Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2: genes and variants

Genes linked to Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2

• COL1A2: Collagen alpha-2(I) chain

  It contributes one of the three chains of type I collagen, providing tensile strength to bone, skin, tendon, blood vessels, and other connective tissues. Pathogenic variants can cause osteogenesis imperfecta, Ehlers-Danlos phenotypes, and related connective-tissue disorders.

  11 disease-causing and 7 uncertain variants in COL1A2 are linked to Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2.

• COL1A1: Collagen alpha-1(I) chain

  The alpha-1 chain of type I collagen, the main fibrillar collagen in connective tissue, bone, and skin. Together with its partner chain, it forms strong extracellular fibers, and COL1A1 variants are associated with osteogenesis imperfecta and several Ehlers-Danlos syndromes.

  6 disease-causing and 1 uncertain variants in COL1A1 are linked to Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2.

Known disease-causing variants in Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2

Which prediction tools work for Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• CATVariant: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 96 out of 100

Same protein, different disease

• Osteogenesis imperfecta is also caused by COL1A2 variants; they fall mostly in different places as the Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 variants (332 disease-causing).
• Ehlers-Danlos syndrome, classic type, 1 is also caused by COL1A2 variants; they fall mostly in different places as the Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 variants (265 disease-causing).
• Osteogenesis imperfecta with normal sclerae, dominant form is also caused by COL1A2 variants; they fall mostly in different places as the Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 variants (51 disease-causing).
• Osteogenesis imperfecta, perinatal lethal is also caused by COL1A2 variants; they fall mostly in different places as the Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 variants (42 disease-causing).
• Ehlers-Danlos syndrome, arthrochalasia type is also caused by COL1A2 variants; they fall mostly in different places as the Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 variants (7 disease-causing).
• Osteogenesis imperfecta is also caused by COL1A1 variants; they fall mostly in different places as the Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 variants (239 disease-causing).
• Osteogenesis imperfecta, perinatal lethal is also caused by COL1A1 variants; they fall mostly in different places as the Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 variants (52 disease-causing).
• Osteogenesis imperfecta with normal sclerae, dominant form is also caused by COL1A1 variants; they fall mostly in different places as the Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 variants (34 disease-causing).
• Infantile cortical hyperostosis is also caused by COL1A1 variants; they fall mostly in different places as the Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 variants (15 disease-causing).
• Ehlers-Danlos syndrome, arthrochalasia type is also caused by COL1A1 variants; they fall mostly in different places as the Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 variants (10 disease-causing).

Diseases related to Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2

• Osteogenesis imperfecta, also linked to COL1A1 and COL1A2
• Ehlers-Danlos syndrome, classic type, 1, also linked to COL1A1 and COL1A2
• Ehlers-Danlos syndrome, also linked to COL1A1 and COL1A2
• Osteogenesis imperfecta, perinatal lethal, also linked to COL1A1 and COL1A2
• Osteogenesis imperfecta with normal sclerae, dominant form, also linked to COL1A1 and COL1A2
• Connective tissue disorder, also linked to COL1A1 and COL1A2
• Ehlers-Danlos syndrome, arthrochalasia type, also linked to COL1A1 and COL1A2
• Osteoporosis, also linked to COL1A1 and COL1A2
• Postmenopausal osteoporosis, also linked to COL1A1 and COL1A2
• Phenylketonuria, also linked to COL1A1
• Infantile cortical hyperostosis, also linked to COL1A1
• Fetal anomalies with a likely genetic cause, also linked to COL1A1

Frequently asked questions

Which genes are linked to Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2?

In CATVariant, Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 is linked to 2 analyzed proteins: COL1A2 (Collagen alpha-2(I) chain) and COL1A1 (Collagen alpha-1(I) chain).

How many genetic variants are linked to Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2?

36 variants: 17 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 8 are of uncertain significance or have conflicting reports.

Which uncertain variants in Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

Which variant effect predictor works best for Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.96, based on 10 disease-causing and 99 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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