Details for: THBS3

Gene ID: 7059

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: THBS3

Ensembl ID: ENSG00000169231

Description: thrombospondin 3

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • skin fibroblast CL0002620
    CSI 3.79
    rCSI 3.27%
    PRS 98.12
  • ependymal cell CL0000065
    CSI 3.76
    rCSI 7.62%
    PRS 90.67
  • chondrocyte CL0000138
    CSI 3.08
    rCSI 4.9%
    PRS 96.48
  • ciliated epithelial cell CL0000067
    CSI 2.75
    rCSI 2.42%
    PRS 94.7
  • alveolar adventitial fibroblast CL4028006
    CSI 2.46
    rCSI 3.89%
    PRS 98.83
  • peripheral nervous system neuron CL2000032
    CSI 2.05
    rCSI 2.79%
    PRS 95.78
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.51
    rCSI 1.83%
    PRS 86.6
  • melanocyte of skin CL1000458
    CSI 1.4
    rCSI 1.91%
    PRS 82.44
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.79
    rCSI 2.83%
    PRS 93.24

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [THBS3](/details-gene/7059) (thrombospondin 3) is a protein-coding gene located on chromosome 1q22 that encodes a member of the thrombospondin family of secreted, extracellular matrix (ECM) proteins. Functionally, [THBS3](/details-gene/7059) is implicated in cell-matrix interactions, tissue development, and structural integrity, with roles in processes such as bone formation ([GO:0060346](https://www.ebi.ac.uk/QuickGO/term/GO:0060346)) and cell adhesion ([GO:0007160](https://www.ebi.ac.uk/QuickGO/term/GO:0007160)). Its molecular functions include calcium ion binding ([GO:0005509](https://www.ebi.ac.uk/QuickGO/term/GO:0005509)) and heparin binding ([GO:0008201](https://www.ebi.ac.uk/QuickGO/term/GO:0008201)), consistent with its role as a structural constituent of the ECM ([GO:0005201](https://www.ebi.ac.uk/QuickGO/term/GO:0005201)). The gene is associated with the OMIM entry [188062](https://omim.org/entry/188062). Expression data indicates its primary significance in mesenchymal and secretory cell types, including [skin fibroblast](/details-cell/CL0002620) and [chondrocyte](/details-cell/CL0000138), underscoring its importance in connective tissue homeostasis. The gene's structure and genomic context have been well-characterized ([Link](https://doi.org/10.1006/geno.1995.1050), [Link](https://doi.org/10.1101/gr.7.10.1020)). ## Cellular Roles and Expression Landscape The expression profile of [THBS3](/details-gene/7059) highlights its role as a key component of tissues responsible for structural support and secretion. **Overall**, the gene shows the highest significance in cells of mesenchymal origin that actively remodel the extracellular matrix. * **Connective and Structural Tissues:** [THBS3](/details-gene/7059) is most significant in [skin fibroblast](/details-cell/CL0002620) (CSI: 3.79), [chondrocyte](/details-cell/CL0000138) (CSI: 3.08), and [alveolar adventitial fibroblast](/details-cell/CL4028006) (CSI: 2.46). This pattern strongly suggests a fundamental role in synthesizing and organizing the ECM in skin, cartilage, and lung tissue. * **Specialized Secretory and Barrier Cells:** High significance is also observed in [ependymal cell](/details-cell/CL0000065) (CSI: 3.76) and [ciliated epithelial cell](/details-cell/CL0000067) (CSI: 2.75). In [ependymal cells](/details-cell/CL0000065), which line the brain ventricles, [THBS3](/details-gene/7059) may contribute to the composition of the cerebrospinal fluid or the structural integrity of the ventricular lining. * **Nervous System and Other Cell Types:** The gene also shows relevance in the nervous system, with notable significance in [peripheral nervous system neuron](/details-cell/CL2000032) (CSI: 2.05) and [L5 extratelencephalic projecting glutamatergic cortical neuron](/details-cell/CL4023041) (CSI: 0.79). This may indicate a role in synaptic organization or axonal guidance via ECM interactions. Lower, yet still positive, significance in cells like [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) (CSI: 1.51) suggests potential secondary roles in immune cell trafficking or adhesion within tissues. ## Pathways and Molecular Function The functional annotations for [THBS3](/details-gene/7059) are highly consistent with its expression pattern in ECM-producing cells. It is a key