gene

TH

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about TH: 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.

743Connections

30Hypotheses

2Analyses

50Outgoing

50Incoming

12Experiments

2Debates

Summary

TH is a gene implicated in neurodegeneration research. Key relationships include: co discussed, associated with, regulates. Associated with CANCER, PARKINSON, TUMOR. Connected to 76 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	TH
Full Name	Tyrosine Hydroxylase
Chromosome	11p15.5
Protein Type	Enzyme
Target Class	Enzyme
Function	is an important component in the neurobiology of neurodegenerative diseases.
Mechanism of Action	Enzyme replacement therapy via L-DOPA supplementation to bypass reduced TH activity
Druggability	Medium (0.54)
Clinical Stage	Approved
Pathways	MAPK
UniProt ID	E7EQI0
NCBI Gene ID	7067
Ensembl ID	ENSG00000180176
OMIM	191290
GeneCards	TH
Human Protein Atlas	TH
Associated Diseases	AUTOPHAGY, DOPAMINE, ER STRESS, FIBROSIS, FRONTOTEMPORAL DEMENTIA, INFLAMMATION
Known Drugs/Compounds	curcumin, dimethyl fumarate, L-DOPA, levodopa, LEVODOPA, rapamycin
Interactions	AADC, ACHE, AD, AIF, AKT, AMPK
SciDEX Target	View Target Profile (8 clinical trials)
KG Connections	742 knowledge graph edges
Databases	GeneCards HPA STRING

🧬 3D Structure Comparison — TH Experimental (PDB) vs Predicted (AlphaFold) — click to expand

📄 Experimental Structure

1TOH — X-ray / Cryo-EM

🔮 AI Predicted Structure

P07101 — AlphaFold

Left: Experimental structure from RCSB PDB | Right: AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (17)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    TH["TH"]
    ULK1["ULK1"]
    TH -->|"associated with"| ULK1
    TNF["TNF"]
    TH -->|"co discussed"| TNF
    VEGFA["VEGFA"]
    TH -->|"associated with"| VEGFA
    TREM2["TREM2"]
    TH -->|"co discussed"| TREM2
    neurodegeneration{"neurodegeneration"}
    TH -->|"implicated in"| neurodegeneration
    TH -->|"associated with"| neurodegeneration
    AADC["AADC"]
    TH -->|"interacts with"| AADC
    h_7bb47d7a["h-7bb47d7a"]
    h_7bb47d7a -->|"therapeutic target"| TH
    h_7bb47d7a -->|"targets"| TH
    AUTOPHAGY["AUTOPHAGY"]
    AUTOPHAGY -->|"associated with"| TH
    SNCA["SNCA"]
    SNCA -->|"associated with"| TH
    AIF1["AIF1"]
    AIF1 -->|"co discussed"| TH
    ATG5["ATG5"]
    ATG5 -->|"co discussed"| TH
    ATG7["ATG7"]
    ATG7 -->|"co discussed"| TH
    AUTOPHAGY -->|"co discussed"| TH
    BECN1["BECN1"]
    BECN1 -->|"co discussed"| TH
    CASP1["CASP1"]
    CASP1 -->|"co discussed"| TH
    GFAP["GFAP"]
    GFAP -->|"co discussed"| TH
    IL1B["IL1B"]
    IL1B -->|"co discussed"| TH
    style TH fill:#1a3a4a,stroke:#4fc3f7,stroke-width:3px,color:#e0e0e0

Outgoing (240)

Target	Relation	Type	Str
TH	encodes	protein	0.00
ventral tegmental area	expressed_in	brain_region	0.95
neurons	associated_with	cell_type	0.90
dopamine_synthesis	regulates	pathway	0.90
oxidative stress response	participates_in	pathway	0.90
Midbrain	expressed_in	brain_region	0.85
Parkinson's Disease	biomarker_for	disease	0.80
Substantia Nigra	expressed_in	cell_type	0.80
Dopaminergic Neurons	expressed_in	cell_type	0.75
OXIDATIVE STRESS	causes	phenotype	0.70
NEUROINFLAMMATION	destabilizes	phenotype	0.70
DEMYELINATION	inhibits	phenotype	0.70
DOPAMINE	regulates	phenotype	0.70
MITOPHAGY	causes	phenotype	0.70
DOPAMINE	activates	phenotype	0.70
LIPID PEROXIDATION	activates	phenotype	0.70
AUTOPHAGY	produces	phenotype	0.70
autophagy pathway	participates_in	pathway	0.70
NEUROINFLAMMATION	exacerbates	phenotype	0.70
mitochondrial dynamics	participates_in	pathway	0.70
STEM CELLS	activates	cell_type	0.70
MITOPHAGY	treats	phenotype	0.70
PARKINSON'S DISEASE	protects_against	disease	0.70
NEURON	protects_against	cell_type	0.70
ALS	regulates	disease	0.70
NEURODEGENERATION	interacts_with	phenotype	0.70
neurons	activates	cell_type	0.70
NEURON	regulates	cell_type	0.70
VEGF	inhibits	gene	0.70
VEGF	regulates	gene	0.70
MTOR	inhibits	gene	0.70
ULK1	phosphorylates	gene	0.70
TAU	modifies	protein	0.70
ULK1	treats	gene	0.70
PROTEOSTASIS	activates	phenotype	0.70
DDC	interacts_with	gene	0.70
L-DOPA	regulates	drug	0.70
L-DOPA	causes	drug	0.70
L-DOPA	activates	drug	0.70
BACE1	regulates	gene	0.70
BDNF	protects_against	gene	0.70
BDNF	activates	gene	0.70
BDNF	regulates	gene	0.70
MYD88	inhibits	gene	0.70
MYD88	interacts_with	gene	0.70
TLR4	regulates	gene	0.70
neurodegeneration	associated_with	disease	0.70
CYTOKINES	activates	phenotype	0.65
DRP1	activates	gene	0.65
DRP1	interacts_with	gene	0.65

Incoming (503)

Source	Relation	Type	Str
TH	encodes	gene	0.00
Rotenone	downregulates	compound	0.95
h-7bb47d7a	targets	hypothesis	0.90
AADC	associated_with	gene	0.80
SLC16A2	associated_with	gene	0.70
levodopa	targets	drug	0.70
APP	associated_with	gene	0.70
ALZHEIMER'S DISEASE	treats	disease	0.70
levodopa	associated_with	compound	0.70
NEURODEGENERATION	destabilizes	phenotype	0.70
TLR4	inhibits	gene	0.70
APP	inhibits	gene	0.70
CYCLOSPORINE	regulates	drug	0.70
DDC	associated_with	gene	0.70
MULTIPLE SCLEROSIS	regulates	disease	0.70
EZH2	inhibits	gene	0.70
MTOR	activates	gene	0.70
TREM2	protects_against	gene	0.65
DOPAMINERGIC	expressed_in	cell_type	0.65
RAPAMYCIN	regulates	drug	0.65
TREM2	activates	gene	0.65
DOPAMINE	targets	phenotype	0.65
SUBSTANTIA NIGRA	causes	brain_region	0.65
NEUROINFLAMMATION	inhibits	phenotype	0.65
CURCUMIN	protects_against	drug	0.65
DRD2	associated_with	gene	0.65
SCHIZOPHRENIA	inhibits	disease	0.65
DOPAMINE	produces	phenotype	0.65
TAU	associated_with	protein	0.65
AUTOPHAGY	associated_with	gene	0.65
MYC	expressed_in	gene	0.65
TREM2	exacerbates	gene	0.65
NLRP3	activates	gene	0.65
TREM2	regulates	gene	0.65
NEURON	inhibits	cell_type	0.65
FERROPTOSIS	regulates	phenotype	0.65
TAU	phosphorylates	protein	0.65
FERROPTOSIS	inhibits	phenotype	0.65
SNCA	associated_with	gene	0.65
MICROGLIA	treats	cell_type	0.65
DEPRESSION	activates	disease	0.60
NEURODEGENERATION	activates	disease	0.60
NEURONS	activates	cell_type	0.60
AKT	associated_with	gene	0.60
ASC	disrupts	gene	0.60
MMP9	associated_with	gene	0.60
SQSTM1	interacts_with	gene	0.60
LC3	treats	gene	0.60
curcumin	treats	compound	0.60
PINK1	treats	gene	0.60

