FMOD (gene)

Aliases FMOD, FM, SLRR2E, fibromodulin
External IDs MGI: 1328364 HomoloGene: 1530 GeneCards: FMOD
RNA expression pattern
More reference expression data
Species Human Mouse









RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 1: 203.34 – 203.35 Mb Chr 1: 134.04 – 134.05 Mb
PubMed search [1] [2]
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Fibromodulin is a protein that in humans is encoded by the FMOD gene.[3][4]

Fibromodulin is a 42kDa protein of a family of small interstitial leucine-rich repeat proteoglycans (SLRPs). It can have up to four N-linked keratan sulfate chains attached to the core protein within the leucine-rich region. It shares significant sequence homology with biglycan and decorin.[5]


Fibromodulin participates in the assembly of the collagen fibers of the extracellular matrix. It binds to the same site on the collagen type I molecule as lumican.[6] It also inhibits fibrillogenesis of collagen type I and collagen type III in vitro.[7][8] It regulates TGF-beta activities by sequestering TGF-beta into the extracellular matrix.[4]

Clinical significance

There is an age-dependent decline in the synthesis of keratan sulfate chains, so non-glycated forms of fibromodulin can accumulate in tissues such as cartilage.[9]

Fibromodulin is found in the epidermis of human skin and is expressed by skin cells (keratinocytes) in culture. Mice with the gene for fibromodulin knocked out (Fmod-/-) have very fragile skin[10] and abnormal tail and Achilles tendons.[11] The collagen fiber bundles in these tendons are fewer and disorganised and there is less endotenon surrounding the tendon tissue. The levels of lumican, a SLRP with one of the same collagen binding sites as fibromodulin, is increased 4 fold in the tail tendons of the Fmod-knockout mice.


  1. "Human PubMed Reference:".
  2. "Mouse PubMed Reference:".
  3. Sztrolovics R, Chen XN, Grover J, Roughley PJ, Korenberg JR (Mar 1995). "Localization of the human fibromodulin gene (FMOD) to chromosome 1q32 and completion of the cDNA sequence". Genomics. 23 (3): 715–7. doi:10.1006/geno.1994.1567. PMID 7851907.
  4. 1 2 "Entrez Gene: FMOD fibromodulin".
  5. Antonsson P, Heinegård D, Oldberg A (1993). "Structure and deduced amino acid sequence of the human fibromodulin gene". Biochim Biophys Acta. 1174 (2): 204–6. doi:10.1016/0167-4781(93)90117-V. PMID 8357838.
  6. Halper J (2014). "Proteoglycans and diseases of soft tissues". Adv. Exp. Med. Biol. 802: 49–58. doi:10.1007/978-94-007-7893-1_4. PMID 24443020.
  7. Ezura Y, Chakravarti S, Oldberg A, Chervoneva I, Birk DE (2000). "Differential expression of lumican and fibromodulin regulate collagen fibrillogenesis in developing mouse tendons". J. Cell Biol. 151 (4): 779–88. doi:10.1083/jcb.151.4.779. PMID 11076963.
  8. Kalamajski S, Oldberg A (2007). "Fibromodulin binds collagen type I via Glu-353 and Lys-355 in leucine-rich repeat 11.". J Biol Chem. 282 (37): 26740–5. doi:10.1074/jbc.M704026200. PMID 17623650.
  9. Roughley PJ, White RJ, Cs-Szabo G, Mort JS (1996). "Changes with age in the structure of fibromodulin in human articular cartilage". Osteoarthritis Cartilage. 4: 153–61. doi:10.1016/s1063-4584(96)80011-2. PMID 8895216.
  10. Smith MM, Melrose J (2015). "Proteoglycans in normal and healing skin". Adv Wound Care. 4 (3): 152–73. doi:10.1089/wound.2013.0464. PMID 25785238.
  11. Juneja SC, Veillette C (2013). "Defects in tendon, ligament, and enthesis in response to genetic alterations in key proteoglycans and glycoproteins: a review". Arthritis. 2013: 154812. doi:10.1155/2013/154812. PMID 24324885.

Further reading

  • Roughley PJ, Lee ER (Aug 1994). "Cartilage proteoglycans: structure and potential functions". Microscopy Research and Technique. 28 (5): 385–97. doi:10.1002/jemt.1070280505. PMID 7919526. 
  • Hildebrand A, Romarís M, Rasmussen LM, Heinegård D, Twardzik DR, Border WA, Ruoslahti E (Sep 1994). "Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta". The Biochemical Journal. 302 (2): 527–34. doi:10.1042/bj3020527. PMC 1137259Freely accessible. PMID 8093006. 
  • Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548. 
  • Westergren-Thorsson G, Norman M, Björnsson S, Endrésen U, Stjernholm Y, Ekman G, Malmström A (Mar 1998). "Differential expressions of mRNA for proteoglycans, collagens and transforming growth factor-beta in the human cervix during pregnancy and involution". Biochimica et Biophysica Acta. 1406 (2): 203–13. doi:10.1016/S0925-4439(98)00005-2. PMID 9573366. 
  • Font B, Eichenberger D, Goldschmidt D, Boutillon MM, Hulmes DJ (Jun 1998). "Structural requirements for fibromodulin binding to collagen and the control of type I collagen fibrillogenesis--critical roles for disulphide bonding and the C-terminal region". European Journal of Biochemistry / FEBS. 254 (3): 580–7. doi:10.1046/j.1432-1327.1998.2540580.x. PMID 9688269. 
  • Schaefer L, Gröne HJ, Raslik I, Robenek H, Ugorcakova J, Budny S, Schaefer RM, Kresse H (Oct 2000). "Small proteoglycans of normal adult human kidney: distinct expression patterns of decorin, biglycan, fibromodulin, and lumican". Kidney International. 58 (4): 1557–68. doi:10.1046/j.1523-1755.2000.00317.x. PMID 11012890. 
  • Gori F, Schipani E, Demay MB (2001). "Fibromodulin is expressed by both chondrocytes and osteoblasts during fetal bone development". Journal of Cellular Biochemistry. 82 (1): 46–57. doi:10.1002/jcb.1115. PMID 11400162. 
  • Mayr C, Bund D, Schlee M, Moosmann A, Kofler DM, Hallek M, Wendtner CM (Feb 2005). "Fibromodulin as a novel tumor-associated antigen (TAA) in chronic lymphocytic leukemia (CLL), which allows expansion of specific CD8+ autologous T lymphocytes". Blood. 105 (4): 1566–73. doi:10.1182/blood-2004-04-1233. PMID 15471955. 
  • Mikaelsson E, Danesh-Manesh AH, Lüppert A, Jeddi-Tehrani M, Rezvany MR, Sharifian RA, Safaie R, Roohi A, Osterborg A, Shokri F, Mellstedt H, Rabbani H (Jun 2005). "Fibromodulin, an extracellular matrix protein: characterization of its unique gene and protein expression in B-cell chronic lymphocytic leukemia and mantle cell lymphoma". Blood. 105 (12): 4828–35. doi:10.1182/blood-2004-10-3941. PMID 15741214. 
  • Sjöberg A, Onnerfjord P, Mörgelin M, Heinegård D, Blom AM (Sep 2005). "The extracellular matrix and inflammation: fibromodulin activates the classical pathway of complement by directly binding C1q". The Journal of Biological Chemistry. 280 (37): 32301–8. doi:10.1074/jbc.M504828200. PMID 16046396. 
  • Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. 
  • Sjöberg AP, Trouw LA, Clark SJ, Sjölander J, Heinegård D, Sim RB, Day AJ, Blom AM (Apr 2007). "The factor H variant associated with age-related macular degeneration (His-384) and the non-disease-associated form bind differentially to C-reactive protein, fibromodulin, DNA, and necrotic cells". The Journal of Biological Chemistry. 282 (15): 10894–900. doi:10.1074/jbc.M610256200. PMID 17293598. 
  • Kalamajski S, Oldberg A (Sep 2007). "Fibromodulin binds collagen type I via Glu-353 and Lys-355 in leucine-rich repeat 11". The Journal of Biological Chemistry. 282 (37): 26740–5. doi:10.1074/jbc.M704026200. PMID 17623650. 

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