TBXAS1

Chr 7AR

thromboxane A synthase 1

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

NCBI Gene: 6916 ENSG00000059377 UniProt: P24557 OMIM: 274180

This gene encodes thromboxane A2 synthase, which catalyzes the conversion of prostaglandin H2 to thromboxane A2, a potent vasoconstrictor and platelet aggregation inducer. Mutations cause Ghosal hematodiaphyseal syndrome, a rare autosomal recessive disorder affecting the hematopoietic and skeletal systems. The gene is not highly constrained against loss-of-function variants (LOEUF 1.39), consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Ghosal hematodiaphyseal syndromeMIM #231095

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · ghosal hematodiaphyseal dysplasia · AR · ClinGen 2025

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.39

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

-0.81Z-score

OE missense 1.12 (1.03–1.22)

381 obs / 339.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.03 (0.77–1.39)

0≤0.351.4

Missense OE?1.12 (1.03–1.22)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 30 / 29.2Missense obs/exp: 381 / 339.2Syn Z: -1.21

Background carrier burden — how many people carry a rare variant somewhere in TBXAS1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 48

813 rare PASS variants

Rare truncating (LoF)

1 in 630

153 rare PASS variants

Rare synonymous (reference)

1 in 100

338 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TBXAS1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 51	1 in 770
South Asian	~43k	1 in 46	1 in 500
Remaining (unassigned)	~30k	1 in 49	1 in 320
European (Finnish)	~27k	1 in 180	≈ 1 in 7,600
Admixed American	~22k	1 in 54	1 in 620
African / African American	~21k	1 in 42	1 in 220
East Asian	~20k	1 in 63	1 in 290
Ashkenazi Jewish	~13k	1 in 140	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 51	≈ 1 in 720

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 13 coding exons well covered in gnomAD exomes and genomes.? see exons ↓