COL4A1 gene


Gene (OMIM No.)
Function of gene/protein
  • Protein: collagen, type IV, alpha-1 chain
  • A component of type IV collagen, a flexible protein important for the structure of many tissues
  • Type IV collagen is the main component of cell basement membranes, particularly in blood vessels
  • Helps maintain structural stability of the basement membrane and facilitates interaction with surrounding cells (cell movement, growth, maturation and survival)
Clinical phenotype
(OMIM phenotype no.)
  • Brain small vessel disease with or without ocular anomalies (#175780)
  • Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps (#611773)
  • Hemorrhage, intracerebral, susceptibility to (#614519)
  • Microangiopathy and leukoencephalopathy, pontine, autosomal dominant (#618564)
  • Autosomal dominant
Ocular features
Systemic featuresBrain small vessel disease with or without ocular anomalies:
  • Cerebrovascular disease (stroke, transient ischaemia attacks)
  • Leukoencephalopathy (brain white-matter diseases)
  • Proencephaly (cystic cerebral cavities that communicate with ventricles)
  • Resulting in a range of neurological consequences with variable severity within and between families
Key investigations
  • B-scan USS to measure axial length to document microphthalmia and detect posterior segment abnormalities
  • Electrophysiology
  • MRI brain and orbit
  • Systemic assessment by a paediatrician/stroke physician/neurologist depending on age
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (MAC/ASD)
  • Whole genome sequencing
  • Multidisciplinary approach
Therapies under research
  • None at present
Further information

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  1.  Bhave G, Colon S, Ferrell N. The sulfilimine cross-link of collagen IV contributes to kidney tubular basement membrane stiffness. Am J Physiol Renal Physiol. 2017;313(3):F596‐F602
  2.  Colorado PC, Torre A, Kamphaus G, et al. Anti-angiogenic cues from vascular basement membrane collagen. Cancer Res. 2000;60(9):2520‐2526
  3.  Gould DB, Phalan FC, van Mil SE, et al. Role of COL4A1 in small-vessel disease and hemorrhagic stroke. N Engl J Med. 2006;354(14):1489‐1496
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  6.  van der Knaap MS, Smit LM, Barkhof F, et al. Neonatal porencephaly and adult stroke related to mutations in collagen IV A1. Ann Neurol. 2006;59(3):504‐511
  7.  Yoneda Y, Haginoya K, Kato M, et al. Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly. Ann Neurol. 2013;73(1):48‐57
  8.  Coupry I, Sibon I, Mortemousque B, Rouanet F, Mine M, Goizet C. Ophthalmological features associated with COL4A1 mutations. Arch Ophthalmol. 2010;128(4):483‐489
  9.  Kuo DS, Labelle-Dumais C, Gould DB. COL4A1 and COL4A2 mutations and disease: insights into pathogenic mechanisms and potential therapeutic targets. Hum Mol Genet. 2012;21(R1):R97‐R110

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Updated on November 30, 2020
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