RGD Reference Report - Arg60 to Leu mutation of the human thromboxane A2 receptor in a dominantly inherited bleeding disorder. - Rat Genome Database

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Arg60 to Leu mutation of the human thromboxane A2 receptor in a dominantly inherited bleeding disorder.

Authors: Hirata, T  Kakizuka, A  Ushikubi, F  Fuse, I  Okuma, M  Narumiya, S 
Citation: Hirata T, etal., J Clin Invest. 1994 Oct;94(4):1662-7.
RGD ID: 1578439
Pubmed: PMID:7929844   (View Abstract at PubMed)
PMCID: PMC295328   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI117510   (Journal Full-text)

Recent advances in molecular genetics have revealed the mechanisms underlying a variety of inherited human disorders. Among them, mutations in G protein-coupled receptors have clearly demonstrated two types of abnormalities, namely loss of function and constitutive activation of the receptors. Thromboxane A2 (TXA2) receptor is a member of the family of G protein-coupled receptors and performs an essential role in hemostasis by interacting with TXA2 to induce platelet aggregation. Here we identify a single amino acid substitution (Arg60-->Leu) in the first cytoplasmic loop of the TXA2 receptor in a dominantly inherited bleeding disorder characterized by defective platelet response to TXA2. This mutation was found exclusively in affected members of two unrelated families with the disorder. The mutant receptor expressed in Chinese hamster ovary cells showed decreased agonist-induced second messenger formation despite its normal ligand binding affinities. These results suggest that the Arg60 to Leu mutation is responsible for the disorder. Moreover, dominant inheritance of the disorder suggests the possibility that the mutation produces a dominant negative TXA2 receptor.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
blood platelet disease  IAGP 1578439DNA:mutation:cds:p.R60L(human)RGD 
blood platelet disease  ISOTBXA2R (Homo sapiens)1578439; 1578439DNA:mutation:cds:p.R60L(human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Impaired platelet aggregation  IAGP 1578439DNA:mutation:cds:p.R60L(human)RGD 
Objects Annotated

Genes (Rattus norvegicus)
Tbxa2r  (thromboxane A2 receptor)

Genes (Mus musculus)
Tbxa2r  (thromboxane A2 receptor)

Genes (Homo sapiens)
TBXA2R  (thromboxane A2 receptor)


Additional Information