Osteogenesis imperfecta, perinatal lethal: genes and variants

Genes linked to Osteogenesis imperfecta, perinatal lethal

• 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.

  52 disease-causing and 5 uncertain variants in COL1A1 are linked to Osteogenesis imperfecta, perinatal lethal.

• 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.

  42 disease-causing and 7 uncertain variants in COL1A2 are linked to Osteogenesis imperfecta, perinatal lethal.

Known disease-causing variants in Osteogenesis imperfecta, perinatal lethal

Showing 60 of 94.

Which prediction tools work for Osteogenesis imperfecta, perinatal lethal

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)
• REVEL: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• AlphaMissense: 98 out of 100
• ESM1b (LLR): 97 out of 100
• MetaLR: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 95 out of 100
• PolyPhen-2: 94 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CADD: 92 out of 100
• phyloP: 88 out of 100

Same protein, different disease

• Osteogenesis imperfecta is also caused by COL1A1 variants; they fall mostly in different places as the Osteogenesis imperfecta, perinatal lethal variants (239 disease-causing).
• Osteogenesis imperfecta with normal sclerae, dominant form is also caused by COL1A1 variants; they fall mostly in different places as the Osteogenesis imperfecta, perinatal lethal variants (34 disease-causing).
• Infantile cortical hyperostosis is also caused by COL1A1 variants; they fall mostly in different places as the Osteogenesis imperfecta, perinatal lethal variants (15 disease-causing).
• Ehlers-Danlos syndrome, arthrochalasia type is also caused by COL1A1 variants; they fall mostly in different places as the Osteogenesis imperfecta, perinatal lethal variants (10 disease-causing).
• Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 is also caused by COL1A1 variants; they fall mostly in different places as the Osteogenesis imperfecta, perinatal lethal variants (6 disease-causing).
• Osteogenesis imperfecta is also caused by COL1A2 variants; they fall mostly in different places as the Osteogenesis imperfecta, perinatal lethal variants (332 disease-causing).
• Ehlers-Danlos syndrome, classic type, 1 is also caused by COL1A2 variants; they fall mostly in different places as the Osteogenesis imperfecta, perinatal lethal 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 Osteogenesis imperfecta, perinatal lethal variants (51 disease-causing).
• Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 is also caused by COL1A2 variants; they fall mostly in different places as the Osteogenesis imperfecta, perinatal lethal variants (11 disease-causing).
• Ehlers-Danlos syndrome, arthrochalasia type is also caused by COL1A2 variants; they fall mostly in different places as the Osteogenesis imperfecta, perinatal lethal variants (7 disease-causing).

Diseases related to Osteogenesis imperfecta, perinatal lethal

• 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 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
• 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 Osteogenesis imperfecta, perinatal lethal?

In CATVariant, Osteogenesis imperfecta, perinatal lethal 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 Osteogenesis imperfecta, perinatal lethal?

109 variants: 94 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 12 are of uncertain significance or have conflicting reports.

Which uncertain variants in Osteogenesis imperfecta, perinatal lethal 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 Osteogenesis imperfecta, perinatal lethal?

Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 0.98, based on 66 disease-causing and 85 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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