TBXAS1

Chr 7AR

thromboxane A synthase 1

Also known as: BDPLT14, CYP5, CYP5A1, GHOSAL, THAS, TS, TXAS, TXS

NCBI Gene: 6916ENSG00000059377UniProt: P24557

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. However, this protein is considered a member of the cytochrome P450 superfamily on the basis of sequence similarity rather than functional similarity. This endoplasmic reticulum membrane protein catalyzes the conversion of prostglandin H2 to thromboxane A2, a potent vasoconstrictor and inducer of platelet aggregation. The enzyme plays a role in several pathophysiological processes including hemostasis, cardiovascular disease, and stroke. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

Primary Disease Associations & Inheritance

Ghosal hematodiaphyseal syndromeMIM #231095
AR
423
ClinVar variants
69
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TBXAS1
🧬
Gene-Disease Validity (ClinGen)
ghosal hematodiaphyseal dysplasia · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
69 Pathogenic / Likely Pathogenic· 169 VUS of 423 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.39LOEUF
pLI 0.000
Z-score -0.13
OE 1.03 (0.77–1.39)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.81Z-score
OE missense 1.12 (1.03–1.22)
381 obs / 339.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.03 (0.77–1.39)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.12 (1.03–1.22)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.13
0≤1.21.6
LoF obs/exp: 30 / 29.2Missense obs/exp: 381 / 339.2Syn Z: -1.21

ClinVar Variant Classifications

423 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic56
Likely Pathogenic13
VUS169
Likely Benign126
Benign31
Conflicting28
56
Pathogenic
13
Likely Pathogenic
169
VUS
126
Likely Benign
31
Benign
28
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
3
47
0
56
Likely Pathogenic
9
2
2
0
13
VUS
4
140
23
2
169
Likely Benign
1
11
47
67
126
Benign
0
8
15
8
31
Conflicting
—28
Total2016413477423

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TBXAS1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TBXAS1-related ghosal hematodiaphyseal syndrome

definitive
ARUndeterminedAltered Gene Product Structure
Dev. DisordersSkeletal
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Ghosal hematodiaphyseal syndrome

MIM #231095

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Human prostacyclin and thromboxane synthases: Molecular interactions, regulation, and pharmacology.
Ershov PV et al.·Biochimie
2025Review
A Recurrent Biallelic Pathogenic Variant in TBXAS1 Gene Causing Ghosal Hematodiaphyseal Dysplasia.
Selina A et al.·Indian J Pediatr
2021
Characterization of Novel Variants in P2YRY12, GP6 and TBXAS1 in Patients with Lifelong History of Bleeding.
Zamora-Cánovas A et al.·Biomolecules
2025Cohort
Insights into Natural History, Phenotypic, and Molecular Spectrum in a Large Cohort of Osteosclerotic Disorders.
Uludağ Alkaya D et al.·Calcif Tissue Int
2025Cohort
Novel TBXAS1 variants in two Indian children with Ghosal hematodiaphyseal dysplasia: A concise report.
Sudhakar M et al.·Eur J Med Genet
2022
TBXAS1 deficiency: a novel monogenic cause of chronic nonbacterial osteomyelitis responsive to COX inhibitors.
Kisla Ekinci RM et al.·Expert Rev Clin Immunol
2025Case report
Novel compound heterozygous variants of TBXAS1 presenting with Ghosal hematodiaphyseal dysplasia treated with steroids.
Kim SY et al.·Mol Genet Genomic Med
2021Case report
The Role and Regulation of Thromboxane A(2) Signaling in Cancer-Trojan Horses and Misdirection.
Ashton AW et al.·Molecules
2022Review
Association analysis of thromboxane A synthase 1 gene polymorphisms with aspirin intolerance in asthmatic patients.
Oh SH et al.·Pharmacogenomics
2011Cohort
Focusing on DC cells to optimize the prediction of prognosis and innovative treatment strategies for colon cancer.
Chen C et al.·Sci Rep
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools