer and Activator of Transcription Proteins at the Nexus of Immunodeficiency, Autoimmunity and Cancer.Biomedicines · 2023Review
- JAKs and STATs from a Clinical Perspective: Loss-of-Function Mutations, Gain-of-Function Mutations, and Their Multidimensional Consequences.Journal of clinical immunology · 2023Review
- Editorial: Non-canonical NF-κB signaling in immune-mediated inflammatory diseases and malignancies.Frontiers in immunology · 2023Article
- Activated PI3Kδ syndrome - reviewing challenges in diagnosis and treatment.Frontiers in immunology · 2023Review
- Skin manifestations of inborn errors of NF-κB.Frontiers in pediatrics · 2022Review
- Chronic oral mucocutaneous candidiasis, recurrent respiratory infection, hepatosplenomegaly, and autoimmune diabetes mellitus: A case report of a gain-of-function mutation ofFrontiers in pediatrics · 2022Article
- Identification of discriminative gene-level and protein-level features associated with pathogenic gain-of-function and loss-of-function variants.American journal of human genetics · 2021Article
- Novel STAT-3 gain-of-function variant with hypogammaglobulinemia and recurrent infection phenotype.Clinical and experimental immunology · 2021Article
- Immunodeficiency and bone marrow failure with mosaic and germline TLR8 gain of function.Blood · 2021Article
- Immunity and Genetics at the Revolving Doors of Diagnostics in Primary Immunodeficiencies.Diagnostics (Basel, Switzerland) · 2021Article
- Negative selection on human genes underlying inborn errors depends on disease outcome and both the mode and mechanism of inheritance.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Primary Immunodeficiencies: Diseases of Children and Adults - A Review.Advances in experimental medicine and biology · 2021Review
- Case Report: Intestinal Nodular Lymphoid Hyperplasia as First Manifestation of Activated PI3Kδ Syndrome Due to a NovelFrontiers in pediatrics · 2021Article
- Immune Monitoring of Patients With Primary Immune Regulation Disorders Unravels Higher Frequencies of Follicular T Cells With Different Profiles That Associate With Alterations in B Cell Subsets.Frontiers in immunology · 2020Article
- Gain-of-function CEBPE mutation causes noncanonical autoinflammatory inflammasomopathy.The Journal of allergy and clinical immunology · 2019Article
- Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies.Genome medicine · 2019Article
- Clinical implications of systematic phenotyping and exome sequencing in patients with primary antibody deficiency.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
All the human primary immunodeficiencies (PIDs) recognized as such in the 1950s were Mendelian traits and, whether autosomal or X-linked, displayed recessive inheritance. The first autosomal dominant (AD) PID, hereditary angioedema, was recognized in 1963. However, since the first identification of autosomal recessive (AR), X-linked recessive (XR) and AD PID-causing genes in 1985 (ADA; severe combined immunodeficiency), 1986 (CYBB, chronic granulomatous disease) and 1989 (SERPING1; hereditary angioedema), respectively, the number of genetically defined AD PIDs has increased more rapidly than that of any other type of PID. AD PIDs now account for 61 of the 260 known conditions (23%). All known AR PIDs are caused by alleles with some loss-of-function (LOF). A single XR PID is caused by gain-of-function (GOF) mutations (WASP-related neutropenia, 2001). In contrast, only 44 of 61 AD defects are caused by LOF alleles, which exert dominance by haploinsufficiency or negative dominance. Since 2003, up to 17 AD disorders of the third kind, due to GOF alleles, have been described. Remarkably, six of the 17 genes concerned also harbor monoallelic (STAT3), biallelic (C3, CFB, CARD11, PIK3R1) or both monoallelic and biallelic (STAT1) LOF alleles in patients with other clinical phenotypes. Most heterozygous GOF alleles result in auto-inflammation, auto-immunity, or both, with a wide range of immunological and clinical forms. Some also underlie infections and, fewer, allergies, by impairing or enhancing immunity to non-self. Malignancies are also rare. The enormous diversity of immunological and clinical phenotypes is thought provoking and mirrors the diversity and pleiotropy of the underlying genotypes. These experiments of nature provide a unique insight into the quantitative regulation of human immunity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.