ReviewMatrix biology : journal of the International Society for Matrix Biology2017
Genotype-phenotype correlations in pathology caused by collagen type IV alpha 1 and 2 mutations.
Review in Matrix biology : journal of the International Society for Matrix Biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 134 citations in OpenAlex.
- Genome-wide meta-analysis identifies 3 novel loci associated with stroke.Annals of neurology · 2018Pooled it
- Whole-Exome Sequencing in 22 Young Ischemic Stroke Patients With Familial Clustering of Stroke.Stroke · 2020Trial
- Cell-to-Cell Signaling Networks at the Blood-Brain Barrier in Health and Disease.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Late Cognitive or Mood Alterations With 'Status Cribrosum' and Diffuse White Matter Lesions: A New Cerebral Small Vessel Disease Phenotype Associated With Rare COL4A1 Variants Located Within Exon 23.European journal of neurology · 2026Article
- Stratification of Phenotypes in Childhood-OnsetNeurology. Genetics · 2026Article
- Zebrafish col4a1 loss-of-function models mirror key neurovascular and ocular features of COL4A1/A2 syndrome and enable human variants assessment in vivo.Matrix biology : journal of the International Society for Matrix Biology · 2026Article
- Late-onset intracerebral hemorrhage associated with COL4A1 variants: clinical and genetic perspectives.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Novel COL4A2 splice-site variant associated with cerebral small vessel disease and progressive leukoencephalopathy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- Functional Validation of a Novel <italic>PBX1</italic> Missense Variant in a 46,XY Girl.Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation · 2026Article
- Review
- Collagen IV in Gould syndrome and Alport syndrome.Nature reviews. Nephrology · 2025Review
- Decoding Stroke Etiology: Multi-Omics Advancements in Genetic Mechanisms and Clinical Implication.Brain and behavior · 2025Review
- Collagen IV biosynthesis: Intracellular choreography of post-translational modifications.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- Basement membranes at a glance.Journal of cell science · 2025Review
- The pathogenesis of cerebral small vessel disease and vascular cognitive impairment.Physiological reviews · 2025Review
- A multifunction murine Col4a1 allele reveals potential gene therapy parameters for Gould syndrome.The Journal of cell biology · 2025Article
- A collagen IV fluorophore knock-in toolkit reveals trimer diversity in C. elegans basement membranes.The Journal of cell biology · 2025Article
- Phenotype and surgical management of drug-resistant epilepsy in patients with COL4A1 and COL4A2 variants.Epilepsia open · 2025Article
- Decoding collagen's thermally induced unfolding and refolding pathways.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Collagen IV of basement membranes: I. Origin and diversification of COL4 genes enabling metazoan multicellularity, evolution, and adaptation.The Journal of biological chemistry · 2025Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
COL4A1 and COL4A2 are extracellular matrix proteins that form heterotrimers and are present in nearly all basement membranes in every organ. In the past decade, COL4A1 and COL4A2 mutations have been identified to cause a multi-system disorder for which penetrance and severity of constituent phenotypes can greatly vary. Here, we compare the outcomes of more than 100 mutations identified in patients and data from a murine allelic series to explore the presence of genotype-phenotype correlations - many of which are shared among other types of collagen. We find that there is a frequency bias for COL4A1 over COL4A2 mutations and that glycine (Gly) substitutions within the triple helical domain are the most common class of mutations. Glycine is most often replaced by a charged amino acid, however the position of the mutation, and not the properties of the substituting amino acid, appears to have a greater influence on disease severity. Moreover, the impact of position is not straightforward. Observations from a murine allelic series suggest that mutations in the NC1 domain may result in relatively mild phenotypes via a 'quantitative' mechanism similar to other types of collagens, however, this effect was not apparent in human reports. Importantly, other position-dependent effects had differential impacts depending on the phenotype of interest. For example, the severity of cerebrovascular disease correlated with an amino-to-carboxy severity gradient for triple-helical glycine substitutions whereas the penetrance and severity of myopathy and nephropathy appear to involve a functional sub-domain(s). Greater understanding of genotype-phenotype correlations and the interaction of consequences of different mutations will be important for patient prognosis and care and for developing mechanism-based therapeutics to treat individual components of this emerging syndrome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.