- Human pathology

Home > A. Molecular pathology > COLs


Wednesday 4 June 2003


Definition : Collagen is the most common protein in the animal world, providing the extracellular framework for all multicellular organisms.

The collagens are composed of a triple helix of three polypeptide α chains, having a gly-x-y repeating sequence. Currently 27 different types of collagens encoded by 41 genes (COLs) dispersed on at least 14 chromosomes are known.

Types I (COL1s), II (COL2s), III (COL3s) and V (COL5s), and XI (COL9s) are the interstitial or fibrillar collagens and the most abundant.

Type IV (COL4s) is nonfibrillar (forms sheets instead of fibrils) and is the main component of the basal membrane, together with laminin. Other collagens may form meshworks and may function as anchors in epidermal-dermal junctions, cartilage, and blood vessel wall.

Types I (COL1s), II (COL2s), and III (COL3s) collagen, the so-called interstitial collagens, are in many ways distinct from basement membrane collagen (COL4s).

Type IV collagen (COL4s) does not form ordered fibrillar structures; rather, a meshwork is formed by 4 molecules held together at the ends.

Collagen synthesis

Fibrillar collagen is synthesized from procollagen, a precursor molecule derived from preprocollagen, which is transcribed from collagen genes. After hydroxylation of proline and lysine residues and lysine glycosylation, three procollagen chains align in phase to form the triple helix.

Procollagen is secreted from the cell and cleaved by proteases to form the basic unit of the fibrils.

collagen cross-linking

Collagen fibril formation is associated with the oxidation of specific lysine and hydroxylysine residues by the extracellular enzyme lysyl oxidase. This results in cross-linking between the chains of adjacent molecules, thus stabilizing the array that is characteristic of collagen (collagen cross-linking). Cross-linking is a major contributor to the tensile strength of collagen.

Vitamin C is required for the hydroxylation of procollagen, a requirement that explains the inadequate wound healing in scurvy.


The collagens fall into 2 major classes: the fibril-forming collagens and the nonfibril-forming collagens.

A long central triple-helical domain, without gly-Xaa-Xaa interruptions, is the hallmark of the fibril-forming collagens; collagens type I (COL1s), II (COL2s), III (COL3S), V (COL5s), and XI (COL9s), which form highly organized fibrils in a quarter-staggered fashion, are members of this class.

The remaining collagens belong to the nonfibril-forming collagens with a common feature being the presence of imperfections in the gly-Xaa-Xaa repeating pattern.

Within the nonfibril-forming collagens, collagens type IX, XII, and XIV form a subgroup called the FACIT collagens (for ’fibril-associated collagens with interrupted triple helices’). These collagens are associated with type I or II collagen fibrils and play a role in interaction of these fibrils with other matrix components.


COL1s COL2s COL3s COL4s COL5s COL6s COL7s COL8s COL9s COL10s
COL11s COL12s COL13s COL14s COL15s COL16s COL17s COL18s COL19s

Pathology (collagen diseases)

Genetic defects in collagen production cause many inherited syndromes, including various forms of the Ehlers-Danlos syndromes and osteogenesis imperfecta.

- Type I collagens (COL1s)

  • COL1A1 : osteogenesis imperfecta

- Type II collagens (COL2s)

  • COL2A1 : autosomal dominant spondyloepiphyseal dysplasia congenita (MIM.183900)
  • COL2A1 : type II achondrogenesis-hypochondrogenesis (MIM.200610)
  • COL2A1 : osteoarthritis associated with mild chondrodysplasia (MIM.604864)
  • COL2A1 : spondyloepiphyseal dysplasia (MIM.183900)
  • COL2A1 : type I Stickler syndrome (MIM.108300)
  • COL2A1 : Kniest dysplasia (MIM.156550)
  • COL2A1 : Wagner syndrome (MIM.143200)
  • COL2A1 : Torrance type of platyspondylic skeletal dysplasia (MIM.151210)
  • COL2A1 : spondyloperipheral dysplasia (MIM.271700)

- Type III collagens (COL3s)

  • COL3A1 : Ehlers-Danlos syndrome type III (MIM.130020)
  • COL3A1 : type IV Ehlers-Danlos syndrome (MIM.130050)
  • COL3A1 : aortic aneurysms (MIM.100070)
  • COL3A1 : dissecting aneurysm and generalized fibromuscular dysplasia (MIM.135580)

- Type IV collagens (COL4s)

- Type V collagens (COL5s)

  • COL5A1 : mutations in Ehlers-Danlos syndrome type I)
  • COL5A2 : mutations in Ehlers-Danlos syndrome type I)

- Type VI collagens (COL6s)

- Type VII collagens (COL7s)

  • COL7A1 : autosomal recessive epidermolysis bullosa dystrophica (MIM.226600)
  • COL7A1 : autosomal dominant epidermolysis bullosa dystrophica (MIM.131750)
  • COL7A1 : pretibial epidermolysis bullosa (MIM.131850)
  • COL7A1 : mild form of localized recessive epidermolysis bullosa dystrophica (MIM.226600)
  • COL7A1 : transient bullous dermolysis of the newborn (TBDN) (MIM.131705)
  • COL7A1 : autosomal dominant epidermolysis bullosa pruriginosa (MIM.604129)
  • COL7A1 : autosomal recessive epidermolysis bullosa pruriginosa (MIM.604129)
  • COL7A1 : isolated nail dystrophy (MIM.607523)

- Type VIII collagens (COL8s)

  • COL8A2 : Fuchs endothelial corneal dystrophy (FECD)(MIM.136800)

- Type IX collagens (COL9s)

  • COL9A1 : autosomal dominant multiple epiphyseal dysplasia (MIM.12210)
  • COL9A2 : type 2 multiple epiphyseal dysplasia (EDM2) (MIM.600204)
  • COL9A2 : intervertebral disc disease (IDD) (MIM.603932)
  • COL9A3 : type 3 multiple epiphyseal dysplasia (EDM3) (MIM.600969)
  • COL9A3 : intervertebral disc disease (IDD) (MIM.603932)

- Type X collagens (COL10s)

  • COL10A1 : Schmid metaphyseal chondrodysplasia (MIM.156500)
  • COL10A1 : autosomal dominant spondylometaphyseal dysplasia

- Type XI collagens (COL11s)

  • COL11A1 : Stickler syndrome type 1 (MIM.604841)
  • COL11A1 : Marshall syndrome (MIM.154780)
  • COL11A2 : Stickler syndrome type 2 (MIM.184840)

- Type XII collagens (COL12s)

- Type XIII collagens (COL13s)

  • No pathology known

- Type XIV collagens (COL14s)

  • No pathology known

- Type XV collagens (COL15s)

  • No pathology known

- Type XVI collagens (COL16s)

  • No pathology known

- Type XVII collagens (COL17s)

  • No pathology known

- Type XVIII collagens (COL18s)

  • COL18A1 (21q22.3) : mutations in the Knobloch syndrome

- Type XIX collagens (COL19s)

  • No pathology known


- Regular connective tissue (by Washington Deceit)

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