Ehlers-Danlos syndrome, arthrochalasia type: genes and variants

Genes linked to Ehlers-Danlos syndrome, arthrochalasia type

• 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.

  10 disease-causing and 21 uncertain variants in COL1A1 are linked to Ehlers-Danlos syndrome, arthrochalasia type.

• 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.

  7 disease-causing and 19 uncertain variants in COL1A2 are linked to Ehlers-Danlos syndrome, arthrochalasia type.

Known disease-causing variants in Ehlers-Danlos syndrome, arthrochalasia type

Which prediction tools work for Ehlers-Danlos syndrome, arthrochalasia type

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

• CATVariant: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• ESM1b (LLR): 95 out of 100
• AlphaMissense: 95 out of 100
• SIFT: 92 out of 100
• PolyPhen-2: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Osteogenesis imperfecta is also caused by COL1A1 variants; they fall mostly in different places as the Ehlers-Danlos syndrome, arthrochalasia type variants (239 disease-causing).
• Osteogenesis imperfecta, perinatal lethal is also caused by COL1A1 variants; they fall mostly in different places as the Ehlers-Danlos syndrome, arthrochalasia type 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 Ehlers-Danlos syndrome, arthrochalasia type variants (34 disease-causing).
• Infantile cortical hyperostosis is also caused by COL1A1 variants; they fall mostly in different places as the Ehlers-Danlos syndrome, arthrochalasia type variants (15 disease-causing).
• Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 is also caused by COL1A1 variants; they fall mostly in different places as the Ehlers-Danlos syndrome, arthrochalasia type variants (6 disease-causing).
• Osteogenesis imperfecta is also caused by COL1A2 variants; they fall mostly in different places as the Ehlers-Danlos syndrome, arthrochalasia type variants (332 disease-causing).
• Ehlers-Danlos syndrome, classic type, 1 is also caused by COL1A2 variants; they fall mostly in different places as the Ehlers-Danlos syndrome, arthrochalasia type 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 Ehlers-Danlos syndrome, arthrochalasia type variants (51 disease-causing).
• Osteogenesis imperfecta, perinatal lethal is also caused by COL1A2 variants; they fall mostly in different places as the Ehlers-Danlos syndrome, arthrochalasia type variants (42 disease-causing).
• Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 is also caused by COL1A2 variants; they fall mostly in different places as the Ehlers-Danlos syndrome, arthrochalasia type variants (11 disease-causing).

Diseases related to Ehlers-Danlos syndrome, arthrochalasia type

• 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
• Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2, 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 Ehlers-Danlos syndrome, arthrochalasia type?

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

How many genetic variants are linked to Ehlers-Danlos syndrome, arthrochalasia type?

60 variants: 17 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 40 are of uncertain significance or have conflicting reports.

Which uncertain variants in Ehlers-Danlos syndrome, arthrochalasia type 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 Ehlers-Danlos syndrome, arthrochalasia type?

Among tools not trained on clinical labels, ESM1b (LLR) separates this disease's known disease-causing variants from harmless ones best (AUROC 0.95, based on 10 disease-causing and 84 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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