Evidence map›Paper›PMID 35320039›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2022

KCNQ2 and KCNQ5 form heteromeric channels independent of KCNQ3.

Heun Soh, Kristen Springer, Klarita Doci, Jeremy L Balsbaugh, Anastasios V Tzingounis

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.5field-weighted citation impact, top 10% of its field
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

19 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
  2. Mislocalization of KCNQ2 Channels as a Pathogenic Mechanism in KCNQ2 Developmental and Epileptic Encephalopathy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Phosphatidylinositol 4,5-bisphosphate activation mechanism of human KCNQ5.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  7. Article
  8. Novel KCNQ2 missense variant expands the genotype spectrum of DEE7.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024
    Article
  9. Article
  10. Review
  11. KAddiction biology · 2024
    Article
  12. Article
  13. Glial KCNQ KNeuron · 2024
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. 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

5 authors at 1 institution in 1 country.

Heun SohDepartment of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269.
Kristen SpringerDepartment of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269.
Klarita DociDepartment of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269.
Jeremy L BalsbaughProteomics & Metabolomics Facility, Center for Open Research Resources & Equipment, University of Connecticut, Storrs, CT 06269.ORCID 0000-0002-1852-8749
Anastasios V TzingounisDepartment of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269.
University of Connecticut · US

Funding

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
Identification and validation of the epilepsy associated KCNQ2 complexes in the brainR21NS118262 · NINDS · UNIVERSITY OF CONNECTICUT STORRS · PI SOH, HEUN, TZINGOUNIS, ANASTASIOS · 2020 to 2020
$443k
NHLBI NIH HHS R01 HL137094NINDS NIH HHS R01 NS101596NINDS NIH HHS R21 NS118262
6 · The paper itself

Abstract

KCNQ2 and KCNQ3 channels are associated with multiple neurodevelopmental disorders and are also therapeutic targets for neurological and neuropsychiatric diseases. For more than two decades, it has been thought that most KCNQ channels in the brain are either KCNQ2/3 or KCNQ3/5 heteromers. Here, we investigated the potential heteromeric compositions of KCNQ2-containing channels. We applied split-intein protein trans-splicing to form KCNQ2/5 tandems and coexpressed these with and without KCNQ3. Unexpectedly, we found that KCNQ2/5 tandems form functional channels independent of KCNQ3 in heterologous cells. Using mass spectrometry, we went on to demonstrate that KCNQ2 associates with KCNQ5 in native channels in the brain, even in the absence of KCNQ3. Additionally, our functional heterologous expression data are consistent with the formation of KCNQ2/3/5 heteromers. Thus, the composition of KCNQ channels is more diverse than has been previously recognized, necessitating a re-examination of the genotype/phenotype relationship of KCNQ2 pathogenic variants.

Indexed as

KCNQ3 Potassium ChannelKCNQ Potassium ChannelsAnimalsBrainGenotypeKCNQ2 Potassium ChannelMiceNerve Tissue ProteinsPhenotypeProtein SplicingKCNQ2 Potassium ChannelKcnq2 protein, mouseKCNQ3 Potassium ChannelKcnq3 protein, mouseKCNQ Potassium ChannelsNerve Tissue ProteinsautismepilepsyKCNQ2KCNQ3KCNQ5

Identifiers

PMID35320039
PMCPMC9060518
OpenAlexW4220883387

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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 OpenQuestion graph.