Evidence map›Paper›PMID 41419331›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2026

Mislocalization of KCNQ2 Channels as a Pathogenic Mechanism in KCNQ2 Developmental and Epileptic Encephalopathy.

Kristen Springer, Heun Soh, Raquel Paz Zavala, Nissi Varghese, Cathleen Lutz, Aamir R Zuberi, Alexander C Jackson, Anastasios V Tzingounis

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

8 authors.

Kristen SpringerDepartment of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269.
Heun SohDepartment of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269.
Raquel Paz ZavalaDepartment of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269.
Nissi VargheseDepartment of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269.
Cathleen LutzRare Disease Translational Center at The Jackson Laboratory, Bar Harbor, Maine 04609.
Aamir R ZuberiRare Disease Translational Center at The Jackson Laboratory, Bar Harbor, Maine 04609.
Alexander C JacksonDepartment of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269.ORCID 0000-0001-7489-3946
Anastasios V TzingounisDepartment of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269 anastasios.tzingounis@uconn.edu.ORCID 0000-0002-4605-3437

Funding

Inhibitory Cell Types and Circuits in the Lateral HypothalamusR01MH112739 · NIMH · UNIVERSITY OF CONNECTICUT STORRS · PI Alexander Choi Jackson · 2017 to 2026
$5.1M
Role of KCNQ2 Channels in Control of BreathingR01HL137094 · NHLBI · UNIVERSITY OF CONNECTICUT STORRS · PI MULKEY, DANIEL K, TZINGOUNIS, ANASTASIOS · 2018 to 2025
$4.1M
KCNQ2/3 channels and interneuron physiologyR01NS101596 · NINDS · UNIVERSITY OF CONNECTICUT STORRS · PI TZINGOUNIS, ANASTASIOS · 2017 to 2021
$1.7M
Thermo Scientific Orbitrap Eclipse Tribrid ETD Mass Spectrometer for UConn ProteomicsS10OD028445 · OD · UNIVERSITY OF CONNECTICUT STORRS · PI BALSBAUGH, JEREMY · 2021 to 2021
$994k
NHLBI NIH HHS R01 HL137094NIH HHS S10 OD028445NIMH NIH HHS R01 MH112739NINDS NIH HHS R01 NS101596
6 · The paper itself

Abstract

KCNQ2 potassium channel variants are linked to developmental and epileptic encephalopathy (DEE). However, the mechanisms by which pathogenic variants, especially those outside known hotspots, such as the S4-S5 linker, lead to disease remain unknown. Here, we examined the H228R variant, a pathogenic mutation in the S4-S5 linker associated with DEE. We tested whether H228R induces KCNQ2 channel mistargeting in addition to its biophysical effects, given recent evidence of impaired trafficking in KCNQ2 DEE variants. We confirmed the H228R variant as a loss-of-function (LOF) when expressed as a homomer and as a dominant-negative when coexpressed with wild-type (WT) KCNQ3. Surprisingly, it exhibited some gain-of-function effects when coexpressed with WT KCNQ2. To determine its cellular localization in vivo, we used male and female heterozygous

Indexed as

EpilepsyKCNQ2 Potassium ChannelAnimalsFemaleHEK293 CellsHippocampusHumansMaleMiceMice, Inbred C57BLMice, TransgenicNerve Tissue ProteinsProtein TransportKCNQ2 Potassium ChannelKcnq2 protein, mouseNerve Tissue Proteinsantibodyautismdevelopmental and epileptic encephalopathyKCNQ2Kv7.2potassium channels

Identifiers

PMID41419331
PMCPMC12758638

What OpenQuestion holds

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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 OpenQuestion graph.