Details for: TNMD

Gene ID: 64102

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: TNMD

Ensembl ID: ENSG00000000005

Description: tenomodulin

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • tendon cell CL0000388
    CSI 11.08
    rCSI 28.79%
    PRS 99.78
  • myofibroblast cell CL0000186
    CSI 10.28
    rCSI 14.24%
    PRS 99.02
  • fibroblast CL0000057
    CSI 4.16
    rCSI 11.95%
    PRS 96.07
  • vascular associated smooth muscle cell CL0000359
    CSI 3.32
    rCSI 10.77%
    PRS 99.35
  • enteric smooth muscle cell CL0002504
    CSI 2.46
    rCSI 3.52%
    PRS 99.45

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

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  • Node Color (Target Cell CSI, relative to current network):
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  • 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 [TNMD](/details-gene/64102), or tenomodulin, is a protein-coding gene located on the X chromosome that encodes a type II transmembrane protein. Functionally, [TNMD](/details-gene/64102) is implicated in the negative regulation of angiogenesis and endothelial cell proliferation. Its expression is highly specific to cells of mesenchymal origin, serving as a key molecular marker for [tendon cell](/details-cell/CL0000388)s, where it is believed to play a crucial role in tendon maturation and maintenance. It is also significantly expressed in other connective tissue cells, such as [myofibroblast cell](/details-cell/CL0000186)s and [fibroblast](/details-cell/CL0000057)s, suggesting a broader role in the development and homeostasis of structural tissues. ## Cellular Roles and Expression Landscape The expression profile of [TNMD](/details-gene/64102) demonstrates high specificity for cells involved in the formation and maintenance of connective and structural tissues. **Overall**, the gene shows its most significant expression in [tendon cell](/details-cell/CL0000388) (CSI: 11.08) and [myofibroblast cell](/details-cell/CL0000186) (CSI: 10.28). This is consistent with initial studies that identified [TNMD](/details-gene/64102) as a tendon- and ligament-selective gene essential for tenocyte proliferation and tendon organization ([Link](https://doi.org/10.1002/dvdy.1126), [Link](https://doi.org/10.1002/jor.20999)). Beyond these primary cell types, [TNMD](/details-gene/64102) is also a significant marker in [fibroblast](/details-cell/CL0000057)s (CSI: 4.16) and smooth muscle cells, including [vascular associated smooth muscle cell](/details-cell/CL0000359) (CSI: 3.32) and [enteric smooth muscle cell](/details-cell/CL0002504) (CSI: 2.46). This pattern highlights its importance across a spectrum of mesenchymal-derived cells responsible for generating extracellular matrix and providing structural support. The absence of hematopoietic, epithelial, or neuronal cells in its top expression profile underscores its highly specialized role. Interestingly, research has also documented high expression of [TNMD](/details-gene/64102) in adipose tissue, with levels correlating with obesity and decreasing upon weight loss, suggesting a potential role in adipocyte biology ([Link](https://doi.org/10.1210/jc.2009-0292)). ## Pathways and Molecular Function Functionally, [TNMD](/details-gene/64102) is annotated as a membrane-bound protein ([GO:0016020](https://www.ebi.ac.uk/QuickGO/term/GO:0016020)) primarily involved in vascular regulation. Its biological roles include the negative regulation of angiogenesis ([GO:0016525](https://www.ebi.ac.uk/QuickGO/term/GO:0016525)) and the negative regulation of endothelial cell proliferation ([GO:0001937](https://www.ebi.ac.uk/QuickGO/term/GO:0001937)). This anti-angiogenic function is critical in avascular or hypovascular tissues like tendons, where it helps maintain tissue integrity by preventing unwanted blood vessel infiltration. This role is consistent with its expression in [vascular associated smooth muscle cell](/details-cell/CL0000359)s, which are integral to blood vessel structure and function. Clinically, mutations in [TNMD](/details-gene/64102) are associated with X-linked distal arthrogryposis, a condition characterized by congenital joint contractures ([300459](https://omim.org/entry/300459)). This genetic link provides strong evidence for its indispensable role in the proper development and function of tendons and related joint structures in humans. ## Research Directions The specific expression of [TNMD](/details-gene/64102) in structural cells, combined with its anti-angiogenic function, opens several avenues for future research into tissue repair, fibrosis, and metabolic disease. **Proposed Hypotheses:** 1. Given its high significance in [myofibroblast cell](/details-cell/CL0000186)s and its anti-angiogenic properties, [TNMD](/details-gene/64102) likely acts as a key regulator in wound healing and fibrosis, coordinating extracellular matrix deposition by myofibroblasts while simultaneously restricting neovascularization within the developing scar tissue. 2. The observed link between [TNMD](/details-gene/64102) expression, adipose tissue, and obesity suggests that it may regulate the angiogenic remodeling necessary for adipose tissue expansion. Its downregulation during weight loss implies a role in the metabolic plasticity of adipose tissue, possibly by modulating the cross-talk between adipocytes and endothelial cells. **Suggested Experimental Approach:** To test the first hypothesis regarding the role of [TNMD](/details-gene/64102) in fibrosis, a knockout mouse model could be employed. Following a fibrotic injury (e.g., bleomycin-induced skin fibrosis or cardiac ischemia-reperfusion), *Tnmd*-knockout and wild-type mice could be compared. The extent of fibrosis could be quantified using histological methods like Masson's trichrome staining and immunohistochemistry for collagen I and alpha-smooth muscle actin (a myofibroblast marker). Concurrently, microvessel density within the fibrotic lesions could be assessed via CD31 staining to determine if the loss of [TNMD](/details-gene/64102) leads to aberrant angiogenesis, thereby validating its dual role in matrix remodeling and vascular control. **Therapeutic Potential:** As a cell-surface protein highly expressed in cells driving fibrosis, [TNMD](/details-gene/64102) presents a potential therapeutic target. In diseases characterized by excessive fibrosis, such as idiopathic pulmonary fibrosis or scleroderma, a strategy involving **inhibition** of [TNMD](/details-gene/64102) function using monoclonal antibodies or small molecule inhibitors could potentially reduce myofibroblast activity and pathological matrix deposition. Conversely, in the context of regenerative medicine, **activation** or targeted delivery of [TNMD](/details-gene/64102) could be explored to promote proper tendon healing and prevent the formation of weak, scar-like tissue after injury.

Genular Protein ID: 838205636

Symbol: TNMD_HUMAN

Name: Tenomodulin

UniProtKB Accession Codes:

Q9H2S6 Q9HBX0 Q9UJG0

Database IDs:

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

Citations:

PubMed ID: 11162640

Title: Molecular cloning and characterization of ChM1L, a novel membrane molecule similar to chondromodulin-I.

PubMed ID: 11162640

DOI: 10.1006/bbrc.2000.4245

PubMed ID: 11162673

Title: Molecular cloning of tenomodulin, a novel chondromodulin-I related gene.

PubMed ID: 11162673

DOI: 10.1006/bbrc.2001.4271

PubMed ID: 11357195

Title: A novel gene, tendin, is strongly expressed in tendons and ligaments and shows high homology with chondromodulin-I.

PubMed ID: 11357195

DOI: 10.1002/dvdy.1126

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

PubMed ID: 19602561

Title: Tenomodulin is highly expressed in adipose tissue, increased in obesity, and down-regulated during diet-induced weight loss.

PubMed ID: 19602561

DOI: 10.1210/jc.2009-0292

PubMed ID: 19780194

Title: Tendon-selective genes identified from rat and human musculoskeletal tissues.

PubMed ID: 19780194

DOI: 10.1002/jor.20999

PubMed ID: 22700804

Title: Differential expression and cellular localization of novel isoforms of the tendon biomarker tenomodulin.

PubMed ID: 22700804

DOI: 10.1152/japplphysiol.00198.2012

Sequence Information:

  • Length: 317
  • Mass: 37130
  • Checksum: D17507D7E2EA0C68
  • Sequence:
    • MAKNPPENCE DCHILNAEAF KSKKICKSLK ICGLVFGILA LTLIVLFWGS KHFWPEVPKK 
AYDMEHTFYS NGEKKKIYME IDPVTRTEIF RSGNGTDETL EVHDFKNGYT GIYFVGLQKC 
FIKTQIKVIP EFSEPEEEID ENEEITTTFF EQSVIWVPAE KPIENRDFLK NSKILEICDN 
VTMYWINPTL ISVSELQDFE EEGEDLHFPA NEKKGIEQNE QWVVPQVKVE KTRHARQASE 
EELPINDYTE NGIEFDPMLD ERGYCCIYCR RGNRYCRRVC EPLLGYYPYP YCYQGGRVIC 
RVIMPCNWWV ARMLGRV