TPH2

tryptophan hydroxylase 2

Basic information

Region (hg38): 12:71938845-72186618

Links

ENSG00000139287 ∙ NCBI:121278 ∙ OMIM:607478 ∙ HGNC:20692 ∙ Uniprot:Q8IWU9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Attention deficit-hyperactivity disorder, susceptibility to, 7	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	18347598

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TPH2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TPH2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5		3	8
missense			13	2		15
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2	1		3
non coding			20	1	2	23
Total	0	0	38	3	5

Variants in TPH2

This is a list of pathogenic ClinVar variants found in the TPH2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-71938899-G-T		Tryptophan 5-monooxygenase deficiency	Uncertain significance (Jan 12, 2018)
12-71938905-C-T		Tryptophan 5-monooxygenase deficiency	Uncertain significance (Jan 13, 2018)
12-71938935-A-G		Tryptophan 5-monooxygenase deficiency	Benign (Mar 06, 2018)
12-71938953-C-G		Tryptophan 5-monooxygenase deficiency	Uncertain significance (Jan 13, 2018)
12-71939023-T-G		not specified	Uncertain significance (Dec 27, 2023)
12-71941584-C-G		Tryptophan 5-monooxygenase deficiency	Benign/Likely benign (Jun 12, 2018)
12-71941585-T-C		Tryptophan 5-monooxygenase deficiency	Uncertain significance (Apr 28, 2017)
12-71941600-C-A		Tryptophan 5-monooxygenase deficiency • Attention deficit-hyperactivity disorder, susceptibility to, 7;Major depressive disorder	Likely benign (May 04, 2022)
12-71944282-G-A		Tryptophan 5-monooxygenase deficiency	Uncertain significance (Jan 13, 2018)
12-71944300-C-T		Tryptophan 5-monooxygenase deficiency	Uncertain significance (Jan 12, 2018)
12-71944337-G-A			Uncertain significance (-)
12-71944398-T-G		not specified	Uncertain significance (Dec 19, 2022)
12-71944434-T-A		Tryptophan 5-monooxygenase deficiency	Uncertain significance (Jan 12, 2018)
12-71944451-C-T		Tryptophan 5-monooxygenase deficiency	Uncertain significance (Jan 13, 2018)
12-71944462-T-G		not specified	Uncertain significance (Oct 26, 2024)
12-71944486-G-A		Tryptophan 5-monooxygenase deficiency	Uncertain significance (Jan 13, 2018)
12-71944686-A-G		Tryptophan 5-monooxygenase deficiency	Benign/Likely benign (May 21, 2018)
12-71949602-T-A		not specified	Uncertain significance (Nov 30, 2021)
12-71949645-G-T		not specified	Uncertain significance (Nov 25, 2024)
12-71972512-T-C		Tryptophan 5-monooxygenase deficiency	Uncertain significance (Jan 13, 2018)
12-71972526-C-T		Bipolar affective disorder, susceptibility to • Tryptophan 5-monooxygenase deficiency • Attention deficit-hyperactivity disorder, susceptibility to, 7;Major depressive disorder	Uncertain significance (Dec 09, 2021)
12-71972546-T-C			Benign (Jul 23, 2018)
12-71972588-G-A		Tryptophan 5-monooxygenase deficiency	Uncertain significance (Jan 13, 2018)
12-71972636-C-T		Tryptophan 5-monooxygenase deficiency	Uncertain significance (Jan 12, 2018)
12-71979018-T-G		not specified	Uncertain significance (Feb 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TPH2	protein_coding	protein_coding	ENST00000333850	11	247773

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.54e-7	0.979	125721	0	26	125747	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.998	214	259	0.826	0.0000144	3207
Missense in Polyphen		83	117.85	0.70428		1421
Synonymous	-0.763	105	95.5	1.10	0.00000517	932
Loss of Function	2.16	15	27.1	0.553	0.00000158	323

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000181
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000132	0.000132
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Disease: DISEASE: 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. {ECO:0000269|PubMed:15629698}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:18347598}. Note=Disease susceptibility is associated with variations 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: Folate biosynthesis - Homo sapiens (human);Tryptophan metabolism - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);Selective Serotonin Reuptake Inhibitor Pathway, Pharmacodynamics;Serotonin Transporter Activity;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Monoamine Transport;serotonin and melatonin biosynthesis;Metabolism of amino acids and derivatives;Metabolism;superpathway of tryptophan utilization;Serotonin and melatonin biosynthesis;Amine-derived hormones (Consensus)

Intolerance Scores

• loftool: 0.130
• rvis_EVS: -0.07
• rvis_percentile_EVS: 48.54

Haploinsufficiency Scores

• pHI: 0.302
• hipred: Y
• hipred_score: 0.653
• ghis: 0.399

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.956

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tph2
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: tph2
• Affected structure: hematopoietic multipotent progenitor cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: circadian rhythm;aromatic amino acid family metabolic process;response to activity;response to nutrient levels;serotonin biosynthetic process;response to estrogen;response to glucocorticoid;response to calcium ion;oxidation-reduction process;cellular response to lithium ion
• Cellular component: cytosol;neuron projection
• Molecular function: tryptophan 5-monooxygenase activity;iron ion binding