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

13Experiments

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
dopamine_synthesis	regulates	pathway	0.90
oxidative stress response	participates_in	pathway	0.90
neurons	associated_with	cell_type	0.90
Midbrain	expressed_in	brain_region	0.85
Substantia Nigra	expressed_in	cell_type	0.80
Parkinson's Disease	biomarker_for	disease	0.80
Dopaminergic Neurons	expressed_in	cell_type	0.75
AUTOPHAGY	produces	phenotype	0.70
STEM CELLS	activates	cell_type	0.70
DOPAMINE	activates	phenotype	0.70
mitochondrial dynamics	participates_in	pathway	0.70
MITOPHAGY	treats	phenotype	0.70
autophagy pathway	participates_in	pathway	0.70
MITOPHAGY	causes	phenotype	0.70
DEMYELINATION	inhibits	phenotype	0.70
DOPAMINE	regulates	phenotype	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
PARKINSON'S DISEASE	protects_against	disease	0.70
ALS	regulates	disease	0.70
NEURON	regulates	cell_type	0.70
NEURON	protects_against	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
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
BDNF	protects_against	gene	0.70
NEUROINFLAMMATION	destabilizes	phenotype	0.70
NEUROINFLAMMATION	exacerbates	phenotype	0.70
OXIDATIVE STRESS	causes	phenotype	0.70
NEURODEGENERATION	interacts_with	phenotype	0.70
LIPID PEROXIDATION	activates	phenotype	0.70
neurons	activates	cell_type	0.70
BDNF	activates	gene	0.70
STRIATUM	causes	brain_region	0.65
TLR4	treats	gene	0.65
TLR4	protects_against	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
DDC	associated_with	gene	0.70
MTOR	activates	gene	0.70
APP	inhibits	gene	0.70
levodopa	targets	drug	0.70
CYCLOSPORINE	regulates	drug	0.70
APP	associated_with	gene	0.70
ALZHEIMER'S DISEASE	treats	disease	0.70
NEURODEGENERATION	destabilizes	phenotype	0.70
EZH2	inhibits	gene	0.70
TLR4	inhibits	gene	0.70
SLC16A2	associated_with	gene	0.70
MULTIPLE SCLEROSIS	regulates	disease	0.70
levodopa	associated_with	compound	0.70
TREM2	activates	gene	0.65
TREM2	exacerbates	gene	0.65
SUBSTANTIA NIGRA	causes	brain_region	0.65
RAPAMYCIN	regulates	drug	0.65
TREM2	protects_against	gene	0.65
TREM2	regulates	gene	0.65
MICROGLIA	treats	cell_type	0.65
TAU	associated_with	protein	0.65
NLRP3	activates	gene	0.65
NEURON	inhibits	cell_type	0.65
DOPAMINERGIC	expressed_in	cell_type	0.65
NEUROINFLAMMATION	inhibits	phenotype	0.65
DRD2	associated_with	gene	0.65
SCHIZOPHRENIA	inhibits	disease	0.65
SNCA	associated_with	gene	0.65
FERROPTOSIS	inhibits	phenotype	0.65
TAU	phosphorylates	protein	0.65
FERROPTOSIS	regulates	phenotype	0.65
AUTOPHAGY	associated_with	gene	0.65
MYC	expressed_in	gene	0.65
DOPAMINE	targets	phenotype	0.65
DOPAMINE	produces	phenotype	0.65
CURCUMIN	protects_against	drug	0.65
FUS	co_discussed	gene	0.60
NRF2	activates	gene	0.60
OXIDATIVE STRESS	activates	pathway	0.60
ASTROCYTE	activates	cell_type	0.60
ASTROCYTES	activates	cell_type	0.60
MLKL	co_discussed	gene	0.60
MICROGLIA	co_discussed	cell_type	0.60
MICROGLIA	causes	cell_type	0.60
MITOPHAGY	expresses	pathway	0.60
APOPTOSIS	causes	pathway	0.60

