Details for: FMOD

Gene ID: 2331

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: FMOD

Ensembl ID: ENSG00000122176

Description: fibromodulin

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • conventional dendritic cell CL0000990
    CSI 43.81
    rCSI 36.57%
    PRS 98.26
  • regulatory T cell CL0000815
    CSI 32.31
    rCSI 37.46%
    PRS 98.26
  • skin fibroblast CL0002620
    CSI 28.63
    rCSI 24.68%
    PRS 99.61
  • chondrocyte CL0000138
    CSI 27.85
    rCSI 44.29%
    PRS 99.11
  • innate lymphoid cell CL0001065
    CSI 24.91
    rCSI 51.42%
    PRS 98.72
  • mucous neck cell CL0000651
    CSI 24.37
    rCSI 35.13%
    PRS 99.76
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 23.45
    rCSI 28.41%
    PRS 96.06
  • helper T cell CL0000912
    CSI 23.35
    rCSI 33.02%
    PRS 98.72
  • mast cell CL0000097
    CSI 23.11
    rCSI 49.89%
    PRS 97.79
  • basal cell of epidermis CL0002187
    CSI 22.85
    rCSI 40.5%
    PRS 94.74
  • myofibroblast cell CL0000186
    CSI 21.42
    rCSI 29.67%
    PRS 99.93
  • melanocyte of skin CL1000458
    CSI 20.99
    rCSI 28.61%
    PRS 96.01
  • bronchus fibroblast of lung CL2000093
    CSI 19.98
    rCSI 16.23%
    PRS 99.84
  • goblet cell CL0000160
    CSI 18.61
    rCSI 17.59%
    PRS 99.86
  • fibroblast of lung CL0002553
    CSI 18
    rCSI 16.75%
    PRS 99.98
  • vascular associated smooth muscle cell CL0000359
    CSI 17.76
    rCSI 57.61%
    PRS 99.92
  • suprabasal keratinocyte CL4033013
    CSI 17.4
    rCSI 28.4%
    PRS 96.33
  • intestine goblet cell CL0019031
    CSI 16.84
    rCSI 14.95%
    PRS 99.78
  • basal cell CL0000646
    CSI 15.02
    rCSI 20.08%
    PRS 99.85
  • interstitial cell of Cajal CL0002088
    CSI 13.46
    rCSI 17.13%
    PRS 99.98
  • alveolar type 1 fibroblast cell CL4028004
    CSI 13.11
    rCSI 14.36%
    PRS 99.98
  • colon goblet cell CL0009039
    CSI 12.73
    rCSI 30.27%
    PRS 99.85
  • fallopian tube secretory epithelial cell CL4030006
    CSI 11.72
    rCSI 11.28%
    PRS 99.76
  • tendon cell CL0000388
    CSI 11.02
    rCSI 28.65%
    PRS 99.95
  • smooth muscle cell CL0000192
    CSI 8.93
    rCSI 21.29%
    PRS 99.94
  • alveolar adventitial fibroblast CL4028006
    CSI 8.87
    rCSI 14.02%
    PRS 99.93
  • mesodermal cell CL0000222
    CSI 7.36
    rCSI 8.84%
    PRS 99.93
  • myoepithelial cell CL0000185
    CSI 7.18
    rCSI 18.16%
    PRS 99.96
  • mucus secreting cell CL0000319
    CSI 7.14
    rCSI 11.34%
    PRS 99.87
  • adventitial cell CL0002503
    CSI 6.99
    rCSI 16.69%
    PRS 100
  • enteric smooth muscle cell CL0002504
    CSI 6.97
    rCSI 9.95%
    PRS 99.91
  • mesenchymal cell CL0008019
    CSI 6.35
    rCSI 16.12%
    PRS 99.9
  • stromal cell of ovary CL0002132
    CSI 5.84
    rCSI 16.03%
    PRS 99.92
  • paneth cell CL0000510
    CSI 4.81
    rCSI 7.1%
    PRS 99.97
  • cytotoxic T cell CL0000910
    CSI 4.77
    rCSI 27.33%
    PRS 98.87
  • pancreatic stellate cell CL0002410
    CSI 4.16
    rCSI 24.2%
    PRS 99.67
  • mesenchymal stem cell CL0000134
    CSI 3.93
    rCSI 43.01%
    PRS 99.66
  • keratocyte CL0002363
    CSI 3.85
    rCSI 9.25%
    PRS 99.89
  • blood vessel smooth muscle cell CL0019018
    CSI 3.74
    rCSI 30.43%
    PRS 99.96
  • M cell of gut CL0000682
    CSI 3.64
    rCSI 3.86%
    PRS 99.76
  • microcirculation associated smooth muscle cell CL0008035
    CSI 3.43
    rCSI 9.92%
    PRS 99.91
  • endocardial cell CL0002350
    CSI 3.02
    rCSI 14.45%
    PRS 99.76
  • peptic cell CL0000155
    CSI 2.38
    rCSI 23.44%
    PRS 99.57

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 Fibromodulin, encoded by the [FMOD](/details-gene/2331) gene, is a small leucine-rich proteoglycan that is a critical component of the extracellular matrix (ECM). Its primary function is in the organization of collagen fibrils ([GO:0030199](https://www.ebi.ac.uk/QuickGO/term/GO:0030199)), thereby contributing to the structural integrity and compression resistance of connective tissues ([GO:0030021](https://www.ebi.ac.uk/QuickGO/term/GO:0030021)). A notable aspect of its function is its interaction with transforming growth factor-beta (TGF-beta), suggesting a role in modulating cell growth and differentiation ([Link](https://doi.org/10.1042/bj3020527)). **Overall**, [FMOD](/details-gene/2331) shows significant expression in a diverse range of cell types, including stromal cells like [skin fibroblast](/details-cell/CL0002620) and [chondrocyte](/details-cell/CL0000138), as well as key immune cells such as [conventional dendritic cell](/details-cell/CL0000990) and [regulatory T cell](/details-cell/CL0000815). This expression pattern points to a dual role for [FMOD](/details-gene/2331) in both maintaining tissue architecture and influencing the immune microenvironment. Genetic associations for this protein are cataloged under OMIM entry [600245](https://omim.org/entry/600245). ## Cellular Roles and Expression Landscape The expression profile of [FMOD](/details-gene/2331) highlights its importance across both structural and immune cell lineages. **Overall**, the highest significance is observed in [conventional dendritic cell](/details-cell/CL0000990) (CSI: 43.81), suggesting a potential role in antigen presentation or immune surveillance within the ECM. High significance is also seen in multiple immune populations, including [regulatory T cell](/details-cell/CL0000815) (CSI: 32.31), [innate lymphoid cell](/details-cell/CL0001065) (CSI: 24.91), and [mast cell](/details-cell/CL0000097) (CSI: 23.11), indicating that [FMOD](/details-gene/2331) may be involved in modulating immune cell function and trafficking within tissues. Concurrently, [FMOD](/details-gene/2331) is a prominent marker in mesenchymal and stromal cell types responsible for producing and remodeling the ECM. These include [skin fibroblast](/details-cell/CL0002620) (CSI: 28.63), [chondrocyte](/details-cell/CL0000138) (CSI: 27.85), [myofibroblast cell](/details-cell/CL0000186) (CSI: 21.42), and [fibroblast of lung](/details-cell/CL0002553) (CSI: 18.00). This is consistent with its established role in collagen fibrillogenesis. The co-expression in both immune and stromal compartments suggests that [FMOD](/details-gene/2331) may function as a key communication link between these cell types, potentially influencing processes such as wound healing, fibrosis, and tumor microenvironment development. ## Pathways and Molecular Function The functional annotations for [FMOD](/details-gene/2331) firmly place it within the biology of the extracellular space. As a key structural component, it is integral to the '[Collagen-containing extracellular matrix](/details-go/GO:0062023)' and participates directly in '[Extracellular matrix organization](/details-reactome/R-HSA-1474244)'. Its molecular function in '[Collagen fibril organization](/details-go/GO:0030199)' is central to the proper assembly and stability of connective tissues. Beyond its structural role, [FMOD](/details-gene/2331) is deeply involved in glycosaminoglycan metabolism, particularly '[Keratan sulfate biosynthesis](/details-reactome/R-HSA-2022854)', which is a key post-translational modification of the protein. This is further highlighted by its association with Reactome pathways for '[Diseases associated with glycosaminoglycan metabolism](/details-reactome/R-HSA-3560782)'. A critical regulatory function is suggested by its involvement in '[Transforming growth factor beta receptor complex assembly](/details-go/GO:0007181)', which is supported by evidence that it binds to and modulates the activity of TGF-beta ([Link](https://doi.org/10.1042/bj3020527)). This interaction positions [FMOD](/details-gene/2331) as a modulator of a major signaling pathway that governs fibrosis, inflammation, and cellular differentiation. ## Research Directions The dual expression of [FMOD](/details-gene/2331) in both stromal and immune cells, coupled with its ability to modulate TGF-beta signaling, suggests it is a pivotal mediator of tissue homeostasis and pathology. **Testable Hypotheses:** 1. **Hypothesis 1:** Given its high expression in both [regulatory T cell](/details-cell/CL0000815) and various fibroblast populations ([skin fibroblast](/details-cell/CL0002620), [bronchus fibroblast of lung](/details-cell/CL2000093)), [FMOD](/details-gene/2331) may act as a crucial mediator in the crosstalk that governs immune tolerance and tissue fibrosis. [FMOD](/details-gene/2331) secreted by fibroblasts could sequester or present TGF-beta, thereby enhancing the suppressive function of Tregs in the local microenvironment. 2. **Hypothesis 2:** The high significance of [FMOD](/details-gene/2331) in [conventional dendritic cell](/details-cell/CL0000990) suggests that it may function as a damage-associated molecular pattern (DAMP). Fragments of [FMOD](/details-gene/2331) released during ECM turnover or injury could be recognized by pattern recognition receptors on dendritic cells, leading to their activation and the initiation of adaptive immune responses. **Proposed Experimental Approach:** To test Hypothesis 1, the role of fibroblast-derived [FMOD](/details-gene/2331) on Treg function could be investigated using a co-culture system. Human lung fibroblasts could be subjected to CRISPR-Cas9-mediated knockout of [FMOD](/details-gene/2331). These knockout and wild-type fibroblasts would then be co-cultured with isolated human CD4+ T cells under conditions that promote Treg differentiation. The impact of fibroblast-derived [FMOD](/details-gene/2331) could be assessed by measuring the percentage of FOXP3+ Tregs via flow cytometry and evaluating their suppressive capacity in a functional assay. **Therapeutic Potential:** As an extracellular protein, [FMOD](/details-gene/2331) is an accessible therapeutic target. Its established role in collagen organization and TGF-beta modulation makes it a compelling candidate for anti-fibrotic therapies. In diseases like idiopathic pulmonary fibrosis or scleroderma, where excessive ECM deposition is a hallmark, a strategy involving the **inhibition** of [FMOD](/details-gene/2331) function using a monoclonal antibody or a small molecule inhibitor could disrupt pathologic collagen assembly and dampen pro-fibrotic TGF-beta signaling. Such an approach could potentially slow or reverse tissue scarring.

Genular Protein ID: 2563950772

Symbol: FMOD_HUMAN

Name: Fibromodulin

UniProtKB Accession Codes:

Q06828 Q15331 Q8IV47

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 ExpressionAtlas 1 GO 8 Gene3D 1 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 5 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 4 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 6 RefSeq 1 SMART 3 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8357838

Title: Structure and deduced amino acid sequence of the human fibromodulin gene.

PubMed ID: 8357838

DOI: 10.1016/0167-4781(93)90117-v

PubMed ID: 8093006

Title: Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta.

PubMed ID: 8093006

DOI: 10.1042/bj3020527

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: 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: 14551184

Title: Identification of tyrosine sulfation in extracellular leucine-rich repeat proteins using mass spectrometry.

PubMed ID: 14551184

DOI: 10.1074/jbc.m308689200

PubMed ID: 19159218

Title: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.

PubMed ID: 19159218

DOI: 10.1021/pr8008012

Sequence Information:

  • Length: 376
  • Mass: 43179
  • Checksum: DC19D5E6724AB004
  • Sequence:
    • MQWTSLLLLA GLFSLSQAQY EDDPHWWFHY LRSQQSTYYD PYDPYPYETY EPYPYGVDEG 
PAYTYGSPSP PDPRDCPQEC DCPPNFPTAM YCDNRNLKYL PFVPSRMKYV YFQNNQITSI 
QEGVFDNATG LLWIALHGNQ ITSDKVGRKV FSKLRHLERL YLDHNNLTRM PGPLPRSLRE 
LHLDHNQISR VPNNALEGLE NLTALYLQHN EIQEVGSSMR GLRSLILLDL SYNHLRKVPD 
GLPSALEQLY MEHNNVYTVP DSYFRGAPKL LYVRLSHNSL TNNGLASNTF NSSSLLELDL 
SYNQLQKIPP VNTNLENLYL QGNRINEFSI SSFCTVVDVV NFSKLQVLRL DGNEIKRSAM 
PADAPLCLRL ASLIEI

Genular Protein ID: 3252752637

Symbol: B3KS64_HUMAN

Name: N/A

UniProtKB Accession Codes:

B3KS64

Database IDs:

ARBA 6 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 1 Gene3D 1 InterPro 4 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 1 PeptideAtlas 1 Pfam 3 RefSeq 1 SAM 1 SMART 2 SUPFAM 1

Citations:

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

Sequence Information:

  • Length: 287
  • Mass: 32117
  • Checksum: 099CF6BF6CC35128
  • Sequence:
    • MKMTLIGGST TSAASSPPTT IPMTLTRMRP TSLTPMGWMK GQPTPTALHP LQIPATAPRK 
VFSKLRHLER LYLDHNNLTR MPGPLPRSLR ELHLDHNQIS RVPNNALEGL ENLTALYLQH 
NEIQEVGSSM RGLRSLILLD LSYNHLRKVP DGLPSALEQL YMEHNNVYTV PDSYFRGAPK 
LLYVRLSHNS LTNNGLASNT FNSSSLLELD LSYNQLQKIP PVNTNLENLY LQGNRINEFS 
ISSFCTVVDV VNFSKLQVLR LDGNEIKRSA MPADAPLCLR LASLIEI

Genular Protein ID: 2260105598

Symbol: Q12833_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q12833

Database IDs:

AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PeptideAtlas 1 PharmGKB 1 RefSeq 1

Sequence Information:

  • Length: 58
  • Mass: 6470
  • Checksum: 822B24A3ACDD4D80
  • Sequence:
    • YLQGNRINEF SISSFCTVVD VVNFSKLQVL RLDGNEIKRS AMPADAPLCL RLASLIEI