gene

HCN1

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about HCN1: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

326Connections

2Hypotheses

3Analyses

50Outgoing

50Incoming

9Experiments

3Debates

Summary

HCN1 is a gene implicated in neurodegeneration research. Key relationships include: implicated in, associated with, regulates. Associated with AD, ALI, ALS. Connected to 86 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	HCN1
Protein Type	Ion Channel
Target Class	Ion Channel
Function	HCN1 is a cyclic nucleotide-gated channel with unique properties
Mechanism of Action	HCN1 encodes a hyperpolarization-activated cyclic nucleotide-gated channel critical for neuronal pacemaking and synaptic integration, with dysregulation linked to hyperexcitability disorders and potential neurodegeneration mechanisms. Specifically, HCN1 channel dysfunction can alter neuronal excitability, synaptic plasticity, and potentially contribute to neuronal death or dysfunction in conditions like epilepsy and neurodegenerative diseases.
Subcellular Localization	Dendritic shafts, dendritic spines, axon initial segment
Druggability	Medium (0.51)
Clinical Stage	Approved
Pathways	HCN1-Mediated Resonance Frequency Stabilization Th, Scotopic Pathway
UniProt ID	A0A0U1RQR7
GeneCards	HCN1
Human Protein Atlas	HCN1
Channel Type	Hyperpolarization-activated cyclic nucleotide-gated channel (HCN1)
Primary Structure	Six transmembrane segments (S1-S6) with cyclic nucleotide-binding domain (CNBD) in C-terminus
Biophysical Properties	Activated by hyperpolarization, modulated by cAMP, slow kinetics
Associated Diseases	Absence Seizures, AD, ALI, Als, Alzheimer's disease
Known Drugs/Compounds	ketamine, propofol, Propofol, Zd7288
Interactions	AND, App, BDNF, C1Q, EPILEPSY, Fus
SciDEX Target	View Target Profile (8 clinical trials)
SciDEX Hypotheses	HCN1-Mediated Resonance Frequency Stabilization Th HCN1-Selective Blockade Normalizes Thalamic Reboun
KG Connections	325 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

🔮 Predicted Structure: HCN1 — AlphaFold A0A0U1RQR7 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (3)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    HCN1["HCN1"] -->|"regulates"| HCN1_Mediated_Resonance_Freque["HCN1-Mediated Resonance Frequency Stabilization Th"]
    HCN1["HCN1"] -->|"protects against"| Epilepsy["Epilepsy"]
    HCN1["HCN1"] -->|"associated"| Ms["Ms"]
    HCN1["HCN1"] -->|"associated"| Epilepsy_1["Epilepsy"]
    HCN1["HCN1"] -.->|"inhibits"| Ms_2["Ms"]
    HCN1["HCN1"] -->|"associated"| Als["Als"]
    h_d40d2659["h-d40d2659"] -->|"therapeutic target"| HCN1["HCN1"]
    h_d40d2659_3["h-d40d2659"] -->|"targets"| HCN1["HCN1"]
    JUN["JUN"] -.->|"inhibits"| HCN1["HCN1"]
    HCN2["HCN2"] -.->|"inhibits"| HCN1["HCN1"]
    style HCN1 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:2px,color:#e0e0e0

Outgoing (251)

Target	Relation	Type	Str
hyperpolarization-activated current	mediates	process	0.95
Retinal Photoresponse	modulates	process	0.95
Retinal Photoresponse	regulates	process	0.95
Epileptogenesis	associated_with	process	0.95
dorsal CA1	expressed_in	brain_region	0.95
Supragranular Pyramidal Neuron	expressed_in	cell_type	0.95
Ih Current	mediates	mechanism	0.95
Absence Seizures	associated_with	disease	0.95
temporal cortex	expressed_in	brain_region	0.95
supragranular pyramidal neurons	expressed_in	cell_type	0.95
Hcn Channel	involved_in	protein	0.94
Voltage-Dependent Gating	mediates	mechanism	0.90
Scotopic Pathway	involved_in	pathway	0.90
Retina	expressed_in	cell_type	0.90
RETINA	expressed_in	entity	0.90
Neocortex	expressed_in	cell_type	0.90
ABSENCE SEIZURES	associated_with	entity	0.90
HIPPOCAMPUS	expressed_in	entity	0.90
Rod System Response	modulates	process	0.90
CORTEX	expressed_in	entity	0.90
Rod System Response	regulates	phenotype	0.90
Seizures	involved_in	phenotype	0.90
cation channel activity	mediates	process	0.90
Membrane Potential	regulates	phenotype	0.90
Light Response Duration	regulates	phenotype	0.90
Pacemaking Activity	essential_for	biological_process	0.90
Ih	mediates	process	0.90
Stress-Induced Neuronal Dysfunction	mediates	mechanism	0.90
Epileptic Seizures	associated_with	phenotype	0.90
PACEMAKING ACTIVITY	involved_in	entity	0.90
NEURAL SIGNALLING	involved_in	entity	0.90
neuronal excitability	regulates	process	0.90
Adaptive Stress Responses	involved_in	phenotype	0.90
Retinal Photoresponses	shapes	biological_process	0.90
Light Response Duration	modulates	phenotype	0.90
Heart	expressed_in	cell_type	0.85
light stimulus threshold	regulates	phenotype	0.85
Neuropathic Pain	therapeutic_target	disease	0.85
Neural Signalling	involved_in	process	0.85
Central Nervous System	expressed_in	brain_region	0.85
Repetitive Light Stimulation Processing	involved_in	process	0.85
Pacemaking Activity	involved_in	process	0.85
EPILEPSY	associated_with	entity	0.85
SEIZURES	therapeutic_target	entity	0.85
Ih Current	regulates	mechanism	0.85
Flicker Fusion Frequency	regulates	phenotype	0.85
Response Waveform Width	modulates	phenotype	0.85
Rod Inner Segment	expressed_in	cell_type	0.85
Flicker Fusion Frequency	modulates	phenotype	0.85
Childhood Absence Epilepsy	associated_with	disease	0.85

Incoming (75)

Source	Relation	Type	Str
Propofol	associated_with	drug	0.98
PROPOFOL	binds_to	entity	0.95
Ketamine-Aln	associated_with	drug	0.95
PROPOFOL	inhibits	entity	0.95
Propofol	inhibits	drug	0.95
Zd7288	inhibits	drug	0.90
glutamatergic neurons	expressed_in	cell_type	0.90
chronic epilepsy	downregulates	phenotype	0.90
propofol	inhibits	drug	0.90
propofol	restores_voltage_gating	drug	0.90
h-d40d2659	targets	hypothesis	0.90
M305L MUTATION	associated_with	entity	0.90
D401H MUTATION	associated_with	entity	0.90
R590Q MUTATION	associated_with	entity	0.90
corticosterone	upregulates	compound	0.90
L2/3 IT_1 transcriptomic cell type	expressed_in	cell_type	0.88
HCN1 R590Q mutation	causes	process	0.85
glucocorticoid signaling	activates	pathway	0.85
M305L	destabilizes_closed_state	genetic_variant	0.80
Ketamine	downregulates	drug	0.80
R590Q Mutation	associated_with	biomarker	0.80
predator-scent stress	upregulates	process	0.80
D401H	destabilizes_closed_state	genetic_variant	0.80
HCN	activates	gene	0.70
NEURODEGENERATION	activates	gene	0.60
EPILEPSY	causes	gene	0.60
HCN	associated_with	gene	0.60
JUN	inhibits	gene	0.60
HCN2	inhibits	gene	0.60
HCN4	associated_with	gene	0.60
HCN2	associated_with	gene	0.60
JUN	causes	gene	0.60
ACSL4	associated_with	gene	0.60
ketamine	activates	compound	0.60
ketamine	expressed_in	compound	0.60
BDNF	activates	gene	0.60
BDNF	regulates	gene	0.60
ketamine	regulates	compound	0.60
BDNF	implicated_in	gene	0.60
ketamine	implicated_in	compound	0.60
HCN	regulates	gene	0.60
GENES	associated_with	gene	0.60
GENES	causes	gene	0.60
NEURODEGENERATIVE DISEASES	regulates	gene	0.60
PARKINSON'S DISEASE	regulates	gene	0.60
PARKINSON	regulates	gene	0.60
EPILEPSY	protects_against	entity	0.60
EPILEPSY	interacts_with	entity	0.60
EPILEPSY	associated_with	entity	0.60
EPILEPSY	activates	entity	0.60

Targeting Hypotheses (2)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
HCN1-Mediated Resonance Frequency Stabilization Therapy	0.562	neurodegeneration	Selective vulnerability of entorhinal co
HCN1-Selective Blockade Normalizes Thalamic Rebound Bursting	0.526	synaptic biology	How do P/Q channel deficits paradoxicall

Mentioning Analyses (3)

