gene

HCRTR2

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about HCRTR2: 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.

252Connections

2Hypotheses

2Analyses

50Outgoing

50Incoming

3Experiments

2Debates

Summary

HCRTR2 is a gene implicated in neurodegeneration research. Key relationships include: associated with, co discussed, activates. Associated with ALS, Als, Cardiovascular. Connected to 71 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	HCRTR2
Protein Type	Gpcr
Target Class	Gpcr
Function	Small molecule antagonist blocking orexin receptor signaling
Mechanism of Action	Small molecule antagonist blocking orexin receptor signaling
Druggability	Medium (0.60)
Clinical Stage	Approved
Pathways	Circadian rhythm / glymphatic clearance, Microglial activation / TREM2 signaling, Sleep-Wake Transition, hyperarousal
UniProt ID	S4WX84
GeneCards	HCRTR2
Human Protein Atlas	HCRTR2
Associated Diseases	Als, Alzheimer, Alzheimer's disease
Known Drugs/Compounds	Dexmedetomidine
Interactions	ACE, ADRA1A, ADRA1B, AND, ANXIETY, AQP4
SciDEX Target	View Target Profile (8 clinical trials)
SciDEX Hypotheses	Night-phase orexin receptor antagonism rescues AD Orexin-Microglia Modulation Therapy
KG Connections	243 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

🔮 Predicted Structure: HCRTR2 — AlphaFold S4WX84 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Pathway Diagram

graph TD
    HCRTR2["HCRTR2"] -->|"associated"| neurodegeneration["neurodegeneration"]
    HCRTR2["HCRTR2"] -->|"interacts"| HCRTR1["HCRTR1"]
    HCRTR2["HCRTR2"] -->|"co discussed"| CLOCK["CLOCK"]
    HCRTR2["HCRTR2"] -->|"co discussed"| BDNF["BDNF"]
    HCRTR2["HCRTR2"] -->|"co discussed"| AQP4["AQP4"]
    HCRTR2["HCRTR2"] -->|"co discussed"| MTNR1A["MTNR1A"]
    HCRTR1_1["HCRTR1"] -->|"interacts"| HCRTR2["HCRTR2"]
    BMAL1["BMAL1"] -->|"co discussed"| HCRTR2["HCRTR2"]
    AQP1["AQP1"] -->|"co discussed"| HCRTR2["HCRTR2"]
    KCNK2["KCNK2"] -->|"co discussed"| HCRTR2["HCRTR2"]
    style HCRTR2 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:2px,color:#e0e0e0

Outgoing (180)

Target	Relation	Type	Str
Arousal	mediates	process	0.90
Wakefulness	promotes	process	0.90
sleep-wake control	modulates	process	0.90
therapeutic_target	therapeutic_target	process	0.85
Relapse Free Survival	biomarker_for	phenotype	0.85
Sleep-Wake Transition	regulates	process	0.85
Sleep-Wake Transition	associated_with	process	0.85
Executive Function	regulates	phenotype	0.85
CRF	interacts_with	protein	0.85
Attention	regulates	phenotype	0.85
Memory	regulates	phenotype	0.85
Interindividual Variability In Anesthetic Response	contributes_to	phenotype	0.82
Loss Of Consciousness	associated_with	phenotype	0.80
Time To Wake	associated_with	phenotype	0.80
Time To Loss Of Consciousness	associated_with	phenotype	0.80
Hemodynamic Stability	associated_with	phenotype	0.80
Narcolepsy	implicated_in	disease	0.80
BNST neuronal excitability	regulates	phenotype	0.80
anxiety	modulates	phenotype	0.80
CX3CR1	modulates_via_microglia	gene	0.80
hemodynamic stability	regulates	phenotype	0.75
Dexmedetomidine	interacts_with	drug	0.75
sleep-wake transition	associated_with	biological_process	0.70
Alzheimer'S Disease	associated_with	disease	0.70
HCRTR1	interacts_with	gene	0.70
neurodegeneration	associated_with	disease	0.70
Ms	activates	disease	0.65
Ptsd	associated_with	disease	0.65
Addiction	activates	disease	0.65
Schizophrenia	associated_with	disease	0.65
Als	activates	disease	0.65
Ms	regulates	disease	0.65
Als	associated_with	disease	0.65
Obesity	therapeutic_target	disease	0.65
ALS	inhibits	disease	0.65
Anxiety	activates	disease	0.65
Diabetes	associated_with	disease	0.65
Cardiovascular	associated_with	disease	0.65
ALS	expressed_in	disease	0.65
Ms	associated_with	disease	0.65
ALS	regulates	disease	0.65
Obesity	causes	disease	0.65
Dementia	regulates	disease	0.65
Als	expressed_in	disease	0.65
Alzheimer	associated_with	disease	0.65
Als	inhibits	disease	0.65
ALS	associated_with	disease	0.65
Cancer	associated_with	disease	0.65
Obesity	associated_with	disease	0.65
Depression	inhibits	disease	0.65

