TPH2

Summary

TPH2 (tryptophan hydroxylase 2, HGNC:20692) is a protein-coding gene on chromosome 12q21.1, encoding Tryptophan 5-hydroxylase 2 (Q8IWU9).

This gene encodes a member of the pterin-dependent aromatic acid hydroxylase family. The encoded protein catalyzes the first and rate limiting step in the biosynthesis of serotonin, an important hormone and neurotransmitter. Mutations in this gene may be associated with psychiatric diseases such as bipolar affective disorder and major depression.

Source: NCBI Gene 121278 — RefSeq curated summary.

At a glance

• Gene–disease (curated): attention deficit-hyperactivity disorder, susceptibility to, 7 (Limited, GenCC)
• Clinical variants (ClinVar): 78 total
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_173353

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20692
Approved symbol	TPH2
Name	tryptophan hydroxylase 2
Location	12q21.1
Locus type	gene with protein product
Status	Approved
Aliases	NTPH, FLJ37295
Ensembl gene	ENSG00000139287
Ensembl biotype	protein_coding
OMIM	607478
Entrez	121278

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000333850, ENST00000546576, ENST00000547278, ENST00000547348, ENST00000550403, ENST00000551074

RefSeq mRNA: 1 — MANE Select: NM_173353 NM_173353

CCDS: CCDS31859

Canonical transcript exons

ENST00000333850 — 11 exons

Exon	Start	End
ENSE00001291881	72031521	72032440
ENSE00001293573	71972519	71972715
ENSE00001302379	72022399	72022494
ENSE00001312687	72031258	72031391
ENSE00001313536	71978952	71979087
ENSE00001339312	71938845	71939091
ENSE00001716058	71994439	71994565
ENSE00003495110	71944586	71944686
ENSE00003496311	71949588	71949655
ENSE00003503906	71944294	71944477
ENSE00003561457	71941584	71941733

Expression profiles

Bgee: expression breadth ubiquitous, 111 present calls, max score 86.40.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3706 / max 122.9257, expressed in 39 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126839	0.2383	18
126842	0.0589	6
126840	0.0487	21
126841	0.0152	4
126844	0.0061	2
126845	0.0034	2

Top tissues by expression

204 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	86.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.39	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.38	gold quality
oocyte	CL:0000023	73.00	gold quality
superior vestibular nucleus	UBERON:0007227	70.33	gold quality
islet of Langerhans	UBERON:0000006	61.57	gold quality
sural nerve	UBERON:0015488	60.61	silver quality
prefrontal cortex	UBERON:0000451	56.10	gold quality
adenohypophysis	UBERON:0002196	52.80	gold quality
pituitary gland	UBERON:0000007	52.16	gold quality
medulla oblongata	UBERON:0001896	51.83	silver quality
testis	UBERON:0000473	50.68	gold quality
leukocyte	CL:0000738	50.14	gold quality
monocyte	CL:0000576	50.08	gold quality
left testis	UBERON:0004533	49.05	gold quality
frontal cortex	UBERON:0001870	48.61	gold quality
ganglionic eminence	UBERON:0004023	48.45	gold quality
right uterine tube	UBERON:0001302	48.35	gold quality
right testis	UBERON:0004534	48.09	gold quality
stromal cell of endometrium	CL:0002255	47.87	gold quality
pancreas	UBERON:0001264	47.72	gold quality
hindlimb stylopod muscle	UBERON:0004252	47.71	gold quality
gastrocnemius	UBERON:0001388	47.67	gold quality
neocortex	UBERON:0001950	47.33	gold quality
Brodmann (1909) area 9	UBERON:0013540	46.76	gold quality
muscle of leg	UBERON:0001383	46.64	gold quality
spleen	UBERON:0002106	46.61	gold quality
upper leg skin	UBERON:0004262	46.58	silver quality
skin of leg	UBERON:0001511	46.40	gold quality
mucosa of stomach	UBERON:0001199	46.30	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.83
E-MTAB-7249	no	53.42
E-GEOD-100618	no	29.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting TPH2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-642A-3P	99.23	67.67	1258

Literature-anchored findings (GeneRIF, showing 40)

• a second tryptophan hydroxylase isoform described (PMID:12511643)
• Single-nucleotide polymorphism (SNP), haplotype and linkage disequlibrium studies were performed on depressed patients and healthy controls with 10 SNPs in the TPH2 gene. Significant association was detected between one SNP and major depression. (PMID:15124006)
• complex behavioral phenotypes or as actual risk factors. Structural polymorphisms are extremely rare in TPH2 and cannot therefore act as substantial risk factors for behavioral disorders in African-American and Caucasian populations. (PMID:15167691)
• It is unlikely that the hCV245410-hCV8376173-rs-1487280 haplotypes of TPH2 were involved in the suicidal behavior of 336 Canadian bipolar patients. (PMID:15197398)
• Single nucleotide polymorphism data support existence of an affective disorder-associated haplotype in the THP2 gene. (PMID:15263906)
• The findings of this study provide evidence for an involvement of genetic variants in the TPH2 gene in suicidal behavior. (PMID:15476687)
• Identification of a loss-of-function mutation in hTPH2 suggests that defect in brain serotonin synthesis may represent an important risk factor for unipolar major depression. (PMID:15629698)
• TPH2 may play a modest role in autism susceptibility. (PMID:15768392)
• Eight single nucleotide polymorphisms in the TPH2 gene for association with attention-deficit hyperactivity disorder in 179 Irish nuclear families. (PMID:15940290)
• TPH2 mRNA levels in postmortem parietal cortex of unipolar-depressed, bipolar, and schizophrenic patients vs control subjects, using real-time reverse transcription polymerase chain reaction. No significant difference in TPH2 mRNA levels was found. (PMID:15968084)
• In vivo evidence that a relatively frequent regulatory variant (G(-844)T) of hTPH2 biases the reactivity of the amygdala, a neural structure critical in the generation and regulation of emotional behaviors. (PMID:16044172)
• Preferential transmissions were detected for the two SNPs in TPH2’s regulatory region (rs4570625, rs11178997). (PMID:16116490)
• Here, we used functional magnetic resonance imaging (fMRI) to demonstrate that a potentially functional variant of TPH2 modulates amygdala responsiveness to emotional stimuli of both negative and positive valence. (PMID:16245070)
• this first study of TPH2 in panic disorder argue against an importance of allelic variation of TPH2 in the pathogenesis of panic disorder (PMID:16401665)
• No association with history of suicide was found for the -473T > A and -8396G > C polymorphisms of the TPH2 gene in subjects with schizophrenia or bipolar disorder. (PMID:16436194)
• our results do not confirm the role of the R441H mutation of the hTPH2 gene in the susceptibility to unipolar major depression (PMID:16581035)
• the NH(2)-terminal regulatory domain is the source of hTPH2 instability and reduced solubility. (PMID:16864580)
• Variant is not a major determinant of genetic risk for depression in aged patients. (PMID:16936760)
• It appears unlikely that the TPH1 and TPH2 genes play a significant role in the susceptibility to autism or to autism endophenotypes including severe obsessive-compulsive behaviors and self-stimulatory behaviors. (PMID:16958027)
• The A allele was significantly less frequent in patients with suicide behavior. Individuals with the A/A genotype showed a significantly lower risk of suicide behavior than those with the A/G or G/G genotype. (PMID:17011525)
• Haplotype-based analysis of TPH2 in patients with UP and BP disorder provides preliminary evidence for protective association in both disorders and thus supports a central role for TPH2 in the pathogenesis of affective disorders. (PMID:17015812)
• A larger sample size will be required to clarify if TPH2 alleles are or are not associated with ADHD. (PMID:17123708)
• an association with rs1386494 SNP was observed in the subgroup of female patients with pure PD phenotype, indicating a possible gender-specific effect of TPH2 gene variants in panic disorder. (PMID:17123728)
• Case-control studies support the presence of a susceptibility locus for bipolar disorder in tryptophan hydroxylase 2. (PMID:17167340)
• A significant association between harm avoidance (HA), a trait related to anxiety, and tryptophan hydroxylase 2 polymorphism (PMID:17176491)
• these findings implicate alterations of serotonin synthesis in emotion regulation and confirm TPH2 as a susceptibility and/or modifier gene of affective spectrum disorders (PMID:17176492)
• Absence of the Arg441His polymorphism in the tryptophan hydroxylase 2 gene in adults with anxiety disorders and depression. (PMID:17192895)
• study reports the learning process of decision-making in suicide attempters to be modulated by four serotonergic gene polymorphisms, 5HTTLPR, TPH1 A218C, MAOA u-VNTR, and TPH2 rs1118997 (PMID:17221847)
• Haplotypes of the TPH2 gene are unlikely to play a major role in the pathophysiology of alcohol dependence or the alcoholism-related phenotype suicidal behavior. (PMID:17251907)
• single-nucleotide polymorphism on the TPH2 gene explained more than 10% of the variance in both indicators of attention (PMID:17335389)
• TPH2 gene variants are unlikely to contribute to autism or to the presence/absence of prominent repetitive behaviors in our sample, although an influence on the intensity of these behaviors in autism cannot be excluded (PMID:17346350)
• Polymorphism in this enzyme is not associated with schizophrenia in a Japanese population. (PMID:17413454)
• Results reveal the presence of a functional cis-acting polymorphism, with high frequency in normal human subjects, resulting in increased TPH2 expression levels. (PMID:17453063)
• These data identify a region between the C-terminal oligomerization domain and the catalytic domain, which is indispensable for TPH2 activity. (PMID:17539919)
• human TPH2 promoter polymorphism impacts on gene expression, which might have implications for the development and function of the serotonergic system in the brain (PMID:17568567)
• Results link TPH2 variations to pathogenesis of Tourette syndrome and support the relevance of serotonin signalling in Tourette’s. (PMID:17592484)
• No association was detected between the rs4131347 (-C8347G) SNP in the promoter region of the TPH2 gene and mood disorders, suicidal behavior or monoamine function. (PMID:17604842)
• hopelessness, negative life-events and family history of suicide were risk factors of attempted suicide in major deprbssion while TPH2 gene rs7305115 A/A might be the protective factor. (PMID:17649681)
• This study supports the involvement of TPH2 in the etiology of BPD, and the functional single-nucleotide polymorphisms identified herein might be the susceptibility loci for BPD (PMID:17768266)
• The results of this study underscore the role of the TPH2 G-703T polymorphism in the modulation of behavior and cognition. (PMID:17892388)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tph2	ENSDARG00000057239
mus_musculus	Tph2	ENSMUSG00000006764
rattus_norvegicus	Tph2	ENSRNOG00000003880
drosophila_melanogaster	Trhn	FBGN0035187
caenorhabditis_elegans		WBGENE00006600

Paralogs (3): TPH1 (ENSG00000129167), PAH (ENSG00000171759), TH (ENSG00000180176)

Protein

Protein identifiers

Tryptophan 5-hydroxylase 2 — Q8IWU9 (reviewed: Q8IWU9)

Alternative names: Neuronal tryptophan hydroxylase, Tryptophan 5-monooxygenase 2

All UniProt accessions (1): Q8IWU9

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with DNAJC12.

Tissue specificity. Brain specific.

Disease relevance. Major depressive disorder (MDD) [MIM:608516] A common psychiatric disorder. It is a complex trait characterized by one or more major depressive episodes without a history of manic, mixed, or hypomanic episodes. A major depressive episode is characterized by at least 2 weeks during which there is a new onset or clear worsening of either depressed mood or loss of interest or pleasure in nearly all activities. Four additional symptoms must also be present including changes in appetite, weight, sleep, and psychomotor activity; decreased energy; feelings of worthlessness or guilt; difficulty thinking, concentrating, or making decisions; or recurrent thoughts of death or suicidal ideation, plans, or attempts. The episode must be accompanied by distress or impairment in social, occupational, or other important areas of functioning. Disease susceptibility is associated with variants affecting the gene represented in this entry. Attention deficit-hyperactivity disorder 7 (ADHD7) [MIM:613003] A neurobehavioral developmental disorder primarily characterized by the coexistence of attentional problems and hyperactivity, with each behavior occurring infrequently alone. Disease susceptibility is associated with variants affecting the gene represented in this entry. Naturally occurring variants of TPH2 with impaired enzyme activity could cause deficiency of serotonin production and result in an increased risk of developing behavioral disorders.

Pathway. Aromatic compound metabolism; serotonin biosynthesis; serotonin from L-tryptophan: step 1/2.

Similarity. Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IWU9-1	a	yes
Q8IWU9-2	b

RefSeq proteins (1): NP_775489* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001273	ArAA_hydroxylase	Family
IPR002912	ACT_dom	Domain
IPR005963	Trp_5_mOase	Family
IPR018301	ArAA_hydroxylase_Fe/CU_BS	Binding_site
IPR019773	Tyrosine_3-monooxygenase-like	Family
IPR019774	Aromatic-AA_hydroxylase_C	Domain
IPR036329	Aro-AA_hydroxylase_C_sf	Homologous_superfamily
IPR036951	ArAA_hydroxylase_sf	Homologous_superfamily
IPR041904	TrpOH_cat	Domain
IPR045865	ACT-like_dom_sf	Homologous_superfamily

Pfam: PF00351

Enzyme classification (BRENDA):

• EC 1.14.16.4 — tryptophan 5-monooxygenase (BRENDA: 37 organisms, 147 substrates, 229 inhibitors, 123 Km, 18 kcat entries)

Substrate kinetics (BRENDA)

23 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-TRYPTOPHAN	0.002–1.67	46
TETRAHYDROBIOPTERIN	0.0067–0.324	18
(6R)-L-ERYTHO-5,6,7,8-TETRAHYDROBIOPTERIN	0.0128–0.281	9
L-PHENYLALANINE	0.022–0.102	7
(6R)-L-ERYTHRO-5,6,7,8-TETRAHYDROBIOPTERIN	0.0179–0.796	4
2-AMINO-4-HYDROXY-6-METHYLTETRAHYDROPTERIDINE	0.055–0.125	4
2-AMINO-4-HYDROXY-6,7-DIMETHYL-5,6,7,8-TETRAHYDR	0.006–0.13	3
O2	0.039–0.273	3
TRYPTOPHAN	0.05–0.29	3
6-METHYL-TETRAHYDROPTERIN	0.053–0.802	2
6-METHYLTETRAHYDROPTERIN	0.0146–0.177	2
(6R)-5,6,7,8-TETRAHYDROBIOPTERIN	0.045	1
(7R)-5,6,7,8-TETRAHYDROBIOPTERIN	2.1	1
2-AMINO-4-HYDROXY-6-METHYL-5,6,7,8-TETRAHYDROPTE	0.05	1
2-AZAISOTRYPTOPHAN	0.0865	1

Catalyzed reactions (Rhea), 1 shown:

• (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-tryptophan + O2 = 5-hydroxy-L-tryptophan + (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin (RHEA:16709)

UniProt features (63 total): helix 19, strand 16, sequence variant 12, turn 5, binding site 3, compositionally biased region 2, chain 1, domain 1, region of interest 1, sequence conflict 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
4V06	X-RAY DIFFRACTION	2.63
9HB8	X-RAY DIFFRACTION	2.9
9HB7	X-RAY DIFFRACTION	2.96
7WIY	ELECTRON MICROSCOPY	3.09
7QRI	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IWU9-F1	83.55	0.55

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 318; 323; 363

Post-translational modifications (1): 19

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-209931	Serotonin and melatonin biosynthesis

MSigDB gene sets: 104 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_PHENOL_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, TAL1ALPHAE47_01, GOBP_AROMATIC_AMINO_ACID_METABOLIC_PROCESS, BRN2_01, chr12q21, GATA6_01, GOBP_INDOLE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOCC_NEURON_PROJECTION, YKACATTT_UNKNOWN, GOMF_IRON_ION_BINDING, CHEN_METABOLIC_SYNDROM_NETWORK, TAL1BETAITF2_01

