THSD1

thrombospondin type 1 domain containing 1

Basic information

Region (hg38): 13:52377167-52416373

Links

ENSG00000136114 ∙ NCBI:55901 ∙ OMIM:616821 ∙ HGNC:17754 ∙ Uniprot:Q9NS62 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• non-immune hydrops fetalis (Definitive), mode of inheritance: AR
• intracranial berry aneurysm (Supportive), mode of inheritance: AD
• aneurysm, intracranial berry, 12 (Limited), mode of inheritance: AD
• multiple congenital anomalies/dysmorphic syndrome (Limited), mode of inheritance: AR
• aneurysm, intracranial berry, 12 (Strong), mode of inheritance: AD
• lymphatic malformation 13 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Aneurysm, intracranial berry, 12; Lymphatic malformation 13	AD/AR	Cardiovascular	Individuals with Aneurysm, intracranial berry, 12 have been described with intracranial aneurysms, some of which progressed to subarachnoid hemorrhage, and awareness may allow early diagnosis and management; Individuals with Lymphatic malformation 13 may have cardiovascular anomalies, and awareness may allow early diagnosis and management	Cardiovascular	26036949; 27895300; 28749478; 30055085; 33569873

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the THSD1 gene.

• Lymphatic malformation 13 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the THSD1 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				17	5	22
missense		1	36	4	1	42
nonsense	1	1	2			4
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding			1	1		2
Total	1	3	39	22	6

Variants in THSD1

This is a list of pathogenic ClinVar variants found in the THSD1 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-52377479-C-G		not specified	Uncertain significance (Dec 01, 2022)
13-52377523-G-A		not specified	Uncertain significance (Jul 06, 2022)
13-52377607-C-G		not specified	Uncertain significance (May 11, 2022)
13-52377626-C-A		not specified	Uncertain significance (Mar 20, 2023)
13-52377643-G-A		not specified	Uncertain significance (Jan 25, 2023)
13-52377667-T-C		THSD1-related disorder	Benign (Jul 23, 2024)
13-52377677-G-T		not specified	Uncertain significance (Dec 07, 2023)
13-52377689-G-A			Uncertain significance (Aug 22, 2022)
13-52377691-C-A		not specified	Uncertain significance (Feb 05, 2024)
13-52377733-C-T		THSD1-related disorder	Uncertain significance (Apr 26, 2023)
13-52377752-G-A			Uncertain significance (Dec 01, 2023)
13-52377760-T-C		not specified	Uncertain significance (Mar 08, 2024)
13-52377784-T-C		not specified	Uncertain significance (Sep 01, 2021)
13-52377834-G-A		THSD1-related disorder	Likely benign (Mar 29, 2021)
13-52377855-A-G			Likely benign (Jan 01, 2023)
13-52377914-G-A		not specified	Uncertain significance (May 16, 2023)
13-52377974-G-A		not specified • Lymphatic malformation 13	Uncertain significance (Nov 26, 2023)
13-52378026-G-A		THSD1-related disorder	Likely benign (Sep 05, 2019)
13-52378061-C-A		not specified	Uncertain significance (Mar 16, 2024)
13-52378171-C-T			Likely benign (May 01, 2022)
13-52378179-G-A		THSD1-related disorder	Likely benign (Jun 26, 2019)
13-52378182-C-G			Benign (Oct 24, 2018)
13-52378182-C-T		THSD1-related disorder	Likely benign (Nov 01, 2023)
13-52378186-G-A		not specified	Uncertain significance (Jan 04, 2022)
13-52378187-G-A		not specified	Uncertain significance (Jun 23, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
THSD1	protein_coding	protein_coding	ENST00000258613	4	29325

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.55e-8	0.964	125677	0	71	125748	0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.497	452	483	0.936	0.0000276	5572
Missense in Polyphen		105	122.51	0.85706		1510
Synonymous	0.0347	200	201	0.997	0.0000127	1745
Loss of Function	2.04	16	27.5	0.581	0.00000157	315

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000691	0.000691
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.000324	0.000323
European (Non-Finnish)	0.000241	0.000193
Middle Eastern	0.000272	0.000272
South Asian	0.000594	0.000588
Other	0.000655	0.000489

dbNSFP

Source: dbNSFP

• Pathway: Post-translational protein modification;Metabolism of proteins;O-glycosylation of TSR domain-containing proteins;O-linked glycosylation (Consensus)

Recessive Scores

• pRec: 0.112

Intolerance Scores

• loftool: 0.878
• rvis_EVS: 0.09
• rvis_percentile_EVS: 60.68

Haploinsufficiency Scores

• pHI: 0.121
• hipred: N
• hipred_score: 0.306
• ghis: 0.517

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.119

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Thsd1
• Phenotype: hematopoietic system phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: thsd1
• Affected structure: cranial vasculature
• Phenotype tag: abnormal
• Phenotype quality: hemorrhagic

Gene ontology

• Cellular component: extracellular region;cytosol;integral component of membrane