Evidence map›Paper›PMID 42636812›Full record

ArticleNeuron2026

An inherited hypomorphic variant in PIEZO2 reveals structural features of mechanotransduction.

Alec R Nickolls, Eric M Mulhall, Daniel J Orlin, Oleg Yarishkin, Luis O Romero, Briar Bell, Xin Hu, Caitlin A Madden, Raiza R Hardy, Gabrielle S O'Brien and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 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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0citing papers in PubMed
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1 · What the graph read from it

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.

2 · The registry

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3 · Its place in the literature

Who cites it

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4 · The record

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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

22 authors.

Alec R NickollsNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Eric M MulhallHoward Hughes Medical Institute, Department of Neuroscience, Dorris Neuroscience Center, Scripps Research, La Jolla, CA 92037, USA.
Daniel J OrlinNational Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD 20892, USA.
Oleg YarishkinHoward Hughes Medical Institute, Department of Neuroscience, Dorris Neuroscience Center, Scripps Research, La Jolla, CA 92037, USA.
Luis O RomeroDepartment of Biochemistry and Molecular Biology, Center for Membrane Biology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Briar BellDepartment of Biochemistry and Molecular Biology, Center for Membrane Biology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Xin HuNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
Caitlin A MaddenNational Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD 20892, USA.
Raiza R HardyNational Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD 20892, USA.
Gabrielle S O'BrienNational Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD 20892, USA.
Sandra DonkervoortNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Dimah N SaadeNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Tanya J LehkyNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
A Reghan FoleyNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Diana X Bharucha-GoebelNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA; Division of Neurology, Children's National Hospital, Washington, DC 20010, USA.
Jahannaz DastgirRegenxbio, Rockville, MD 20850, USA.
Valeria VásquezDepartment of Biochemistry and Molecular Biology, Center for Membrane Biology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Julio F Cordero-MoralesDepartment of Biochemistry and Molecular Biology, Center for Membrane Biology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Carsten G BönnemannNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Ardem PatapoutianHoward Hughes Medical Institute, Department of Neuroscience, Dorris Neuroscience Center, Scripps Research, La Jolla, CA 92037, USA.
Melanie FalgairolleNational Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: melanie.falgairolle@nih.gov.
Alexander T CheslerNational Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: alexander_chesler@vrtx.com.

Funding

Joint Center for Mendelian GenomicsUM1HG008900 · NHGRI · BROAD INSTITUTE, INC. · PI O'DONNELL-LURIA, ANNE, REHM, HEIDI L · 2016 to 2020
$16.5M
Studies on the molecular, cells, and circuit that underlie somatosensation and painZIAAT000028 · NCCIH · NATIONAL CENTER FOR COMPLEMENTARY & INTEGRATIVE HEALTH · PI CHESLER, ALEXANDER · 2014 to 2025
$12.0M
A powerful web-based discovery platform for rare disease geneticsR01HG009141 · NHGRI · BROAD INSTITUTE, INC. · PI QUINLAN, AARON R, REHM, HEIDI L · 2017 to 2020
$2.9M
The Role of Sensory Receptors in Angelman SyndromeR01NS131184 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Julio Francisco Cordero-Morales, Valeria Vasquez · 2023 to 2026
$1.9M
Training Core: Houston Area Incubator for Kidney, Urologic and Hematologic Research Training (HAIKUH)TL1DK147564 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI MARGARET A. GOODELL · 2025 to 2026
$1.8M
The Molecular Basis of PIEZO Ion Channel FunctionK99GM155547 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI MULHALL, ERIC MICHAEL · 2024 to 2025
$250k
Intramural NIH HHS Z99 AT999999Intramural NIH HHS ZIA AT000028NHGRI NIH HHS R01 HG009141NHGRI NIH HHS UM1 HG008900NIDDK NIH HHS TL1 DK147564NIGMS NIH HHS K99 GM155547NINDS NIH HHS R01 NS131184
6 · The paper itself

Abstract

PIEZO2 is the principal mechanosensory channel for proprioception, touch, and many interoceptive processes, yet key details of how PIEZO channels convert force into electrochemical signals remain unclear. Here, we report fraternal twins with proprioceptive ataxia and scoliosis who carry an unreported PIEZO2 missense variant (N2434K) in compound heterozygosity with a null variant. Gene-edited mice confirm that N2434K is disease-causing, with in vivo recordings demonstrating deficits in sensory neuron mechanical responses. Despite normal membrane expression, the variant has severely reduced mechanically evoked current, which is suggestive of defective gating. N2434 is conserved between PIEZO1 and PIEZO2 and resides in the cap-pore linker, which bridges the extracellular cap and ion-conducting pore. Computational modeling, site-directed mutagenesis, and single-molecule imaging reveal that this region is essential for channel-wide conformational changes during gating. By explaining how a single amino acid change produces a hypomorphic PIEZO2 allele, our findings broaden the clinical spectrum of PIEZO2 disorders and offer structural insight into mechanotransduction.

Indexed as

dorsal root gangliamechanotransductionPIEZO1PIEZO2PIEZO channelssensory neurons

Identifiers

PMID42636812
PMCPMC13588269

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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.