Incoming (72)

Source	Relation	Type	Str
Orexinergic Neurons	expressed_in	cell_type	0.92
Oveporexton	binds	drug	0.90
h-9e9fee95	targets	hypothesis	0.90
h-8597755b	targets	hypothesis	0.90
NEURON	interacts_with	cell_type	0.90
HCRTR1	associated_with	gene	0.90
HCRT	associated_with	gene	0.90
Rs2653349	biomarker_for	biomarker	0.75
HCRTR1	interacts_with	gene	0.70
HCRTR1	treats	gene	0.60
CD4	expressed_in	gene	0.60
HCRT2	associated_with	gene	0.60
DRD2	activates	gene	0.60
HRH3	activates	gene	0.60
PNOC	therapeutic_target	gene	0.60
HCRTR1	regulates	gene	0.60
TRPC6	associated_with	gene	0.60
PNOC	associated_with	gene	0.60
HCRTR1	activates	gene	0.60
HCRTR1	expressed_in	gene	0.60
HCRT	expressed_in	gene	0.60
HCRT	regulates	gene	0.60
ACE	associated_with	gene	0.60
TRPC6	therapeutic_target	gene	0.60
GHRL	associated_with	gene	0.60
ANXIETY	activates	gene	0.60
DEMENTIA	regulates	gene	0.60
ACE	interacts_with	gene	0.60
HCRT	interacts_with	gene	0.60
HCRTR1	biomarker_for	gene	0.60
HCRTR1	inhibits	gene	0.60
CD4	associated_with	gene	0.60
GENES	therapeutic_target	gene	0.60
HCRTR1	targets	gene	0.60
ALZHEIMER	associated_with	gene	0.60
DNA	associated_with	gene	0.60
HCRT1	associated_with	gene	0.60
GENES	associated_with	gene	0.60
AQP4	activates	gene	0.55
GENES	co_discussed	gene	0.50
CLOCK	co_mentioned_with	gene	0.50
narcolepsy	expressed_in	disease	0.50
narcolepsy	regulates	disease	0.50
narcolepsy	inhibits	disease	0.50
CX3CR1	debate_co_mention	gene	0.45
CACNA1G	debate_co_mention	gene	0.45
CLOCK	debate_co_mention	gene	0.45
AQP4	debate_co_mention	gene	0.45
excitotoxicity	debate_co_mention	process	0.45
AQP1	debate_co_mention	gene	0.45

Targeting Hypotheses (2)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Night-phase orexin receptor antagonism rescues AD by restori	0.733	neurodegeneration	Orexin-A manipulation in AD cognition an
Orexin-Microglia Modulation Therapy	0.707	neurodegeneration	Sleep disruption as cause and consequenc

Mentioning Analyses (2)