player in tissue development and maintenance through its role as an extracellular structural protein. * **Biological Processes:** [THBS3](/details-gene/7059) is directly involved in skeletal development, including [bone trabecula formation](/details-cell/GO:0060346), [growth plate cartilage development](/details-cell/GO:0003417), and [ossification involved in bone maturation](/details-cell/GO:0043931). This aligns with its high significance in [chondrocytes](/details-cell/CL0000138). Its role in [cell-matrix adhesion](/details-cell/GO:0007160) is a core function relevant to all high-expressing cell types, particularly [fibroblasts](/details-cell/CL0002620). * **Molecular Functions:** As an [extracellular matrix structural constituent](/details-cell/GO:0005201), [THBS3](/details-gene/7059) participates in building the scaffold of connective tissues. Its ability to bind calcium ([GO:0005509](https://www.ebi.ac.uk/QuickGO/term/GO:0005509)), heparin ([GO:0008201](https://www.ebi.ac.uk/QuickGO/term/GO:0008201)), and other proteins ([GO:0005515](https://www.ebi.ac.uk/QuickGO/term/GO:0005515)) allows it to act as a molecular bridge, connecting different components of the ECM and interacting with cell surface receptors. * **Signaling Pathways:** According to Reactome, [THBS3](/details-gene/7059) is associated with general [signal transduction](/details-cell/R-HSA-162582), including [signaling by receptor tyrosine kinases](/details-cell/R-HSA-9006934) and specifically [signaling by PDGF](/details-cell/R-HSA-186797). This suggests that [THBS3](/details-gene/7059) may not only be a structural protein but may also modulate cell behavior, such as proliferation and migration, by influencing key growth factor signaling pathways, a critical function in wound healing and tissue homeostasis driven by [fibroblasts](/details-cell/CL0002620). ## Research Directions The specific expression pattern and functional annotations of [THBS3](/details-gene/7059) position it as a potential modulator of tissue remodeling in both physiological and pathological states. **Proposed Hypotheses:** 1. Given its high significance in [fibroblasts](/details-cell/CL0002620) and its role in ECM organization and PDGF signaling, **[THBS3](/details-gene/7059) may be a critical regulator of pathological fibrosis.** Overexpression or dysregulation of [THBS3](/details-gene/7059) in response to tissue injury could promote excessive ECM deposition, leading to scarring in organs such as the skin, lungs, and heart. 2. Based on its prominent expression in [chondrocytes](/details-cell/CL0000138) and its annotated role in cartilage and bone development, **impaired [THBS3](/details-gene/7059) function could contribute to the pathogenesis of degenerative joint diseases like osteoarthritis.** A reduction in [THBS3](/details-gene/7059) expression or function might compromise the structural integrity of articular cartilage, accelerating its degradation. **Key Experimental Approach:** To test the hypothesis that [THBS3](/details-gene/7059) is a driver of fibrosis, an *in vitro* study could be conducted. Primary human dermal [fibroblasts](/details-cell/CL0002620) would be cultured and stimulated with the pro-fibrotic cytokine TGF-β1. The role of [THBS3](/details-gene/7059) would be assessed by comparing control cells to cells where [THBS3](/details-gene/7059) has been knocked down using siRNA. Key readouts would include quantification of collagen production (via Western blot or ELISA), analysis of fibroblast-to-myofibroblast differentiation (by measuring α-SMA expression), and assessment of cell contractility using a collagen gel contraction assay. **Therapeutic Potential:** As a secreted, extracellular protein, [THBS3](/details-gene/7059) is a potentially accessible therapeutic target. If its role in fibrosis is confirmed, [THBS3](/details-gene/7059) could be targeted for **inhibition**. Therapeutic strategies might include monoclonal antibodies that neutralize [THBS3](/details-gene/7059) activity or small molecule inhibitors that block its interaction with cell surface receptors or other ECM components. Such a strategy could be valuable in treating conditions characterized by excessive scarring, such as idiopathic pulmonary fibrosis or systemic sclerosis.

Genular Protein ID: 288554209

Symbol: TSP3_HUMAN

Name: Thrombospondin-3

UniProtKB Accession Codes:

P49746 B1AVR8 B4DQ20 Q8WV34

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 2 CTD 1 ChiTaRS 1 ComplexPortal 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 2 ExpressionAtlas 1 GO 9 Gene3D 4 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 13 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PROSITE 5 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 4 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 1 RefSeq 3 SMART 3 SMR 1 STRING 1 SUPFAM 4 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 7558000

Title: Structure and organization of the human thrombospondin 3 gene (THBS3).

PubMed ID: 7558000

DOI: 10.1006/geno.1995.1050

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 9331372

Title: Identification of three additional genes contiguous to the glucocerebrosidase locus on chromosome 1q21: implications for Gaucher disease.

PubMed ID: 9331372

DOI: 10.1101/gr.7.10.1020

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 16959974

Title: The consensus coding sequences of human breast and colorectal cancers.

PubMed ID: 16959974

DOI: 10.1126/science.1133427

Sequence Information:

  • Length: 956
  • Mass: 104201
  • Checksum: AE9B136DF0FFE5B8
  • Sequence:
    • METQELRGAL ALLLLCFFTS ASQDLQVIDL LTVGESRQMV AVAEKIRTAL LTAGDIYLLS 
TFRLPPKQGG VLFGLYSRQD NTRWLEASVV GKINKVLVRY QREDGKVHAV NLQQAGLADG 
RTHTVLLRLR GPSRPSPALH LYVDCKLGDQ HAGLPALAPI PPAEVDGLEI RTGQKAYLRM 
QGFVESMKII LGGSMARVGA LSECPFQGDE SIHSAVTNAL HSILGEQTKA LVTQLTLFNQ 
ILVELRDDIR DQVKEMSLIR NTIMECQVCG FHEQRSHCSP NPCFRGVDCM EVYEYPGYRC 
GPCPPGLQGN GTHCSDINEC AHADPCFPGS SCINTMPGFH CEACPRGYKG TQVSGVGIDY 
ARASKQVCND IDECNDGNNG GCDPNSICTN TVGSFKCGPC RLGFLGNQSQ GCLPARTCHS 
PAHSPCHIHA HCLFERNGAV SCQCNVGWAG NGNVCGTDTD IDGYPDQALP CMDNNKHCKQ 
DNCLLTPNSG QEDADNDGVG DQCDDDADGD GIKNVEDNCR LFPNKDQQNS DTDSFGDACD 
NCPNVPNNDQ KDTDGNGEGD ACDNDVDGDG IPNGLDNCPK VPNPLQTDRD EDGVGDACDS 
CPEMSNPTQT DADSDLVGDV CDTNEDSDGD GHQDTKDNCP QLPNSSQLDS DNDGLGDECD 
GDDDNDGIPD YVPPGPDNCR LVPNPNQKDS DGNGVGDVCE DDFDNDAVVD PLDVCPESAE 
VTLTDFRAYQ TVVLDPEGDA QIDPNWVVLN QGMEIVQTMN SDPGLAVGYT AFNGVDFEGT 
FHVNTVTDDD YAGFLFSYQD SGRFYVVMWK QTEQTYWQAT PFRAVAQPGL QLKAVTSVSG 
PGEHLRNALW HTGHTPDQVR LLWTDPRNVG WRDKTSYRWQ LLHRPQVGYI RVKLYEGPQL 
VADSGVIIDT SMRGGRLGVF CFSQENIIWS NLQYRCNDTV PEDFEPFRRQ LLQGRV

Genular Protein ID: 973040200

Symbol: F5H4Z8_HUMAN

Name: N/A

UniProtKB Accession Codes:

F5H4Z8

Database IDs:

ARBA 7 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CDD 2 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 1 Ensembl 2 ExpressionAtlas 1 GO 4 Gene3D 4 GeneTree 1 HGNC 1 InterPro 13 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 7 PROSITE-ProRule 2 PeptideAtlas 2 Pfam 4 Proteomes 2 ProteomicsDB 2 RefSeq 1 SAM 2 SMART 3 SMR 1 SUPFAM 4 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

Sequence Information:

  • Length: 947
  • Mass: 103252
  • Checksum: 6AF1BBAEA5713511
  • Sequence:
    • METQELRGAL ALLLLCFFTS ASQDLQVIDL LTVGESRQMV AVAEKIRTAL LTAGDIYLLS 
TFRLPPKQGG VLFGLYSRQD NTRWLEASVV GKINKVLVRY QREDGKVHAV NLQQAGLADG 
RTHTVLLRLR GPSRPSPALH LYVDCKLGDQ HAGLPALAPI PPAEVDGLEI RTGQKAYLRM 
QGFVESMKII LGGSMARVGA LSECPFQGDE SIHSAGEQTK ALVTQLTLFN QILVELRDDI 
RDQVKEMSLI RNTIMECQVC GFHEQRSHCS PNPCFRGVDC MEVYEYPGYR CGPCPPGLQG 
NGTHCSDINE CAHADPCFPG SSCINTMPGF HCEACPRGYK GTQVSGVGID YARASKQVCN 
DIDECNDGNN GGCDPNSICT NTVGSFKCGP CRLGFLGNQS QGCLPARTCH SPAHSPCHIH 
AHCLFERNGA VSCQCNVGWA GNGNVCGTDT DIDGYPDQAL PCMDNNKHCK QDNCLLTPNS 
GQEDADNDGV GDQCDDDADG DGIKNVEDNC RLFPNKDQQN SDTDSFGDAC DNCPNVPNND 
QKDTDGNGEG DACDNDVDGD GIPNGLDNCP KVPNPLQTDR DEDGVGDACD SCPEMSNPTQ 
TDADSDLVGD VCDTNEDSDG DGHQDTKDNC PQLPNSSQLD SDNDGLGDEC DGDDDNDGIP 
DYVPPGPDNC RLVPNPNQKD SDGNGVGDVC EDDFDNDAVV DPLDVCPESA EVTLTDFRAY 
QTVVLDPEGD AQIDPNWVVL NQGMEIVQTM NSDPGLAVGY TAFNGVDFEG TFHVNTVTDD 
DYAGFLFSYQ DSGRFYVVMW KQTEQTYWQA TPFRAVAQPG LQLKAVTSVS GPGEHLRNAL 
WHTGHTPDQV RLLWTDPRNV GWRDKTSYRW QLLHRPQVGY IRVKLYEGPQ LVADSGVIID 
TSMRGGRLGV FCFSQENIIW SNLQYRCNDT VPEDFEPFRR QLLQGRV