GO Biological Process (2): aromatic amino acid metabolic process (GO:0009072), serotonin biosynthetic process (GO:0042427)

GO Molecular Function (6): tryptophan 5-monooxygenase activity (GO:0004510), iron ion binding (GO:0005506), monooxygenase activity (GO:0004497), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced pteridine as one donor, and incorporation of one atom of oxygen (GO:0016714), metal ion binding (GO:0046872)

GO Cellular Component (2): cytosol (GO:0005829), neuron projection (GO:0043005)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of amine-derived hormones	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
amino acid metabolic process	1
carboxylic acid metabolic process	1
serotonin metabolic process	1
indole-containing compound biosynthetic process	1
phenol-containing compound biosynthetic process	1
primary amino compound biosynthetic process	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced pteridine as one donor, and incorporation of one atom of oxygen	1
transition metal ion binding	1
oxidoreductase activity	1
catalytic activity	1
monooxygenase activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
cation binding	1
cytoplasm	1
cellular anatomical structure	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

1538 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TPH2	SLC6A4	P31645	926
TPH2	YWHAZ	P29213	868
TPH2	HTR1B	P28222	805
TPH2	HTR2A	P28223	762
TPH2	HTR2C	P28335	752
TPH2	YWHAH	Q04917	710
TPH2	SLC18A2	Q05940	707
TPH2	MAOB	P27338	692
TPH2	HTR1D	P28221	692
TPH2	HTR1A	P08908	690
TPH2	MAOA	P21397	687
TPH2	YWHAB	P31946	682
TPH2	DDC	P20711	676
TPH2	DRD4	P21917	669
TPH2	YWHAE	P29360	651

IntAct

5 interactions, top by confidence:

A	B	Type	Score
TPH2	DNAJC12	psi-mi:“MI:0915”(physical association)	0.400
TPH2	TPH1	psi-mi:“MI:0915”(physical association)	0.400
SYBU	SNPH	psi-mi:“MI:0914”(association)	0.350
TPH2	YWHAE	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): DNAJC12 (Affinity Capture-MS), TPH2 (Affinity Capture-MS), DNAJC12 (Affinity Capture-MS), TPH2 (Affinity Capture-MS), TPH1 (Affinity Capture-MS), TPH2 (Protein-peptide), EEF2 (Cross-Linking-MS (XL-MS)), TPH2 (Affinity Capture-RNA)

ESM2 similar proteins: A0A060X6Z0, A8HQD7, A8X3V8, E5KBU3, E5KBU4, G8BAW7, O17446, O42091, O80452, P00365, P00439, P04176, P04177, P07101, P09810, P11982, P15274, P16331, P17276, P17289, P17290, P17532, P17752, P18459, P23225, P24529, P34466, P50998, P70080, P90925, P90986, Q0EAB8, Q0U2R3, Q10289, Q2HZ26, Q2KIH7, Q4W9F7, Q4WED9, Q54XS1, Q6BIV1

Diamond homologs: A0A060X6Z0, A8HQD7, A8X3V8, E5KBU3, E5KBU4, F5BFC8, O17446, O42091, P00439, P04176, P04177, P07101, P09810, P11982, P16331, P17276, P17289, P17290, P17532, P17752, P18459, P24529, P30967, P43334, P70080, P90925, P90986, Q0EAB8, Q2HZ26, Q2KIH7, Q54XS1, Q76IQ3, Q8CGU9, Q8CGV2, Q8IWU9, Q8XU39, Q92142, Q98D72, Q9A7V7, Q9KLB8

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PRKACA	up-regulates	TPH2	phosphorylation
TPH2	“down-regulates quantity”	tryptophan	“chemical modification”
TPH2	“up-regulates quantity”	5-hydroxy-L-tryptophan	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

78 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	2
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3217 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:71944670:T:C	L175P	1.000
12:71944682:A:G	H179R	1.000
12:71944683:C:A	H179Q	1.000
12:71944683:C:G	H179Q	1.000
12:71949591:T:C	F182L	1.000
12:71949593:T:A	F182L	1.000
12:71949593:T:G	F182L	1.000
12:71949610:G:C	R188P	1.000
12:71949619:G:C	R191T	1.000
12:71949620:A:C	R191S	1.000
12:71949620:A:T	R191S	1.000
12:71949640:C:A	A198D	1.000
12:71972590:T:C	L227P	1.000
12:71978963:T:C	F273L	1.000
12:71978965:C:A	F273L	1.000
12:71978965:C:G	F273L	1.000
12:71978984:G:A	G280R	1.000
12:71978984:G:C	G280R	1.000
12:71978985:G:A	G280E	1.000
12:71978987:T:C	Y281H	1.000
12:71979005:T:C	F287L	1.000
12:71979006:T:C	F287S	1.000
12:71979007:T:A	F287L	1.000
12:71979007:T:G	F287L	1.000
12:71979009:T:C	L288P	1.000
12:71979018:T:C	L291P	1.000
12:71979021:C:A	A292D	1.000
12:71979027:G:C	R294T	1.000
12:71979027:G:T	R294I	1.000
12:71979032:T:C	F296L	1.000

dbSNP variants (sampled 300 via entrez): RS1000026031 (12:72026831 A>C), RS1000043973 (12:71945023 T>C), RS1000099492 (12:72017633 C>T), RS1000136718 (12:71989123 G>A,T), RS1000139716 (12:71946338 G>C), RS1000144395 (12:71965996 G>A,C,T), RS1000202524 (12:71990551 T>C), RS1000228416 (12:71984538 G>C), RS1000279561 (12:71972420 A>G), RS1000280072 (12:71996200 C>T), RS1000291433 (12:71995967 C>T), RS1000310752 (12:72024724 G>A), RS1000316845 (12:71952680 C>A), RS1000374745 (12:71959258 G>A), RS1000390184 (12:71966238 C>A)

Disease associations

OMIM: gene MIM:607478 | disease phenotypes: MIM:613003, MIM:608516

GenCC curated gene-disease

Disease	Classification	Inheritance
attention deficit-hyperactivity disorder, susceptibility to, 7	Limited	Autosomal dominant

Mondo (2): attention deficit-hyperactivity disorder, susceptibility to, 7 (MONDO:0013076), major depressive disorder (MONDO:0002009)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D003865	Depressive Disorder, Major	F03.600.300.375

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3831287 (PROTEIN FAMILY), CHEMBL5433 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 554 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL2103855	TELOTRISTAT	4	310
CHEMBL2105695	TELOTRISTAT ETHYL	4	191
CHEMBL4104957	RODATRISTAT	2	53

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Amino acid hydroxylases

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
rodatristat	Inhibition	8.15	pIC50
TPT-004	Inhibition	7.8	pIC50

Binding affinities (BindingDB)

44 measured of 57 human assays (57 total across all organisms); most potent 44 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
KM-05-179/(I-201)	IC50	40 nM	US-10214530
KM-05-185/(I-204)	IC50	240 nM	US-10214530
KM-05-193/(I-209)	IC50	300 nM	US-10214530
MW-01-157/(I-207)	IC50	350 nM	US-10214530
KM-05-166/(I-206)	IC50	360 nM	US-10214530
KM-05-130/(I-19)	IC50	410 nM	US-10214530
AG-01-128/(I-202)	IC50	430 nM	US-10214530
KM-05-139/(I-23)	IC50	590 nM	US-10214530
MW-01-153/(I-47)	IC50	760 nM	US-10214530
MW-01-139/(I-46)	IC50	830 nM	US-10214530
KM-05-80/(I-1)	IC50	850 nM	US-10214530
KM-05-125/(I-13)	IC50	960 nM	US-10214530
KM-06-20/(I-211)	IC50	1070 nM	US-10214530
KM-05-173/(I-203)	IC50	1210 nM	US-10214530
KM-05-89/(I-2)	IC50	1330 nM	US-10214530
KM-06-11/(I-210)	IC50	1560 nM	US-10214530
KM-05-135/(I-15)	IC50	1600 nM	US-10214530
KM-05-128/(I-17)	IC50	1620 nM	US-10214530
KM-05-126/(I-12)	IC50	1800 nM	US-10214530
KM-05-174/(I-205)	IC50	1960 nM	US-10214530
2-amino-3-[4-[2-amino-6-[(1R)-2,2,2-trifluoro-1-[4-(3-methoxyphenyl)phenyl]ethoxy]pyrimidin-4-yl]phenyl]propanoic acid	IC50	2010 nM	US-10214530
KM-05-60/(I-10)	IC50	2220 nM	US-10214530
KM-05-93/(I-9)	IC50	2700 nM	US-10214530
KM480/(I-41)	IC50	2950 nM	US-10214530
KM-05-55 Fr16-17/(I-7)	IC50	4110 nM	US-10214530
KM-05-100/(I-11)	IC50	4140 nM	US-10214530
KM-05-127/(I-16)	IC50	4200 nM	US-10214530
KM-05-50/(I-4)	IC50	5830 nM	US-10214530
KM-05-55 Fr10-12/(l-6)	IC50	6190 nM	US-10214530
KM430/(I-31)	IC50	7400 nM	US-10214530
KM-05-16/(I-3)	IC50	8280 nM	US-10214530
KM406/(I-24)	IC50	9050 nM	US-10214530
KM422/(I-25)	IC50	9480 nM	US-10214530
KM477/(I-40)	IC50	9720 nM	US-10214530
KM-05-68/(I-8)	IC50	10700 nM	US-10214530
KM501/(I-45)	IC50	14500 nM	US-10214530
KM446/(I-35)	IC50	15000 nM	US-10214530
KM424/(I-27)	IC50	20000 nM	US-10214530
KM-05-180/(I-208)	IC50	20800 nM	US-10214530
KM447/(I-36)	IC50	25200 nM	US-10214530
KM489/(I-43)	IC50	33000 nM	US-10214530
KM448/(I-37)	IC50	42200 nM	US-10214530
KM495/(I-44)	IC50	63600 nM	US-10214530
KM483/(I-42)	IC50	76000 nM	US-10214530

