ArticleJCI insight2022
Partial loss-of-function mutations in GINS4 lead to NK cell deficiency with neutropenia.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Expanding Phenotype of GINS1 Deficiency: A Case Report and Review of the Literature.Clinical genetics · 2026Review
- Autosomal dominant CDC45 deficiency with allelic expression bias causes a novel genetic disease of the immune system.bioRxiv : the preprint server for biology · 2026Article
- Inborn errors of immunity with DNA repair disorders: at the interface of immune deficiency, immune dysregulation, and malignancy.Frontiers in immunology · 2026Review
- Allelic bias contributes to heterogeneous phenotypes of NK cell deficiency.Cell reports · 2025Article
- Expanding the phenotypic and genetic landscape of congenital neutropenia through whole-exome and genome sequencing.HemaSphere · 2025Article
- Human inborn errors of immunity: 2024 update on the classification from the International Union of Immunological Societies Expert Committee.Journal of human immunity · 2025Article
- Replication stress, microcephalic primordial dwarfism, and compromised immunity in ATRIP deficient patients.The Journal of experimental medicine · 2025Article
- Clinical, immunologic, and genetic characteristics of 148 patients with natural killer cell deficiency.The Journal of allergy and clinical immunology · 2025Article
- The Golgi complex governs natural killer cell lytic granule positioning to promote directionality in cytotoxicity.Cell reports · 2025Article
- The replicative helicase CMG is required for the divergence of cell fates during asymmetric cell division in vivo.Nature communications · 2024Article
- Replication Stress in Activated Human NK Cells Induces Sensitivity to Apoptosis.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- An Immature NK Cell Compartment in Functional DBF4 Deficiency.Journal of clinical immunology · 2024Article
- Unraveling the dynamic mechanisms of natural killer cells in viral infections: insights and implications.Virology journal · 2024Review
- A critical threshold of MCM10 is required to maintain genome stability during differentiation of induced pluripotent stem cells into natural killer cells.Open biology · 2024Article
- The expanding genetic and clinical landscape associated with Meier-Gorlin syndrome.European journal of human genetics : EJHG · 2023Review
- Comment on: "The expanding genetic and clinical landscape associated with Meier-Gorlin syndrome" by Nielsen-Dandoroff et al.European journal of human genetics : EJHG · 2023Article
- Unwinding the Role of the CMG Helicase in Inborn Errors of Immunity.Journal of clinical immunology · 2023Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
Human NK cell deficiency (NKD) is a primary immunodeficiency in which the main clinically relevant immunological defect involves missing or dysfunctional NK cells. Here, we describe a familial NKD case in which 2 siblings had a substantive NKD and neutropenia in the absence of other immune system abnormalities. Exome sequencing identified compound heterozygous variants in Go-Ichi-Ni-San (GINS) complex subunit 4 (GINS4, also known as SLD5), an essential component of the human replicative helicase, which we demonstrate to have a damaging impact upon the expression and assembly of the GINS complex. Cells derived from affected individuals and a GINS4-knockdown cell line demonstrate delayed cell cycle progression, without signs of improper DNA synthesis or increased replication stress. By modeling partial GINS4 depletion in differentiating NK cells in vitro, we demonstrate the causal relationship between the genotype and the NK cell phenotype, as well as a cell-intrinsic defect in NK cell development. Thus, biallelic partial loss-of-function mutations in GINS4 define a potentially novel disease-causing gene underlying NKD with neutropenia. Together with the previously described mutations in other helicase genes causing NKD, and with the mild defects observed in other human cells, these variants underscore the importance of this pathway in NK cell biology.
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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.