Gene Report

Basic information

Related studies

Functional annotation

Related other genetic factors

Overlap with SZ and MDD

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Basic Info

Approved Symbol	TPH1
Previous Symbol	TPRH, TPH
Approved Name	tryptophan hydroxylase 1
Previous Name	tryptophan hydroxylase (tryptophan 5-monooxygenase)
Name Alias	tryptophan 5-monooxygenase
Location	11p15.3-p14
Position	chr11:18017564-18042426, -1
External Links	HGNC: 12008 Entrez Gene: 7166 Ensembl: ENSG00000129167 UCSC: uc001mnp.2
No. of Studies	14 (Positive: 5; Negative: 9; trend: 0)
Overlap with SZ?	YES
Overlap with MDD?	YES

Gene related studies (count: 14)

Reference	Tested Markers	Statistical Values/Author Comments	Result Category	Comment on Study
Chen, C., 2008		The pooled OR for the AA genotype relative to the CC genotype was significant (z = 2.18, p = 0.029), with a value of 1.41 and a 95% CI of 1.04-1.93. The AA genotype was also a significant risk factor (z = 2.72, p = 0.006) in relation to the AC genotype, with a pooled OR of 1.37 and a 95% CI of 1.09-1.72. The AC and CC genotypes had approximately equal nonsignificant effects (z = 0.16, p = 0.870) on risk for BPD (OR = 1.02, 95% CI: 0.83-1.25).. This pattern of results suggested that the A allele may increase risk for BPD in a recessive manner.	Positive	Comment on Study
Rietschel, M.,2000	Other variant: TPH1_A218C	Our results, therefore, do not support the hypothesis that the TPH gene is involved in the etiology of bipolar disorder.	Negative	Comment on Study
Serretti, A.,2002	Other variant: TPH1_A218C	Our study did not support the involvement of 5-HTTLPR, TPH, MAO-A, or DRD4 polymorphisms in bipolar disorder.	Negative	Comment on Study
Chen, D.,2011	SNP: rs1800532	The TPH1 A218C polymorphism is a potential biomarker for bipolar disorder and alcohol dependence risk in Caucasian population.	Positive	Comment on Study
Lai, T. J.,2005	SNP: rs1800532, rs2108977, rs211105, rs2237907, rs623580, rs684302 Haplotype: (TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)(G-G-G-A-G-A-C-C-C-A), (TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)(G-G-T-A-G-A-C-C-C-A), (TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)(G-G-T-T-G-C-C-C-T-A), (TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)(G-G-T-T-G-C-C-C-T-G), (TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)(T-A-G-A-G-A-C-A-T-G), (TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)(T-A-G-A-G-A-C-C-T-G), (TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)(T-A-G-T-A-A-C-A-C-A), (TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)(T-A-G-T-A-A-C-C-T-G), (TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)(T-A-G-T-A-A-G-A-C-A), (TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)(T-A-G-T-A-A-G-A-T-A), (TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)(T-A-G-T-G-A-C-C-T-G), (TPH1_5'flanking_T-1721G) - (TPH1_5'flanking_A-1067G) - (TPH1_5'flanking_G-347T) - (TPH1_Intron1_T3804A) - (TPH1_Intron2_G7465A) - (TPH1_Intron3_A12517C) - (TPH1_Intron6_C18626G) - (TPH1_Intron7_A20004C) - (TPH1_3'UTR_C27224T) - (TPH1_3'UTR_A27237G)(T-A-G-T-G-C-G-A-C-A) Other variant: TPH1_3'UTR_A27237G, TPH1_5'flanking_A-1067G, TPH1_5'flanking_G-347T, TPH1_5'flanking_T-1721G	Results of this study did not support the role of TPH1 gene in BPD etiology.	Negative	Comment on Study
Choi, K. Y., 2010	Other variant: TPH1_promoter_218A/C	There was no association of variant in this gene with bipolar disorder.	Negative	Comment on Study
Bellivier, F., 1998 (a)	Other variant: TPH1_A218C	This result suggests the involvement of the TPH gene in susceptibility to manic-depressive illness. This preliminary result requires confirmation in further groups of patients and controls.	Positive	Comment on Study
Lin, Y. M., 2007	Haplotype: TPH1_-346G - rs4570625 - rs11178997 - rs11178998(G, T-A-G), TPH1_-346T - rs4570625 - rs11178997 - rs11178998(T, T-A-G), TPH1_G-346T - rs4570625 - rs11178997 - rs11178998(G/T, T-A-G), TPH1_G-346T - rs4570625 - rs11178997 - rs11178998(G/T, non T-A-G)	The effect of TPH2 on BPD etiology can be influenced by the presence of TPH1.	Positive	Comment on Study
Vincent, J. B.,1999(a)	Other variant: TPH1_BfaI Polymorphism	No significant differences were found in bipolar groups.	Negative	Comment on Study
McQuillin, A.,1999	Other variant: TPH1_intron 7_218A/C	We found no association between TPH variant and bipolar disorder in our caucasian populations.	Negative	Comment on Study
Kunugi, H.,1999(a)	Other variant: TPH1_intron 7_218A/C	The authors conclude that the examined polymorphisms are unlikely to have major relevance to the pathogenesis of affective disorders or suicidal behavior.	Negative	Comment on Study
Serretti, A.,2001(a)	Other variant: TPH1_A218C	TPH variants were not associated with major psychoses, but a trend was observed toward an excess of TPH*A/A in bipolar disorder.	Positive	Comment on Study
Souery, D.,2001	Other variant: TPH1_A218C	We failed to detect an association between the A218C polymorphism of the TPH gene and BPAD and UPAD in a large European sample.	Negative	Comment on Study
Rotondo, A.,2002	Other variant: TPH1_A218C	TPH A218C variants are not, therefore, a major liability factor for the symptoms of major psychoses to have in the present sample.	Negative	Comment on Study

Gene functional annotation

Gene related GO terms (count: 17)

GO terms by PBA (count: 0)

GO terms by database search (count: 17)

ID	Name	Type	Evidence[PMID]	No. of Genes in BDgene
GO:0016597	amino acid binding	molecular function	IEA	4
GO:0005829	cytosol	cellular component	TAS	223
GO:0046849	bone remodeling	biological process	IEA	2
GO:0060749	mammary gland alveolus development	biological process	IEA	4
GO:0043005	neuron projection	cellular component	IEA	38
GO:0030279	negative regulation of ossification	biological process	IEA	2
GO:0035902	response to immobilization stress	biological process	IEA	5
GO:0007623	circadian rhythm	biological process	IEA	40
GO:0004510	tryptophan 5-monooxygenase activity	molecular function	IEA	2
GO:0034641	cellular nitrogen compound metabolic process	biological process	TAS	20
GO:0044281	small molecule metabolic process	biological process	TAS	117
GO:0009072	aromatic amino acid family metabolic process	biological process	IEA	2
GO:0046219	indolalkylamine biosynthetic process	biological process	TAS	5
GO:0042427	serotonin biosynthetic process	biological process	IEA	3
GO:0055114	oxidation-reduction process	biological process	IEA	43
GO:0005506	iron ion binding	molecular function	IEA	8
GO:0045600	positive regulation of fat cell differentiation	biological process	IEA	9

Gene related KEGG pathways (count: 1)

KEGG pathways by PBA (count: 0)

KEGG pathways by database search (count: 1)

ID	Name	No. of Genes in BDgene	Brief Description
hsa00380	Tryptophan metabolism	9

Gene related BioCarta pathways (count: 0)

Gene related interactors from protein-protein interactions data in HPRD (count: 2)

Gene	Interactor	Interactor in BDgene?	Experiment Type	PMID
TPH1	PRKACA	NO	in vitro	9109552
TPH1	YWHAZ	NO	in vivo	8101440

Related other genetic factors

Gene related SNPs (count: 16)

Literature-origin SNPs (count: 6)

rs_ID	Location	Functional Annotation	No. of Studies (Positive/Negative/Trend)
rs1800532	chr11:18026269 - 18026269(1)	downstream_gene_variant; intron_variant; NMD_transcript_variant; upstream_gene_variant	3(1/2/0)
rs211105	chr11:18033757 - 18033757(1)	intron_variant; NMD_transcript_variant	1(0/1/0)
rs684302	chr11:18038806 - 18038806(1)	intron_variant; NMD_transcript_variant	1(0/1/0)
rs623580	chr11:18042430 - 18042430(1)	upstream_gene_variant	2(1/1/0)
rs2237907	chr11:18027646 - 18027646(1)	downstream_gene_variant; intron_variant; NMD_transcript_variant; upstream_gene_variant	1(0/1/0)
rs2108977	chr11:18019049 - 18019049(1)	3_prime_UTR_variant; downstream_gene_variant; intron_variant; non_coding_transcript_variant	1(0/1/0)

LD-proxies (count: 10)

rs_ID	Location	Functional Annotation
rs169806	chr11:18037745 - 18037745(1)	intron_variant; NMD_transcript_variant
rs685657	chr11:18039122 - 18039122(1)	intron_variant; NMD_transcript_variant
rs2056246	chr11:18029899 - 18029899(1)	intron_variant; NMD_transcript_variant
rs211107	chr11:18036794 - 18036794(1)	intron_variant; NMD_transcript_variant
rs7933505	chr11:18024440 - 18024440(1)	intron_variant; NMD_transcript_variant; upstream_gene_variant
rs1607395	chr11:18028189 - 18028189(1)	downstream_gene_variant; intron_variant; NMD_transcript_variant
rs172423	chr11:18034678 - 18034678(1)	intron_variant; NMD_transcript_variant
rs10741734	chr11:18023101 - 18023101(1)	intron_variant; NMD_transcript_variant; non_coding_transcript_exon_variant; non_coding_transcript_variant; upstream_gene_variant
rs546383	chr11:18044116 - 18044116(1)	upstream_gene_variant
rs508924	chr11:18039353 - 18039353(1)	intron_variant; NMD_transcript_variant

Gene related CNVs (count: 0)

Gene related other variants (count: 8)

Variant Name	Variant Type	Location in Gene	No. of Studies (Positive/Negative/Trend)
TPH1_3'UTR_A27237G	point mutation	3'UTR	1 (0/1/0)
TPH1_5'flanking_T-1721G	point mutation	5'flanking	1 (0/1/0)
TPH1_A218C	point mutation	intron 7	6 (2/4/0)
TPH1_5'flanking_A-1067G	point mutation	5'flanking	1 (0/1/0)
TPH1_5'flanking_G-347T	point mutation	5'flanking	1 (0/1/0)
TPH1_intron 7_218A/C	SNP	intron 7	2 (0/2/0)
TPH1_promoter_218A/C	point mutation	promoter	1 (0/1/0)
TPH1_BfaI Polymorphism	SNP		1 (0/1/0)

Gene related regions (count: 2)

Region Name	Position	No. of Studies (Positive/Negative/Trend)
Chr 11	chr11:0-135086622	2 (0/2/0)
11p15	chr11:0-22000000	5 (0/4/1)

Overlap with schizophrenia (SZ) and major depressive disorder (MDD)

Gene relationship with SZ

Overlap with SZ from cross-disorder studies (count: 1)

Reference	Description	Result Category
11472792	TPH variants were not associated with major psychoses, but a trend was observed toward an excess of TPH*A/A in bipolar disorder.	Negative

Overlap with SZ from candidate gene intersection analysis (count: 16)

Reference	ID in SZGene	Result Category
19526457	111	Positive
20144688	111	Negative
16716203	111	Negative
20421849	111	Negative
11343864	111	Positive
16467214	111	Positive
17870198	111	Negative
20046510	111	Negative
17521439	111	Positive
15211625	111	Positive
12532038	111	Positive
16806098	111	Positive
19158809	111	Negative
11324941	111	Negative
11472792	111	Negative
10899755	111	Negative

Gene relationship with MDD

Overlap with MDD from cross-disorder studies (count: 5)

Reference	Description	Category in MDD
10327914	The authors conclude that the examined polymorphisms are unlikely to have major relevance to the pathogenesis of affective disorders or suicidal behavior.	Negative
19032713	P-value > 0.100. None of the three genotypes (AA, AC, CC) significantly increased risk for major depressive disorder relative to any of the other genotypes.	Negative
11274651	We failed to detect an association between the A218C polymorphism of the TPH gene and BPAD and UPAD in a large European sample.	Negative
11472792	TPH variants were not associated with major psychoses, but a trend was observed toward an excess of TPH*A/A in bipolar disorder.	Negative
21601290	The A218C polymorphism of TPH1 did not appear to have any effect on major depressive disorder risk either in Caucasians or in Asians.	Negative

Overlap with MDD from candidate gene intersection analysis (count: 8)

Reference	Description	Category in MDD	Link in MK4MDD
17066254	Subjects carrying TPH1 CC genotype are more likely to belong to the patient sample than to the controls	Pos	TPH1
19874868	TPH1 218A/C polymorphism was associated with the risk of MDD.	Pos	TPH1
18502553	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.	Neg	TPH1
16314762	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.	Neg	TPH1
12960746	Significant difference in genotype frequency between patient and control groups was observed	Pos	TPH1
20945066	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).	Pos	TPH1
16165107	Single marker association analyses showed only one SNP significantly associated with MD. Several haplotypes were associated with MD.	Pos	TPH1
20471034	We found that variations of mRNA levels for NRG1, SORT1 and TPH1 were interesting state-dependent biological markers of the disease.	Pos	TPH1

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Region: chr11:18017564..18042426 View in gBrowse