ChEMBL bioactivities

240 potent at pChembl≥5 of 244 total, top 45 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.15	IC50	7	nM	RODATRISTAT
7.96	IC50	11	nM	CHEMBL5395489
7.85	IC50	14	nM	CHEMBL5191481
7.85	IC50	14	nM	CHEMBL5173430
7.85	IC50	14	nM	CHEMBL5416480
7.82	IC50	15	nM	CHEMBL5424626
7.80	IC50	16	nM	CHEMBL5397485
7.80	IC50	16	nM	CHEMBL5407430
7.80	IC50	16	nM	CHEMBL5404510
7.77	IC50	17	nM	CHEMBL5420432
7.77	IC50	17	nM	CHEMBL5423163
7.77	IC50	17	nM	CHEMBL5435460
7.77	IC50	17	nM	CHEMBL5394253
7.75	IC50	18	nM	CHEMBL5408595
7.75	IC50	18	nM	CHEMBL5438521
7.75	IC50	18	nM	CHEMBL5438308
7.72	IC50	19	nM	CHEMBL5169479
7.70	IC50	20	nM	CHEMBL5203888
7.70	IC50	20	nM	CHEMBL5197055
7.70	IC50	20	nM	CHEMBL5172829
7.70	IC50	20	nM	CHEMBL5413997
7.70	IC50	20	nM	CHEMBL5420586
7.70	IC50	20	nM	CHEMBL5421387
7.70	IC50	20	nM	CHEMBL5169479
7.68	IC50	21	nM	CHEMBL5423736
7.66	IC50	22	nM	CHEMBL5399835
7.64	IC50	23	nM	CHEMBL5407978
7.64	IC50	23	nM	CHEMBL5436189
7.62	IC50	24	nM	CHEMBL5440400
7.62	IC50	24	nM	CHEMBL5438753
7.62	IC50	24	nM	CHEMBL5415902
7.60	IC50	25	nM	CHEMBL5413327
7.60	IC50	25	nM	CHEMBL5416684
7.58	IC50	26	nM	CHEMBL5404599
7.58	IC50	26	nM	CHEMBL5435257
7.54	IC50	29	nM	CHEMBL5396844
7.52	IC50	30	nM	CHEMBL5426838
7.52	IC50	30	nM	CHEMBL5437935
7.52	IC50	30	nM	CHEMBL5424419
7.51	IC50	31	nM	CHEMBL5423548
7.51	IC50	31	nM	CHEMBL5430916
7.50	IC50	32	nM	CHEMBL5440685
7.50	IC50	32	nM	CHEMBL5394907
7.50	IC50	32	nM	CHEMBL5397488
7.47	IC50	34	nM	CHEMBL5438647

PubChem BioAssay actives

107 with measured affinity, of 116 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(3S)-8-[2-amino-6-[(1R)-1-(4-chloro-2-phenylphenyl)-2,2,2-trifluoroethoxy]pyrimidin-4-yl]-2,8-diazaspiro[4.5]decane-3-carboxylic acid	1434619: Inhibition of TPH2 (unknown origin)	ic50	0.0070	uM
7-benzyl-3-ethyl-8-(imidazo[2,1-b][1,3]thiazol-6-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0110	uM
7-benzyl-8-(5H-[1,3]dioxolo[4,5-f]benzimidazol-6-ylmethyl)-3-propylpurine-2,6-dione	1885932: Inhibition of N-terminal MBP-tagged full length human TPH2 assessed as reduction in 5-HTP formation incubated for 5 to 10 mins by fluorescence microplate reader analysis	ic50	0.0140	uM
3-ethyl-8-(imidazo[2,1-b][1,3]thiazol-6-ylmethyl)-7-[[4-(1-methylpyrazol-3-yl)phenyl]methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0140	uM
7-benzyl-8-(5H-[1,3]dioxolo[4,5-f]benzimidazol-6-ylmethyl)-3-ethylpurine-2,6-dione	1885932: Inhibition of N-terminal MBP-tagged full length human TPH2 assessed as reduction in 5-HTP formation incubated for 5 to 10 mins by fluorescence microplate reader analysis	ic50	0.0140	uM
7-benzyl-8-[(2-chloroimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-3-ethylpurine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0150	uM
7-benzyl-3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0160	uM
N-[4-[[3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-2,6-dioxopurin-7-yl]methyl]phenyl]acetamide	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0160	uM
3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-7-(oxetan-3-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0160	uM
3-ethyl-8-(imidazo[1,2-a]pyridin-2-ylmethyl)-7-[[4-(1-methylpyrazol-3-yl)phenyl]methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0170	uM
3-ethyl-8-(imidazo[1,2-a]pyridin-2-ylmethyl)-7-[[4-(1,3-thiazol-2-yl)phenyl]methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0170	uM
3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-7-[[4-(2-oxopyrrolidin-1-yl)phenyl]methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0170	uM
N-[4-[[8-[(2-chloroimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-3-ethyl-2,6-dioxopurin-7-yl]methyl]phenyl]acetamide	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0170	uM
7-benzyl-3-ethyl-8-[(2-methylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0180	uM
3-ethyl-8-(imidazo[1,2-a]pyridin-2-ylmethyl)-7-[[4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0180	uM
3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-7-(pyridin-2-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0180	uM
8-(1H-benzimidazol-2-ylmethyl)-7-benzyl-3-ethylpurine-2,6-dione	1885932: Inhibition of N-terminal MBP-tagged full length human TPH2 assessed as reduction in 5-HTP formation incubated for 5 to 10 mins by fluorescence microplate reader analysis	ic50	0.0190	uM
8-(1H-benzimidazol-2-ylmethyl)-7-benzyl-3-propylpurine-2,6-dione	1885932: Inhibition of N-terminal MBP-tagged full length human TPH2 assessed as reduction in 5-HTP formation incubated for 5 to 10 mins by fluorescence microplate reader analysis	ic50	0.0200	uM
3-ethyl-8-(imidazo[1,2-a]pyridin-2-ylmethyl)-7-[[4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0200	uM
3-ethyl-8-(imidazo[1,2-a]pyridin-2-ylmethyl)-7-[(4-pyrimidin-2-ylphenyl)methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0200	uM
methyl 4-[[3-ethyl-8-(imidazo[1,2-a]pyridin-2-ylmethyl)-2,6-dioxopurin-7-yl]methyl]benzoate	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0200	uM
7-benzyl-8-[(6-hydroxy-1H-benzimidazol-2-yl)methyl]-3-propylpurine-2,6-dione	1885932: Inhibition of N-terminal MBP-tagged full length human TPH2 assessed as reduction in 5-HTP formation incubated for 5 to 10 mins by fluorescence microplate reader analysis	ic50	0.0200	uM
7-benzyl-8-[(6-ethoxy-1H-benzimidazol-2-yl)methyl]-3-ethylpurine-2,6-dione	1885932: Inhibition of N-terminal MBP-tagged full length human TPH2 assessed as reduction in 5-HTP formation incubated for 5 to 10 mins by fluorescence microplate reader analysis	ic50	0.0200	uM
3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-7-[[4-(1-methylpyrazol-3-yl)phenyl]methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0210	uM
methyl 3-[[3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-2,6-dioxopurin-7-yl]methyl]benzoate	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0220	uM
8-[(2-chloroimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-3-ethyl-7-[[4-(1,2,4-triazol-1-yl)phenyl]methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0230	uM
7-(cyclopropylmethyl)-3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0230	uM
8-[(2-chloroimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-3-ethyl-7-[[4-(1-methylpyrazol-3-yl)phenyl]methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0240	uM
3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-7-propan-2-ylpurine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0240	uM
3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-7-[(6-methyl-2-pyridinyl)methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0240	uM
3-ethyl-7-[(4-methoxyphenyl)methyl]-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0250	uM
methyl 3-[[3-ethyl-2,6-dioxo-8-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-ylmethyl)purin-7-yl]methyl]benzoate	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0250	uM
3-ethyl-7-[[4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]methyl]-8-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0260	uM
ethyl 4-[3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-2,6-dioxopurin-7-yl]butanoate	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0260	uM
3-ethyl-7-[(4-imidazol-1-ylphenyl)methyl]-8-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0290	uM
3-ethyl-7-[[4-(2-oxopyrrolidin-1-yl)phenyl]methyl]-8-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0300	uM
3-ethyl-7-[[4-(1-methylpyrazol-3-yl)phenyl]methyl]-8-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0300	uM
7-(1,3-benzodioxol-5-ylmethyl)-3-ethyl-8-(imidazo[1,2-a]pyridin-2-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0300	uM
3-ethyl-8-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-ylmethyl)-7-[[4-(1,2,4-triazol-1-yl)phenyl]methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0310	uM
7-(cyclobutylmethyl)-3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0310	uM
7-[[4-(3,3-difluoroazetidin-1-yl)phenyl]methyl]-3-ethyl-8-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0320	uM
7-(cyclobutylmethyl)-3-ethyl-8-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0320	uM
3-ethyl-7-(3-methylbut-2-enyl)-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0320	uM
7-[(3,5-dimethylphenyl)methyl]-3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0340	uM
3-ethyl-7-[[4-(3-methoxyazetidin-1-yl)phenyl]methyl]-8-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0350	uM
N-[4-[[3-ethyl-2,6-dioxo-8-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-ylmethyl)purin-7-yl]methyl]phenyl]acetamide	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0360	uM
ethyl 2-[3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-2,6-dioxopurin-7-yl]acetate	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0370	uM
8-[(2-chloroimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-3-ethyl-7-(oxetan-3-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0370	uM
methyl 2-[4-[[3-ethyl-8-(imidazo[1,2-a]pyridin-2-ylmethyl)-2,6-dioxopurin-7-yl]methyl]phenyl]acetate	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0380	uM
3-ethyl-7-(3-methoxypropyl)-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0380	uM

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, affects methylation, decreases expression	3
methyleugenol	decreases expression	1
perfluorooctanoic acid	affects cotreatment, decreases expression	1
benzo(e)pyrene	increases methylation	1
perfluorooctane sulfonic acid	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluorohexanesulfonic acid	affects cotreatment, decreases expression	1
Fluoxetine	affects response to substance	1
Methapyrilene	increases methylation	1
N-Nitrosopyrrolidine	decreases expression	1
Phthalic Acids	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	affects expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
Aflatoxin B1	decreases methylation	1
Particulate Matter	increases methylation	1

ChEMBL screening assays

7 unique, capped per target: 6 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1016552	Binding	Inhibition of TPH2 in human BON cells assessed as inhibition of serotonin biosynthesis	Modulation of peripheral serotonin levels by novel tryptophan hydroxylase inhibitors for the potential treatment of functional gastrointestinal disorders. — J Med Chem
CHEMBL4001818	ADMET	Inhibition of TPH2 (unknown origin)	Optimization of spirocyclic proline tryptophan hydroxylase-1 inhibitors. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00000375	PHASE4	COMPLETED	Continuation Electroconvulsive Therapy Vs Medication to Prevent Relapses in Patients With Major Depressive Disorder
NCT00049972	PHASE4	COMPLETED	Major Depressive Disorder Study In Adults
NCT00157547	PHASE4	COMPLETED	Quantitative EEG (QEEG) as a Predictor of Treatment Outcome in Depression
NCT00166114	PHASE4	COMPLETED	Depression, Epinephrine, and Platelet Function
NCT00177996	PHASE4	COMPLETED	Pharmacotherapy in Depression With Panic Spectrum
NCT00178074	PHASE4	COMPLETED	The Effects of Sleep Deprivation on Antidepressant Response
NCT00178100	PHASE4	COMPLETED	Paroxetine and Interpersonal Psychotherapy for Maintaining Health and Well-being in Elderly Individuals With Depression
NCT00182533	PHASE4	TERMINATED	Sertraline in Generalized Social Phobia With Co-Occurring Anxiety and Mood Disorders
NCT00186446	PHASE4	COMPLETED	Treatment of Nicotine Dependence and Acute Depression
NCT00188942	PHASE4	COMPLETED	A Neuroimaging Investigation of Brain Activity in Major Depressive Disorder and Bipolar Disorder
NCT00191932	PHASE4	COMPLETED	Switching to Duloxetine From Other Antidepressants
NCT00203723	PHASE4	TERMINATED	Use of Risperidone in ECT for Treatment Resistant Depression
NCT00208169	PHASE4	COMPLETED	Abilify Therapy for Reducing Comorbid Substance Abuse
NCT00208702	PHASE4	COMPLETED	Thyroid Medication and Antidepressants for Treating Major Depression
NCT00208715	PHASE4	COMPLETED	Provigil in Conjunction With SSRIs for the Treatment of Mild or Moderate Depression With Attendant Symptoms of Sleepiness and Fatigue.
NCT00209807	PHASE4	UNKNOWN	Effect of Escitalopram vs. Reboxetine on Gastro-intestinal Sensitivity of Patients With Major Depressive Disorder
NCT00222820	PHASE4	COMPLETED	Depression: The Search for Treatment-Relevant Phenotypes-Pilot Study
NCT00223197	PHASE4	COMPLETED	Pregnenolone Trial for Depression in Bipolar Disorders or Recurrent Major Depressive Disorder With Substance Abuse
NCT00226356	PHASE4	COMPLETED	Natural Supplements for Unipolar Depression
NCT00234195	PHASE4	COMPLETED	Wellbutrin XL, Major Depressive Disorder and Breast Cancer
NCT00269334	PHASE4	UNKNOWN	Clinical Pharmacogenomics of Antidepressant Response
NCT00291239	PHASE4	UNKNOWN	Effect of Partial Sleep Deprivation on Cognition and Cytokines in Individuals With Major Depression
NCT00296686	PHASE4	TERMINATED	Sequential Tranylcypromine (TC), TC + Dextroamphetamine and TC + Triiodothyronine for Refractory Depression
NCT00296712	PHASE4	COMPLETED	Are Two Antidepressants a Good Initial Treatment for Depression?
NCT00296777	PHASE4	COMPLETED	Treatment of Depression Following Multiple Brain Tests
NCT00313417	PHASE4	TERMINATED	Creatine as a New Therapeutic Strategy in Depression
NCT00316160	PHASE4	COMPLETED	Sexual Functioning Study With Antidepressants
NCT00321152	PHASE4	COMPLETED	A Study of 6(S)-5-MTHF Among Serotonin Reuptake Inhibitor(SSRI)-Resistant Outpatients With Major Depressive Disorder (MDD)
NCT00330174	PHASE4	COMPLETED	Acamprosate in Alcoholics With Comorbid Anxiety or Depression
NCT00335205	PHASE4	UNKNOWN	A Placebo Controlled Trial of the Dopamine D-2 Receptor Agonist Ropinirole in Treatment of 60 Patients With Refractory Bipolar Depression.
NCT00353028	PHASE4	COMPLETED	Fluvoxamine Maleate in the Treatment of Depression/Depressive State : A Post-marketing Clinical Study in Children and Adolescents
NCT00357045	PHASE4	COMPLETED	Antidepressant Prophylaxis for Interferon-Induced Depression: Efficacy of Paroxetine
NCT00374426	PHASE4	COMPLETED	Preventing Depression Recurrence in Diabetes
NCT00384436	PHASE4	COMPLETED	Fixed Dose Comparison of Escitalopram to an Active Comparator in Severely Depressed Patients
NCT00404755	PHASE4	COMPLETED	Dichotic Listening as a Predictor of Medication Response in Depression
NCT00406848	PHASE4	COMPLETED	A Study Comparing the Efficacy and Safety of Duloxetine and Placebo for the Treatment of Depression in Elderly Patients
NCT00419003	PHASE4	COMPLETED	Research Study for Major Depressive Disorder: Investigation of Glutamate Medications
NCT00422162	PHASE4	COMPLETED	A Study Evaluating Duloxetine in Patients Hospitalized for Severe Depression
NCT00427128	PHASE4	COMPLETED	Prozac Treatment of Major Depression: Discontinuation Study
NCT00437125	PHASE4	COMPLETED	Study on the Tolerability of Duloxetine in Depressed Patients With Parkinson’s Disease