TH Gene

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gene909 wordssynced 2026-04-02

TH (Tyrosine Hydroxylase)

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">TH Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>TH</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Tyrosine Hydroxylase</td>
</tr>
<tr>
<td class="label">Alternative Names</td>
<td>TYH, DYT5</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>11p15.5</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>7067</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000180176</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P07101</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>191290</td>
</tr>
<tr>
<td class="label">Drug</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Levodopa/Carbidopa</td>
<td>Dopamine precursor</td>
</tr>
<tr>
<td class="label">Levodopa/Benserazide</td>
<td>Dopamine precursor</td>
</tr>
<tr>
<td class="label">Sinemet</td>
<td>Dopamine precursor</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/cancer" style="color:#ef9a9a">CANCER</a>, <a href="/wiki/depression" style="color:#ef9a9a">DEPRESSION</a>, <a href="/wiki/parkinson" style="color:#ef9a9a">PARKINSON</a>, <a href="/wiki/parkinson's-disease" style="color:#ef9a9a">Parkinson's Disease</a>, <a href="/wiki/tumor" style="color:#ef9a9a">TUMOR</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" styl

...

TH (Tyrosine Hydroxylase)

Pathway Diagram

Mermaid diagram (expand to render)

Knowledge graph relationships for TH (282 total edges in KG)

Introduction

Th Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

TH (Tyrosine Hydroxylase) is the rate-limiting enzyme in the biosynthesis of catecholamines including dopamine, norepinephrine, and epinephrine. It converts tyrosine to L-DOPA, the immediate precursor to dopamine. TH is critical for dopaminergic neuron function and is a major therapeutic target in Parkinson's disease. [@kumer1996]

Gene Information

Function

Normal Cellular Function

Tyrosine hydroxylase is a tetrahydrobiopterin (BH4)-dependent enzyme that catalyzes the rate-limiting step in catecholamine biosynthesis:

DOPA Synthesis: Converts L-tyrosine to L-DOPA
Dopamine Production: L-DOPA is then decarboxylated to form dopamine
Norepinephrine/Epinephrine: Dopamine is further converted to norepinephrine and epinephrine
Regulation: Phosphorylated by multiple kinases (PKA, CaMKII, MAPK) in response to neuronal activity
BH4 Dependency: Requires tetrahydrobiopterin as an essential cofactor

Expression Pattern

TH is expressed primarily in:

Substantia nigra pars compacta (dopaminergic neurons)
Ventral tegmental area
Locus coeruleus (noradrenergic neurons)
Adrenal medulla
Peripheral sympathetic [neurons](/entities/neurons)

Disease Associations

Parkinson's Disease

TH is central to PD pathophysiology:

Dopaminergic Neuron Loss: Degeneration of TH-positive neurons in substantia nigra
TH Activity Reduction: Decreased TH activity contributes to dopamine deficiency
Therapeutic Target: Levodopa (L-DOPA) supplementation is the main PD treatment
Biomarker: TH activity in CSF may reflect dopaminergic neuron integrity

Segawa Syndrome (Dystonia)

TH mutations cause autosomal recessive Segawa syndrome:

Symptoms: Dystonia, parkinsonism, diurnal fluctuation
Onset: Childhood
Treatment: Levodopa responsive

Tyrosine Hydroxylase Deficiency

Rare autosomal recessive disorder:

Infantile onset: Severe movement disorders
Symptoms: Hypotonia, dystonia, cognitive impairment
Treatment: L-DOPA therapy

ADHD

TH polymorphisms have been associated with attention-deficit/hyperactivity disorder.

Therapeutic Targeting

Levodopa Therapy

Investigational Approaches

Gene Therapy: AAV-TH delivery to restore dopamine synthesis
Cell Therapy: TH-expressing stem cell transplantation
BH4 Cofactor Therapy: Enhance TH activity
TH Activators: Small molecules to increase TH activity

Key Publications

Nagatsu T, et al. (1964). Tyrosine hydroxylase - the initial step in norepinephrine biosynthesis. J Biol Chem 239:2910-2917. PMID: 14216443(https://pubmed.ncbi.nlm.nih.gov/14216443/)

Kumer SC, Vrana KE. (1996). Intricate regulation of tyrosine hydroxylase activity and gene expression. J Neurochem 67(2):443-462. PMID: 8760708(https://pubmed.ncbi.nlm.nih.gov/8760708/)

Bezard E, et al. (2001). Relationship between the appearance of motor symptoms and the loss of striatal dopamine fibers in parkinsonian monkeys. Neuroscience 106(4):687-695. PMID: 11682158(https://pubmed.ncbi.nlm.nih.gov/11682158/)

