TPH1 Gene: Tryptophan Hydroxylase 1
Key enzyme in serotonin biosynthesis, linked to mood disorders and carcinoid syndrome
Gene Information Card
| Symbol | TPH1 |
|---|---|
| Full Name | Tryptophan Hydroxylase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 11p15.3-p14 |
| NCBI Gene ID | 7166 ncbi.nlm.nih.gov/gene/7166 |
| Ensembl ID | ENSG00000129167 |
| UniProt ID | P17752 |
| OMIM ID | 191060 |
| HGNC ID | 12008 |
| Aliases | TPH, TPRH, TPH1 |
Description
TPH1 encodes tryptophan hydroxylase 1, the rate-limiting enzyme in serotonin (5-hydroxytryptamine) biosynthesis. It catalyzes the conversion of L-tryptophan to 5-hydroxy-L-tryptophan (5-HTP) using molecular oxygen and tetrahydrobiopterin as cofactors. TPH1 is primarily expressed in peripheral tissues (e.g., gut, pineal gland) and is distinct from TPH2, which is neuron-specific. Variants in TPH1 are associated with altered serotonin levels, contributing to psychiatric disorders, carcinoid syndrome, and other serotonergic pathologies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Carcinoid syndrome | TPH1 overexpression in neuroendocrine tumors leads to excessive serotonin production, causing flushing, diarrhea, and cardiac fibrosis. | ClinVar, COSMIC |
| Major depressive disorder | Reduced TPH1 activity or expression may lower peripheral serotonin, contributing to depressive symptoms. | OMIM, NCBI |
| Bipolar disorder | Polymorphisms in TPH1 (e.g., rs1800532) have been linked to altered serotonin synthesis and mood instability. | OMIM, NCBI |
| Autism spectrum disorder | TPH1 variants may affect serotonin levels during neurodevelopment, though evidence is limited. | ClinVar |
| Irritable bowel syndrome | Altered TPH1 expression in gut enterochromaffin cells influences serotonin-mediated motility and secretion. | NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Small intestine | 12.5 | High |
| Duodenum | 11.8 | High |
| Stomach | 8.2 | Medium |
| Pineal gland | 7.5 | Medium |
| Pancreas | 3.1 | Low |
| Liver | 1.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 (colorectal adenocarcinoma) | 14.3 | High expression; used in serotonin studies |
| BON-1 (carcinoid) | 18.7 | Very high; model for carcinoid syndrome |
| SH-SY5Y (neuroblastoma) | 0.8 | Low; TPH2 dominant in neuronal cells |
| HEK293 (embryonic kidney) | 0.2 | Minimal endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.803C>T (p.Pro268Leu) | Missense | <0.1% | Reduced enzyme activity; associated with depression |
| c.1096G>A (p.Gly366Ser) | Missense | <0.1% | Decreased catalytic efficiency; linked to bipolar disorder |
| c.1463C>T (p.Pro488Leu) | Missense | <0.1% | Loss of function; reported in autism |
| c.1A>G (p.Met1Val) | Start loss | <0.1% | Complete loss of protein; rare |
Mutation functional classification
Loss of Function (LOF)
Missense variants (e.g., Pro268Leu, Gly366Ser) reduce or abolish TPH1 enzymatic activity, lowering serotonin synthesis.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in TPH1; overexpression in carcinoid tumors is due to transcriptional upregulation.
Dominant Negative (DN)
No dominant-negative mutations described for TPH1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Serotonin biosynthesis (Reactome: R-HSA-209931)
• Tryptophan metabolism (KEGG: hsa00380)
• Neuroactive ligand-receptor interaction (KEGG: hsa04080)
Protein Summary
TPH1 is a 444-amino acid enzyme (51 kDa) belonging to the aromatic amino acid hydroxylase family. It contains a catalytic domain with a non-heme iron center and a regulatory domain. The enzyme is homotetrameric and requires tetrahydrobiopterin as a cofactor. TPH1 is the peripheral isoform of tryptophan hydroxylase, responsible for serotonin production in the gut, pineal gland, and other non-neuronal tissues. Its activity is regulated by phosphorylation (e.g., at Ser58) and by interaction with 14-3-3 proteins. Structural studies (PDB: 1MLW) reveal a conserved fold similar to phenylalanine and tyrosine hydroxylases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TPH1 Knockout HEK293 Cell Line | EDJ-KQ2224 | Human | 7166 | Details Get a Quote |
| TPH1 Knockout HCT 116 Cell Line | EDJ-KQ21193 | Human | 7166 | Details Get a Quote |
| TPH1 Knockout HeLa Cell Line | EDJ-KQ54685 | Human | 7166 | Details Get a Quote |
| TPH1 Knockout A-549 Cell Line | EDJ-KQ63170 | Human | 7166 | Details Get a Quote |
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