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
GluN2B-Mediated Thalamocortical Control of Glymphatic Tau Cl	0.964	neuroscience	Circuit-level neural dynamics in neurode
Closed-loop transcranial focused ultrasound targeting EC-II	0.958	Alzheimer's disease	Circuit-level neural dynamics in neurode
Closed-loop optogenetic targeting PV interneurons to restore	0.952	Alzheimer's disease	Circuit-level neural dynamics in neurode
Gamma entrainment therapy to restore hippocampal-cortical sy	0.895	Alzheimer's disease	Circuit-level neural dynamics in neurode
Hypothesis 4: Metabolic Coupling via Lactate-Shuttling Colla	0.895	neurodegeneration	View

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
p38α Inhibitor and PRMT1 Activator Combination to Restore Ph	0.879	neurodegeneration	What is the therapeutic window between i
eIF2α Phosphorylation Imbalance Creates Integrated Stress Re	0.866	ALS	-
Gamma Oscillation Entrainment Enhances lncRNA-9969-Mediated	0.865	molecular neurobiology	View
Closed-loop focused ultrasound targeting EC-II PV interneuro	0.863	Alzheimer's disease	Circuit-level neural dynamics in neurode
TREM2 R47H Variant-Driven Metabolic Dysfunction as the Prima	0.862	neurodegeneration	Variant Annotation and Prioritization of
RBM45 Liquid-Liquid Phase Separation Dominance Hijacks RNA P	0.858	ALS	-
Closed-loop tACS targeting EC-II parvalbumin interneurons to	0.849	Alzheimer's disease	Circuit-level neural dynamics in neurode
Beta-frequency entrainment therapy targeting PV interneuron-	0.846	Alzheimer's disease	Circuit-level neural dynamics in neurode
Hypothesis 7: SST-SST1R/Gamma Entrainment-Enhanced Astrocyte	0.839	neurodegeneration	View
Sequential Iron Chelation (Deferoxamine) and GPX4 Restoratio	0.838	neurodegeneration	View
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
SLC7A11 System Activation Restores Cystine Uptake and GSH Sy	0.812	neurodegeneration	View
CLU/APOE Duality in Amyloid Clearance Determines Cell-Type-S	0.811	neurodegeneration	What are the cell-type-specific transcri
Targeting the Mechanistic Link Between AQP4 Dysfunction and	0.803	neurodegeneration	View
CSF sTREM2 as Pharmacodynamic Biomarker for Therapeutic Wind	0.801	neuroimmunology	TREM2 in Alzheimer's Disease: Mechanisms
Hypothesis 1: MANF/CDNF Signaling as Primary Neuroprotective	0.798	neurodegeneration	View
Microglial TREM2-SYK Pathway Enhancement	0.798	neurodegeneration	Cell type vulnerability in Alzheimers Di
Closed-loop transcranial focused ultrasound targeting CA1 PV	0.797	Alzheimer's disease	Circuit-level neural dynamics in neurode
Targeting SASP-Complement Amplification Through HIF-1α Downs	0.793	neurodegeneration	What molecular mechanism causes VCP muta
G2019S primarily raises baseline LRRK2 kinase activity rathe	0.790	neurodegeneration	Do pathogenic LRRK2 mutations amplify vo
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

Mentioning Analyses (2)

Scientific analyses that reference this entity

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

neurodegeneration | 2026-04-11 | 0 hypotheses

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

neurodegeneration | 2026-04-01 | 13 hypotheses Top: 0.907

Experiments (13)

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
Autophagy receptor identification for stress granule elimination	exploratory	neurodegenerative diseases	0.900	0.00	cultured cells under arsenite	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 (13)

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

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

Optimized Temporal Window for Metabolic Boosting Therapy Determines Success of M

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

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

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

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

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

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

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

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

SLC7A11 System Activation Restores Cystine Uptake and GSH Synthesis to Prevent N

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 (13)

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

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

Optimized Temporal Window for Metabolic Boosting Therapy Determines Success of M

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

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

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

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

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

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

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

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

SLC7A11 System Activation Restores Cystine Uptake and GSH Synthesis to Prevent N