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.

344Connections

2Hypotheses

2Analyses

50Outgoing

50Incoming

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
Region	Expression Level
[Cortex](/brain-regions/cortex) (Layer 5)	High
Hippocampus CA1	High
Associated Diseases	AD, ALI, ALS, AMI, ARM, Absence Seizures
Known Drugs/Compounds	Propofol, ketamine, Zd7288, propofol
Interactions	HCN2, JUN, NPY, KCNH2, NEURODEGENERATION, AND
SciDEX Target	View Target Profile (8 clinical trials)
SciDEX Hypotheses	HCN1-Selective Blockade Normalizes Thalamic Reboun HCN1-Mediated Resonance Frequency Stabilization Th
KG Connections	344 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 (21)

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 (268)

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

Incoming (76)

Source	Relation	Type	Str
Propofol	binds	drug	0.98
Propofol	inhibits	drug	0.95
Ketamine-Aln	associated_with	drug	0.95
PROPOFOL	inhibits	entity	0.95
PROPOFOL	binds_to	entity	0.95
Propofol	associated_with	drug	0.90
M305L MUTATION	associated_with	entity	0.90
D401H MUTATION	associated_with	entity	0.90
R590Q MUTATION	associated_with	entity	0.90
chronic epilepsy	downregulates	phenotype	0.90
glutamatergic neurons	expressed_in	cell_type	0.90
corticosterone	upregulates	compound	0.90
Zd7288	inhibits	drug	0.90
propofol	inhibits	drug	0.90
propofol	restores_voltage_gating	drug	0.90
h-d40d2659	targets_gene	hypothesis	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
h-d40d2659	targets	hypothesis	0.80
R590Q Mutation	associated_with	biomarker	0.80
Ketamine	downregulates	drug	0.80
predator-scent stress	upregulates	process	0.80
M305L	destabilizes_closed_state	genetic_variant	0.80
D401H	destabilizes_closed_state	genetic_variant	0.80
HCN	activates	gene	0.70
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	associated_with	gene	0.60
HCN	inhibits	gene	0.60
HCN	implicated_in	gene	0.60
CDKL5	associated_with	gene	0.60
GRIN1	associated_with	gene	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

Targeting Hypotheses (2)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
HCN1-Selective Blockade Normalizes Thalamic Rebound Bursting	0.526	synaptic biology	How do P/Q channel deficits paradoxicall
HCN1-Mediated Resonance Frequency Stabilization Therapy	0.444	neurodegeneration	Selective vulnerability of entorhinal co

Mentioning Analyses (2)

Scientific analyses that reference this entity

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

neurodegeneration | 2026-04-12 | 0 hypotheses

Selective vulnerability of entorhinal cortex layer II neurons in AD

neurodegeneration | 2026-04-01 | 7 hypotheses Top: 0.484

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
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
HCN channels reveal conserved and divergent physiology in supragranular pyramida [PMID:40894563]	["Radaelli C", "Schmitz M", "Liu X", "Sa	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

HCN1

Understanding Entity Pages

Summary

Wiki Pages (21)

HCN1 Gene

Myoclonus and Cortical Hyperexcitability in Corticobasal Syndrome

CSF Neurofilament Light Chain (NfL) in Neurodegeneration

Mitochondrial Dysfunction in Neurodegeneration

proteasome-ubiquitin-system-dysfunction-parkinsons

Section 153: Virtual Reality Therapy Protocols in CBS/PSP

nfl-blood-test-guided-therapy

Gut-Microbiome-Neurodegeneration Axis

MDS 2026 — Fluid Biomarker Advances in Neurodegeneration

MDS 2026 — Fluid Biomarker Advances in Neurodegeneration

ventral-anterior-thalamic-nucleus

ubiquitin-proteasome-dysfunction-neurodegeneration

Section 156: Pet Therapy and Animal-Assisted Interventions in CBS/PSP

cGMP Signaling Pathway in Neurodegeneration

Lipid Metabolism Dysregulation in Neurodegeneration

Amyotrophic Lateral Sclerosis (ALS)

Iron Homeostasis Dysregulation in Neurodegeneration

Section 249: Advanced LSVT Voice and Speech Therapy in CBS/PSP

Brazilian Neurodegeneration Biotech Companies

Liver-Brain Neurodegeneration Axis

ion-channel-dysfunction-disease-comparison