Infantile cortical hyperostosis: genes and variants

Genes linked to Infantile cortical hyperostosis

• 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.

  15 disease-causing and 15 uncertain variants in COL1A1 are linked to Infantile cortical hyperostosis.

Known disease-causing variants in Infantile cortical hyperostosis

Which prediction tools work for Infantile cortical hyperostosis

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

• ESM1b (LLR): 99 out of 100
• CATVariant: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• AlphaMissense: 96 out of 100
• SIFT: 91 out of 100

Same protein, different disease

• Osteogenesis imperfecta is also caused by COL1A1 variants; they fall mostly in different places as the Infantile cortical hyperostosis variants (239 disease-causing).
• Osteogenesis imperfecta, perinatal lethal is also caused by COL1A1 variants; they fall mostly in different places as the Infantile cortical hyperostosis 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 Infantile cortical hyperostosis variants (34 disease-causing).
• Ehlers-Danlos syndrome, arthrochalasia type is also caused by COL1A1 variants; they fall mostly in different places as the Infantile cortical hyperostosis 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 Infantile cortical hyperostosis variants (6 disease-causing).

Diseases related to Infantile cortical hyperostosis

• Osteogenesis imperfecta, also linked to COL1A1
• Ehlers-Danlos syndrome, classic type, 1, also linked to COL1A1
• Ehlers-Danlos syndrome, also linked to COL1A1
• Osteogenesis imperfecta, perinatal lethal, also linked to COL1A1
• Osteogenesis imperfecta with normal sclerae, dominant form, also linked to COL1A1
• Phenylketonuria, also linked to COL1A1
• Connective tissue disorder, also linked to COL1A1
• Ehlers-Danlos syndrome, arthrochalasia type, also linked to COL1A1
• Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2, also linked to COL1A1
• Fetal anomalies with a likely genetic cause, also linked to COL1A1
• Osteoporosis, also linked to COL1A1
• Postmenopausal osteoporosis, also linked to COL1A1

Frequently asked questions

Which genes are linked to Infantile cortical hyperostosis?

In CATVariant, Infantile cortical hyperostosis is linked to 1 analyzed protein: COL1A1 (Collagen alpha-1(I) chain).

How many genetic variants are linked to Infantile cortical hyperostosis?

32 variants: 15 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 15 are of uncertain significance or have conflicting reports.

Which uncertain variants in Infantile cortical hyperostosis 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 Infantile cortical hyperostosis?

Among tools not trained on clinical labels, ESM1b (LLR) separates this disease's known disease-causing variants from harmless ones best (AUROC 0.99, based on 15 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.

Download every variant as CSV · Browse all diseases · Methods · About the Center