Evidence map›Paper›PMID 40024461›Full record

ArticleClinical immunology (Orlando, Fla.)2025

IKAROS protein stability is regulated by its early N-terminal region and C-terminal dimerization domain.

Natchanun Klangkalya, Ana Esteve-Sole, Agustin A Gil Silva, Jennifer L Stoddard, Julie E Niemela, Seraina Prader, Gregor Dueckers, Lina Igel, Tim Niehues, Benjamin C Stewart-Bates and 4 more

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In one paragraph

Article in Clinical immunology (Orlando, Fla.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. IKZF-associated inborn errors of immunity.Journal of human immunity · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Natchanun KlangkalyaImmunology Service, Department of Laboratory Medicine, NIH Clinical Center, NIH, Bethesda, MD, USA; Department of Pediatric, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Ana Esteve-SoleImmunology Service, Department of Laboratory Medicine, NIH Clinical Center, NIH, Bethesda, MD, USA.
Agustin A Gil SilvaImmunology Service, Department of Laboratory Medicine, NIH Clinical Center, NIH, Bethesda, MD, USA.
Jennifer L StoddardImmunology Service, Department of Laboratory Medicine, NIH Clinical Center, NIH, Bethesda, MD, USA.
Julie E NiemelaImmunology Service, Department of Laboratory Medicine, NIH Clinical Center, NIH, Bethesda, MD, USA.
Seraina PraderDivision of Immunology and the Children's Research Center, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.
Gregor DueckersCentre for Child and Adolescent Health, Helios Klinikum Krefeld, Academic Hospital of the RWTH, Aachen, Germany.
Lina IgelCentre for Child and Adolescent Health, Helios Klinikum Krefeld, Academic Hospital of the RWTH, Aachen, Germany.
Tim NiehuesCentre for Child and Adolescent Health, Helios Klinikum Krefeld, Academic Hospital of the RWTH, Aachen, Germany.
Benjamin C Stewart-BatesDivision of Pediatric Allergy and Immunology, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
Talal MousallemDivision of Pediatric Allergy and Immunology, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
Thomas A FleisherImmunology Service, Department of Laboratory Medicine, NIH Clinical Center, NIH, Bethesda, MD, USA.
Sergio D RosenzweigImmunology Service, Department of Laboratory Medicine, NIH Clinical Center, NIH, Bethesda, MD, USA. Electronic address: srosenzweig@cc.nih.gov.
Hye Sun KuehnImmunology Service, Department of Laboratory Medicine, NIH Clinical Center, NIH, Bethesda, MD, USA. Electronic address: hyesun.kuehn@nih.gov.

Funding

Studies of Inherited Causes of Fungal SusceptabilityZIAAI001122 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ROSENZWEIG, SERGIO · 2010 to 2025
$26.0M
Mutation Analysis Of Selected Lymphoid Immune DisordersZIACL010304 · CLC · CLINICAL CENTER · PI ROSENZWEIG, SERGIO · 2009 to 2025
$0k
Intramural NIH HHS ZIA AI001122Intramural NIH HHS ZIA CL010304
6 · The paper itself

Abstract

IKAROS, encoded by IKZF1, is a six zinc-finger (ZF) transcription factor integral to lymphocyte development and function. IKZF1 mutations affecting DNA-binding (ZF1-4) and dimerization (ZF5-6) have been extensively reported and result in human disease. Herein, we investigated IKZF1 mutations affecting protein stability. We identified ten individuals in three families carrying IKZF1 mutations mapping either to the pre-ZF1 area (D22N), or the dimerization domain (M494Vfs*86, Y503*) presenting with infections, immune dysregulation and/or lymphoproliferation with incomplete clinical penetrance. IKAROS expression was reduced in all mutation-carrier evaluated. Protein stability was decreased for D22N, V52L (another pre-ZF1 variant reported in COSMIC), Y503* and Del1-116, a laboratory-designed mutant encompassing the pre-ZF1 area. Mutants Y503* and Del1-116 also exhibited other impaired functions. IKAROS N-terminal pre-ZF1 area, encompassing a previously uncharacterized protein stability-associated region (PSAR), is crucial for IKAROS stability. Variants in the IKAROS PSAR leading to decreased protein stability and IKAROS haploinsufficiency seem sufficient to result in immune defects and IKAROS-associated diseases.

Indexed as

Ikaros Transcription FactorAdultChildFemaleHumansMaleMutationPedigreeProtein DomainsProtein MultimerizationProtein StabilityIkaros Transcription FactorIKZF1 protein, humanHaploinsufficiencyIKZF1Inborn errors of immunityPrimary immunodeficiencyProtein stabilityTranscription factors

Identifiers

PMID40024461
PMCPMC11929600

What Socratic holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

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 Socratic graph.