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Last update 08 May 2025

KCNAB2

Last update 08 May 2025

Basic Info

Synonyms

AKR6A5, hKvbeta2, HKvbeta2.1

+ [8]

Introduction

Regulatory subunit of the voltage-gated potassium (Kv) Shaker channels composed of pore-forming and potassium-conducting alpha subunits and of regulatory beta subunits (PubMed:11825900, PubMed:7649300). The beta-2/KCNAB2 cytoplasmic subunit promotes potassium channel closure via a mechanism that does not involve physical obstruction of the channel pore (PubMed:11825900, PubMed:7649300). Promotes the inactivation of Kv1.4/KCNA4 and Kv1.5/KCNA5 alpha subunit-containing channels (PubMed:11825900, PubMed:7649300). Displays nicotinamide adenine dinucleotide phosphate (NADPH)-dependent aldoketoreductase activity by catalyzing the NADPH-dependent reduction of a wide range of aldehyde and ketone substrates (By similarity). Substrate specificity includes methylglyoxal, 9,10-phenanthrenequinone, prostaglandin J2, 4-nitrobenzaldehyde, 4-nitroacetophenone and 4-oxo-trans-2-nonenal (in vitro, no physiological substrate identified yet) (By similarity). The binding of oxidized and reduced nucleotide alters Kv channel gating and may contribute to dynamic fine tuning of cell excitability (By similarity). Contributes to the regulation of nerve signaling, and prevents neuronal hyperexcitability (By similarity).

Drugs associated with KCNAB2

EAG2-Kvβ2 targeted peptides (SickKids)

Target

KCNAB2 x KCNH5

Mechanism

KCNAB2 blockers [+1]

Active Org.

The Hospital for Sick Children

Originator Org.

The Hospital for Sick Children

Active Indication

Glioblastoma

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with KCNAB2

100 Translational Medicine associated with KCNAB2

0 Patents (Medical) associated with KCNAB2

276

Literatures (Medical) associated with KCNAB2

01 Apr 2025·Journal of Biochemical and Molecular Toxicology

FTO‐mediated m6A Methylation of KCNAB2 Inhibits Tumor Property of Non‐Small Cell Lung Cancer Cells and M2 Macrophage Polarization by Inactivating the PI3K/AKT Pathway

Article

Author: Sun, Zhiguang ; Niu, Jieting ; Li, Yanguang ; Liu, Junfeng

ABSTRACTPotassium voltage‐gated channel subfamily A regulatory beta subunit 2 (KCNAB2) is a potassium voltage‐gated channel subfamily A member that plays a role in non‐small cell lung cancer (NSCLC). However, its functional impact and mechanism in NSCLC are not fully understood. Here, we analyzed its effects on NSCLC cell behaviors and the underlying mechanism.mRNA expression levels were detected by quantitative real‐time polymerase chain reaction (qRT‐PCR),(qRT‐PCR), while protein expression was quantified by western blotting blot analysis or immunohistochemistry assay. NSCLC cell proliferation, migration, invasion, macrophage polarization, and apoptosis were evaluated through cell‐based assays including cell counting kit‐8 (CCK‐8)(CCK‐8) assay, flow cytometry, Tunel assay, wound‐healing assay, and transwell invasion assay. The role of FTO alpha‐ketoglutarate dependent dioxygenase (FTO)‐mediated(FTO)‐mediated m6A methylation in the regulation of KCNAB2 expression and their impacts on NSCLC cell behavior and M2 macrophage polarization were assessed through m6A RNA immunoprecipitation assay and rescue experiments. Xenograft mouse model assay was used to determine the effect of KCNAB2 on tumor formation in vivo.in vivo.KCNAB2 expression was downregulated and FTO expression was upregulated in NSCLC tissues and cells when compared with controls. Moreover, the expression of KCNAB2 was found to be lower in stage III NSCLC patients compared to those at stages I and II, and it was also lower in patients with positive lymph node metastasis compared to those with negative lymph node metastasis. Overexpression of KCNAB2 inhibited NSCLC cell proliferation, migration, invasion, and M2 macrophage polarization, while inducing cell apoptosis. These effects were mediated, at least partially, by inactivating the phosphoinositide 3‐kinase (PI3K)/AKT(PI3K)/AKT pathway. Moreover, ectopic expression of KCNAB2 delayed tumor formation in vivo. FTOin vivo. FTO was found to mediate m6A methylation of KCNAB2, and knockdown of FTO resulted in the upregulation of KCNAB2 expression, leading to inhibition of NSCLC cell behavior and M2 macrophage polarization.KCNAB2 overexpression inhibited NSCLC cell behavior and M2 macrophage polarization by inactivating the PI3KPI3K/AKT/AKT pathway. Furthermore, FTOFTO‐mediated‐mediated m6A methylation was involved in the regulation of KCNAB2 expression in NSCLC. These results enhance our understanding of the role of KCNAB2 in NSCLC and suggest its potential as a therapeutic target.

01 Mar 2024·The Laryngoscope

Cochlear Nucleus Transcriptome of a Fragile X Mouse Model Reveals Candidate Genes for Hyperacusis

Article

Author: Sakano, Hitomi ; Kundu, Paromita ; Castle, Michael S.

ObjectiveFragile X Syndrome (FXS) is a hereditary form of autism spectrum disorder. It is caused by a trinucleotide repeat expansion in the Fmr1 gene, leading to a loss of Fragile X Protein (FMRP) expression. The loss of FMRP causes auditory hypersensitivity: FXS patients display hyperacusis and the Fmr1‐ knock‐out (KO) mouse model for FXS exhibits auditory seizures. FMRP is strongly expressed in the cochlear nucleus and other auditory brainstem nuclei. We hypothesize that the Fmr1‐KO mouse has altered gene expression in the cochlear nucleus that may contribute to auditory hypersensitivity.MethodsRNA was isolated from cochlear nuclei of Fmr1‐KO and WT mice. Using next‐generation sequencing (RNA‐seq), the transcriptomes of Fmr1‐KO mice and WT mice (n = 3 each) were compared and analyzed using gene ontology programs.ResultsWe identified 270 unique, differentially expressed genes between Fmr1‐KO and WT cochlear nuclei. Upregulated genes (67%) are enriched in those encoding secreted molecules. Downregulated genes (33%) are enriched in neuronal function, including synaptic pathways, some of which are ideal candidate genes that may contribute to hyperacusis.ConclusionThe loss of FMRP can affect the expression of genes in the cochlear nucleus that are important for neuronal signaling. One of these, Kcnab2, which encodes a subunit of the Shaker voltage‐gated potassium channel, is expressed at an abnormally low level in the Fmr1‐KO cochlear nucleus. Kcnab2 and other differentially expressed genes may represent pathways for the development of hyperacusis. Future studies will be aimed at investigating the effects of these altered genes on hyperacusis.Level of EvidenceN/A Laryngoscope, 134:1363–1371, 2024

01 Jul 2023·Genes, chromosomes & cancer

TP53 and RB1 alterations characterize poor prognostic subgroups in pediatric acute myeloid leukemia.

Article

Author: Adachi, Souichi ; Hayashi, Yasuhide ; Taki, Tomohiko ; Miyano, Satoru ; Shiba, Norio ; Ohki, Kentaro ; Shiozawa, Yusuke ; Takizawa, Takumi ; Kawasaki, Hirohide ; Kaburagi, Taeko ; Ito, Etsuro ; Matsuo, Hidemasa ; Horibe, Keizo ; Kawamura, Machiko ; Kiyokawa, Nobutaka ; Shimada, Akira ; Ogawa, Seishi ; Yamato, Genki ; Shiraishi, Yuichi ; Hara, Yusuke ; Tomizawa, Daisuke ; Taga, Takashi ; Sotomatsu, Manabu ; Yoshida, Kenichi

Pediatric acute myeloid leukemia (AML) is a poor prognostic subtype of pediatric leukemia. However, the detailed characteristics of many genetic abnormalities are yet to be established in this disease. Although TP53 and RB1 are established as representative tumor suppressor genes in various cancers, alterations of these two genes, especially RB1, have not been characterized in pediatric AML. We performed next-generation sequencing in 328 pediatric AML patients from the Japanese AML-05 trial to ascertain TP53 and RB1 alterations, and their prognostic implications. We identified seven patients with TP53 alterations (2.1%) and six patients with RB1 alterations (1.8%). These alterations were found in only patients without RUNX1::RUNX1T1, CBFB::MYH11, or KMT2A rearrangements. TP53 and RB1 were frequently co-deleted with their neighboring genes PRPF8 and ELF1, respectively. Patients with TP53 alterations had significantly lower 5-year overall survival (OS; 14.3% vs. 71.4%, p < 0.001) and lower 5-year event-free survival (EFS; 0% vs. 56.3%, p < 0.001); similarly, patients with RB1 had significantly lower 5-year OS (0% vs. 71.8%, p < 0.001) and lower 5-year EFS (0% vs. 56.0%, p < 0.001) when compared to patients without these alterations. In gene expression analyses, oxidative phosphorylation, glycolysis, and protein secretion were upregulated in patients with TP53 and/or RB1 alterations. Additionally, Kaplan-Meier analysis revealed that high expressions of SLC2A5, KCNAB2, and CD300LF were related to poor OS of non-core-binding factor AML patients (p < 0.001, p = 0.001, and p = 0.021, respectively). This study will contribute to the development of risk-stratified therapy and precision medicine in pediatric AML.

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KCNAB2

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