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COL1A1

collagen type I alpha 1 chain

The COL1A1 gene provides instructions for producing a key component of type I collagen, a protein vital for strengthening various connective tissues throughout the body. COL1A1 is crucial for forming type I collagen, the most abundant collagen in humans, found in bone, skin, tendons, and cartilage.

Chromosome 17q21.33 Autosomal dominant HGNC:2197 Tier C
COL1A1 17q21.33 p arm q arm 17

COL1A1 is located on the long (q) arm of chromosome 17, at band 17q21.33. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 17 in the library →

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Clinical tests that include this

Newborn Genetic Screening panel
COL1A1 is 1 of 258 genes on this panel
Genomic newborn screening for actionable paediatric conditions
KNOVA NIPT
COL1A1 is 1 of 56 genes on this panel
Prenatal NIPT screening (trisomies, microdeletions, single-gene conditions)

Overview

The COL1A1 gene encodes the pro-alpha1(I) chain, a fundamental building block of type I collagen. Type I collagen is a primary structural protein, providing strength and support to a wide range of tissues including bone, skin, tendons, and the sclera of the eye.

Inherited changes within the COL1A1 gene can impair the proper formation and function of type I collagen, leading to a spectrum of connective tissue disorders.

What the gene does

The COL1A1 gene instructs cells to create the pro-alpha1(I) chain, which is one of the three polypeptide chains that assemble to form type I procollagen molecules. Specifically, type I collagen is typically composed of two pro-alpha1(I) chains, derived from COL1A1, and one pro-alpha2(I) chain, derived from the COL1A2 gene. These three chains intertwine to form a triple-helical structure.

After their initial formation, these procollagen molecules undergo further processing and modifications both inside and outside cells. They then aggregate and cross-link to create strong, insoluble collagen fibrils. These fibrils subsequently arrange into robust collagen fibres, which are crucial for the structural integrity and mechanical properties of connective tissues throughout the body.

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Chromosome location

The COL1A1 gene is situated on chromosome 17, specifically at position 17q21.33. This chromosomal location indicates where the gene resides within the human genome.

Protein structure

The COL1A1 protein is 1464 amino acids long and features several distinct regions and domains. An N-terminal VWFC domain is located between amino acids 38-96, followed by a large Disordered region spanning amino acids 98-1214. Within this disordered region are the Nonhelical region (N-terminal) from amino acids 162-178, and the crucial Triple-helical region from amino acids 179-1192. There are also two Cell attachment site motifs identified at amino acids 745-747 and 1093-1095. The protein concludes with a Nonhelical region (C-terminal) spanning amino acids 1193-1218, and a Fibrillar collagen NC1 domain from amino acids 1229-1464.

Domain map · 1,464 amino acids
VWFC (38–96)Nonhelical region (N-terminal) (162–178)Triple-helical region (179–1192)Cell attachment site (745–747)Cell attachment site (1093–1095)Nonhelical region (C-terminal) (1193–1218)Fibrillar collagen NC1 (1229–1464)VWFC38–96Triple-helical region179–1192Fibrillar collagen NC11229–14641~7321,464
Domain - independent functional unit
Region - functional region
Motif - short conserved sequence
🧬 Explore 3D structure on AlphaFold
UniProt:P02452Length:1,464 aaStructure:AlphaFold

Key variants

Variants in the COL1A1 gene can influence the production and structure of type I collagen. These genetic changes can range from single nucleotide alterations to larger deletions or insertions, impacting the protein's ability to form correctly or function efficiently. The clinical outcome of a COL1A1 variant depends on its specific nature and location, affecting how it interferes with collagen synthesis or stability.

3,694
Total variants catalogued in ClinVar
View all on ClinVar →
1,465 Pathogenic / Likely pathogenic 767 Uncertain significance 1,185 Benign / Likely benign 277 Conflicting or other

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
g.50198185_50198186delinsT
Indel
 - Pathogenic ★★☆☆ Osteogenesis imperfecta type I
c.700delG
Deletion
 - Pathogenic ★★☆☆ Osteogenesis imperfecta
c.700dup
Duplication
 - Pathogenic ★★☆☆ not provided
c.1001del
Deletion
 p.Pro334fs Pathogenic ★★☆☆ Osteogenesis imperfecta
c.1003-1G>A
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ not provided
c.1012G>A
single nucleotide variant
 p.Gly338Ser Pathogenic/Likely pathogenic ★★☆☆ Osteogenesis imperfecta type I
c.1017del
Deletion
 p.Ala340fs Pathogenic ★★☆☆ Osteogenesis imperfecta type I
c.103+1G>A
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ COL1A1-related disorder
c.103+2T>C
single nucleotide variant
 - Pathogenic ★★☆☆ Osteogenesis imperfecta type I
c.104-1G>T
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ not provided

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the COL1A1 gene are primarily associated with conditions affecting connective tissues. These include osteogenesis imperfecta, characterised by fragile bones that break easily, and Ehlers-Danlos syndrome (arthrochalasia type), which involves joint hypermobility and skin fragility. COL1A1 variants have also been linked to otosclerosis and, in some somatic cases, to dermatofibrosarcoma protuberans.

Inheritance pattern

Conditions caused by pathogenic COL1A1 variants typically follow autosomal dominant inheritance.

♀ Affected parent 1 altered copy ♂ Unaffected parent 2 typical copies Affected Unaffected Unaffected Affected Affected Carrier Unaffected Circles = females · Squares = males

Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.

UK clinical status

The COL1A1 gene is included in several NHS Genomic Medicine Service approved panels. It is listed on the DDG2P panel and specific panels for conditions such as Ehlers Danlos syndrome with a likely monogenic cause (R101), Foetal anomalies (R21), Inherited bleeding disorders, Osteogenesis imperfecta (R102), Skeletal dysplasia (R104), and Thoracic aortic aneurysm or dissection (R125).

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Ehlers Danlos syndrome with a likely monogenic cause · R101 NHS GMS → Fetal anomalies · R21 NHS GMS → Osteogenesis imperfecta · R102 NHS GMS → Skeletal dysplasia · R104 NHS GMS → Thoracic aortic aneurysm or dissection (GMS) · R125 NHS GMS → DDG2P NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the main function of the COL1A1 gene?

The COL1A1 gene provides instructions for making part of type I collagen, which is the most abundant structural protein in the human body. This protein is essential for giving strength and support to various connective tissues like bones, skin, and tendons.

What health conditions are associated with COL1A1 variants?

Variants in the COL1A1 gene are primarily associated with osteogenesis imperfecta, characterised by fragile bones, and Ehlers-Danlos syndrome (arthrochalasia type), which affects joint stability and skin elasticity.

How does COL1A1 contribute to collagen formation?

COL1A1 produces the pro-alpha1(I) chain, which combines with other chains to form a triple-helical procollagen molecule. These molecules are then processed and assembled into strong collagen fibrils and fibres, providing structural integrity to tissues.

References

  1. Lim J, Grafe I, Alexander S. Genetic causes and mechanisms of Osteogenesis Imperfecta. Bone. 2017. PMID: 28232077
  2. Brady AF, Demirdas S, Fournel-Gigleux S. The Ehlers-Danlos syndromes, rare types. American journal of medical genetics. Part C, Seminars in medical genetics. 2017. PMID: 28306225
  3. Malfait F, Francomano C, Byers P. The 2017 international classification of the Ehlers-Danlos syndromes. American journal of medical genetics. Part C, Seminars in medical genetics. 2017. PMID: 28306229
  4. Marini JC, Forlino A, Bächinger HP. Osteogenesis imperfecta. Nature reviews. Disease primers. 2017. PMID: 28820180
  5. Van Dijk FS, Sillence DO. Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment. American journal of medical genetics. Part A. 2014. PMID: 24715559
  6. Malfait F, Symoens S, Goemans N. Helical mutations in type I collagen that affect the processing of the amino-propeptide result in an Osteogenesis Imperfecta/Ehlers-Danlos Syndrome overlap syndrome. Orphanet journal of rare diseases. 2013. PMID: 23692737
  7. Suphapeetiporn K, Tongkobpetch S, Mahayosnond A. Expanding the phenotypic spectrum of Caffey disease. Clinical genetics. 2007. PMID: 17309652
  8. Gensure RC, Mäkitie O, Barclay C. A novel COL1A1 mutation in infantile cortical hyperostosis (Caffey disease) expands the spectrum of collagen-related disorders. The Journal of clinical investigation. 2005. PMID: 15864348
  9. Sirvent N, Maire G, Pedeutour F. Genetics of dermatofibrosarcoma protuberans family of tumors: from ring chromosomes to tyrosine kinase inhibitor treatment. Genes, chromosomes & cancer. 2003. PMID: 12661001
  10. Mann V, Ralston SH. Meta-analysis of COL1A1 Sp1 polymorphism in relation to bone mineral density and osteoporotic fracture. Bone. 2003. PMID: 12810179
  11. Ralston SH. Genetic control of susceptibility to osteoporosis. The Journal of clinical endocrinology and metabolism. 2002. PMID: 12050200
  12. Shimizu A, O'Brien KP, Sjöblom T. The dermatofibrosarcoma protuberans-associated collagen type Ialpha1/platelet-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGF-BB. Cancer research. 1999. PMID: 10446987
  13. Greco A, Fusetti L, Villa R. Transforming activity of the chimeric sequence formed by the fusion of collagen gene COL1A1 and the platelet derived growth factor b-chain gene in dermatofibrosarcoma protuberans. Oncogene. 1998. PMID: 9771975
  14. Simon MP, Pedeutour F, Sirvent N. Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell fibroblastoma. Nature genetics. 1997. PMID: 8988177
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 27 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .