Differential negative dominance by <i>KCNA2</i> variants associated with global developmental delay suggests <i>KCNA2</i> haploinsufficiency in humans
-channels: p.H310D and p.G318D. In frog oocytes and in primate cells, both variants cause loss of KCNA2 function, abolishing currents and surface trafficking, and inhibiting channel voltage-dependent opening. p.H310D is strongly negative-dominant, potently suppressing wild-type subunit functional expression. In contrast, p.G318D is weakly negative-dominant, leaving wild-type subunits largely unaffected. This suggests that KCNA2 is a haploinsufficient gene in humans.
Authors
- Serena Pozzi (ORCID: https://orcid.org/0009-0009-2688-1575)
- Pei Xin Boon
- Amelle Shillington (ORCID: https://orcid.org/0000-0002-7447-8117)
- Urban Karlsson (ORCID: https://orcid.org/0000-0002-9228-1625)
- Ammar Husami (ORCID: https://orcid.org/0000-0002-4287-2857)
- Amaia Jauregi‐Miguel (ORCID: https://orcid.org/0000-0003-0938-7734)
- Charmaine Ko
- S. Suheda Yasarbas
- Antonios Pantazis
Institutions
- Linköping University (SE)
- Cincinnati Children's Hospital Medical Center (US)
Publication Details
- Journal
- The Journal of Physiology
- Published
- 2026-03-31
- DOI
- https://doi.org/10.1113/jp290728
- Primary Topic
- Cardiac electrophysiology and arrhythmias
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Region Östergötland
- Hjärnfonden
- Linköpings Universitet
- Vetenskapsrådet