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Closed-loop transcranial focused ultrasound targeting EC-II	0.968	alzheimers	Circuit-level neural dynamics in neurode
GluN2B-Mediated Thalamocortical Control of Glymphatic Tau Cl	0.964	neuroscience	Circuit-level neural dynamics in neurode
Closed-loop optogenetic targeting PV interneurons to restore	0.959	alzheimers	Circuit-level neural dynamics in neurode
Gamma entrainment therapy to restore hippocampal-cortical sy	0.946	alzheimers	Circuit-level neural dynamics in neurode
eIF2α Phosphorylation Imbalance Creates Integrated Stress Re	0.896	als	-

Hypothesis 4: Metabolic Coupling via Lactate-Shuttling Colla	0.895	neurodegeneration	Which specific factors in conditioned me
p38α Inhibitor and PRMT1 Activator Combination to Restore Ph	0.895	neurodegeneration	What is the therapeutic window between i
Multi-Target Hypothesis: Aβ-Induced Cholinergic Damage is Pa	0.887	-	Do β-amyloid plaques and neurofibrillary
Optimized Temporal Window for Metabolic Boosting Therapy Det	0.887	neurodegeneration	How do different microglial subtypes (DA
Beta-frequency entrainment therapy targeting PV interneuron-	0.884	alzheimers	Circuit-level neural dynamics in neurode
Closed-loop tACS targeting EC-II parvalbumin interneurons to	0.869	alzheimers	Circuit-level neural dynamics in neurode
RBM45 Liquid-Liquid Phase Separation Dominance Hijacks RNA P	0.868	als	-
Gamma Oscillation Entrainment Enhances lncRNA-9969-Mediated	0.865	molecular-neurobiology	How does lncRNA-0021 achieve sequence-sp
Closed-loop focused ultrasound targeting EC-II PV interneuro	0.863	alzheimers	Circuit-level neural dynamics in neurode
TREM2 R47H Variant-Driven Metabolic Dysfunction as the Prima	0.862	neurodegeneration	Variant Annotation and Prioritization of
Hypothesis 7: SST-SST1R/Gamma Entrainment-Enhanced Astrocyte	0.839	neurodegeneration	Which specific factors in conditioned me
Sequential Iron Chelation (Deferoxamine) and GPX4 Restoratio	0.838	neurodegeneration	Can ferroptosis inhibitors prevent BBB d
J-protein co-chaperone system mediates selective autophagy t	0.831	protein-biochemistry	Do chaperones selectively recognize path
IL-6 Trans-Signaling Blockade at the Oligodendrocyte-Microgl	0.831	neuroinflammation	How do oligodendrocytes initiate neuroin
Microglial AIM2 Inflammasome as the Primary Driver of TDP-43	0.824	neurodegeneration	What are the mechanisms by which gut mic
STING Antagonists as ALS Therapeutics: Drug Repurposing	0.821	neuroinflammation	How does chronic cGAS/STING activation d
Autophagy-Lysosomal Pathway Dysfunction as a Unifying Proteo	0.820	neurodegeneration	Cross-disease neurodegeneration mechanis
CYP46A1 Small Molecule Activator Therapy	0.819	neurodegeneration	Lipid raft composition changes in synapt
Kinetic Modeling Predicts Threshold-Dependent Efficacy—Early	0.815	protein-folding	Can chaperone enhancement approaches ove
Alpha-theta entrainment therapy to enhance default mode netw	0.000	alzheimers	Circuit-level neural dynamics in neurode
TBK1 Loss Triggers Astrocyte-to-Neuron Senescence Propagatio	0.000	als	What are the mechanisms by which microgl
TBK1 Loss Triggers eIF2α-Mediated Translational Repression T	0.000	als	What are the mechanisms by which microgl
Closed-loop transcranial focused ultrasound with gamma entra	0.000	alzheimers	Circuit-level neural dynamics in neurode
LDLR-Primed LRP1 Transcytosis with pH-Responsive Escape Stra	0.000	neuropharmacology	What is the actual quantitative contribu
Cell-Type-Specific TFEB Modulation Combined with Trehalose f	0.000	proteomics	Quantitative proteomics of the aging syn

Mentioning Analyses (2)

Scientific analyses that reference this entity

Does reduced Prevotellaceae abundance cause PD pathology or result from it?

neurodegeneration | 2026-04-11 | 7 hypotheses

What are the mechanisms by which gut microbiome dysbiosis influences Parkinson's

neurodegeneration | 2026-04-01 | 13 hypotheses Top: 0.924

Experiments (12)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Plant-based dietary patterns and Alzheimer's disease risk in multiethn	clinical	Alzheimer's disease and relate	0.950	0.00	human patients	proposed	N/A
Tet2 modulation in Aβ42-injured mouse hippocampal neurons	exploratory	Alzheimer's disease	0.900	0.00	primary mouse hippocampal neur	proposed	N/A
MAPK pathway inhibition by QTJD through butyrate mechanism	exploratory	Mycoplasma pneumoniae pneumoni	0.900	0.00	Mouse macrophages	proposed	N/A
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
AD Amyloid-Resilient Phenotype Study — Why Some amyloid-Positive Indiv	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$6,550,000
AD Combination Therapy Trial: Anti-Aβ + Anti-Tau	clinical	Alzheimer's Disease	0.400	0.50	cell_line	proposed	$180,000
Biomarker-Guided Sequential Therapy Selection in Alzheimer's Disease	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$5,460,000
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
Cognitive Reserve Mechanisms in Alzheimer's Disease — Molecular Basis	clinical	Alzheimer's Disease	0.400	0.50	human	completed	$6,550,000
Cholinergic System Dysfunction in DLB — Mechanisms and Therapeutic Res	clinical	Alzheimer'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
Complement C1q/C3-CR3 signaling pathway mediates abnormal microglial phagocytosi [PMID:38642614]	Han QQ, Shen SY, Liang LF, Chen XR, Yu J	Brain Behav Immun	2024	1
Metabolic orchestration of cell death by AMPK-mediated phosphorylation of RIPK1. [PMID:37384704]	Zhang T, Xu D, Trefts E, Lv M, Inuzuka H	Science	2023	1
Anatomical and neurochemical profiles of somatostatin-positive neurons in the mo [PMID:41796787]	Tomioka R, Kobayashi K, Song WJ	Neuroscience	2026	0
Subtype-Specific Roles of Anterior Cingulate Cortex Neurons in Pain-Induced Soci [PMID:41799202]	Wan X, Yan Z, Zhang Z, Liu X, Yang D, Zh	Theranostics	2026	0
A comparative analysis of pig-to-rhesus corneal xenotransplantation with various [PMID:41928466]	Lee SH, Yoon CH, Choi HJ, Lee HJ, Kang H	Korean J Ophthalmol	2026	0
Epigenetically regulated pancreatic GABA-somatostatin signaling underlies gestat [PMID:41779871]	Zhu H, Luo S, Liu C, Cheng Y, Ren Z, Mo	Science translational medicine	2026	0
Therapeutic Potential of Somatostatin and Its Analogues in Alzheimer's Disease: [PMID:41854733]	Liu K, Zhang XY, Wang YT, Wang R, Jin RH	Molecular neurobiology	2026	0
Altered Expression of GABA-Related Genes in Schizophrenia: Insights from Meta-An [PMID:41788138]	Singer Y, Yitzhaky A, Hertzberg L	Alpha psychiatry	2026	0
Paracrine inhibition via G protein inwardly rectifying potassium channels regula [PMID:41824458]	Panzer JK, Lang AL, Levi NJ, Garcia PA,	Cell reports	2026	0
Enhancing TREM2 expression activates microglia and modestly mitigates tau pathol [PMID:40122810]	["Chen Kai", "Li Fuyao", "Zhang Shuwen",	Journal of neuroinflammation	2025	0
Licochalcone A prevents cognitive decline in a lipopolysaccharide-induced neuroi [PMID:39930360]	Carrasco M, Guzman L, Olloquequi J, Cano	Molecular medicine (Cambridge,	2025	0
GADD45G operates as a pathological sensor orchestrating reactive gliosis and neu [PMID:40409253]	Shen T, Tai W, Jiang D, Ma S, Zhong X, Z	Neuron	2025	0
Molecular hallmarks of excitatory and inhibitory neuronal resilience to Alzheime [PMID:41035073]	Castanho I, Naderi Yeganeh P, Boix CA, M	Molecular neurodegeneration	2025	0
The cholesterol 24-hydroxylase CYP46A1 promotes α-synuclein pathology in Parkins [PMID:39964974]	Dai L, Wang J, Meng L, Zhang X, Xiao T,	PLoS biology	2025	0
Molecular hallmarks of excitatory and inhibitory neuronal resilience and resista [PMID:39868232]	Castanho I, Yeganeh PN, Boix CA, Morgan	bioRxiv : the preprint server	2025	0
From stress to Alzheimer's: A circuit-based framework for prefrontal cognitive d [PMID:41115499]	Yi JH	Neuroscience letters	2025	0
Enhancing TREM2 expression activates microglia and modestly mitigates tau pathol [PMID:40122810]	["Chen Kai", "Li Fuyao", "Zhang Shuwen",	Journal of neuroinflammation	2025	0
Increased Neuronal Expression of the Early Endosomal Adaptor APPL1 Replicates Al [PMID:40514243]	Jiang Y, Sachdeva K, Goulbourne CN, Berg	The Journal of neuroscience :	2025	0
Hippocampal Interneurons Shape Spatial Coding Alterations in Neurological Disord [PMID:40392508]	Ikebara JM, Jorge RS, Marinho LSR, Higa	Molecular neurobiology	2025	0
Somatostatin and the pathophysiology of Alzheimer's disease. [PMID:38484981]	Almeida VN	Ageing Res Rev	2024	0

