TPH2 — Tryptophan Hydroxylase 2

TPH2 — Tryptophan Hydroxylase 2

Introduction

Tph2 — Tryptophan Hydroxylase 2 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene"> [@uniprot]

TPH2 [@tph2021]

• Tryptophan Hydroxylase 2

| | |
|---|---|
| Symbol | TPH2 |
| Full Name | Tryptophan Hydroxylase 2 |
| Chromosome | 12q15 |
| NCBI Gene ID | [121556](https://www.ncbi.nlm.nih.gov/gene/121556) |
| OMIM | [607478](https://www.omim.org/entry/607478) |
| Ensembl ID | [ENSG00000139287](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000139287) |
| UniProt ID | [Q8IWU6](https://www.uniprot.org/uniprot/Q8IWU6) |
| Encoded Protein | [Tryptophan Hydroxylase 2](/proteins/tph2-protein) |
| Associated Diseases | [Parkinson's Disease](/diseases/parkinsons-disease), [Depression](/cell-types/dorsal-raphe-depression) |

</div>

Overview

This section provides a summary of the gene/protein's function, expression, and relevance to neurodegenerative diseases.

Function

...

TPH2 — Tryptophan Hydroxylase 2

Introduction

Tph2 — Tryptophan Hydroxylase 2 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene"> [@uniprot]

TPH2 [@tph2021]

• Tryptophan Hydroxylase 2

| | |
|---|---|
| Symbol | TPH2 |
| Full Name | Tryptophan Hydroxylase 2 |
| Chromosome | 12q15 |
| NCBI Gene ID | [121556](https://www.ncbi.nlm.nih.gov/gene/121556) |
| OMIM | [607478](https://www.omim.org/entry/607478) |
| Ensembl ID | [ENSG00000139287](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000139287) |
| UniProt ID | [Q8IWU6](https://www.uniprot.org/uniprot/Q8IWU6) |
| Encoded Protein | [Tryptophan Hydroxylase 2](/proteins/tph2-protein) |
| Associated Diseases | [Parkinson's Disease](/diseases/parkinsons-disease), [Depression](/cell-types/dorsal-raphe-depression) |

</div>

Overview

This section provides a summary of the gene/protein's function, expression, and relevance to neurodegenerative diseases.

Function

Tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in the biosynthesis of serotonin (5-hydroxytryptamine or 5-HT) in the central nervous system. Unlike TPH1, which is primarily expressed in peripheral tissues, TPH2 is specifically expressed in neuronal cells of the raphe nuclei and other brain regions. The enzyme catalyzes the conversion of the essential amino acid L-tryptophan to 5-hydroxytryptophan (5-HTP), which is subsequently decarboxylated to form serotonin.

TPH2 is a tetrahydrobiopterin-dependent enzyme that requires iron, oxygen, and tetrahydrobiopterin (BH4) as cofactors for its catalytic activity. The expression of TPH2 is tightly regulated at both transcriptional and post-translational levels, and its activity is modulated by phosphorylation through various protein kinases including PKA, CaMKII, and PKC.

Disease Associations

| Disease | Inheritance | Key Mutations |
|---------|-------------|---------------|
| Parkinson's Disease | Complex | Reduced TPH2 expression in raphe nuclei |
| Depression | Complex | rs4570625 promoter variant affecting expression |
| Serotonin Deficiency | Various | Reduced TPH2 activity |

Expression

TPH2 is primarily expressed in serotonergic [neurons](/entities/neurons) of the raphe nuclei, including the dorsal raphe nucleus (DRN) and median raphe nucleus (MRN). These brainstem nuclei give rise to widespread serotonergic projections throughout the forebrain, including the [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), thalamus, hypothalamus, and basal ganglia.

High expression is also found in:

• Dorsal Raphe Nucleus
• Median Raphe Nucleus
• Projections to prefrontal cortex
• Hippocampal formation

Serotonin Biosynthesis Pathway

Key Publications

[TPH2: a key biomarker for central serotonin deficiency (2021)](https://doi.org/10.1016/j.neuropharm.2020.108300)

[TPH2 polymorphisms and Parkinson's disease (2019)](https://doi.org/10.1002/mds.27755)

Cross-Links

• [Protein: TPH2](/proteins/tph2-protein)
• [Serotonergic Neurons](/cell-types/serotonin-neurons)
• [Raphe Nuclei](/brain-regions/raphe-nuclei)
• [Parkinson's Disease](/diseases/parkinsons-disease)

Background

The study of Tph2 — Tryptophan Hydroxylase 2 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.

See Also

• [Serotonin](/mechanisms/serotonergic-signaling)
• Tryptophan
• Brain Serotonin System
• Monoamine Neurotransmitters

External Links

• [TPH2 Gene - NCBI](https://www.ncbi.nlm.nih.gov/gene/121028)
• [TPH2 - UniProt](https://www.uniprot.org/uniprot/Q8WU66)

References

Unknown, NCBI Gene Entry (n.d.)

Unknown, UniProt Entry (n.d.)

[Unknown, TPH2: a key biomarker for central serotonin deficiency (2021) (2021)](https://doi.org/10.1016/j.neuropharm.2020.108300)

Pathway Diagram

The following diagram shows the key molecular relationships involving TPH2 — Tryptophan Hydroxylase 2 discovered through SciDEX knowledge graph analysis: