TPH1
protein-codingtryptophan hydroxylase 1
Gene summary
This gene encodes a member of the aromatic amino 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 have been associated with an elevated risk for a variety of diseases and disorders, including schizophrenia, somatic anxiety, anger-related traits, bipolar disorder, suicidal behavior, addictions, and others.[provided by RefSeq, Apr 2009]
- TPRH
- TPH
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~28.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TPH1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004179.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 48 | 3 | 2 | 53 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 50 | 3 | 3 | 56 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004170.1 | 10 | MANE Select | |
| Ensembl | ENSP00000508368.1 | 10 | MANE Select | |
| Ensembl | ENSP00000250018.2 | 10 | Standard | |
| Ensembl | ENSP00000250018.2 | 10 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| tph1b | Danio rerio | Structure: whole organism Quality: decreased weight abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Folate biosynthesis - Homo sapiens (human)
- Tryptophan metabolism - Homo sapiens (human)
- Serotonergic synapse - Homo sapiens (human)
- Selective Serotonin Reuptake Inhibitor Pathway, Pharmacodynamics
- Tryptophan Metabolism
Biological Process
- circadian rhythm
- aromatic amino acid family metabolic process
- negative regulation of ossification
- response to immobilization stress
- serotonin biosynthetic process
Molecular Function
- tryptophan 5-monooxygenase activity
- iron ion binding
Cellular Component
- cytosol
- neuron projection
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000250018
- Coding exons
- 10
- Length
- 24863
- Individuals with no LoFs
- 125591
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 157
- Defined
- 125748
- p
- 0.000624
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.734 | 204 | 236 | 0.865 | 0.0000123 | 2941 |
| Missense (PolyPhen) | 80 | 92.38 | 0.86599 | 1111 | ||
| Synonymous | 0.159 | 82 | 83.9 | 0.978 | 0.00000420 | 818 |
| Loss of Function | 1.81 | 14 | 23.5 | 0.597 | 0.00000131 | 296 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00099 | 0.00098 | rare |
| Latino/Admixed American | 0.00043 | 0.00035 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.0016 | 0.0016 | notable |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00077 | 0.00076 | rare |
| South Asian | 0.00023 | 0.00023 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.396
Intolerance Scores
- LoFtool
- 0.354
- RVIS EVS
- -0.38
- RVIS percentile EVS
- 28.01
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.987
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |