Book a test
On this page
⚠ Educational content only Not medical or genetic advice. Speak with a healthcare provider or genetic counsellor before acting on anything here.

COL11A1

collagen type XI alpha 1 chain

The COL11A1 gene provides instructions for creating a vital component of type XI collagen, a protein essential for the structure and strength of various connective tissues throughout the body. COL11A1 is crucial for developing and maintaining the structural integrity of tissues such as cartilage, the inner ear, and the vitreous of the eye.

Chromosome 1p21.1 Autosomal recessive HGNC:2186 Tier C
COL11A1 1p21.1 p arm q arm 1

COL11A1 is located on the short (p) arm of chromosome 1, at band 1p21.1. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 1 in the library →

Available at Jeen Health

Clinical tests that include this

Carrier Screening panel
COL11A1 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions
KNOVA NIPT
COL11A1 is 1 of 56 genes on this panel
Prenatal NIPT screening (trisomies, microdeletions, single-gene conditions)

Overview

The COL11A1 gene encodes the alpha-1 chain of type XI collagen, a complex protein that plays a fundamental role in the extracellular matrix. This gene is vital for the development and maintenance of cartilage, a flexible connective tissue found in joints, the nose, and external ears. Beyond cartilage, type XI collagen is also present in other critical structures, including the inner ear, the vitreous humour of the eye, and the intervertebral discs of the spine.

What the gene does

The COL11A1 gene directs the production of the pro-alpha1(XI) chain, which combines with other collagen chains (pro-alpha2(XI) and pro-alpha1(II)) to form a triple-stranded procollagen molecule. This precursor then undergoes enzymatic processing to yield mature type XI collagen. These mature collagen molecules assemble into robust fibrils, forming cross-links within the extracellular matrix to provide significant structural support and strength to tissues. Type XI collagen also influences the spacing and diameter of type II collagen fibrils, which are crucial for the proper structure and function of cartilage and the vitreous.

Video: Genetics 101

Chromosome location

The COL11A1 gene is situated on chromosome 1, specifically at position 1p21.1. This location indicates its placement on the short (p) arm of chromosome 1, within region 2, band 1, sub-band 1.

Protein structure

The COL11A1 protein, comprising 1806 amino acids, exhibits a complex domain architecture crucial for its function. Key regions include an N-terminal Laminin G-like domain (amino acids 71-243) and several nonhelical regions (amino acids 230-419 and 509-511). The protein features multiple triple-helical regions, including an interrupted segment (amino acids 420-508) and a longer, continuous triple-helical region (amino acids 529-1542). Within these are various Collagen-like domains, such as Collagen-like 1 (amino acids 442-490), Collagen-like 2 (amino acids 532-586), Collagen-like 3 (amino acids 583-641), Collagen-like 4 (amino acids 616-674), Collagen-like 5 (amino acids 643-699), Collagen-like 6 (amino acids 1393-1450), Collagen-like 7 (amino acids 1429-1487), and Collagen-like 8 (amino acids 1483-1541). Disordered regions are also present (amino acids 439-508 and 528-1563), alongside a Telopeptide region (amino acids 512-528) and a C-terminal Fibrillar collagen NC1 domain (amino acids 1577-1805).

Domain map · 1,806 amino acids
Laminin G-like (71–243)Collagen-like 3 (583–641)Collagen-like 4 (616–674)Collagen-like 5 (643–699)Collagen-like 6 (1393–1450)Collagen-like 7 (1429–1487)Collagen-like 8 (1483–1541)Fibrillar collagen NC1 (1577–1805)Laminin G-like71–243Collagen-like 3583–641Fibrillar collagen NC11577–18051~9031,806
Domain - independent functional unit
🧬 Explore 3D structure on AlphaFold
UniProt:P12107Length:1,806 aaStructure:AlphaFold

Key variants

Variants in the COL11A1 gene can alter the structure or function of type XI collagen, leading to a spectrum of inherited conditions. These genetic changes can impair the protein's ability to assemble correctly or interact with other collagen types, affecting the integrity of connective tissues throughout the body. The severity and presentation of associated conditions can vary widely depending on the specific variant.

3,402
Total variants catalogued in ClinVar
View all on ClinVar →
250 Pathogenic / Likely pathogenic 1,239 Uncertain significance 1,598 Benign / Likely benign 315 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
c.1003G>T
single nucleotide variant
 p.Glu335Ter Pathogenic/Likely pathogenic ★★☆☆ not provided
c.1190dup
Duplication
 p.Pro397_Asn398insTer Pathogenic/Likely pathogenic ★★☆☆ not provided
c.1191del
Deletion
 p.Asn398fs Pathogenic ★★☆☆ Stickler syndrome type 2
c.1245+1G>A
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ not provided
c.1245+1G>T
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Fibrochondrogenesis 1
c.1630-1G>T
single nucleotide variant
 - Pathogenic ★★☆☆ Stickler syndrome
c.1630-2del
Deletion
 - Pathogenic ★★☆☆ not provided
c.1951C>T
single nucleotide variant
 p.Arg651Ter Pathogenic/Likely pathogenic ★★☆☆ Stickler syndrome type 2
c.2241+5G>T
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ not provided
c.2513G>A
single nucleotide variant
 p.Gly838Glu 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 COL11A1 gene are associated with several inherited connective tissue disorders, including Stickler syndrome. These variants can also lead to more severe conditions such as fibrochondrogenesis, characterised by significant skeletal abnormalities, vision loss, and hearing impairment. Less commonly, COL11A1 variants have been linked to nonsyndromic hearing loss. Research suggests that COL11A1 may be one of many genes that collectively influence risk for complex conditions such as intervertebral disc degeneration [PMID:17968846].

Inheritance pattern

Conditions caused by pathogenic COL11A1 variants typically follow autosomal recessive inheritance.

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

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

Carrier frequency by population How common is heterozygous COL11A1 carrier status across ancestry groups?

UK clinical status

The COL11A1 gene is part of several accredited testing panels within the UK National Health Service (NHS) Genomic Medicine Service. These include panels for Bilateral congenital or childhood onset cataracts (R31), Clefting, DDG2P, Foetal anomalies (R21), Monogenic hearing loss (R67), Retinal disorders (R32), Skeletal dysplasia (R104), and Stickler syndrome (R45). This indicates its recognised clinical significance for diagnosis in the UK.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Bilateral congenital or childhood onset cataracts · R31 NHS GMS → Fetal anomalies · R21 NHS GMS → Monogenic hearing loss · R67 NHS GMS → Retinal disorders · R32 NHS GMS → Skeletal dysplasia · R104 NHS GMS → Stickler syndrome · R45 NHS GMS → Clefting 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 primary function of the COL11A1 gene?

The COL11A1 gene provides instructions for making the pro-alpha1(XI) chain, a critical component of type XI collagen. This collagen type is essential for giving structure and strength to connective tissues like cartilage, the inner ear, and the vitreous of the eye.

Which conditions are associated with variants in the COL11A1 gene?

Variants in COL11A1 are primarily associated with Stickler syndrome and fibrochondrogenesis. They can also be linked to conditions such as nonsyndromic hearing loss. Some evidence suggests COL11A1 may contribute to the risk of intervertebral disc degeneration, which is a complex condition [PMID:17968846].

How does type XI collagen influence other collagen types?

Beyond its structural role, type XI collagen helps regulate the spacing and diameter of type II collagen fibrils. This interaction is crucial for maintaining the normal structure and function of tissues where type II collagen is abundant, such as cartilage and the vitreous [PMID:10714073].

References

  1. Rodriguez-Fontenla C, Calaza M, Evangelou E. Assessment of osteoarthritis candidate genes in a meta-analysis of nine genome-wide association studies. Arthritis & rheumatology (Hoboken, N.J.). 2014. PMID: 24757145
  2. Akawi NA, Ali BR, Al-Gazali L. A response to Dr. Alzahrani's letter to the editor regarding the mechanism underlying fibrochondrogenesis. Gene. 2013. PMID: 23906683
  3. Akawi NA, Al-Gazali L, Ali BR. Clinical and molecular analysis of UAE fibrochondrogenesis patients expands the phenotype and reveals two COL11A1 homozygous null mutations. Clinical genetics. 2012. PMID: 21668896
  4. Alzahrani F, Alshammari MJ, Alkuraya FS. Molecular pathogenesis of fibrochondrogenesis: is it really simple COL11A1 deficiency? Gene. 2012. PMID: 23026214
  5. Tompson SW, Bacino CA, Safina NP. Fibrochondrogenesis results from mutations in the COL11A1 type XI collagen gene. American journal of human genetics. 2010. PMID: 21035103
  6. Majava M, Hoornaert KP, Bartholdi D. A report on 10 new patients with heterozygous mutations in the COL11A1 gene and a review of genotype-phenotype correlations in type XI collagenopathies. American journal of medical genetics. Part A. 2007. PMID: 17236192
  7. Annunen S, Körkkö J, Czarny M. Splicing mutations of 54-bp exons in the COL11A1 gene cause Marshall syndrome, but other mutations cause overlapping Marshall/Stickler phenotypes. American journal of human genetics. 1999. PMID: 10486316
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 18 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .