TPH1

tryptophan hydroxylase 1

Basic information

Region (hg38): 11:18017554-18046269

Previous symbols: [ "TPRH", "TPH" ]

Links

ENSG00000129167 ∙ NCBI:7166 ∙ OMIM:191060 ∙ HGNC:12008 ∙ Uniprot:P17752 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TPH1 gene.

• Inborn genetic diseases (16 variants)
• not provided (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TPH1 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					1	1
missense			16	1	1	18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region						0
non coding						0
Total	0	0	17	1	2

Variants in TPH1

This is a list of pathogenic ClinVar variants found in the TPH1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-18021028-T-C		not specified	Uncertain significance (Aug 30, 2021)
11-18021050-G-C		not specified	Conflicting classifications of pathogenicity (Dec 16, 2022)
11-18021090-T-A		not specified	Uncertain significance (May 30, 2023)
11-18021143-G-A			Uncertain significance (Jan 12, 2022)
11-18021145-T-C		not specified	Uncertain significance (May 30, 2023)
11-18022863-A-G			Benign (Jul 13, 2018)
11-18022915-T-C		not specified	Uncertain significance (Mar 24, 2023)
11-18025669-G-A		not specified	Uncertain significance (Sep 17, 2021)
11-18025708-G-T		TPH1-related disorder	Benign (Oct 18, 2019)
11-18026502-T-C		not specified	Uncertain significance (Sep 16, 2021)
11-18026508-G-T		not specified	Uncertain significance (May 31, 2023)
11-18026622-C-T		not specified	Uncertain significance (Mar 13, 2023)
11-18029176-T-C		not specified	Uncertain significance (Jun 29, 2022)
11-18029259-T-G		not specified	Uncertain significance (May 24, 2023)
11-18029303-C-T			Likely benign (Apr 01, 2023)
11-18029548-C-T		not specified	Uncertain significance (Sep 13, 2023)
11-18029551-C-T		not specified	Uncertain significance (Dec 06, 2022)
11-18033286-A-T		not specified	Uncertain significance (Jan 23, 2024)
11-18033287-T-C		not specified	Uncertain significance (Dec 13, 2021)
11-18033296-G-T		not specified	Uncertain significance (Jan 23, 2024)
11-18033364-AGTTTCCATACCT-A			Uncertain significance (May 31, 2019)
11-18036028-G-A			Benign (Aug 22, 2018)
11-18036090-T-A		TPH1-related disorder	Benign (Jan 06, 2020)
11-18040660-G-C		not specified	Uncertain significance (Dec 07, 2021)
11-18040669-T-C		not specified	Uncertain significance (Dec 14, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TPH1	protein_coding	protein_coding	ENST00000250018	10	24863

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.19e-7	0.934	125591	0	157	125748	0.000624

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.734	204	236	0.865	0.0000123	2941
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00142	0.00142
Ashkenazi Jewish	0.000101	0.0000992
East Asian	0.00163	0.00163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000766	0.000765
Middle Eastern	0.00163	0.00163
South Asian	0.000229	0.000229
Other	0.000491	0.000489

dbNSFP

Source: dbNSFP

• Pathway: Folate biosynthesis - Homo sapiens (human);Tryptophan metabolism - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);Selective Serotonin Reuptake Inhibitor Pathway, Pharmacodynamics;Tryptophan Metabolism;Amino Acid metabolism;Tryptophan metabolism;Biogenic Amine Synthesis;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;serotonin and melatonin biosynthesis;Metabolism of amino acids and derivatives;Metabolism;Tryptophan degradation;superpathway of tryptophan utilization;Serotonin and melatonin biosynthesis;Amine-derived hormones (Consensus)

Recessive Scores

• pRec: 0.396

Intolerance Scores

• loftool: 0.354
• rvis_EVS: -0.38
• rvis_percentile_EVS: 28.01

Haploinsufficiency Scores

• pHI: 0.429
• hipred: N
• hipred_score: 0.369
• ghis: 0.478

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.987

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tph1
• Phenotype: skeleton 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); 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); growth/size/body region phenotype

Zebrafish Information Network

• Gene name: tph1b
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased weight

Gene ontology

• Biological process: circadian rhythm;aromatic amino acid family metabolic process;negative regulation of ossification;response to immobilization stress;serotonin biosynthetic process;positive regulation of fat cell differentiation;bone remodeling;oxidation-reduction process;mammary gland alveolus development
• Cellular component: cytosol;neuron projection
• Molecular function: tryptophan 5-monooxygenase activity;iron ion binding