TBXA2R gene variants associated with bleeding

Figures & data

Table I. Variants of TBXA2R.

Description	Variation in coding DNA	Inheritance	Region	Defect	Platelet TP receptor phenotype	Reference
Insertion variant causing frameshift	c.167dupG	Heterozygous		Reduced receptor expression	Small and transient platelet aggregation in response to U46619 (2.5 μM) with marked impairment at higher concentration of U46619 (10 μM).	(2)
R60L	c.179G> T	Homozygous or heterozygous	ICL1	Reduced receptor coupling to Gq	Absence of platelet response to 9,1 1-epithio-1 1,12-methano-TXA2 (2 μM).	(9)
D304N	c.190G> A	Heterozygous	TMD7	Reduced ligand binding	Absence of platelet aggregation in response to 0.5 mM AA with reduced level of aggregation to higher AA (1 mM and 1.5 mM) concentrations.	(6)
W29C	c.87G> C	Heterozygous	TMD1	Reduced surface expression	Platelet aggregation in response to AA (1.5 and 2 mM) markedly reduced.	(7)
N42S	c.125A> G	Heterozygous	TMD1	Reduced surface expression	Platelet aggregation and secretion to AA (1 and 1.5 mM) absent.	(8)

The numbering used to describe coding region variants relates to the Ref Seq transcript NM_001060.5. ICL: intracellular loop. TMD: transmembrane domain.

Figure 1. Thromboxane (TP-α) receptor snake plot.

Sites of naturally occurring variants found in patients with a bleeding history are highlighted in green. Key amino acid regulatory motifs are highlighted in yellow (specifically RXR ER retention motif; D/NPXXY motif, E/DRY motif).

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