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ADAMTS2

ADAM metallopeptidase with thrombospondin type 1 motif 2

The ADAMTS2 gene provides instructions for making an enzyme essential for processing procollagen, a precursor to collagen, which is vital for the strength and elasticity of connective tissues. ADAMTS2 encodes an enzyme responsible for cleaving procollagen molecules, a critical step in the formation of mature collagen fibrils.

Chromosome 5q35.3 Autosomal recessive HGNC:218 Tier C
ADAMTS2 5q35.3 p arm q arm 5

ADAMTS2 is located on the long (q) arm of chromosome 5, at band 5q35.3. Arm ratio per GRCh38 - banding schematic.

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Clinical tests that include this

Carrier Screening panel
ADAMTS2 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The ADAMTS2 gene, full name ADAM metallopeptidase with thrombospondin type 1 motif 2, is crucial for the proper formation of collagen. Collagen is a fundamental component of connective tissues, providing strength, support, and elasticity to skin, bones, blood vessels, and other organs. The enzyme produced from ADAMTS2 performs a specific cut on procollagen molecules, enabling them to assemble into strong, functional collagen fibres.

What the gene does

The ADAMTS2 gene directs the production of an enzyme involved in the post-translational modification of collagen. Specifically, this enzyme acts as a procollagen N-proteinase, cleaving short segments from the N-terminal end of procollagen molecules. Procollagens are the precursor forms of collagen, and this enzymatic processing is a necessary step for collagen molecules to correctly assemble into stable, cross-linked fibrils. These fibrils are vital for the structural integrity and mechanical properties of extracellular matrix in connective tissues. Without proper processing by the ADAMTS2 enzyme, collagen fibrils may not form correctly, leading to weakened connective tissues.

Video: Genetics 101

Chromosome location

The ADAMTS2 gene is located on chromosome 5, specifically at position 5q35.3. This means it resides on the long arm (q) of chromosome 5, within band 35, sub-band 3. Genes at this location are transcribed and translated to produce the ADAMTS2 enzyme.

Protein structure

The ADAMTS2 protein is 1211 amino acids long and features several distinct functional regions. It contains a Peptidase M12B domain (amino acids 266-470) responsible for its enzymatic activity, and a Disintegrin domain (amino acids 480-560). The protein also includes multiple TSP type-1 domains: TSP type-1 1 (amino acids 561-616), TSP type-1 2 (amino acids 854-912), TSP type-1 3 (amino acids 914-971), and TSP type-1 4 (amino acids 975-1029). Other notable features include a Cell attachment site motif (amino acids 691-693), a Spacer region (amino acids 723-851), a PLAC domain (amino acids 1059-1097), and a Disordered region (amino acids 1170-1191).

Domain map · 1,211 amino acids
Peptidase M12B (266–470)Disintegrin (480–560)TSP type-1 1 (561–616)Cell attachment site (691–693)TSP type-1 2 (854–912)TSP type-1 3 (914–971)TSP type-1 4 (975–1029)PLAC (1059–1097)Peptidase M12B266–470Disintegrin480–560TSP type-1 2854–9121~6061,211
Domain - independent functional unit
Motif - short conserved sequence
🧬 Explore 3D structure on AlphaFold
UniProt:O95450Length:1,211 aaStructure:AlphaFold

Key variants

Variants within the ADAMTS2 gene can alter the structure or function of the encoded enzyme. These genetic changes can impair the protein's ability to properly process procollagen, leading to disruptions in collagen formation and connective tissue integrity. As an autosomal recessive gene, an individual must inherit two copies of a pathogenic variant (one from each parent) to typically manifest associated conditions.

2,041
Total variants catalogued in ClinVar
View all on ClinVar →
126 Pathogenic / Likely pathogenic 674 Uncertain significance 1,141 Benign / Likely benign 100 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.100_130del
Deletion
 p.Pro34fs Pathogenic/Likely pathogenic ★★☆☆ Ehlers-Danlos syndrome, dermatosparaxis type
c.102_123dup
Duplication
 p.Ala42fs Pathogenic/Likely pathogenic ★★☆☆ Ehlers-Danlos syndrome, dermatosparaxis type
c.1360C>T
single nucleotide variant
 p.Gln454Ter Pathogenic/Likely pathogenic ★★☆☆ Ehlers-Danlos syndrome, dermatosparaxis type
c.137del
Deletion
 p.Pro46fs Pathogenic/Likely pathogenic ★★☆☆ Ehlers-Danlos syndrome, dermatosparaxis type
c.1599dup
Duplication
 p.Asp535fs Pathogenic/Likely pathogenic ★★☆☆ Ehlers-Danlos syndrome, dermatosparaxis type
c.1701G>A
single nucleotide variant
 p.Trp567Ter Pathogenic/Likely pathogenic ★★☆☆ Ehlers-Danlos syndrome, dermatosparaxis type
c.1822C>T
single nucleotide variant
 p.Gln608Ter Pathogenic/Likely pathogenic ★★☆☆ not provided
c.1977C>A
single nucleotide variant
 p.Cys659Ter Pathogenic/Likely pathogenic ★★☆☆ Ehlers-Danlos syndrome, dermatosparaxis type
c.2372del
Deletion
 p.Met791fs Pathogenic/Likely pathogenic ★★☆☆ Ehlers-Danlos syndrome, dermatosparaxis type
c.2398G>T
single nucleotide variant
 p.Glu800Ter Pathogenic/Likely pathogenic ★★☆☆ Ehlers-Danlos syndrome, dermatosparaxis type

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 ADAMTS2 gene are primarily associated with Ehlers-Danlos syndrome (dermatosparaxis type). This is a rare, inherited connective tissue disorder characterised by extremely fragile, soft, and hyperelastic skin that tears and bruises easily. Individuals may also experience significant skin laxity and delayed wound healing due to the impaired collagen structure.

Inheritance pattern

Conditions caused by pathogenic ADAMTS2 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 ADAMTS2 carrier status across ancestry groups?

UK clinical status

The ADAMTS2 gene is included in clinical genetic testing panels within the UK National Health Service (NHS). It is listed on PanelApp UK under the 'Ehlers Danlos syndrome with a likely monogenic cause' panel (R101), where it has a 'green' rating, indicating strong evidence for its association with the condition.

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 →
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 role of the ADAMTS2 gene?

The ADAMTS2 gene provides instructions for making an enzyme that is critical for processing procollagen into mature collagen. This processing step is essential for forming strong, functional collagen fibrils that give strength and elasticity to connective tissues.

What condition is associated with variants in ADAMTS2?

Variants in the ADAMTS2 gene are primarily associated with Ehlers-Danlos syndrome, specifically the dermatosparaxis type. This condition affects connective tissues, leading to symptoms such as very fragile and easily bruised skin.

How is Ehlers-Danlos syndrome (dermatosparaxis type) inherited?

Ehlers-Danlos syndrome, dermatosparaxis type, is inherited in an autosomal recessive pattern. This means an individual must inherit two copies of a pathogenic variant in the ADAMTS2 gene, one from each parent, to develop the condition.

References

  1. Kelwick R, Desanlis I, Wheeler GN. The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family. Genome biology. 2015. PMID: 26025392
  2. Le Goff C, Cormier-Daire V. The ADAMTS(L) family and human genetic disorders. Human molecular genetics. 2011. PMID: 21880666
  3. Colige A, Nuytinck L, Hausser I. Novel types of mutation responsible for the dermatosparactic type of Ehlers-Danlos syndrome (Type VIIC) and common polymorphisms in the ADAMTS2 gene. The Journal of investigative dermatology. 2004. PMID: 15373769
  4. Wang WM, Lee S, Steiglitz BM. Transforming growth factor-beta induces secretion of activated ADAMTS-2. A procollagen III N-proteinase. The Journal of biological chemistry. 2003. PMID: 12646579
  5. Colige A, Sieron AL, Li SW. Human Ehlers-Danlos syndrome type VII C and bovine dermatosparaxis are caused by mutations in the procollagen I N-proteinase gene. American journal of human genetics. 1999. PMID: 10417273
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 6 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .