Last update 19 Sep 2024

KCNIP4

Last update 19 Sep 2024

Basic Info

Synonyms

A-type potassium channel modulatory protein 4, CALP, Calsenilin-like protein

+ [6]

Introduction

Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly inactivating A-type potassium channels. Modulates KCND2 channel density, inactivation kinetics and rate of recovery from inactivation in a calcium-dependent and isoform-specific manner (PubMed:11847232, PubMed:18957440, PubMed:23576435). Modulates KCND3/Kv4.3 currents (PubMed:23576435). Isoform 4 does not increase KCND2 expression at the cell membrane (PubMed:18957440). Isoform 4 retains KCND3 in the endoplasmic reticulum and negatively regulates its expression at the cell membrane.

Drugs associated with KCNIP4

IQM-266

Target

KCNIP4

Mechanism

KCNIP4 inhibitors

Active Org.

Instituto de Química Médica

Originator Org.

Instituto de Química Médica

Active Indication

Alzheimer Disease

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with KCNIP4

100 Translational Medicine associated with KCNIP4

0 Patents (Medical) associated with KCNIP4

134

Literatures (Medical) associated with KCNIP4

01 Aug 2024·Ecotoxicology and Environmental Safety

Fluoride-induced hypertension by regulating RhoA/ROCK pathway and phenotypic transformation of vascular smooth muscle cells: In vitro and in vivo evidence

Article

Author: Yang, Xiyue ; Wang, Sheng ; Gao, Yanhui ; Ma, Hao ; Yang, Wenjing ; Chu, Fang ; Jiao, Zhe ; Lu, Chunqing ; Wang, Qiaoyu ; Bu, Keming ; Sun, Dianjun ; Sun, Hongna

Fluoride exposure has been implicated as a potential risk factor for hypertension, but the underlying mechanisms remain unclear. This study investigated the role of the RhoA/ROCK signaling pathway in fluoride-induced hypertension. Male Wistar rats were divided into different groups and exposed to varying concentrations of sodium fluoride (NaF) or sodium chloride (NaCl) via drinking water. The rats' blood pressure was measured, and their aortic tissue was utilized for high-throughput sequencing analysis. Additionally, rat and A7r5 cell models were established using NaF and/or Fasudil. The study evaluated the effects of fluoride exposure on blood pressure, pathological changes in the aorta, as well as the protein/mRNA expression levels of phenotypic transformation indicators (a-SMA, calp, OPN) in vascular smooth muscle cells (VSMCs), along with the RhoA/ROCK signaling pathway (RhoA, ROCK1, ROCK2, MLC/p-MLC). The results demonstrated that fluoride exposure in rats led to increased blood pressure. High-throughput sequencing analysis revealed differential gene expression associated with vascular smooth muscle contraction, with the RhoA/ROCK signaling pathway emerging as a key regulator. Pathological changes in the rat aorta, such as elastic membrane rupture and collagen fiber deposition, were observed following NaF exposure. However, fasudil, a ROCK inhibitor, mitigated these pathological changes. Both in vitro and in vivo models confirmed the activation of the RhoA/ROCK signaling pathway and the phenotypic transformation of VSMCs from a contractile to a synthetic state upon fluoride exposure. Fasudil effectively inhibited the activities of ROCK1 and ROCK2 and attenuated the phenotypic transformation of VSMCs. In conclusion, fluoride has the potential to induce hypertension through the activation of the RhoA/ROCK signaling pathway and phenotypic changes in vascular smooth muscle cells. These results provide new insights into the mechanism of fluoride-induced hypertension.

28 Aug 2023·Animals : an open access journal from MDPI

Genome-Wide Association Study to Identify QTL for Carcass Traits in Korean Hanwoo Cattle.

Article

Author: Park, Byoungho ; Kim, Nam-Young ; Jin, Shil ; Kim, Jong-Joo ; Alam, Mohammad Zahangir ; Won, Jeong Il ; Iqbal, Asif ; Haque, Md Azizul ; Lee, Yun-Mi ; Ha, Jae-Jung

This study aimed to identify genetic associations with carcass traits in Hanwoo cattle using a genome-wide association study. A total of 9302 phenotypes were analyzed, and all animals were genotyped using the Illumina Bovine 50K v.3 SNP chip. Heritabilities for carcass weight (CWT), eye muscle area (EMA), backfat thickness (BF), and marbling score (MS) were estimated as 0.42, 0.36, 0.36, and 0.47, respectively, using the GBLUP model, and 0.47, 0.37, 0.36, and 0.42, respectively, using the Bayes B model. We identified 129 common SNPs using DGEBV and 118 common SNPs using GEBV on BTA6, BTA13, and BTA14, suggesting their potential association with the traits of interest. No common SNPs were found between the GBLUP and Bayes B methods when using residuals as a response variable in GWAS. The most promising candidate genes for CWT included SLIT2, PACRGL, KCNIP4, RP1, XKR4, LYN, RPS20, MOS, FAM110B, UBXN2B, CYP7A1, SDCBP, NSMAF, TOX, CA8, LAP3, FAM184B, and NCAPG. For EMA, the genes IBSP, LAP3, FAM184B, LCORL, NCAPG, SLC30A9, and BEND4 demonstrated significance. Similarly, CYP7B1, ARMC1, PDE7A, and CRH were associated with BF, while CTSZ, GNAS, VAPB, and RAB22A were associated with MS. This finding offers valuable insights into genomic regions and molecular mechanisms influencing Hanwoo carcass traits, aiding efficient breeding strategies.

25 Jul 2023·Schizophrenia (Heidelberg, Germany)

Genome-wide association study identified six loci associated with adverse drug reactions to aripiprazole in schizophrenia patients.

Article

Author: Wang, Xueping ; Lu, Zhe ; Yue, Weihua ; Sun, Yaoyao ; Zhang, Yuyanan ; Lu, Tianlan ; Mei, Dongli ; Yan, Hao

Aripiprazole is recommended for routine use in schizophrenia patients. However, the biological mechanism for the adverse drug reactions (ADRs) among schizophrenia patients with the antipsychotic drug aripiprazole is far from clear. To explore the potential genetic factors that may cause movement-related adverse antipsychotic effects in patients, we conducted an association analysis between movement-related ADRs and SNPs in schizophrenia patients receiving aripiprazole monotherapy. In this study, multiple ADRs of 384 patients were quantified within 6-week treatment, and the scores of movement-related ADRs at baseline and follow-up time points during treatment were obtained. The highest score record was used as the quantitative index in analysis, and genetic analysis at the genome-wide level was conducted. The SNP rs4149181 in SLC22A8 [P = 2.28 × 10^-8] showed genome-wide significance, and rs2284223 in ADCYAP1R1 [P = 9.76 × 10^-8], rs73258503 in KCNIP4 [P = 1.39 × 10^-7], rs678428 in SMAD9 [P = 4.70 × 10^-7], rs6421034 in NAP1L4 [P = 6.80 × 10^-7], and rs1394796 in ERBB4 [P = 8.60 × 10^-7] were found to be significantly associated with movement-related ADRs. The combined prediction model of these six loci showed acceptable performance in predicting adverse events [area under the curve (AUC): 0.84]. Combined with the function and network of the above genes and other candidate loci (KCNA1, CACNG1, etc.), we hypothesize that SLC22A8 and KCNIP4-Kv channel perform their respective functions as transporter or channel and participate in the in vivo metabolism or effects of aripiprazole. The above results imply the important function of ion transporters and channels in movement-related adverse antipsychotic effects in aripiprazole monotherapy schizophrenia patients.

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