THBS1
thrombospondin 1, the group of Thrombospondin family
Basic information
Region (hg38): 15:39581079-39599466
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the THBS1 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 | 13 | 22 | ||||
| missense | 43 | 46 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | ||||
| non coding | 1 | |||||
| Total | 0 | 0 | 43 | 16 | 10 |
Variants in THBS1
This is a list of pathogenic ClinVar variants found in the THBS1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 15-39581891-C-T | Benign (Dec 31, 2019) | |||
| 15-39582190-CAG-C | THBS1-related disorder | Uncertain significance (Jun 03, 2024) | ||
| 15-39582200-C-T | Benign (Dec 31, 2019) | |||
| 15-39582202-G-C | not specified | Uncertain significance (Jan 05, 2022) | ||
| 15-39582246-C-A | not specified | Uncertain significance (Oct 20, 2023) | ||
| 15-39582249-A-G | not specified | Uncertain significance (Mar 29, 2022) | ||
| 15-39582268-T-A | THBS1-related disorder | Uncertain significance (Aug 26, 2024) | ||
| 15-39582279-C-T | not specified | Uncertain significance (Aug 02, 2022) | ||
| 15-39582337-C-G | not specified | Uncertain significance (Aug 16, 2022) | ||
| 15-39582360-G-A | not specified | Uncertain significance (Sep 21, 2021) | ||
| 15-39582456-G-A | not specified | Uncertain significance (Feb 28, 2023) | ||
| 15-39582466-G-A | not specified | Uncertain significance (Dec 30, 2023) | ||
| 15-39582667-T-C | Uncertain significance (Mar 31, 2022) | |||
| 15-39582707-C-T | Benign (Dec 31, 2019) | |||
| 15-39582722-C-T | Likely benign (Apr 10, 2018) | |||
| 15-39582733-G-T | not specified | Uncertain significance (Jul 13, 2021) | ||
| 15-39583642-T-A | not specified | Uncertain significance (Apr 20, 2024) | ||
| 15-39583664-C-T | Benign (Dec 31, 2019) | |||
| 15-39583687-C-A | not specified • Hearing impairment | Uncertain significance (Jul 11, 2023) | ||
| 15-39583689-A-G | not specified | Uncertain significance (Jul 31, 2023) | ||
| 15-39584060-T-C | not specified | Uncertain significance (Jun 28, 2022) | ||
| 15-39584094-C-T | THBS1-related disorder | Likely benign (Oct 28, 2019) | ||
| 15-39584131-G-A | not specified | Conflicting classifications of pathogenicity (Jan 10, 2022) | ||
| 15-39584360-G-A | not specified | Uncertain significance (Oct 29, 2021) | ||
| 15-39584380-C-T | Likely benign (Dec 31, 2019) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| THBS1 | protein_coding | protein_coding | ENST00000260356 | 21 | 18388 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000150 | 125728 | 0 | 20 | 125748 | 0.0000795 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.72 | 516 | 721 | 0.715 | 0.0000434 | 7833 |
| Missense in Polyphen | 181 | 316.89 | 0.57117 | 3482 | ||
| Synonymous | 1.70 | 248 | 284 | 0.872 | 0.0000186 | 2167 |
| Loss of Function | 6.06 | 7 | 56.0 | 0.125 | 0.00000273 | 624 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000268 | 0.000268 |
| Ashkenazi Jewish | 0.0000992 | 0.0000992 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.0000464 | 0.0000462 |
| European (Non-Finnish) | 0.0000705 | 0.0000703 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000339 | 0.0000327 |
| Other | 0.000200 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. Binds heparin. May play a role in dentinogenesis and/or maintenance of dentin and dental pulp (By similarity). Ligand for CD36 mediating antiangiogenic properties. Plays a role in ER stress response, via its interaction with the activating transcription factor 6 alpha (ATF6) which produces adaptive ER stress response factors (By similarity). {ECO:0000250, ECO:0000269|PubMed:11134179, ECO:0000269|PubMed:15014436}.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);ECM-receptor interaction - Homo sapiens (human);Focal adhesion - Homo sapiens (human);TGF-beta signaling pathway - Homo sapiens (human);Bladder cancer - Homo sapiens (human);p53 signaling pathway - Homo sapiens (human);Phagosome - Homo sapiens (human);Malaria - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);miR-targeted genes in leukocytes - TarBase;miR-targeted genes in muscle cell - TarBase;miR-targeted genes in squamous cell - TarBase;Human Complement System;Bladder Cancer;Apoptosis-related network due to altered Notch3 in ovarian cancer;miRNA targets in ECM and membrane receptors;Focal Adhesion;TGF-beta Signaling Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;PI3K-Akt Signaling Pathway;Inflammatory Response Pathway;TGF-beta Receptor Signaling;Senescence and Autophagy in Cancer;Signal Transduction;Gene expression (Transcription);Generic Transcription Pathway;Integrin cell surface interactions;Post-translational protein modification;Metabolism of proteins;Signaling by PDGF;RNA Polymerase II Transcription;Extracellular matrix organization;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Beta3 integrin cell surface interactions;Hemostasis;Syndecan interactions;Non-integrin membrane-ECM interactions;Signaling by Receptor Tyrosine Kinases;Transcriptional regulation by RUNX1;O-glycosylation of TSR domain-containing proteins;Beta1 integrin cell surface interactions;O-linked glycosylation;Alpha4 beta1 integrin signaling events;Syndecan-4-mediated signaling events
(Consensus)
Recessive Scores
- pRec
- 0.935
Intolerance Scores
- loftool
- 0.104
- rvis_EVS
- -1.74
- rvis_percentile_EVS
- 2.39
Haploinsufficiency Scores
- pHI
- 0.935
- hipred
- Y
- hipred_score
- 0.736
- ghis
- 0.569
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.955
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Thbs1
- Phenotype
- endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; limbs/digits/tail phenotype; digestive/alimentary phenotype; muscle phenotype; neoplasm; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; renal/urinary system phenotype; skeleton phenotype; immune system phenotype; vision/eye phenotype;
Gene ontology
- Biological process
- activation of MAPK activity;response to hypoxia;negative regulation of endothelial cell proliferation;negative regulation of cell-matrix adhesion;sprouting angiogenesis;chronic inflammatory response;platelet degranulation;negative regulation of antigen processing and presentation of peptide or polysaccharide antigen via MHC class II;negative regulation of dendritic cell antigen processing and presentation;inflammatory response;immune response;response to unfolded protein;cell cycle arrest;cell adhesion;positive regulation of cell population proliferation;response to mechanical stimulus;response to glucose;positive regulation of endothelial cell migration;negative regulation of endothelial cell migration;negative regulation of plasma membrane long-chain fatty acid transport;negative regulation of nitric oxide mediated signal transduction;negative regulation of cGMP-mediated signaling;negative regulation of plasminogen activation;positive regulation of macrophage chemotaxis;positive regulation of fibroblast migration;cell migration;negative regulation of angiogenesis;peptide cross-linking;positive regulation of blood coagulation;extracellular matrix organization;positive regulation of cell migration;positive regulation of transforming growth factor beta receptor signaling pathway;response to magnesium ion;response to progesterone;negative regulation of interleukin-12 production;positive regulation of transforming growth factor beta1 production;response to testosterone;cellular response to heat;response to endoplasmic reticulum stress;negative regulation of fibroblast growth factor receptor signaling pathway;positive regulation of phosphorylation;response to drug;positive regulation of tumor necrosis factor biosynthetic process;positive regulation of macrophage activation;negative regulation of apoptotic process;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;positive regulation of blood vessel endothelial cell migration;negative regulation of blood vessel endothelial cell migration;engulfment of apoptotic cell;regulation of megakaryocyte differentiation;positive regulation of translation;positive regulation of angiogenesis;behavioral response to pain;positive regulation of smooth muscle cell proliferation;positive regulation of chemotaxis;response to calcium ion;negative regulation of focal adhesion assembly;positive regulation of protein kinase B signaling;negative regulation of fibrinolysis;cellular response to tumor necrosis factor;cellular response to growth factor stimulus;negative regulation of cell migration involved in sprouting angiogenesis;positive regulation of extrinsic apoptotic signaling pathway via death domain receptors;negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis;negative regulation of sprouting angiogenesis;positive regulation of endothelial cell apoptotic process;positive regulation of reactive oxygen species metabolic process;negative regulation of endothelial cell chemotaxis;negative regulation of extrinsic apoptotic signaling pathway
- Cellular component
- extracellular region;fibrinogen complex;extracellular space;endoplasmic reticulum;endoplasmic reticulum lumen;external side of plasma membrane;cell surface;sarcoplasmic reticulum;secretory granule;extracellular matrix;platelet alpha granule;platelet alpha granule lumen;collagen-containing extracellular matrix;extracellular exosome
- Molecular function
- phosphatidylserine binding;fibronectin binding;integrin binding;extracellular matrix structural constituent;calcium ion binding;protein binding;heparin binding;fibroblast growth factor binding;low-density lipoprotein particle binding;identical protein binding;laminin binding;proteoglycan binding;transforming growth factor beta binding;fibrinogen binding;collagen V binding