Disease Score gda Association Type Type Original DB Sentence supporting the association PMID PMID Year
CUI: C0037052
Disease: Sick Sinus Syndrome
Sick Sinus Syndrome
0.440 AlteredExpression disease BEFREE This study is to investigate how mitochondrial oxidative stress induces HCN4 downregulation associated with in sick sinus syndrome. 31751569 2020
CUI: C0004238
Disease: Atrial Fibrillation
Atrial Fibrillation
0.490 GeneticVariation disease BEFREE Together with the common KCNE1 variant S38G, previously proposed as a genetic modifier of AF, HCN4-P883R may provide a substrate for the development of AF and TIC. 31481236 2019
CUI: C0004238
Disease: Atrial Fibrillation
Atrial Fibrillation
0.490 Biomarker disease BEFREE In this review, we summarize the current knowledge of the HCN4 channel and ivabradine, including the function of HCN4 in cardiac pacemaking, the mechanism of action of I<sub>f</sub> inhibition by ivabradine, and the pharmacological and clinical effects of ivabradine in cardiac diseases as HF, coronary artery disease, and atrial fibrillation. 30606942 2019
CUI: C1142166
Disease: Brugada Syndrome (disorder)
Brugada Syndrome (disorder)
0.320 GeneticVariation disease BEFREE In the present study, the potential correlation between HCN4 gene variations and the occurrence of SUNDS was investigated. 30452770 2019
CUI: C0205682
Disease: Waist-Hip Ratio
Waist-Hip Ratio
0.100 GeneticVariation phenotype GWASCAT Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry. 30239722 2019
CUI: C0003811
Disease: Cardiac Arrhythmia
Cardiac Arrhythmia
0.080 GeneticVariation phenotype BEFREE Mutations of genes specific for the developmental processes and/or functional status of cardiac conduction system including ion channel promoter (minK-lacZ), GATA family of zinc finger proteins (GATA4), the homeodomain transcription factor (Nkx2.5), the homeodomain-only protein (Hop) and the T-box transcription factors (Tbx2, Tbx3 and Tbx5), hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) and connexins, may cause fetal arrhythmias. 30478614 2019
CUI: C0018801
Disease: Heart failure
Heart failure
0.040 AlteredExpression disease BEFREE We generated transgenic mice (HCN4<sup>tg/wt</sup>) to assess functional consequences of HCN4 overexpression-mediated I<sub>f</sub> increase in cardiomyocytes to levels observed in human heart failure. 31337768 2019
CUI: C0018801
Disease: Heart failure
Heart failure
0.040 Biomarker disease BEFREE In this review, we summarize the current knowledge of the HCN4 channel and ivabradine, including the function of HCN4 in cardiac pacemaking, the mechanism of action of I<sub>f</sub> inhibition by ivabradine, and the pharmacological and clinical effects of ivabradine in cardiac diseases as HF, coronary artery disease, and atrial fibrillation. 30606942 2019
CUI: C0018802
Disease: Congestive heart failure
Congestive heart failure
0.040 Biomarker disease BEFREE In this review, we summarize the current knowledge of the HCN4 channel and ivabradine, including the function of HCN4 in cardiac pacemaking, the mechanism of action of I<sub>f</sub> inhibition by ivabradine, and the pharmacological and clinical effects of ivabradine in cardiac diseases as HF, coronary artery disease, and atrial fibrillation. 30606942 2019
CUI: C0018802
Disease: Congestive heart failure
Congestive heart failure
0.040 AlteredExpression disease BEFREE We generated transgenic mice (HCN4<sup>tg/wt</sup>) to assess functional consequences of HCN4 overexpression-mediated I<sub>f</sub> increase in cardiomyocytes to levels observed in human heart failure. 31337768 2019
CUI: C0018799
Disease: Heart Diseases
Heart Diseases
0.010 Biomarker group BEFREE HCN4 is implicated in spontaneous excitation of the sinoatrial node, while channel dysfunction has been associated with sinus bradycardia, AF and structural heart disease. 31481236 2019
CUI: C0020456
Disease: Hyperglycemia
Hyperglycemia
0.010 Biomarker disease BEFREE In streptozotocin-induced diabetic mice, ivabradine treatment significantly inhibited left ventricular hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) and HCN4 (major components of the I<sub>f</sub> current), activated PP2Ac, and attenuated NF-κB signaling activation and apoptosis, in line with improved histological abnormalities, fibrosis, and cardiac dysfunction without affecting hyperglycemia. 30998977 2019
CUI: C0036572
Disease: Seizures
Seizures
0.010 AlteredExpression phenotype BEFREE Specifically, seizure activity has been shown to alter the messenger RNA (mRNA) and protein expression of voltage-gated sodium channels (Na<sub>v</sub> 1.1, Na<sub>v</sub> 1.5), voltage-gated potassium channels (K<sub>v</sub> 4.2, K<sub>v</sub> 4.3), sodium-calcium exchangers (NCX1), and nonspecific cation-conducting channels (HCN2, HCN4). 31353444 2019
CUI: C0040188
Disease: Tic disorder
Tic disorder
0.010 GeneticVariation disease BEFREE Together with the common KCNE1 variant S38G, previously proposed as a genetic modifier of AF, HCN4-P883R may provide a substrate for the development of AF and TIC. 31481236 2019
CUI: C0234533
Disease: Generalized seizures
Generalized seizures
0.010 Biomarker disease BEFREE VB-specific deletion of HCN2, but not of HCN4, also induced these generalized seizures of the absence type, corroborating a key role of HCN2 in this particular nucleus for controlling consciousness. 31045576 2019
CUI: C0264886
Disease: Conduction disorder of the heart
Conduction disorder of the heart
0.010 GeneticVariation group BEFREE The HCN4 gene is often present in targeted genetic testing panels for various cardiac conduction system disorders and there are several reports of HCN4 variants associated with conduction disorders. 30578647 2019
CUI: C0278076
Disease: Behavioral tic
Behavioral tic
0.010 GeneticVariation disease BEFREE Together with the common KCNE1 variant S38G, previously proposed as a genetic modifier of AF, HCN4-P883R may provide a substrate for the development of AF and TIC. 31481236 2019
CUI: C0424295
Disease: Hyperactive behavior
Hyperactive behavior
0.010 AlteredExpression phenotype BEFREE Our data imply GSK3β activity in the protection of neuronal networks from hyper-activation in response to epileptogenic stimuli and indicate that the anti-epileptogenic function of GSK3β involves modulation of HCN4 level and the synaptic AMPA receptors pool. 30502054 2019
CUI: C2169806
Disease: recurrent muscle twitches (symptom)
recurrent muscle twitches (symptom)
0.010 GeneticVariation phenotype BEFREE Together with the common KCNE1 variant S38G, previously proposed as a genetic modifier of AF, HCN4-P883R may provide a substrate for the development of AF and TIC. 31481236 2019
CUI: C0004238
Disease: Atrial Fibrillation
Atrial Fibrillation
0.490 Biomarker disease CTD_human Biobank-driven genomic discovery yields new insight into atrial fibrillation biology. 30061737 2018
CUI: C0235480
Disease: Paroxysmal atrial fibrillation
Paroxysmal atrial fibrillation
0.300 Biomarker disease CTD_human Biobank-driven genomic discovery yields new insight into atrial fibrillation biology. 30061737 2018
CUI: C2585653
Disease: Persistent atrial fibrillation
Persistent atrial fibrillation
0.300 Biomarker phenotype CTD_human Biobank-driven genomic discovery yields new insight into atrial fibrillation biology. 30061737 2018
CUI: C3468561
Disease: familial atrial fibrillation
familial atrial fibrillation
0.300 Biomarker phenotype CTD_human Biobank-driven genomic discovery yields new insight into atrial fibrillation biology. 30061737 2018
CUI: C0003811
Disease: Cardiac Arrhythmia
Cardiac Arrhythmia
0.080 Biomarker phenotype BEFREE The transgenic overexpression of HCN4 did not induce tachycardia, but reduced heart rate variability, while the conditional knockdown of HCN4 gave rise to sinus arrhythmia. 29315578 2018
CUI: C0003811
Disease: Cardiac Arrhythmia
Cardiac Arrhythmia
0.080 Biomarker phenotype BEFREE Unlike beta-adrenoreceptor blockade, HCN4 inhibition while lowering heart rate does not protect from atrial arrhythmias under conditions of experimental cardiac sympathetic activation. 29773827 2018