Scientific analyses that reference this entity

Experiments (9)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Brain Connectivity-Targeted tACS Trial in Early AD	clinical	Alzheimer's Disease	0.509	0.50	human postmortem brain tissue	proposed	$520,000
s:** - Test whether HCN1 knockout specifically in EC layer II accelera	falsification	Alzheimer's Disease	0.400	0.50	cell_line	proposed	$80,000
tACS Connectivity Trial in Early Alzheimer's	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$5,460,000
Brain Connectivity-Targeted tACS Trial in Early AD	clinical	Alzheimer's Disease	0.400	0.50	mouse	proposed	$730,000
DLB Cognitive Fluctuation Mechanism Experiment	clinical	Neurodegeneration	0.400	0.50	human	proposed	$6,550,000
Levodopa Response Determinants in PSP — Biomarker-Guided Prediction St	clinical	Neurodegeneration	0.400	0.50	human	proposed	$5,460,000
Migraine Cortical Hyperexcitability and Alzheimer's Disease Risk: Long	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$5,460,000
Neural Oscillation Dysfunction Validation in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$5,460,000
Biomechanical Impact Profiles and Chronic Traumatic Encephalopathy Phe	clinical	Neurodegeneration	0.400	0.50	in_silico	proposed	$200,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
HCN channels reveal conserved and divergent physiology in supragranular pyramida [PMID:40894563]	["Radaelli C", "Schmitz M", "Liu X", "Sa	bioRxiv (Cold Spring Harbor La	2025	1
Propofol rescues voltage-dependent gating of HCN1 channel epilepsy mutants. [PMID:39085604]	Kim ED, Wu X, Lee S, Tibbs GR, Cunningha	Nature	2024	1
The Impact of Altered HCN1 Expression on Brain Function and Its Relationship wit [PMID:37366350]	Zhao K, Li Y, Yang X, Zhou L	Curr Neuropharmacol	2023	1
HCN channels and absence seizures. [PMID:37001612]	Crunelli V, David F, Morais TP, Lorincz	Neurobiol Dis	2023	1
Cardiac and neuronal HCN channelopathies. [PMID:32424620]	Rivolta I, Binda A, Masi A, DiFrancesco	Pflugers Arch	2020	1
HCN1 channels significantly shape retinal photoresponses. [PMID:22183410]	Tanimoto N, Brombas A, Müller F, Seelige	Adv Exp Med Biol	2012	1
HCN channels reveal conserved and divergent physiology in supragranular pyramida [PMID:41559478]	["Radaelli C", "Schmitz M", "Liu X", "Sa	Communications biology	2026	0
Comprehensive classification of HCN1 variants linked to neurodevelopmental disor [PMID:41890092]	["Castelli R", "Marini C", "Porro A", "C	bioRxiv : the preprint server	2026	0
Impact of subanesthetic ketamine delivered via AmyloLipid nanovesicle (ALN)-base [PMID:41876451]	["Levi G", "Sintov A", "Zohar J", "Todde	Translational psychiatry	2026	0
Subthreshold Kir and I [PMID:41689161]	["Moreno C", "Riquelme D", "Cornejo C",	Biological research	2026	0
Gene expression of the HCN family in rats with pilocarpine-induced epilepsy and [PMID:41903877]	["Dos Santos R", "Dos Santos M", "da Cos	Brain research	2026	0
Effects of post-stress corticosterone on hippocampal excitability and behavior i [PMID:41654499]	["Kim C", "Kim J", "Michael S"]	Translational psychiatry	2026	0
Atenolol rescues premature mortality in genetic mouse models of sudden unexpecte [PMID:40991209]	["Soh M", "Hu A", "Kuanyshbek A", "Moham	Epilepsia	2026	0
Do Subsets of Widefield Vertical Cells Exist in the Mouse Superior Colliculus? [PMID:41846482]	["Naeem N", "Slusarczyk A", "Bickford M"	The Journal of comparative neu	2026	0
Hyperpolarization-activated cation channels confer tonotopic specialization for [PMID:41822824]	["Owusu-Nyantakyi K", "Hamlette L", "Ash	bioRxiv : the preprint server	2025	0
Multilayered genetic dissection of autism: insights from whole-exome sequencing, [PMID:41420732]	["Eser M", "Hekimoglu G", "Kutlubay B"]	Neurogenetics	2025	0
Amelioration of Chemotherapy Induced Neuropathic Pain using Novel Nicotinic Acid [PMID:40504482]	["Saini A", "Sharma S", "Rana P", "Khann	Molecular neurobiology	2025	0
Genetic Etiology of Developmental and Epileptic Encephalopathy in a Turkish Coho [PMID:41153369]	["Sunnetci-Akkoyunlu D", "Kara B", "Ozer	Genes	2025	0
Exosomes as nanocarriers for brain-targeted delivery of therapeutic nucleic acid [PMID:40533746]	["Sanadgol N", "Abedi M", "Hashemzaei M"	Journal of nanobiotechnology	2025	0
Identifying sex similarities and differences in structure and function of the si [PMID:39703520]	Yin Z, Torre E, Marrot M, Peters CH, Fea	Frontiers in medicine	2024	0

Debates (3)

Multi-agent debates referencing this entity

Related Research

Hypotheses and analyses mentioning HCN1 in their description or question text

No additional research found

HCN1

Understanding Entity Pages

Summary

Wiki Pages (3)

HCN1 Gene

HCN1 Neurons

HCN1 Protein

Pathway Diagram

Outgoing (251)

Incoming (75)

Targeting Hypotheses (2)

Mentioning Analyses (3)

How do P/Q channel deficits paradoxically increase thalamic excitability despite

Is HCN1 dysfunction causal or protective in EC layer II neurodegeneration?

Selective vulnerability of entorhinal cortex layer II neurons in AD

Experiments (9)

Related Papers (20)

Debates (3)

The debate revealed conflicting evidence about whether HCN1 downregulation drive

The abstract describes a counterintuitive finding where loss-of-function P/Q mut

Why do entorhinal cortex layer II stellate neurons die first in AD? Their unique

Related Research