Gene Report

Basic Information

Approved Symbol	TPH1
Approved Name	tryptophan hydroxylase 1
Previous Symbol	TPRH, TPH
Previous Name	tryptophan hydroxylase (tryptophan 5-monooxygenase)
Name Alias	tryptophan 5-monooxygenase
Location	11p15.3-p14
Position	chr11:18042084-18062335 (-)
External Links	Entrez Gene: 7166 Ensembl: ENSG00000129167 UCSC: uc001mnp.2 HGNC ID: 12008
No. of Studies (Positive/Negative)	11(9/2)
Type	Literature-origin; SNP mapped

Positive relationships between TPH1 and MDD (count: 6)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
tryptophan hydroxylase gene	Tan, 2003	patients and normal controls		Significant difference in genotype frequency between patient...... Significant difference in genotype frequency between patient and control groups was observed More...
TPH-1	Gizatullin, 2006	patients and normal controls		Single marker association analyses showed only one SNP signi...... Single marker association analyses showed only one SNP significantly associated with MD. Several haplotypes were associated with MD. More...
TPH1	Anttila, 2007	patients and normal controls		Subjects carrying TPH1 CC genotype are more likely to belong...... Subjects carrying TPH1 CC genotype are more likely to belong to the patient sample than to the controls More...
tryptophan hydroxylase 1 (TPH1)	Viikki, 2010	patients and normal controls		TPH1 218A/C polymorphism was associated with the risk of MDD...... TPH1 218A/C polymorphism was associated with the risk of MDD. More...
TPH1	Belzeaux, 2010	patients and normal controls		We found that variations of mRNA levels for NRG1, SORT1 and ...... We found that variations of mRNA levels for NRG1, SORT1 and TPH1 were interesting state-dependent biological markers of the disease. More...
TPH1	Wang, 2011	patients and normal controls	P-value = 0.025	The TPH1 218A/C allele frequencies differed significantly be...... The TPH1 218A/C allele frequencies differed significantly between healthy controls and MDD patients in Taiwan, with a higher prevalence of the A allele in the patient group (p = 0.025). More...

Positive relationships between TPH1 and other components at different levels (count: 3)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Statistical Result	Relation Description
Name in Literature	Related Components
TPH1		Tryptophan(tryptophan)	molecule	Porter RJ, 2008	patients only		There was an interaction between 218A>C and gender in determ...... There was an interaction between 218A>C and gender in determining plasma TRP whereby presence of the 218C allele, in women, was associated with markedly reduced plasma TRP. More...
TPH1		Amygdala(amygdala)	brain morphology and function	Lee, 2009	patients only		Subjects with the A allele of the TPH1 A218C polymorphism sh...... Subjects with the A allele of the TPH1 A218C polymorphism showed greater brain activity in the bilateral amygdala under the sad vs. the neutral condition compared with subjects homozygous for the C allele. More...
TPH		Suicide(suicidal behavior)	symptoms	Abbar M, 2001	nomal people	chi(2) = 11.2; df = 1; P< 0.0008	Significant associations were found between variants in intr...... Significant associations were found between variants in introns 7, 8 and 9 (chi(2) = 11.2, df = 1, P< 0.0008 for the allele distribution; these loci are in complete linkage disequilibrium) and in the 3' noncoding region (chi(2) = 30.94, P = 0.0014) and suicide attempt. More...

Positive relationship network of TPH1 in MK4MDD

Network loading ...

Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between TPH1 and MDD (count: 2)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
TPH	Ham BJ, 2005	Patients and nomal controls		There were no significant differences in genotypes and allel...... There were no significant differences in genotypes and allele frequencies between the MDD patients (n = 93) and the control group (n = 127) and in the antidepressant response among TPH gene variants. More...
TPH	Yoon HK, 2008	Patients and nomal controls		There were no significant differences in the genotype distri...... There were no significant differences in the genotype distributions or allelic frequencies in the two serotonergic polymorphisms between suicide attempters and normal controls. None of the two serotonergic polymorphisms was correlated with lethality. More...

Negative relationships between TPH1 and other components at different levels (count: 0)

TPH1 related SNPs in MK4MDD (count: 3)

#rs	Location	Annotation	No. of Studies (Positive/Negative)
rs4537731	chr11:18068882(Forward)	upstream_gene_variant	1(1/0)
rs684302	chr11:18060353(Forward)	intron_variant; NMD_transcript_variant	1(1/0)
rs1800532	chr11:18047816(Forward)	downstream_gene_variant; intron_variant; NMD_transcript_variant; upstream_gene_variant	1(1/0)

TPH1 related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Tryptophan 5-hydroxylase 1	P17752	0(0/0)	Gene mapped

TPH1 related GO terms (count: 15)

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0030279	negative regulation of ossification	biological process	IEA
GO:0009072	aromatic amino acid family metabolic process	biological process	IEA
GO:0046849	bone remodeling	biological process	IEA
GO:0016597	amino acid binding	molecular function	IEA
GO:0043005	neuron projection	cellular component	IEA
GO:0060749	mammary gland alveolus development	biological process	IEA
GO:0034641	cellular nitrogen compound metabolic process	biological process	TAS
GO:0035902	response to immobilization stress	biological process	IEA
GO:0044281	small molecule metabolic process	biological process	TAS
GO:0007623	circadian rhythm	biological process	IEA
GO:0046219	indolalkylamine biosynthetic process	biological process	TAS
GO:0005829	cytosol	cellular component	TAS
GO:0005506	iron ion binding	molecular function	IEA
GO:0042427	serotonin biosynthetic process	biological process	IEA
GO:0004510	tryptophan 5-monooxygenase activity	molecular function	IEA

TPH1 related KEGG pathways (count: 1)

Gene mapped KEGG pathways
ID	Name	Brief Description	Full Description
hsa00380	tryptophan metabolism	Tryptophan metabolism

TPH1 related BioCarta pathways (count: 1)

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
NEUROTRANSMITTERS_PATHWAY	neurotransmitters pathway	Biosynthesis of neurotransmitters	Neurotransmitters are signaling molecules used by neurons to...... Neurotransmitters are signaling molecules used by neurons to communicate across chemical synapses. The receptors for neurotransmitters include G-protein coupled receptors (GPCRs) and ligand-gated ion channels. The biogenic amines are neurotransmitters derived from amino acids, and include dopamine, epinephrine, GABA, histamine and serotonin. For each of these, decarboxylation of an amino acid is a key step. GABA, gamma-aminobutyric acid, is a key inhibitory neurotransmitter and is synthesized through the decarboxylation of glutamate in a single step. Glutamate is itself an abundant excitatory neurotransmitter. Histamine signals are involved in inflammation and acid secretion in the stomach, acting through GPCRs. Histamine is synthesized in a single step from the amino acid histidine through decarboxylation. Serotonin is a neurotransmitter with a large range of effects, including roles in mood and depression, and is synthesized by first adding a hydroxyl group to tryptophan, followed by decarboxylation. A common mechanism of antidepressant action is to block the reuptake of serotonin at synapses. Dopamine is involved in movement and mood and is derived from tyrosine through addition of a hydroxyl group and decarboxylation. Additional reactions create norepinephrine and epinephrine from dopamine. These molecules, also called adrenalin and noradrenalin, act on the adrenergic receptors to exert responses including alteration of blood pressure, heart rate, metabolic activity, and bronchodilation. Many common drugs such as asthma and heart pressure medications act on adrenergic receptors. Alterations in these biosynthetic pathways can lead to significant clinical consequences. For example, deficiency in tyrosine hydroxylase activity leads to a movement disorder similar to Parkinson's disease and may play a role in Parkinson's disease and the development of an autoimmune response against glutamate decarboxylase (GAD) may trigger the destruction of insulin-secreting cells and type I diabetes. Numerous studies have searched for a potential genetic role of tryptophan hydroxylase mutations in neuropsychiatric indications, with conflicting results. More...

TPH1 related Reactome pathways (count: 5)

ID	Name	Description
Gene mapped Reactome pathways
REACT_15513	amine derived_hormones	Catecholamines and thyroxine are synthesized from tyrosine, ...... Catecholamines and thyroxine are synthesized from tyrosine, and serotonin and melatonin from tryptophan. More...
REACT_13723	neurotransmitter release_cycle	Neurotransmitter is stored in the synaptic vesicle in the pr...... Neurotransmitter is stored in the synaptic vesicle in the pre-synaptic terminal prior to its release in the synaptic cleft upon depolarization of the pre-synaptic membrane. The release of the neurotransmitter is a multi-step process that is controlled by electrical signals passing through the axons in form of action potential. Neurotransmitters include glutamate, acetylcholine, nor-epinephrine, dopamine and seratonin. Each of the neurotransmitter cycle is independently described. More...
REACT_15425	serotonin neurotransmitter_release_cycle	Serotonin is synthesized in the serotonergic neurons in the ...... Serotonin is synthesized in the serotonergic neurons in the central nervous system and the enterochrommaffin cells of the gastroinetstinal system. Serotonin is loaded into the clathrin sculpted monoamine transport vesicles. The vesicles are docked, primed and release after the change in the membrane potential that activates voltage gated calcium channels and the reponse by several proetins to the changes in intracellular Ca2+ increase leads to fusion of the vesicle and release of serotonin into the synapse. More...
REACT_15314	hormone biosynthesis	Hormones are chemicals released in very small quantities by ...... Hormones are chemicals released in very small quantities by cells that affect cellular metabolism in other parts of the body. They can also act as chemical messengers that transport signals from one cell to another. All multicellular organisms produce hormones; these are often transported in the blood. Cells respond to a hormone when they express a specific receptor for that hormone. The hormone binds to the receptor, resulting in the activation of a signal transduction mechanism that ultimately leads to cell type-specific responses. The events annotated here describe the biosynthesis of many types of hormones. More...
REACT_13477	transmission across_chemical_synapses	Chemical synapses are specialized junctions that are used fo...... Chemical synapses are specialized junctions that are used for communication between neurons, neurons and muscle or gland cells. The synapse involves a pre-synaptic neuron and a post-synaptic neuron, muscle cell or glad cell. The pre and the post-synaptic cell are separated by a gap of 20nm called the synaptic cleft. The signals pass in a unidirection from pre-synaptic to post-synaptic. The pre-synaptic neuron communicates via the release of neurotransmitter which bind the receptors on the post-synaptic cell. More...

TPH1 related interactors from protein-protein interaction data in HPRD (count: 3)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
TPH1	YWHAH	No	in vitro	7499362
TPH1	PRKACA	No	in vitro	9109552
TPH1	YWHAZ	No	in vivo	8101440

Gene Report

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped BioCarta pathways

Gene mapped Reactome pathways