Janssen MJ, et al. (2012). Tyrosine hydroxylase deficiency: A treatable neurometabolic disorder. Neurology 79(13):1364-1370. PMID: 23019264(https://pubmed.ncbi.nlm.nih.gov/23019264/)

Haavik J, et al. (2008). Parkinson's disease: Return of an old Harry. Trends Neurosci 31(1):10-17. PMID: 18063225(https://pubmed.ncbi.nlm.nih.gov/18063225/)

Ito S, et al. (2002). GTP cyclohydrolase I gene therapy augments BH4 and dopamine in parkinsonian monkeys. Mol Ther 5(5):466-474. PMID: 11991737(https://pubmed.ncbi.nlm.nih.gov/11991737/)

Background

The study of Th Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

Cross-References

[Parkinson's Disease](/diseases/parkinsons-disease)
[Dystonia](/diseases/dystonia)
[Dopamine Signaling](/mechanisms/dopamine-signaling)
[GCH1 Gene](/proteins/gch1-protein)
[DOPA Decarboxylase](/proteins/dopa-decarboxylase)
[Substantia Nigra](/brain-regions/substantia-nigra)

Last updated: 2026-03-03

Brain Atlas Resources

[Allen Human Brain Atlas - th Expression](https://human.brain-map.org/microarray/search/show?search_term=th)
[Allen Cell Type Atlas - th](https://celltypes.brain-map.org/)
[BrainSpan - th Developmental Expression](https://brainspan.org/)
[Allen Mouse Brain Atlas - th](https://mouse.brain-map.org/)

Allen Brain Atlas Data

Single-cell RNA sequencing data from the Allen Brain Atlas shows TH expression:

Substantia nigra pars compacta: Very high expression in dopaminergic (DA) neurons, the primary source of dopamine in the basal ganglia
Ventral tegmental area (VTA): High expression in mesolimbic dopaminergic neurons
Locus coeruleus: Expression in noradrenergic neurons
Hypothalamus: Moderate expression in scattered neurons
Hippocampus: Low expression in select interneurons

Key observations:

TH is a marker for catecholaminergic neurons in the brain
Expression is highly specific to neurons that produce dopamine or norepinephrine
Loss of TH-expressing neurons in the substantia nigra is the hallmark pathological feature of Parkinson's disease
The Allen Brain Atlas data confirms regional expression patterns consistent with known neuroanatomy of monoamine systems

External Links

[TH Gene - NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/7069)
[TH Gene - OMIM](https://www.omim.org/entry/191290)
[TH Gene - UniProt](https://www.uniprot.org/uniprot/P07101)
[TH Expression - Allen Human Brain Atlas](https://human.brain-map.org/microarray/search/show?search_term=TH)

References

[Nagatsu T, Levitt M, Udenfriend S, Tyrosine hydroxylase: the initial step in norepinephrine biosynthesis (1964)](https://pubmed.ncbi.nlm.nih.gov/14216443/)

[Kumer SC, Vrana KE, Intricate regulation of tyrosine hydroxylase activity and gene expression (1996)](https://pubmed.ncbi.nlm.nih.gov/8760708/)

[Daubner SC, Le T, Wang S, Tyrosine hydroxylase and regulation of dopamine synthesis (2011)](https://doi.org/10.1016/j.abb.2010.12.022)

[Haavik J, Toska K, Tyrosine hydroxylase and Parkinson's disease (1998)](https://doi.org/10.1007/BF02741387)

[Fukushima T, Tan X, Kameyama M, et al, GTP cyclohydrolase I gene therapy augments BH4 and dopamine in parkinsonian monkeys (2002)](https://pubmed.ncbi.nlm.nih.gov/11991737/)

Related Hypotheses

From the [SciDEX Exchange](/exchange) — scored by multi-agent debate

[Bacterial Enzyme-Mediated Dopamine Precursor Synthesis](/hypothesis/h-7bb47d7a) — <span style="color:#ff8a65;font-weight:600">0.35</span> · Target: TH, AADC

Pathway Diagram

The following diagram shows the key molecular relationships involving TH Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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TH Gene

TH (Tyrosine Hydroxylase)

TH (Tyrosine Hydroxylase)

Pathway Diagram

Introduction

Overview

Gene Information

Function

Normal Cellular Function

Expression Pattern

Disease Associations

Parkinson's Disease

Segawa Syndrome (Dystonia)

Tyrosine Hydroxylase Deficiency

ADHD

Therapeutic Targeting

Levodopa Therapy

Investigational Approaches

Key Publications

Background

Cross-References

Brain Atlas Resources

Allen Brain Atlas Data

External Links

See Also

References

Related Hypotheses

Pathway Diagram