TBXAS1

thromboxane A synthase 1, the group of Cytochrome P450 family 5

Basic information

Region (hg38): 7:139777050-140020325

Links

ENSG00000059377 ∙ NCBI:6916 ∙ OMIM:274180 ∙ HGNC:11609 ∙ Uniprot:P24557 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ghosal hematodiaphyseal dysplasia (Definitive), mode of inheritance: AR
• ghosal hematodiaphyseal dysplasia (Supportive), mode of inheritance: AR
• ghosal hematodiaphyseal dysplasia (Strong), mode of inheritance: AR
• ghosal hematodiaphyseal dysplasia (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ghosal hematodiaphyseal syndrome	AR	Hematologic	Steroid therapy has been described as effective for some hematologic manifestations	Hematologic; Musculoskeletal; Neurologic	3385529; 2715908; 8444247; 17203301; 18264100

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TBXAS1 gene.

• not provided (204 variants)
• Inborn genetic diseases (25 variants)
• not specified (16 variants)
• Ghosal hematodiaphyseal dysplasia (13 variants)
• Ghosal hematodiaphyseal syndrome (2 variants)
• TBXAS1-related condition (2 variants)
• Thromboxane synthetase deficiency;Ghosal hematodiaphyseal dysplasia (1 variants)
• Thromboxane synthetase deficiency (1 variants)
• Abnormal bleeding;Thrombocytopenia (1 variants)
• Ghosal hematodiaphyseal dysplasia;Thromboxane synthetase deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TBXAS1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	35	9	46
missense		1	81	9	7	98
nonsense	2		1			3
start loss			1			1
frameshift		2	4			6
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region			5	5	1	11
non coding			1	21	16	38
Total	2	4	91	65	32

Highest pathogenic variant AF is 0.0000263

Variants in TBXAS1

This is a list of pathogenic ClinVar variants found in the TBXAS1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-139828863-G-T			Benign (Nov 12, 2018)
7-139829385-G-A			Uncertain significance (May 21, 2018)
7-139829392-T-C		Inborn genetic diseases	Uncertain significance (Mar 10, 2023)
7-139829405-G-T			Likely benign (Dec 31, 2018)
7-139829421-G-A			Uncertain significance (May 07, 2022)
7-139829421-G-C			Uncertain significance (May 25, 2022)
7-139829440-C-T		TBXAS1-related disorder	Uncertain significance (Dec 20, 2023)
7-139829441-G-A			Uncertain significance (Jun 28, 2016)
7-139829447-C-T			Likely benign (Mar 20, 2022)
7-139829465-G-A			Benign (Jul 22, 2023)
7-139872234-G-C			Likely pathogenic (Aug 01, 2022)
7-139872246-C-T		Inborn genetic diseases	Uncertain significance (Jul 19, 2023)
7-139872257-A-G			Uncertain significance (Dec 22, 2021)
7-139872263-GAGAAGTTAGGCCTC-G		Ghosal hematodiaphyseal dysplasia	Pathogenic (Jul 10, 2023)
7-139872315-C-G			Uncertain significance (May 20, 2022)
7-139872323-C-T			Likely benign (Jun 30, 2023)
7-139872324-G-A		not specified • TBXAS1-related disorder	Conflicting classifications of pathogenicity (Dec 15, 2023)
7-139872324-G-T			Uncertain significance (Jun 28, 2016)
7-139872331-A-G			Uncertain significance (Jul 13, 2021)
7-139872333-G-A		not specified	Benign (Dec 02, 2023)
7-139872335-G-A			Likely benign (Oct 12, 2022)
7-139872346-T-G			Likely benign (Jun 08, 2022)
7-139875570-C-T			Likely benign (May 02, 2023)
7-139875570-CTG-C			Likely benign (Aug 22, 2022)
7-139875585-G-T			Uncertain significance (Oct 13, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TBXAS1	protein_coding	protein_coding	ENST00000416849	14	243276

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.41e-20	0.00138	125599	0	149	125748	0.000593

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.807	381	339	1.12	0.0000216	3788
Missense in Polyphen		142	113.69	1.249		1302
Synonymous	-1.21	155	137	1.13	0.00000927	1162
Loss of Function	-0.133	30	29.2	1.03	0.00000154	341

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00193	0.00193
Ashkenazi Jewish	0.00	0.00
East Asian	0.00185	0.00180
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000398	0.000396
Middle Eastern	0.00185	0.00180
South Asian	0.000849	0.000850
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Note=Thromboxane synthetase deficiency has been detected in some patients with a bleeding disorder due to platelet dysfunction. {ECO:0000269|PubMed:6101498}.
• Pathway: Platelet activation - Homo sapiens (human);Arachidonic acid metabolism - Homo sapiens (human);Phenytoin Pathway, Pharmacokinetics;Celecoxib Pathway, Pharmacodynamics;Platelet Aggregation Inhibitor Pathway, Pharmacodynamics;Etodolac Action Pathway;Ketoprofen Action Pathway;Ibuprofen Action Pathway;Rofecoxib Action Pathway;Acetylsalicylic Acid Action Pathway;Diflunisal Action Pathway;Leukotriene C4 Synthesis Deficiency;Acetaminophen Action Pathway;Celecoxib Action Pathway;Sulindac Action Pathway;Diclofenac Action Pathway;Ketorolac Action Pathway;Naproxen Action Pathway;Etoricoxib Action Pathway;Carprofen Action Pathway;Flurbiprofen Action Pathway;Fenoprofen Action Pathway;Antrafenine Action Pathway;Antipyrine Action Pathway;Lumiracoxib Action Pathway;Magnesium salicylate Action Pathway;Trisalicylate-choline Action Pathway;Nepafenac Action Pathway;Phenylbutazone Action Pathway;Lornoxicam Action Pathway;Salsalate Action Pathway;Tenoxicam Action Pathway;Tiaprofenic Acid Action Pathway;Tolmetin Action Pathway;Salicylic Acid Action Pathway;Salicylate-sodium Action Pathway;Oxaprozin Action Pathway;Valdecoxib Action Pathway;Nabumetone Action Pathway;Indomethacin Action Pathway;Meloxicam Action Pathway;Suprofen Action Pathway;Bromfenac Action Pathway;Mefenamic Acid Action Pathway;Arachidonic Acid Metabolism;Piroxicam Action Pathway;Eicosanoid Synthesis;Prostaglandin Synthesis and Regulation;Phase I - Functionalization of compounds;aspirin blocks signaling pathway involved in platelet activation;eicosanoid metabolism;Metabolism of lipids;Synthesis of Prostaglandins (PG) and Thromboxanes (TX);Prostaglandin Leukotriene metabolism;Arachidonic acid metabolism;Eicosanoids;Cytochrome P450 - arranged by substrate type;Biological oxidations;Metabolism;Fatty acid metabolism;C20 prostanoid biosynthesis (Consensus)

Recessive Scores

• pRec: 0.321

Intolerance Scores

• loftool: 0.983
• rvis_EVS: 0.94
• rvis_percentile_EVS: 89.87

Haploinsufficiency Scores

• pHI: 0.124
• hipred: N
• hipred_score: 0.170
• ghis: 0.481

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.936

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tbxas1
• Phenotype: immune system phenotype; hematopoietic system phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: tbxas1
• Affected structure: cardiac muscle cell
• Phenotype tag: abnormal
• Phenotype quality: shape

Gene ontology

• Biological process: icosanoid metabolic process;cyclooxygenase pathway;oxidation-reduction process
• Cellular component: endoplasmic reticulum membrane;integral component of membrane
• Molecular function: monooxygenase activity;thromboxane-A synthase activity;iron ion binding;oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen;heme binding;12-hydroxyheptadecatrienoic acid synthase activity