TBXA2R

protein-coding

thromboxane A2 receptor, the group of Prostaglandin receptors

Gene summary

This gene encodes a member of the G protein-coupled receptor family. The protein interacts with thromboxane A2 to induce platelet aggregation and regulate hemostasis. A mutation in this gene results in a bleeding disorder. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

MANE transcript

NM_001060.6

Inheritance

ClinVar variants

P:4U:133B:64

Top phenotype

Bleeding disorder, platelet-type 13, susceptibility to

gnomAD constraint

pLI —, LoF o/e 0.73

Max pathogenic AF

—

Genomic locus

chr19:3,594,507-3,606,875

External References & Databases

Ensembl (ENSG00000006638)

Transcript & Mutation Effects

hg38 • Region Span ~12.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

schizophreniaNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0005090

Submitter: Labcorp Genetics (formerly Invitae)

bleeding disorder, platelet-type, 13, susceptibility toMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0800447

Submitter: PanelApp Australia

qualitative platelet defectMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0001197

Submitter: ClinGen

*TBXA2R* was first reported in relation to an autosomal dominant qualitative platelet defect in 1994 (Hirata T, et al, PMID: 7929844). This heritable platelet function defect is characterized by reduced platelet aggregation and secretion responses to high concentrations of arachidonic acid, the metabolic precursor of thromboxane A2, and U46619, which is a specific thromboxane receptor agonist. However, heterozygosity is insufficient to cause platelet dysfunction that is clinically significant; clinical features, including mild mucocutaneous bleeding, occur only in the presence of a 'second hit' affecting platelet function; this second hit may be either in the *TBXA2R* gene or in another gene affecting the coagulation cascade (summary by Mumford et al., 2010; PMID: 19828703). Eleven variants (missense, in-frame indel, frameshift, and splicing) have been reported in 11 probands in 8 publications (PMIDs: 21342433, 19828703, 23279270, 24452735, 31389738, 22517902, 31064749, 28983057). This gene-disease association is also supported by its biochemical function in hemostasis (PMID: 9152406), demonstrated functional alteration in patient (PMID: 21342433) and non-patient (PMID: 19828703) cells, and a mouse model that recapitulates the disease (PMID: 9835625). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This gene-disease pair was originally evaluated by the HT GCEP on 12/16/2020. It was reevaluated on 04/03/2023 and 07/29/2025. As a result of these reevaluations no new evidence was identified and the classification remained at Moderate (SOP Version 11).

bleeding diathesis due to thromboxane synthesis deficiencyLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0013524

Submitter: Labcorp Genetics (formerly Invitae)

bleeding diathesis due to thromboxane synthesis deficiencyMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0013524

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Bleeding disorder, platelet-type 13, susceptibility toAD

Manifestation: Hematologic

Intervention: Hematologic; Pharmacogenomic

Rationale: Surveillance and prompt treatment of bleeding diatheses may be beneficial; Avoidance of agents that may provoke or worsen bleeding episodes is warranted

Comments: Heterozygosity may cause abnormal in vitro platelet functional responses, but do not cause in vivo clinically significant dysfunction; Susceptibility is inherited in an autosomal dominant pattern, but clinical features, including mild mucocutaneous bleeding, occur only in the presence of a second hit affecting platelet function

Refs: 7929844; 19828703; 21070398; 22101342

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TBXA2R variants in ClinVar

8 Conditions Cataloged

not providedTotal: 163

Inborn genetic diseasesTotal: 57

Bleeding disorder, platelet-type, 13, susceptibility toTotal: 13

not specifiedTotal: 13

TBXA2R-related disorderTotal: 8

Impaired thromboxane A2 agonist-induced platelet aggregationTotal: 2

Abnormal platelet aggregationTotal: 2

AsthmaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001060.6. 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			3 clinvar	53 clinvar	2 clinvar	58
missense		2 clinvar	124 clinvar	8 clinvar	1 clinvar	135
nonsense		1 clinvar	3 clinvar			4
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)		1 clinvar				1
Total	0	4	133	61	3	201

Highest pathogenic variant AF is 6.9798773e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001060.6	RefSeq	NP_001051.1	2	MANE Select
ENST00000375190.10	Ensembl	ENSP00000364336.4	2	MANE Select
NM_201636.3	RefSeq	NP_963998.2	3	Standard
ENST00000411851.3	Ensembl	ENSP00000393333.2	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Platelet activation - Homo sapiens (human)
Calcium signaling pathway - Homo sapiens (human)
Neuroactive ligand-receptor interaction - Homo sapiens (human)
Celecoxib Pathway, Pharmacodynamics
Platelet Aggregation Inhibitor Pathway, Pharmacodynamics

Biological Process

inflammatory response
G protein-coupled receptor signaling pathway
adenylate cyclase-activating G protein-coupled receptor signaling pathway
positive regulation of cytosolic calcium ion concentration
response to nutrient

Molecular Function

thromboxane A2 receptor activity
guanyl-nucleotide exchange factor activity
protein binding

Cellular Component

acrosomal vesicle
plasma membrane
integral component of plasma membrane
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000411851
Coding exons: 3
Length: 12335
Individuals with no LoFs: 124197
Homozygous LoFs: 0
Heterozygous LoFs: 27
Defined: 124224
p: 0.000109

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.07	239	290	0.823	0.0000223	2506
Missense (PolyPhen)		91	116.5	0.7811		1057
Synonymous	-0.426	141	135	1.05	0.0000107	946
Loss of Function	0.784	7	9.62	0.727	5.01e-7	86

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00039	0.00039	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for thromboxane A2 (TXA2), a potent stimulator of platelet aggregation. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system. In the kidney, the binding of TXA2 to glomerular TP receptors causes intense vasoconstriction. Activates phospholipase C. Isoform 1 activates adenylyl cyclase. Isoform 2 inhibits adenylyl cyclase. {ECO:0000269|PubMed:8613548}.;
Disease: DISEASE: Bleeding disorder, platelet-type 13 (BDPLT13) [MIM:614009]: A disorder characterized by reduced platelet aggregation and a tendency to mild mucocutaneous bleeding. {ECO:0000269|PubMed:7929844, ECO:0000269|PubMed:8613548}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.313

Intolerance Scores

LoFtool: 0.348
RVIS EVS: -0.14
RVIS percentile EVS: 43.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.767

Gene Damage Prediction

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