TPH2: Tryptophan Hydroxylase 2
Key enzyme in serotonin synthesis, implicated in mood disorders and neuropsychiatric conditions
Gene Information Card
| Symbol | TPH2 |
|---|---|
| Full Name | tryptophan hydroxylase 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 12q21.1 |
| NCBI Gene ID | 121278 ncbi.nlm.nih.gov/gene/121278 |
| Ensembl ID | ENSG00000139219 |
| UniProt ID | Q8IWU9 |
| OMIM ID | 607478 |
| HGNC ID | 20692 |
| Aliases | NTPH, TPH, TPRH, tryptophan 5-monooxygenase 2 |
Description
TPH2 encodes tryptophan hydroxylase 2, the rate-limiting enzyme in serotonin (5-hydroxytryptamine, 5-HT) biosynthesis in the brain. It catalyzes the conversion of L-tryptophan to 5-hydroxy-L-tryptophan, which is then decarboxylated to serotonin. TPH2 is predominantly expressed in the raphe nuclei of the brainstem and regulates central serotonin levels, influencing mood, cognition, and behavior. Variants in TPH2 have been associated with psychiatric disorders including major depression, bipolar disorder, and suicidal behavior.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Major Depressive Disorder | Reduced TPH2 activity leads to lower brain serotonin, contributing to depressive symptoms. | ClinVar; PMID: 15673663 |
| Bipolar Disorder | Genetic variants in TPH2 may alter serotonin synthesis, affecting mood regulation. | ClinVar; PMID: 15866546 |
| Suicidal Behavior | Loss-of-function variants reduce serotonin availability, increasing suicide risk. | ClinVar; PMID: 16385481 |
| Obsessive-Compulsive Disorder | Dysregulation of serotonergic signaling via TPH2 variants implicated in OCD. | ClinVar; PMID: 16936799 |
| Attention-Deficit/Hyperactivity Disorder | TPH2 polymorphisms associated with altered serotonin metabolism in ADHD. | ClinVar; PMID: 17903311 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (raphe nuclei) | None | High |
| Brain (cortex) | None | Moderate |
| Brain (hippocampus) | None | Moderate |
| Brain (amygdala) | None | Low |
| Testis | None | Low |
| Small intestine | None | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | None | Neuronal model; expresses TPH2 |
| SK-N-SH (neuroblastoma) | None | Detectable expression |
| HEK293 (embryonic kidney) | None | Low/absent (non-neuronal) |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R441H | Missense | Rare | Reduced enzyme activity; associated with depression |
| G146S | Missense | Rare | Decreased serotonin production; linked to bipolar disorder |
| P206S | Missense | Rare | Impaired catalytic function; reported in suicide attempters |
| IVS10+12C>A | Intronic | Rare | Splicing alteration; associated with major depression |
Mutation functional classification
Loss of Function (LOF)
R441H, G146S, P206S reduce or abolish TPH2 enzymatic activity, leading to decreased serotonin synthesis.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in TPH2.
Dominant Negative (DN)
No dominant-negative mutations currently documented.
View complete mutation data：
Gene Ontology (GO)
| • tryptophan 5-monooxygenase activity | • iron ion binding |
| • oxygen binding | • serotonin biosynthetic process |
| • response to drug | • nervous system development |
Pathways
• Serotonin synthesis pathway
• Tryptophan metabolism
• Neurotransmitter biosynthesis
Protein Summary
TPH2 is a 490-amino acid enzyme belonging to the aromatic amino acid hydroxylase family. It requires iron and tetrahydrobiopterin as cofactors. The protein is localized to the cytoplasm of serotonergic neurons in the brainstem raphe nuclei. Its structure includes a catalytic domain and a regulatory domain. TPH2 is the primary determinant of brain serotonin levels, and its dysfunction is linked to neuropsychiatric disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TPH2 Knockout HEK293 Cell Line | EDJ-KQ7920 | Human | 121278 | Details Get a Quote |
| TPH2 Knockout HeLa Cell Line | EDJ-KQ58081 | Human | 121278 | Details Get a Quote |
| TPH2 Knockout A-549 Cell Line | EDJ-KQ66568 | Human | 121278 | Details Get a Quote |
| TPH2 Knockout HCT 116 Cell Line | EDJ-KQ74985 | Human | 121278 | Details Get a Quote |
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