THSD4

thrombospondin type 1 domain containing 4, the group of ADAMTS like

Basic information

Region (hg38): 15:71096951-71783383

Links

ENSG00000187720 ∙ NCBI:79875 ∙ OMIM:614476 ∙ HGNC:25835 ∙ Uniprot:Q6ZMP0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial thoracic aortic aneurysm and aortic dissection (Moderate), mode of inheritance: AD
• familial thoracic aortic aneurysm and aortic dissection (Limited), mode of inheritance: AD
• aortic aneurysm, familial thoracic 12 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Aortic aneurysm, familial thoracic 12	AD	Cardiovascular	The condition involves increased risk of aortic aneurysms, and awareness may allow early detection and management	Cardiovascular; Craniofacial; Musculoskeletal; Pulmonary	32855533

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the THSD4 gene.

• Inborn genetic diseases (44 variants)
• Familial thoracic aortic aneurysm and aortic dissection (20 variants)
• not provided (17 variants)
• Aortic aneurysm, familial thoracic 12 (3 variants)
• THSD4-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the THSD4 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				3	5	8
missense			48	6	6	60
nonsense						0
start loss						0
frameshift	1					1
inframe indel					1	1
splice donor/acceptor (+/-2bp)		1				1
splice region			1		3	4
non coding						0
Total	1	1	48	9	12

Variants in THSD4

This is a list of pathogenic ClinVar variants found in the THSD4 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-71111241-G-A			Likely benign (Oct 01, 2022)
15-71111256-T-C			Likely benign (Feb 01, 2023)
15-71141552-C-G		Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (Nov 15, 2023)
15-71154900-G-A		not specified	Uncertain significance (Jun 29, 2023)
15-71215036-T-A		not specified	Uncertain significance (Jul 05, 2022)
15-71215038-C-T		not specified	Uncertain significance (Oct 03, 2023)
15-71215063-C-T		not specified	Uncertain significance (Nov 18, 2023)
15-71215070-G-GGACGACGGC		Aortic aneurysm, familial thoracic 12	Pathogenic (Apr 05, 2022)
15-71215090-C-T		not specified	Uncertain significance (Oct 02, 2023)
15-71215110-T-G		not specified	Uncertain significance (Jun 11, 2021)
15-71215118-C-T		Familial thoracic aortic aneurysm and aortic dissection	Benign (May 08, 2023)
15-71215182-C-G		not specified	Likely benign (Dec 14, 2023)
15-71215207-A-G		not specified	Uncertain significance (Jan 16, 2024)
15-71215215-G-A		not specified	Likely benign (Nov 30, 2022)
15-71215217-C-T		Familial thoracic aortic aneurysm and aortic dissection	Benign (Apr 27, 2023)
15-71215226-G-A		Familial thoracic aortic aneurysm and aortic dissection	Benign (Nov 18, 2022)
15-71215248-G-GTGTC			Pathogenic (Oct 12, 2020)
15-71215264-C-T		not specified	Uncertain significance (Jul 06, 2021)
15-71215281-C-G		not specified	Uncertain significance (Nov 30, 2022)
15-71215363-C-T		not specified	Uncertain significance (Nov 13, 2023)
15-71215374-G-T		not specified	Uncertain significance (Aug 02, 2021)
15-71242690-A-G		not specified	Uncertain significance (Feb 13, 2024)
15-71242732-C-T		not specified	Uncertain significance (Dec 12, 2023)
15-71242738-C-T		not specified	Likely benign (Oct 01, 2023)
15-71242762-A-C		Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (May 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
THSD4	protein_coding	protein_coding	ENST00000355327	17	686432

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.81e-7	1.00	124793	0	62	124855	0.000248

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.399	571	598	0.954	0.0000381	6632
Missense in Polyphen		133	172.12	0.7727		1802
Synonymous	0.213	236	240	0.983	0.0000165	1979
Loss of Function	4.01	20	50.8	0.393	0.00000263	561

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000290	0.000290
Ashkenazi Jewish	0.00199	0.00199
East Asian	0.000446	0.000445
Finnish	0.00	0.00
European (Non-Finnish)	0.000106	0.000106
Middle Eastern	0.000446	0.000445
South Asian	0.000265	0.000261
Other	0.000662	0.000659

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Promotes FBN1 matrix assembly. Attenuates TGFB signaling, possibly by accelerating the sequestration of large latent complexes of TGFB or active TGFB by FBN1 microfibril assembly, thereby negatively regulating the expression of TGFB regulatory targets, such as POSTN (By similarity). {ECO:0000250}.
• Pathway: Post-translational protein modification;Metabolism of proteins;O-glycosylation of TSR domain-containing proteins;O-linked glycosylation (Consensus)

Recessive Scores

• pRec: 0.137

Intolerance Scores

• loftool: 0.539
• rvis_EVS: -0.94
• rvis_percentile_EVS: 9.41

Haploinsufficiency Scores

• pHI: 0.228
• hipred: N
• hipred_score: 0.492
• ghis: 0.485

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.192

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Thsd4

Gene ontology

• Biological process: proteolysis;elastic fiber assembly
• Cellular component: microfibril;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: extracellular matrix structural constituent;peptidase activity