Evidence map›Paper›PMID 41159445›Full record

ArticleGenetics in medicine : official journal of the American College of Medical Genetics2026

KLHL13 functional defects cause neurodevelopmental disorder in humans that can be rescued via inhibition of AURKB in cellular and animal models.

Tehmeena Akhter, Zubair M Ahmed, Yaping Ji, Axel Schmidt, Meron Azage, Maria Palomares, Kirsten Cremer, Hartmut Engels, Jennifer O Murphy, Sophia Peters and 5 more

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Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

15 authors.

Tehmeena AkhterDepartment of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD; Centre of Excellence in Molecular Biology, University of the Punjab, Pakistan.
Zubair M AhmedDepartment of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD; Centre of Excellence in Molecular Biology, University of the Punjab, Pakistan; Department of Molecular Biology and Biochemistry, School of Medicine, University of Maryland, Baltimore, MD; Department of Ophthalmology and Visual Sciences, School of Medicine, University of Maryland, Baltimore, MD; Marlene and Stewart Greenebaum Comprehensive Cancer Center, School of Medicine, University of Maryland, Baltimore, MD.
Yaping JiDepartment of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD.
Axel SchmidtInstitute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, Bonn, Germany.
Meron AzageThe Huntington's Disease Center, University of Pennsylvania, Philadelphia, PA.
Maria PalomaresINGEMM-IdiPaz, Institute of Medical and Molecular Genetics, Madrid, Spain; CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain.
Kirsten CremerInstitute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, Bonn, Germany.
Hartmut EngelsInstitute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, Bonn, Germany.
Jennifer O MurphyThe Huntington's Disease Center, University of Pennsylvania, Philadelphia, PA.
Sophia PetersInstitute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, Bonn, Germany.
Elisabeth MangoldInstitute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, Bonn, Germany.
M L Á Gomez-CanoINGEMM-IdiPaz, Institute of Medical and Molecular Genetics, Madrid, Spain; CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain.
Rodney J TaylorDepartment of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD.
Sheikh RiazuddinJinnah Burn and Reconstructive Surgery Centre, Allama Iqbal Medical Research, University of Health Sciences, Lahore, Pakistan.
Saima RiazuddinDepartment of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD; Department of Molecular Biology and Biochemistry, School of Medicine, University of Maryland, Baltimore, MD. Electronic address: sriazuddin@som.umaryland.edu.

Funding

Genetics and Functional Studies of Autosomal Recessive Neurological DisordersR01NS107428 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI Saima Riazuddin · 2018 to 2026
$4.7M
NINDS NIH HHS R01 NS107428
6 · The paper itself

Abstract

purposeNeurodevelopmental disorders (NDDs) are characterized by limitations in brain development. This study aims to determine the genetic causes of NDD in humans.

methodsExome sequencing was used to detect genetic variants of KLHL13, which encodes Kelch like protein 13 (KLHL13), in four families segregating in an X-linked pattern. In silico protein modeling and overexpression in heterologous cells were used to determine the variant's impact. klhl13 loss of function was modeled in zebrafish, followed by rescue studies using human KLHL13 messenger RNA (mRNA) and an Aurora Kinase B (AURKB) inhibitor.

resultsWe found one frameshift and three missense hemizygous variants of KLHL13 in individuals exhibiting NDD characteristics, such as intellectual disability (ID) and macrocephaly. Three-dimensional protein modeling simulation predicted the alteration of the KLHL13 protein folding for missense variants. Overexpression of NDD-associated variants in HEK293T cells revealed a significant impact on KLHL13-mediated cell-cycle regulation during mitosis, leading to genomic instability. Knocking down klhl13 in zebrafish resulted in developmental deficits, which were rescued by coinjection of human KLHL13

conclusionOur results implicate KLHL13-mediated AURKB regulation as a significant contributor to NDD in humans. Inhibiting AURKB activity could serve as a potential therapeutic approach to improve brain development and cognitive function.

Indexed as

Aurora Kinase BNeurodevelopmental DisordersAnimalsChildDisease Models, AnimalExome SequencingFemaleHEK293 CellsHumansIntellectual DisabilityMaleMutation, MissensePedigreeZebrafishAurora Kinase BAZD1152-HQPAGenomic instabilityIntellectual disabilityKLHL13 - Kelch proteinMacrocephaly

Identifiers

PMID41159445
PMCPMC13403264

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Registered trials

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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.