Scientific analyses that reference this entity

Sleep disruption as cause and consequence of neurodegeneration

neurodegeneration | 2026-04-01 | 7 hypotheses Top: 0.763

Perivascular spaces and glymphatic clearance failure in AD

neurodegeneration | 2026-04-01 | 7 hypotheses Top: 0.841

Experiments (3)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Brainstem Circuit Modulation for PSP	clinical	ALS	0.400	0.50	human	proposed	$5,460,000
Combination Therapy Sequencing in Parkinson's Disease	validation	Parkinson's Disease	0.400	0.50	human	proposed	$2,280,000
Non-Dopaminergic Neurotransmitter Degeneration in PD - Experiment Desi	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$5,460,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Low Rates of Gastrointestinal and Non-Gastrointestinal Complications for Screeni [PMID:29031502]	Wang L, Mannalithara A, Singh G, Ladabau	Gastroenterology	2018	1
Als and Ftd: Insights into the disease mechanisms and therapeutic targets. [PMID:29031901]	Liscic RM	Eur J Pharmacol	2017	1
Lysosomal cholesterol activates mTORC1 via an SLC38A9-Niemann-Pick C1 signaling [PMID:28336668]	Castellano BM, Thelen AM, Moldavski O, F	Science	2017	1
Defining the consequences of genetic variation on a proteome-wide scale. [PMID:27309819]	Chick JM, Munger SC, Simecek P, Huttlin	Nature	2016	1
A comparative examination of thrombocyte/platelet immunity. [PMID:25448707]	F Ferdous, T R Scott	Immunology letters	2015	1
A three-dimensional human neural cell culture model of Alzheimer's disease. [PMID:25307057]	Choi SH, Kim YH, Hebisch M, Sliwinski C,	Nature	2014	1
Dual hypocretin receptor antagonists enhance sleep and nursing behavior in lacta [PMID:41870530]	["Rivas M", "Pe\u00f1a F", "Prota C", "C	Psychopharmacology	2026	0
Prioritizing Neuroactive Ligands Using Motif-Guided Virtual Discovery and Zebraf [PMID:41648545]	["Ginsparg A", "Martinez J", "Patel I",	bioRxiv : the preprint server	2026	0
Effects of Oveporexton, an Orexin Receptor 2-Selective Agonist, on Cognition in [PMID:41359331]	["Lammers G", "Plazzi G", "Mignot E", "P	JAMA neurology	2026	0
Association between genetic polymorphisms in circadian cycle genes ( [PMID:41787892]	["Alves R", "da Cunha L", "Albuquerque A	Chronobiology international	2026	0
Sex-Specific Effects of Hypocretin Receptor Signaling in Corticotropin-Releasing [PMID:41256182]	["Ma Y", "Sardar H", "Benabou M", "Yu A"	Biological psychiatry global o	2026	0
Estimation of the Orexin Receptor Occupancy From Human Plasma Pharmacokinetics o [PMID:41622624]	["Kamigaso S", "Konno Y", "Hikichi H", "	Pharmacology research & perspe	2026	0
Social defeat stress responses in the stress alternative model are dependent on [PMID:41834039]	["Yaeger J", "John M", "Ledesma L", "Gre	Biology of sex differences	2026	0
Signal transduction, dimerization, and therapeutic targeting of Orexin and recep [PMID:41383480]	Zhang S, Wang P, Ji B, Shao Y, Hou S et	Front Pharmacol	2025	0
Acute carbamoylated erythropoietin reduces social stress-induced anxiety and dep [PMID:40514007]	Yaeger JDW, John MM, Ledesma LJ, Krupp K	Neuropharmacology	2025	0
Involvement of the Orexin 1 and 2 Receptors in Nucleus Incertus (NI) on Modulati [PMID:40599447]	Eslami F, Akbari E, Babapour V, Zendehde	Archives of Razi Institute	2024	0
Hypothalamic molecular correlates of photoperiod-induced spring migration in int [PMID:36526025]	Sharma A, Tripathi V, Kumar V	Molecular and cellular endocri	2023	0
Orexin-A differentially modulates inhibitory and excitatory synaptic transmissio [PMID:33582153]	Ruan HZ, Wang LQ, Yuan F, Weng SJ, Zhong	Neuropharmacology	2021	0
Modulation by orexin A of spontaneous excitatory and inhibitory transmission in [PMID:29705705]	Wang C, Fujita T, Kumamoto E	Biochemical and biophysical re	2018	0
Mechanistic insights into influenza vaccine-associated narcolepsy. [PMID:27031682]	Ahmed SS, Steinman L	Human vaccines & immunotherape	2016	0

Debates (2)

Multi-agent debates referencing this entity

Sleep disruption as cause and consequence of neurodegeneration

closed · Rounds: 4 · Score: 0.91 · 2026-04-06

Perivascular spaces and glymphatic clearance failure in AD

closed · Rounds: 4 · Score: 0.95 · 2026-04-06

Related Research

Hypotheses and analyses mentioning HCRTR2 in their description or question text

No additional research found