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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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THSD1
thrombospondin type 1 domain containing 1
Chromosome 13 Β· 13q14.3
NCBI Gene: 55901Ensembl: ENSG00000136114.18HGNC: HGNC:17754UniProt: B3KTY7
22PubMed Papers
22Diseases
0Drugs
6Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingextracellular matrix bindingfocal adhesion assemblyendosomeaneurysm, intracranial berry, 12lymphatic malformation 13Non-immune hydrops fetalisneurodegenerative disease
✦AI Summary

THSD1 (Thrombospondin Type 1 Domain Containing Protein 1) is a novel nascent focal adhesion protein that functions as a positive regulator of focal adhesion assembly and endothelial cell attachment to the extracellular matrix 1. Mechanistically, THSD1 localizes to nascent adhesions alongside FAK, talin, and vinculin, where it promotes talin binding to FAKβ€”a critical step in focal adhesion maturation 1. Additionally, THSD1 operates at the interface between endosome dynamics and focal adhesion assembly through clathrin-mediated endocytosis, which positively regulates its adhesion-promoting function 1. Recently, THSD1 was shown to suppress autophagy-mediated focal adhesion turnover by inhibiting Beclin 1 through FAK-dependent phosphorylation in brain endothelial cells 2. Clinically, THSD1 variants are implicated in intracranial aneurysms and subarachnoid hemorrhage, with patient-identified variants showing compromised focal adhesion assembly capacity 31. Loss-of-function THSD1 mutations cause non-immune hydrops fetalis with congenital cardiac defects and hemangiomas in an autosomal recessive inheritance pattern 4. Genome-wide Mendelian randomization analysis identified THSD1 as a potential druggable target for ischemic stroke prevention 5. The protein's role in cell adhesion mechanisms positions it as central to vascular disease pathophysiology.

Sources cited
1
THSD1 is a nascent adhesion protein that promotes talin-FAK binding and focal adhesion assembly; localizes to endosomes via clathrin-mediated endocytosis; patient variants show impaired function
PMID: 29069646
2
THSD1 has a definitive role in intracranial aneurysm pathogenesis; functions through FAK/focal adhesion kinase signaling and cell adhesion mechanisms
PMID: 31055715
3
THSD1 suppresses autophagy-mediated focal adhesion turnover by negatively regulating Beclin 1 through FAK interactions in brain endothelial cells
PMID: 38396816
4
Loss-of-function THSD1 variants cause non-immune hydrops fetalis, congenital cardiac defects, and hemangiomas in autosomal recessive inheritance
PMID: 30055085
5
THSD1 identified as a potential druggable gene for ischemic stroke risk through genome-wide Mendelian randomization analysis
PMID: 40923186
Disease Associationsβ“˜22
aneurysm, intracranial berry, 12Open Targets
0.70Moderate
lymphatic malformation 13Open Targets
0.58Moderate
Non-immune hydrops fetalisOpen Targets
0.45Moderate
neurodegenerative diseaseOpen Targets
0.38Weak
Familial cerebral saccular aneurysmOpen Targets
0.37Weak
Alzheimer diseaseOpen Targets
0.25Weak
subarachnoid hemorrhageOpen Targets
0.19Weak
aortic aneurysmOpen Targets
0.12Weak
vascular dementiaOpen Targets
0.11Weak
hemoglobin D diseaseOpen Targets
0.06Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.06Suggestive
Hereditary persistence of fetal hemoglobin - beta-thalassemiaOpen Targets
0.06Suggestive
alpha thalassemia-intellectual disability syndrome type 1Open Targets
0.05Suggestive
Alpha-thalassemia - intellectual disability syndrome linked to chromosome 16Open Targets
0.05Suggestive
delta-beta-thalassemiaOpen Targets
0.05Suggestive
Hemoglobin E - beta-thalassemiaOpen Targets
0.05Suggestive
hemoglobin E-beta-thalassemia syndromeOpen Targets
0.05Suggestive
Autosomal dominant methemoglobinemiaOpen Targets
0.05Suggestive
Blackfan-Diamond anemiaOpen Targets
0.05Suggestive
hemoglobin E diseaseOpen Targets
0.05Suggestive
Aneurysm, intracranial berry, 12UniProt
Lymphatic malformation 13UniProt
Pathogenic Variants6
NM_018676.4(THSD1):c.1627_1630del (p.Lys543fs)Pathogenic
not specified|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 543
NM_018676.4(THSD1):c.1561C>T (p.Gln521Ter)Likely pathogenic
Lymphatic malformation 13
β˜…β˜†β˜†β˜†2024β†’ Residue 521
NM_018676.4(THSD1):c.617G>A (p.Cys206Tyr)Likely pathogenic
Non-immune hydrops fetalis|Lymphatic malformation 13
β˜…β˜†β˜†β˜†2024β†’ Residue 206
NM_018676.4(THSD1):c.892G>T (p.Glu298Ter)Pathogenic
Lymphatic malformation 13
β˜…β˜†β˜†β˜†2022β†’ Residue 298
NM_018676.4(THSD1):c.1348C>T (p.Arg450Ter)Pathogenic
Aneurysm, intracranial berry, 12
β˜†β˜†β˜†β˜†2023β†’ Residue 450
NM_018676.4(THSD1):c.1322_1329del (p.Arg441fs)Pathogenic
Lymphatic malformation 13
β˜†β˜†β˜†β˜†2023β†’ Residue 441
View on ClinVar β†—
Related Genes
TSPAN11Shared pathway100%TRIP6Shared pathway25%TESK2Shared pathway25%PEAK1Shared pathway17%WHAMMShared pathway17%CORO2BShared pathway14%
Tissue Expression6 tissues
Heart
100%
Lung
89%
Liver
20%
Ovary
20%
Brain
15%
Bone Marrow
9%
Gene Interaction Network
Click a node to explore
THSD1TSPAN11TRIP6TESK2PEAK1WHAMMCORO2B
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q9NS62
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.86LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.65 [0.49–0.86]
RankingsWhere THSD1 stands among ~20K protein-coding genes
  • #13,770of 20,598
    Most Researched22
  • #3,440of 5,498
    Most Pathogenic Variants6
  • #7,544of 17,882
    Most Constrained (LOEUF)0.86
Genes detectedTHSD1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Intracranial Aneurysms: Pathology, Genetics, and Molecular Mechanisms.
PMID: 31055715
Neuromolecular Med Β· 2019
1.00
2
A recessive truncating variant in thrombospondin-1 domain containing protein 1 gene THSD1 is the underlying cause of nonimmune hydrops fetalis, congenital cardiac defects, and haemangiomas in four patients from a consanguineous family.
PMID: 30055085
Am J Med Genet A Β· 2018
0.90
3
The Intracranial Aneurysm Gene THSD1 Connects Endosome Dynamics to Nascent Focal Adhesion Assembly.
PMID: 29069646
Cell Physiol Biochem Β· 2017
0.80
4
Neuroendocrine, inflammatory, and extracellular vesicle responses during the Navy Special Warfare Screener Selection Course.
PMID: 35695270
Physiol Genomics Β· 2022
0.70
5
THSD1 Suppresses Autophagy-Mediated Focal Adhesion Turnover by Modulating the FAK-Beclin 1 Pathway.
PMID: 38396816
Int J Mol Sci Β· 2024
0.60