Evidence map›Paper›PMID 38904753›Full record

ArticlePediatric nephrology (Berlin, Germany)2024

Recessive variants in MYO1C as a potential novel cause of proteinuric kidney disease.

Izzeldin Elmubarak, Shirlee Shril, Bshara Mansour, Aaron Bao, Caroline M Kolvenbach, Jameela A Kari, Mohamed A Shalaby, Sherif El Desoky, Friedhelm Hildebrandt, Ronen Schneider

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Article in Pediatric nephrology (Berlin, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers 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

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Izzeldin Elmubarak *Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Shirlee Shril *Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Bshara MansourDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Aaron BaoDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Caroline M KolvenbachDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Jameela A KariDepartment of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Mohamed A ShalabyDepartment of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Sherif El DesokyDepartment of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Friedhelm HildebrandtDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Ronen SchneiderDepartment of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. ronen.schneider@childrens.harvard.edu.

Funding

Integrating large scale genomics and functional studies to accelerate FSGS/NS discoveryRC2DK122397 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI HILDEBRANDT, FRIEDHELM, POLLAK, MARTIN R. · 2020 to 2024
$7.4M
Identification and function of new genes causing childhood nephrotic syndromeR01DK076683 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HILDEBRANDT, FRIEDHELM · 2007 to 2021
$5.3M
German Research Foundation 499462148National Institute of Health RC-2-DK1222397NIDDK NIH HHS R01 DK076683NIDDK NIH HHS RC2 DK122397
6 · The paper itself

Abstract

backgroundSteroid-resistant nephrotic syndrome is the second leading cause of chronic kidney disease among patients < 25 years of age. Through exome sequencing, identification of > 65 monogenic causes has revealed insights into disease mechanisms of nephrotic syndrome (NS).

methodsTo elucidate novel monogenic causes of NS, we combined homozygosity mapping with exome sequencing in a worldwide cohort of 1649 pediatric patients with NS.

resultsWe identified homozygous missense variants in MYO1C in two unrelated children with NS (c.292C > T, p.R98W; c.2273 A > T, p.K758M). We evaluated publicly available kidney single-cell RNA sequencing datasets and found MYO1C to be predominantly expressed in podocytes. We then performed structural modeling for the identified variants in PyMol using aligned shared regions from two available partial structures of MYO1C (4byf and 4r8g). In both structures, calmodulin, a common regulator of myosin activity, is shown to bind to the IQ motif. At both residue sites (K758; R98), there are ion-ion interactions stabilizing intradomain and ligand interactions: R98 binds to nearby D220 within the myosin motor domain and K758 binds to E14 on a calmodulin molecule. Variants of these charged residues to non-charged amino acids could ablate these ionic interactions, weakening protein structure and function establishing the impact of these variants.

conclusionWe here identified recessive variants in MYO1C as a potential novel cause of NS in children.

Indexed as

Exome SequencingMutation, MissenseMyosin Type INephrotic SyndromeAdolescentChildChild, PreschoolFemaleGenes, RecessiveHomozygoteHumansMaleModels, MolecularPodocytesProteinuriaMYO1C protein, humanMyosin Type IChronic kidney diseaseExome sequencingSteroid-resistant nephrotic syndrome

Identifiers

PMID38904753
PMCPMC11883449

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