Debates (2)

Multi-agent debates referencing this entity

Does reduced Prevotellaceae abundance cause PD pathology or result from it?

closed · Rounds: 4 · Score: 0.95 · 2026-04-11

What are the mechanisms underlying what are the mechanisms by which gut microbio

closed · Rounds: 4 · Score: 0.95 · 2026-04-01

Related Research

Hypotheses and analyses mentioning TH in their description or question text

TH

Understanding Entity Pages

Summary

Wiki Pages (17)

TH Gene

MTHFR (Methylenetetrahydrofolate Reductase)

THAP1 Gene

THBS4 Gene

STATHMIN — Stathmin-1 (Oncoprotein 18)

TH Protein — Tyrosine Hydroxylase

Pathway Diagram

Outgoing (240)

Incoming (503)

Targeting Hypotheses (30)

Mentioning Analyses (2)

Does reduced Prevotellaceae abundance cause PD pathology or result from it?

What are the mechanisms by which gut microbiome dysbiosis influences Parkinson's

Experiments (12)

Related Papers (20)

Debates (2)

Does reduced Prevotellaceae abundance cause PD pathology or result from it?

What are the mechanisms underlying what are the mechanisms by which gut microbio

Related Research

Hypothesis 4: Metabolic Coupling via Lactate-Shuttling Collapse

p38α Inhibitor and PRMT1 Activator Combination to Restore Physiological TDP-43 P

Multi-Target Hypothesis: Aβ-Induced Cholinergic Damage is Partially Irreversible

Optimized Temporal Window for Metabolic Boosting Therapy Determines Success of M

Beta-frequency entrainment therapy targeting PV interneuron-astrocyte coupling f

Closed-loop tACS targeting EC-II parvalbumin interneurons to restore gamma rhyth

Gamma Oscillation Entrainment Enhances lncRNA-9969-Mediated Autophagy Through PV

Closed-loop focused ultrasound targeting EC-II PV interneurons to restore theta-

TREM2 R47H Variant-Driven Metabolic Dysfunction as the Primary Trigger for Faile

Hypothesis 7: SST-SST1R/Gamma Entrainment-Enhanced Astrocyte Secretome

Sequential Iron Chelation (Deferoxamine) and GPX4 Restoration (Sulforaphane) Pre

J-protein co-chaperone system mediates selective autophagy targeting of pathogen

IL-6 Trans-Signaling Blockade at the Oligodendrocyte-Microglia Interface

Microglial AIM2 Inflammasome as the Primary Driver of TDP-43 Proteinopathy Neuro

TH

Understanding Entity Pages

Summary

Wiki Pages (17)

TH Gene

MTHFR (Methylenetetrahydrofolate Reductase)

THAP1 Gene

THBS4 Gene

STATHMIN — Stathmin-1 (Oncoprotein 18)

TH Protein — Tyrosine Hydroxylase

FTH1 Gene — Ferritin Heavy Chain 1

NTHL1 Gene

Arcuate Nucleus TH Neurons

ETH Zurich

NUDT1 — NUDIX Hydrolase 1 (MTH1)

Ferritin Heavy Chain (FTH1)

LEAF Trial - THC+CBD for Alzheimer's Disease Agitation (NCT05644262)

NUDT1 Protein — NUDIX Hydrolase 1 (MTH1)

Tyrosine Hydroxylase (TH) Neurons in Neurodegeneration

FTH1 Protein — Ferritin Heavy Chain

FTH1 Protein

Pathway Diagram

Outgoing (240)

Incoming (503)

Targeting Hypotheses (30)

Mentioning Analyses (2)

Does reduced Prevotellaceae abundance cause PD pathology or result from it?

What are the mechanisms by which gut microbiome dysbiosis influences Parkinson's

Experiments (12)

Related Papers (20)

Debates (2)

Does reduced Prevotellaceae abundance cause PD pathology or result from it?

What are the mechanisms underlying what are the mechanisms by which gut microbio

Related Research

Hypothesis 4: Metabolic Coupling via Lactate-Shuttling Collapse

p38α Inhibitor and PRMT1 Activator Combination to Restore Physiological TDP-43 P

Multi-Target Hypothesis: Aβ-Induced Cholinergic Damage is Partially Irreversible

Optimized Temporal Window for Metabolic Boosting Therapy Determines Success of M

Beta-frequency entrainment therapy targeting PV interneuron-astrocyte coupling f

Closed-loop tACS targeting EC-II parvalbumin interneurons to restore gamma rhyth

Gamma Oscillation Entrainment Enhances lncRNA-9969-Mediated Autophagy Through PV

Closed-loop focused ultrasound targeting EC-II PV interneurons to restore theta-

TREM2 R47H Variant-Driven Metabolic Dysfunction as the Primary Trigger for Faile

Hypothesis 7: SST-SST1R/Gamma Entrainment-Enhanced Astrocyte Secretome

Sequential Iron Chelation (Deferoxamine) and GPX4 Restoration (Sulforaphane) Pre

J-protein co-chaperone system mediates selective autophagy targeting of pathogen

IL-6 Trans-Signaling Blockade at the Oligodendrocyte-Microglia Interface

Microglial AIM2 Inflammasome as the Primary Driver of TDP-43 Proteinopathy Neuro