Affinage

COL4A1

Collagen alpha-1(IV) chain · UniProt P02462

Length
1669 aa
Mass
160.6 kDa
Annotated
2026-06-09
100 papers in source corpus 34 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COL4A1 encodes the α1 chain of type IV collagen, a core structural component of basement membranes that obligatorily assembles with COL4A2 into an [α1(IV)]₂α2(IV) heterotrimer; mutations in either chain impair secretion of the entire heterotrimer, establishing their physical and functional interdependence (PMID:22209247). The dominant pathogenic mechanism is dominant-negative: glycine substitutions and other mutations in the Gly-X-Y collagen repeat block secretion of both mutant and normal chains, causing intracellular retention, ER stress and activation of the unfolded protein response, alongside structural deficits in vascular, ocular, renal and muscle basement membranes (PMID:15905400, PMID:16598045, PMID:16159887, PMID:17317786, PMID:20056676). Distinct genetic mechanisms also operate: nonsense-mediated decay of truncating alleles produces haploinsufficiency (PMID:23065703), while 3'UTR mutations that disrupt a miR-29 binding site derepress COL4A1 and cause gain-of-expression cerebral small vessel disease (PMID:27666438). Downstream of basement membrane disruption, COL4A1 mutations dysregulate multiple signaling axes — elevated TGFβ signaling drives anterior segment dysgenesis (PMID:35525525), integrin/ILK/FAK signaling (modulated by fibronectin) contributes to ocular and muscular pathology (PMID:34424299), reduced NOS activity produces vascular dysfunction (PMID:20056676), and impaired sarcoplasmic reticulum Ca²⁺ signaling blunts BK/TRPM4 channel activity and myogenic tone in cerebral vascular smooth muscle (PMID:37963192). Pathology arises through cell-type-specific routes, with endothelial and mural cell defects driving myopathy, retinopathy and hemorrhage (PMID:28056338, PMID:26813606, PMID:29266233, PMID:37977146). Collectively these mechanisms underlie a dominant multisystem disorder affecting cerebral vasculature, eyes, kidneys and skeletal muscle, with the folding/secretion defect being pharmacologically targetable by chemical chaperones such as 4-phenylbutyrate, though with tissue- and allele-specific outcomes (PMID:24203695, PMID:31051113, PMID:30351356, PMID:37963192).

Mechanistic history

Synthesis pass · year-by-year structured walk · 30 steps
  1. 2005 High

    Established that a Col4a1 mutation acts dominantly by inhibiting secretion of both mutant and normal type IV collagen, linking the gene to vascular basement membrane integrity and cerebral hemorrhage and revealing an environmental (trauma) trigger.

    Evidence Semidominant mouse mutant characterization with cellular secretion assay, vascular BM histology, and surgical delivery intervention

    PMID:15905400 PMID:16598045

    Open questions at the time
    • Did not resolve the molecular folding defect at residue level
    • Mechanism of trauma sensitization not defined
  2. 2005 High

    Showed that conserved glycine substitutions in the Gly-X-Y repeat exert dominant-negative effects and that allele position predicts phenotype severity, defining genotype-severity correlations across tissues.

    Evidence ENU mutagenesis allelic series in mice with histology, EM, and ophthalmological phenotyping

    PMID:16159887

    Open questions at the time
    • Molecular basis of milder Yaa-residue allele not biochemically dissected
    • Did not address signaling consequences
  3. 2007 High

    Connected non-secretion to intracellular accumulation and ER stress, and showed genetic context (a dominant modifier) can rescue ocular phenotypes, indicating modifiable downstream pathology.

    Evidence Mouse genetics with secretion assay, ER stress markers, and genetic modifier mapping

    PMID:17317786

    Open questions at the time
    • Identity of the modifier locus not defined here
    • Causal chain from ER stress to tissue dysgenesis incomplete
  4. 2007 Medium

    Mapped HANAC-associated mutations to the integrin-binding CB3[IV] region, implicating altered cell–collagen IV interactions in systemic vascular defects.

    Evidence Clinical/genetic characterization with mutation mapping to the integrin-binding domain across families

    PMID:18160688

    Open questions at the time
    • Direct integrin-binding functional assay not reported
    • Causality of altered integrin engagement not experimentally tested
  5. 2010 High

    Demonstrated that mutations produce vascular dysfunction through both structural BM defects and ER stress, including reduced NOS activity and blood pressure abnormalities, broadening the mechanism beyond pure structural failure.

    Evidence Vascular function assays, NOS inhibitor pharmacology, collagen IV imaging, blood pressure and RBC measurement, UPR markers in Col4a1+/Raw mice

    PMID:20056676

    Open questions at the time
    • Link between BM defect and reduced NOS activity not mechanistically resolved
    • RBC volume reduction mechanism unclear
  6. 2011 High

    Proved COL4A1 and COL4A2 form an obligate heterotrimer whose secretion fails when either chain is mutated, unifying the two genes' disease mechanisms.

    Evidence Reciprocal cellular secretion/ER retention assays, UPR markers, and Col4a2 mutant mouse phenotyping with ICH patient sequencing

    PMID:22209247

    Open questions at the time
    • Stoichiometry/assembly kinetics not detailed
    • Tissue-specific differences in heterotrimer handling not addressed
  7. 2011 High

    Distinguished COL4A1 myopathy/ocular pathology from dystroglycanopathies by showing dystroglycan glycosylation is unaltered, defining a mechanistically distinct disease route.

    Evidence Mouse histology, secretion assay, and dystroglycan immunoblot/glycosylation analysis with patient mutation identification

    PMID:21625620

    Open questions at the time
    • Mechanism of neuronal localization defect not defined
    • How BM defect translates to MEB/WWS-like features unresolved
  8. 2012 High

    Identified haploinsufficiency via nonsense-mediated decay as a pathogenic mechanism distinct from dominant-negative missense effects.

    Evidence NMD assay in patient fibroblasts, protein quantification, RT-PCR splice analysis, skin EM

    PMID:23065703

    Open questions at the time
    • Why loss-of-function and dominant-negative converge on similar disease not explained
    • Tissue threshold for haploinsufficiency unknown
  9. 2012 Medium

    Extended the biosynthetic secretion defect to sporadic ICH variants, indicating a shared mechanism across familial and sporadic cerebrovascular disease.

    Evidence Cellular biosynthesis/secretion assay comparing patient vs control variants

    PMID:22522439

    Open questions at the time
    • Only two variants tested in a single lab
    • No in vivo confirmation of these specific variants
  10. 2013 High

    Confirmed ER folding/secretion as a targetable mechanism by showing reduced temperature or 4-phenylbutyrate ameliorates biosynthetic defects, while documenting allele-specific biosynthetic signatures.

    Evidence Biosynthesis assays across allelic series primary cells with pharmacological/temperature rescue

    PMID:24203695

    Open questions at the time
    • Allele-specific signatures not mechanistically explained
    • In vivo efficacy not established in this study
  11. 2013 Medium

    Identified WT1, cooperating with SOX9, as a direct transcriptional activator of Col4a1/Col4a2, linking gene expression control to basement membrane maintenance in Sertoli cells.

    Evidence Conditional Wt1 knockout with RT-PCR, Western blot, immunostaining, and luciferase promoter mutagenesis

    PMID:23325811

    Open questions at the time
    • Generalizability beyond Sertoli cells untested
    • Direct WT1 binding site occupancy in vivo not shown
  12. 2015 High

    Defined a developmental role for the heterotrimer in glomerular basement membrane formation and linked Bowman's capsule defects to metalloproteinase induction and activated parietal epithelial cells expressing ILK and DDR1.

    Evidence G498V knock-in mouse with histology, MMP analysis, and functional renal assays

    PMID:26260163

    Open questions at the time
    • Trigger linking BM defect to MMP induction unclear
    • Cell-intrinsic vs paracrine contributions not separated
  13. 2015 Medium

    Showed TGFβ1 induces COL4A1/COL4A2 expression in vascular SMCs via SMAD3/SMAD4-dependent canonical signaling, identifying an upstream cytokine regulator with regulation beyond direct promoter binding.

    Evidence ALK5 inhibitor, SMAD2/3/4 siRNA, RT-PCR, protein and luciferase assays in human aortic SMCs

    PMID:26310581

    Open questions at the time
    • Mechanism of induction independent of direct promoter activity not resolved
    • Single lab, one cell type
  14. 2016 High

    Demonstrated cell-type-dependent renal mechanisms — structural BM defects driving glomerular filtration impairment versus chronic ER stress driving medullary atrophy — and a BM role in tubular aldosterone responsiveness.

    Evidence Mutant mouse phenotyping with ER stress markers, EM of BMs, and functional renal assays

    PMID:26839400

    Open questions at the time
    • Why ER stress predominates in medulla without tubular BM defects unclear
    • Molecular basis of aldosterone resistance not defined
  15. 2016 High

    Established a primary vascular basis for progressive retinopathy by reproducing pathology with vascular-cell-specific mutation, accompanied by Müller cell activation and pro-angiogenic factor upregulation.

    Evidence Conditional vascular Col4a1 mutation with angiography, OCT, ERG, ultrastructure, and immunostaining

    PMID:26813606

    Open questions at the time
    • Identity of pro-angiogenic signal not specified
    • Müller cell activation cause vs consequence unresolved
  16. 2016 High

    Discovered a gain-of-expression mechanism whereby disruption of a miR-29 3'UTR binding site upregulates COL4A1 and causes ischemic cerebral small vessel disease (PADMAL).

    Evidence Luciferase reporter, RT-qPCR in patient fibroblasts, and linkage/mutation screening

    PMID:27666438

    Open questions at the time
    • How COL4A1 overexpression causes ischemic pathology mechanistically unknown
    • Tissue specificity of miR-29 derepression not addressed
  17. 2017 High

    Identified endothelial cells in muscle capillaries as the primary driver of HANAC myopathy through intracellular mutant heterotrimer accumulation, ER stress, and apoptosis.

    Evidence G498V knock-in ultrastructure, ER stress/apoptosis immunostaining, secretion analysis, and serum CK

    PMID:28056338

    Open questions at the time
    • Contribution of muscle-intrinsic defects not fully separated
    • Apoptotic trigger downstream of ER stress not defined
  18. 2017 High

    Used conditional and temporally controlled mutation to localize ocular pathogenesis to lens cells and to an early developmental window (before E12.5).

    Evidence Cell-type-specific and temporal Col4a1 mutation with slit-lamp, OCT, IOP, and optic nerve histology

    PMID:28237965

    Open questions at the time
    • Mechanism by which lens cell BM defect causes IOP dysregulation unclear
    • Later-stage contributions to optic nerve damage not isolated
  19. 2018 High

    Resolved two mechanistically distinct hemorrhage processes — capillary-level BBB permeability driving microhemorrhages and apoptotic smooth muscle cell loss in deep arteries driving macrohemorrhages — with retinal arterial lesions as a correlated biomarker.

    Evidence Histology, IHC, EM of brain/retinal vessels, BBB permeability assay, and parallel hemorrhage quantification in G498V mice

    PMID:29266233

    Open questions at the time
    • Trigger of smooth muscle cell apoptosis not defined
    • Temporal relationship between micro- and macrohemorrhage unresolved
  20. 2019 High

    Demonstrated tissue-level mechanistic heterogeneity in neuromuscular disease and that secretion-promoting therapy can ameliorate or worsen myopathy depending on the mutation, establishing allele-dependent therapeutic responses.

    Evidence Mutant mouse characterization with histology, pathway analysis, and pharmacological secretion-promoting treatment

    PMID:31051113

    Open questions at the time
    • Molecular basis of opposite therapeutic outcomes per allele unclear
    • Relative weight of muscular vs neural vs vascular insults not quantified
  21. 2019 High

    Showed 4-phenylbutyrate reduces ER stress and intracerebral hemorrhage in vivo but fails to correct eye/kidney defects or fully restore BM structure, defining tissue-specific limits of ER-stress-targeted therapy.

    Evidence Oral PBA treatment (preventive/therapeutic) with ICH quantification, ER stress markers, BM incorporation, and mechanical stress testing

    PMID:30351356

    Open questions at the time
    • Why eye/kidney are PBA-refractory unexplained
    • Residual structural BM defect not addressed by chaperone therapy
  22. 2019 Medium

    Showed the HTLV-1 oncoprotein Tax induces COL4A1/COL4A2, linking the gene to viral biofilm-mediated cell-to-cell Gag transfer.

    Evidence Tax expression, CRISPR/siRNA knockout, luciferase promoter assays, colocalization imaging, and virus transfer assays in T-cells

    PMID:31708905

    Open questions at the time
    • COL4A1-specific (vs COL4A2) contribution to transfer not isolated
    • Single lab
  23. 2020 Medium

    Identified a pro-tumorigenic role for COL4A1 in hepatocellular carcinoma via FAK-Src signaling activation, downstream of RUNX1 transcriptional control, defining a druggable axis.

    Evidence siRNA knockdown, FAK-Src Western blots, RUNX1 manipulation, FAK/Src inhibitors, and proliferation/migration assays

    PMID:32746865

    Open questions at the time
    • Whether secreted vs intracellular COL4A1 drives signaling unclear
    • Single lab, cell-line based
  24. 2021 Medium

    Identified a single modifier locus containing Fn1 that suppresses ocular and muscular (but not cerebral) phenotypes and correlates with increased ILK and FAK phosphorylation, implicating integrin signaling in tissue-specific pathology.

    Evidence Genetic modifier screen, QTL mapping, and molecular expression analysis (Fn1, ILK, pFAK)

    PMID:34424299

    Open questions at the time
    • Direct causal proof that Fn1 is the modifier gene incomplete
    • Why ICH is not suppressed unexplained
  25. 2021 Medium

    Identified a direct COL4A1–NID1 (nidogen-1) interaction promoting OSCC malignancy, with NID1 overexpression rescuing knockdown phenotypes.

    Evidence Co-immunoprecipitation, siRNA knockdown, NID1 rescue, and proliferation/migration/invasion/EMT assays

    PMID:37006878

    Open questions at the time
    • Single Co-IP in one cancer cell line without reciprocal validation
    • Physiological relevance outside cancer untested
  26. 2022 High

    Established TGFβ signaling as a causal driver of ocular anterior segment dysgenesis downstream of COL4A1 mutation, with distinct TGFβ1/TGFβ2 roles and rescue by either secretion-promotion or TGFβ inhibition.

    Evidence Histology, TGFβ pathway analysis, genetic epistasis, and pharmacological treatment with slit-lamp phenotyping

    PMID:35525525

    Open questions at the time
    • Mechanism linking BM defect to elevated TGFβ not defined
    • Whether TGFβ axis operates in non-ocular tissues unaddressed
  27. 2023 High

    Defined a signaling mechanism for cerebral hemorrhage: impaired sarcoplasmic reticulum Ca²⁺ signaling blunts BK/TRPM4 channel activation and myogenic vasoconstriction, disrupting cerebral autoregulation, with 4-PBA restoring function.

    Evidence Patch-clamp electrophysiology, Ca²⁺ imaging, BK/TRPM4 channel assays, myogenic tone, and PBA rescue with ICH quantification

    PMID:37963192

    Open questions at the time
    • How BM/ER defect mechanistically disrupts SR Ca²⁺ handling unresolved
    • Generalizability across alleles untested
  28. 2023 High

    Established in a human iPSC co-culture model that mutant mural cells exhibit apoptosis, ECM remodeling and high MMP expression that paracrine-impair endothelial tight junctions, with MMP inhibition partially rescuing.

    Evidence iPSC-derived mural/endothelial co-culture, transcriptomics, ECM/MMP analysis, MMP inhibition, and tight junction assessment

    PMID:37977146

    Open questions at the time
    • Identity of paracrine factor(s) not defined
    • Incomplete rescue indicates additional MMP-independent mechanisms
  29. 2023 High

    Demonstrated by endogenous fluorescent tagging that basement membrane collagen IV is extremely stable yet pliable, allowing basal cells to deform without detaching during epidermal growth, establishing a functional biomechanical property.

    Evidence mTurquoise2-Col4a1 knock-in mouse, planar-sagittal live imaging, and FRAP

    PMID:38051393

    Open questions at the time
    • Molecular basis of BM pliability not dissected
    • How disease mutations alter this property untested
  30. 2024 Medium

    Identified a COL4A1–ITGB1 ligand-receptor interaction enriched in tumor EMT-type and endothelial cells whose antibody blockade suppresses angiogenesis and reverses gemcitabine resistance.

    Evidence Single-cell RNA-seq, ligand-receptor analysis, and antibody blockade functional assays in urothelial carcinoma

    PMID:38968684

    Open questions at the time
    • Direct biochemical COL4A1-ITGB1 binding not validated
    • Single study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the upstream structural/ER-stress defect mechanistically connects to the diverse downstream signaling derangements (TGFβ elevation, integrin/ILK/FAK activation, SR Ca²⁺ and BK/TRPM4 disruption, NOS reduction) — and why these couplings and therapeutic responses are tissue- and allele-specific — remains unresolved.
  • No unifying molecular link from BM/ER defect to each signaling axis
  • Allele-specific therapeutic divergence mechanistically unexplained
  • Tissue-specificity of refractoriness to chaperone therapy not understood

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4 GO:0098631 cell adhesion mediator activity 2
Localization
GO:0030312 external encapsulating structure 5 GO:0005783 endoplasmic reticulum 4 GO:0005576 extracellular region 2
Pathway
R-HSA-1474244 Extracellular matrix organization 4 R-HSA-1643685 Disease 4 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-162582 Signal Transduction 3
Partners
COL4A2ITGB1NID1
Complex memberships
[α1(IV)]₂α2(IV) type IV collagen heterotrimer

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 A semidominant missense mutation in Col4a1 (in-frame deletion of exon 40) inhibits secretion of both mutant and normal type IV collagen, causing focal disruptions of vascular basement membranes and perinatal cerebral hemorrhage/porencephaly in mice; surgical delivery alleviated birth-associated hemorrhage, demonstrating that environmental trauma conspires with the mutation. Mouse genetics (semidominant mutant characterization), cellular secretion assay, histology of vascular basement membranes, surgical intervention experiment Science High 15905400 16598045
2005 Dominant missense mutations affecting conserved glycine residues in the Gly-X-Y collagen repeat of Col4a1 cause dominant-negative effects on expression and function of the major collagen IV isoform α1(IV), leading to basement membrane defects in the eye (Axenfeld-Rieger-like anterior segment dysgenesis, glaucoma) and kidney (glomerulopathy); a milder allele with a Yaa-residue mutation produces a less severe phenotype, establishing allele-severity correlations. ENU mutagenesis allelic series in mice, histology, electron microscopy of basement membranes, slit-lamp and ophthalmological phenotyping Human molecular genetics High 16159887
2007 A Col4a1 missense mutation causes non-secretion of mutant COL4A1 proteins, which accumulate intracellularly, induces endoplasmic reticulum (ER) stress, and leads to anterior segment dysgenesis and optic nerve hypoplasia; the overall phenotypic consequence depends on genetic context, with a single dominant modifier locus capable of rescuing both ASD and optic nerve hypoplasia. Mouse genetics, protein secretion assay, ER stress markers, genetic modifier mapping Human molecular genetics High 17317786
2010 Col4a1 missense mutation (Col4a1+/Raw) in mice causes focal endothelial detachment from the media, impaired collagen IV deposition in vascular basement membranes, activation of the unfolded protein response, reduced basal nitric oxide synthase (NOS) activity, age-dependent hypersensitivity to acetylcholine abolished by NOS inhibition, and reduced red blood cell volume causing hypotension; together these establish that COL4A1 mutations produce complex vascular dysfunction through both structural basement membrane defects and ER stress. Vascular function assays (vasoconstriction/vasodilation), NOS inhibitor pharmacology, collagen IV immunostaining/electron microscopy, blood pressure measurement, red blood cell counting, unfolded protein response markers Human molecular genetics High 20056676
2011 COL4A2 mutations (identified in ICH patients) cause intracellular retention of both COL4A1 and COL4A2 within the endoplasmic reticulum at the expense of their secretion, trigger ER stress and activate the unfolded protein response; Col4a2 mutant mice have completely penetrant intracerebral hemorrhage, establishing that COL4A1 and COL4A2 form heterotrimers and that mutations in either chain impair secretion of the entire heterotrimer. Cellular secretion assay, ER retention immunostaining, unfolded protein response markers, Col4a2 mutant mouse phenotyping, sequencing of ICH patients American journal of human genetics High 22209247
2011 Heterozygous Col4a1 mutations in mice cause ocular dysgenesis, neuronal localization defects, and myopathy characteristic of MEB/WWS; at least one mutation interferes with secretion of mutant proteins causing intracellular accumulation; dystroglycan expression and post-translational modification are unaltered in Col4a1 mutant mice, establishing that COL4A1 mutations represent a pathogenic mechanism distinct from dystroglycan glycosylation defects. Histology, molecular and biochemical approaches (secretion assay, dystroglycan immunoblot/glycosylation analysis), patient mutation identification PLoS genetics High 21625620
2012 Two novel COL4A1 mutations (a frameshift c.2085del and a splice-site mutation c.2194-1G>A) cause nonsense-mediated decay (NMD) of mutant COL4A1 mRNA and a clear reduction in COL4A1 protein, establishing haploinsufficiency as a distinct pathogenic mechanism (in addition to the dominant-negative mechanism seen with missense mutations) for COL4A1-related cerebral small vessel disease; capillary basement membrane thickening was also documented in patient skin. NMD assay in patient fibroblasts, COL4A1 protein quantification, RT-PCR splice analysis, skin electron microscopy Human molecular genetics High 23065703
2012 Putative COL4A1 mutations found in sporadic ICH patients (P352L and R538G), but not variants from ICH-free controls, impair COL4A1 secretion in a cellular assay, demonstrating a shared biosynthetic mechanism across an allelic series causing both familial and sporadic cerebrovascular disease. COL4A1 biosynthesis/secretion assay in cell culture, sequencing of sporadic ICH patients vs. controls Annals of neurology Medium 22522439
2013 COL4A1 and COL4A2 mutations cause increased intracellular and decreased extracellular protein for most alleles, but allelic heterogeneity produces distinct biosynthetic signatures for some mutations; reduced temperature or 4-phenylbutyrate treatment ameliorated biosynthetic defects in primary cell lines from mutant mice, confirming ER folding/secretion as a targetable mechanism. Biosynthesis assay (intracellular/extracellular protein quantification) in primary cells from allelic series mutant mice, pharmacological rescue with 4-PBA and reduced temperature Human molecular genetics High 24203695
2007 All six COL4A1 mutations associated with HANAC syndrome localize within the CB3[IV] fragment of the collagenous domain, which encompasses major integrin-binding sites, suggesting that abnormal cell–type IV collagen interactions (via integrin binding sites) underlie the systemic vascular defects in HANAC. Clinical and genetic characterization, mutation mapping to functional domain (CB3[IV] integrin-binding region), sequencing of affected families The New England journal of medicine Medium 18160688
2015 The HANAC Col4a1 p.Gly498Val mutation in knock-in mice causes delayed glomerulogenesis and podocyte differentiation, leading to neonatal albuminuria; in adult mice, Bowman's capsule abnormalities are associated with metalloproteinase induction, activation of parietal epithelial cells (expressing CD44, α-SMA, ILK, DDR1), inflammatory infiltrates, and glomerular cyst development; homozygous mice additionally show dysmorphic papillae and urinary concentration defects, revealing a developmental role for the α1α1α2(IV) heterotrimer in the embryonic glomerular basement membrane. Knock-in mouse model, histology/immunostaining, metalloproteinase expression analysis, functional renal assays (albuminuria, hematuria, urinary concentration) Journal of the American Society of Nephrology High 26260163
2016 ER stress and basement membrane defects both contribute to Col4a1 renal disease in mice: glomerular/Bowman's capsule structural BM defects cause glomerular filtration impairment, while medullary atrophy is associated with chronic ER stress without tubular basement membrane defects, demonstrating cell-type-dependent molecular mechanisms; impaired tubular sodium reabsorption despite elevated aldosterone indicates BM modulation of tubular aldosterone response. Col4a1 mutant mouse phenotyping, ER stress marker analysis, electron microscopy of BMs, functional renal assays (proteinuria, aquaporin 2 expression, aldosterone levels) Disease models & mechanisms High 26839400
2016 Disruption of a miR-29 binding site in the 3'UTR of COL4A1 causes upregulation of COL4A1 expression, establishing that gain-of-function COL4A1 overexpression (not just loss-of-function missense mutations) causes a severe ischemic cerebral small vessel disease (PADMAL); demonstrated by luciferase reporter assays and RT-qPCR in patient fibroblasts. Luciferase reporter assay, RT-qPCR of patient fibroblasts, linkage analysis, mutation screening of cSVD cohort Annals of neurology High 27666438
2017 In a HANAC Col4a1 G498V knock-in mouse model, skeletal muscle myopathy is primarily driven by endothelial cell defects in muscle capillaries: endothelial cells accumulate mutant α1α1α2(IV) intracellularly, show ER cisternae dilation, upregulate ER stress markers, and undergo excess apoptosis; reduced extracellular secretion of the mutant heterotrimer contributes to abnormal muscle BMs. Knock-in mouse histology/ultrastructure, immunostaining (ER stress markers, apoptosis), collagen IV secretion analysis, serum creatine kinase measurement The American journal of pathology High 28056338
2017 Conditional Col4a1 mutation expressed selectively in lens cells (but not in neural crest cells alone, nor vascular endothelial cells alone on unsensitized background) causes cataracts, mild ASD, optic nerve hypoplasia, and age-related IOP dysregulation and optic nerve damage; ubiquitous expression at distinct developmental stages indicates pathogenesis occurs before E12.5 in mice. Conditional (cell-type-specific and temporally controlled) Col4a1 mutation in mice, slit-lamp biomicroscopy, OCT, IOP measurement, optic nerve histology Disease models & mechanisms High 28237965
2016 Col4a1 mutations in mice cause progressive retinopathy driven by primary vascular defects: conditional Col4a1 mutation in vascular cells reproduces the retinal pathology (serous chorioretinopathy, hemorrhages, pathogenic angiogenesis); focal Müller cell activation and increased expression of pro-angiogenic factors were detected in Col4a1 mutant retinas. Conditional vascular-specific Col4a1 mutation, fluorescein angiography, funduscopy, OCT, electroretinography, ultrastructural analysis, Müller cell and angiogenic factor immunostaining Scientific reports High 26813606
2019 Col4a1 mutant mice develop progressive neuromuscular pathology with mechanistic heterogeneity across tissues: independent muscular, neural, and vascular insults all contribute to neuromyopathy; a therapeutic strategy promoting [α1(IV)]2α2(IV) secretion can either ameliorate or exacerbate myopathy depending on the specific mutation, demonstrating mutation-dependent therapeutic responses. Col4a1 mutant mouse characterization, histology, molecular pathway analysis, pharmacological secretion-promoting treatment with phenotypic readout American journal of human genetics High 31051113
2019 4-Phenylbutyric acid (PBA) treatment of Col4a1 mutant mice reduces ER stress, increases collagen IV incorporation into basement membranes, and reduces adult intracerebral hemorrhage in both preventive and therapeutic settings; however, PBA does not improve eye or kidney defects, and persistence of structural BM defects indicates that BM matrix integrity is not fully restored—establishing tissue-specific outcomes of targeting ER stress. Oral PBA treatment of mutant mice (preventive and therapeutic), ICH quantification, ER stress markers, collagen IV BM incorporation assay, mechanical stress testing of BM, kidney/eye phenotyping Human molecular genetics High 30351356
2018 In Col4a1 p.G498V mutant mice, microhaemorrhages are associated with transient generalized blood-brain barrier permeability at the capillary level, while macrohaemorrhages originate from deep brain arteries with focal loss of smooth muscle cells via apoptosis-mediated degeneration; the same smooth muscle cell loss occurs in retinal arteries, and retinal arterial lesion load correlates strongly with macrohaemorrhage burden. Histology, immunohistochemistry, electron microscopy of brain/retinal vessels, blood-brain barrier permeability assay, time-course analysis, in-parallel retinal and brain hemorrhage quantification The Journal of pathology High 29266233
2021 A genetic modifier screen in Col4a1 mutant mice identified a single locus (MoGS1) on Chromosome 1 containing Fn1 (fibronectin 1) that suppresses ocular anterior segment dysgenesis and myopathy (but not ICH) in Col4a1 mutants; the MoGS1 locus increases Fn1 expression and is associated with increased integrin-linked kinase levels and focal adhesion kinase phosphorylation, implicating integrin signaling in ocular and muscular COL4A1 pathology. Genetic modifier screen, QTL mapping, molecular expression analysis (Fn1, ILK, FAK phosphorylation), phenotypic scoring of ASD and myopathy Disease models & mechanisms Medium 34424299
2022 TGFβ signaling is elevated in anterior segments from Col4a1 mutant mice; genetically reducing TGFβ signaling partially prevents ASD; TGFβ1 and TGFβ2 play distinct roles in ocular defects; pharmacologically promoting type IV collagen secretion or reducing TGFβ signaling ameliorates ocular pathology. Histology, TGFβ signaling pathway analysis, genetic reduction of TGFβ (epistasis), pharmacological treatment (secretion promoter, TGFβ inhibitor), slit-lamp phenotyping Matrix biology High 35525525
2023 Col4a1 mutations impair sarcoplasmic reticulum (SR) Ca2+ signaling in vascular smooth muscle cells, blunting pressure-induced membrane depolarization and causing loss of myogenic vasoconstriction; this impairs autoregulation of cerebral blood flow and contributes to age-related ICH. Specifically, SR Ca2+ disruption impairs Ca2+-dependent activation of BK and TRPM4 channels. Treatment with 4-phenylbutyrate restored SR Ca2+ signaling, maintained BK and TRPM4 channel activity, preserved myogenic tone, and reduced ICH. Electrophysiology (patch clamp of SMCs), Ca2+ imaging, BK/TRPM4 channel activity assays, myogenic tone measurement, pharmacological treatment (4-PBA), ICH quantification Science signaling High 37963192
2023 In a human iPSC co-culture model of COL4A1/A2 SVD, mutations induce apoptosis, migration defects, ECM remodeling, and high matrix metalloproteinase (MMP) expression in mural cells; these mural cell defects impair endothelial cell tight junctions through paracrine actions; MMP inhibition partially rescues ECM abnormalities and mural cell phenotypic changes. Human iPSC-derived mural/endothelial cell co-culture, transcriptomics, ECM analysis, MMP expression assay, pharmacological MMP inhibition, tight junction assessment Stem cell reports High 37977146
2023 Fluorescently tagged COL4A1 (mTurquoise2-Col4a1 knock-in mouse) shows by FRAP that basement membrane collagen IV is extremely stable even during rapid epidermal growth; live imaging demonstrates that dividing basal cells deform but remain attached to the BM rather than losing adhesion, establishing the BM's pliability as a functional property. Fluorescent knock-in mouse (mTurq2-Col4a1), planar-sagittal live imaging, FRAP The Journal of cell biology High 38051393
1993 At least three different nuclear proteins bind within the shared bidirectional promoter of COL4A1 and COL4A2: a CCAAT-binding protein, Sp1, and a newly identified factor 'CTCBF'; mutagenesis of binding sites showed these factors are essential for efficient transcription of both genes but with differential gene-specific effects, indicating the shared promoter functions as two overlapping gene-specific promoters with shared elements. Nuclear protein binding assays, promoter mutagenesis, transcription assays Biochimica et biophysica acta Medium 8334157
1997 The shared promoter of COL4A1 and COL4A2 has no transcriptional activity alone; efficient transcription requires cooperative effects of downstream gene-specific activating elements; mutual inhibitory interactions between the two activating elements indicate competitive interactions with the shared promoter, explaining coordinated divergent transcription. Transient transfection with reporter constructs, deletion/mutation analyses of cis-elements, factor-binding assays FEBS letters Medium 9094419
2013 WT1 (Wilms tumor gene) directly transactivates the Col4a1 and Col4a2 promoters cooperatively with SOX9 in Sertoli cells; loss of Wt1 causes downregulation of Col4a1/Col4a2 mRNA and protein, leading to basement membrane breakdown and testicular cord disruption, as demonstrated by luciferase and point mutation analyses of the Col4a1 promoter. Conditional Wt1 knockout, RT-PCR, Western blot, immunostaining, luciferase reporter assay, promoter point mutagenesis Biology of reproduction Medium 23325811
2015 TGFβ1 stimulation of human vascular smooth muscle cells increases COL4A1 and COL4A2 mRNA and protein expression through SMAD3- and SMAD4-dependent canonical signaling; pharmacological inhibition of ALK5 (TGFβ receptor) or siRNA knockdown of SMAD3/SMAD4 (but not SMAD2) abolishes this induction; SMAD3 overexpression alone or TGFβ1 treatment does not alter COL4A1/COL4A2 promoter activity in luciferase assays, indicating more complex regulation beyond direct promoter binding. ALK5 inhibitor treatment, siRNA knockdown of SMAD2/3/4 in human aortic SMCs, RT-PCR, protein expression, luciferase reporter assay Atherosclerosis Medium 26310581
2020 COL4A1 facilitates proliferation, migration and invasion of hepatocellular carcinoma cells through activation of FAK-Src signaling; COL4A1 expression is upregulated by transcription factor RUNX1; HCC cells with high COL4A1 expression are sensitive to FAK or Src inhibitor treatment. siRNA knockdown, western blot for FAK-Src pathway activation, RUNX1 overexpression/knockdown, FAK/Src inhibitor treatment, proliferation and migration assays Journal of experimental & clinical cancer research Medium 32746865
2011 In Drosophila, col4a1 mutations have a strong antimorphic (dominant-negative) effect likely due to incorporation of mutant protein into the triple helix; col4a1 mutants display severe myopathy with centronuclear myofibers in oviduct muscle and ultrastructural A/I band disruption in larval body wall muscles; expression of a col4a1 transgene partially rescues dominant and recessive col4a1 mutant alleles but not col4a2 mutations. Complementation analysis of allelic series, transgene rescue, immunohistochemistry, electron microscopy of muscle ultrastructure Matrix biology Medium 22037604
2019 HTLV-1 oncoprotein Tax is sufficient to induce COL4A1 and COL4A2 transcripts in T-cells; continuous Tax expression is required for robust COL4A1/COL4A2 protein induction; Tax activates the COL4A2 and, to a lesser extent, COL4A1 promoter in luciferase assays; COL4A2 knockout in chronically infected T-cells impairs Gag transfer between T-cells but not release of virus-like particles, linking the Tax-COL4A1/A2 axis to viral biofilm formation and transmission. Transient Tax expression, siRNA/CRISPR knockout, luciferase promoter assay, co-localization imaging (COL4/Gag), virus transfer assay Frontiers in microbiology Medium 31708905
2021 COL4A1 binds to nidogen-1 (NID1) in oral squamous cell carcinoma cells as shown by co-immunoprecipitation; NID1 overexpression reverses the inhibitory effects of COL4A1 knockdown on cell proliferation, migration, invasion, and EMT progression, establishing COL4A1–NID1 interaction as a functional axis promoting OSCC malignancy. Co-immunoprecipitation, siRNA knockdown, NID1 overexpression rescue, proliferation/migration/invasion assays, EMT marker western blot Experimental and therapeutic medicine Medium 37006878
2024 A specific COL4A1–ITGB1 interaction is highly enriched in tumorous EMT-type urothelial cells and endothelial cells; targeting COL4A1–ITGB1 with specific antibodies significantly suppresses tumorous angiogenesis and alleviates gemcitabine resistance in urothelial carcinoma. Single-cell RNA sequencing, ligand-receptor interaction analysis, antibody blockade functional assay (angiogenesis, drug resistance) Drug resistance updates Medium 38968684

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Role of COL4A1 in small-vessel disease and hemorrhagic stroke. The New England journal of medicine 432 16598045
2005 Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly. Science (New York, N.Y.) 426 15905400
2007 COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps. The New England journal of medicine 271 18160688
2015 The expanding phenotype of COL4A1 and COL4A2 mutations: clinical data on 13 newly identified families and a review of the literature. Genetics in medicine : official journal of the American College of Medical Genetics 247 25719457
2010 COL4A1 mutations as a monogenic cause of cerebral small vessel disease: a systematic review. Stroke 177 20558831
2011 COL4A2 mutations impair COL4A1 and COL4A2 secretion and cause hemorrhagic stroke. American journal of human genetics 169 22209247
2012 Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly. Annals of neurology 127 23225343
2005 Novel mutations in three families confirm a major role of COL4A1 in hereditary porencephaly. Journal of medical genetics 125 16107487
2007 COL4A1 mutation in Axenfeld-Rieger anomaly with leukoencephalopathy and stroke. Annals of neurology 123 17696175
2005 Dominant mutations of Col4a1 result in basement membrane defects which lead to anterior segment dysgenesis and glomerulopathy. Human molecular genetics 123 16159887
2011 COL4A1 mutations cause ocular dysgenesis, neuronal localization defects, and myopathy in mice and Walker-Warburg syndrome in humans. PLoS genetics 117 21625620
2020 COL4A1 promotes the growth and metastasis of hepatocellular carcinoma cells by activating FAK-Src signaling. Journal of experimental & clinical cancer research : CR 116 32746865
2007 Col4a1 mutation causes endoplasmic reticulum stress and genetically modifiable ocular dysgenesis. Human molecular genetics 115 17317786
2011 Clinical spectrum of type IV collagen (COL4A1) mutations: a novel genetic multisystem disease. Current opinion in neurology 109 21157337
2006 Type IV procollagen missense mutations associated with defects of the eye, vascular stability, the brain, kidney function and embryonic or postnatal viability in the mouse, Mus musculus: an extension of the Col4a1 allelic series and the identification of the first two Col4a2 mutant alleles. Genetics 109 17179069
2015 Common variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease. Neurology 106 25653287
2009 Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. Neurology 102 19949034
2012 COL4A1 mutations in patients with sporadic late-onset intracerebral hemorrhage. Annals of neurology 97 22522439
2007 COL4A1 mutation in a patient with sporadic, recurrent intracerebral hemorrhage. Stroke 96 17379824
2009 COL4A1 mutation in two preterm siblings with antenatal onset of parenchymal hemorrhage. Annals of neurology 94 19194877
2017 Collagen type IV alpha 1 (COL4A1) and collagen type XIII alpha 1 (COL13A1) produced in cancer cells promote tumor budding at the invasion front in human urothelial carcinoma of the bladder. Oncotarget 92 28415608
2016 Disruption of a miR-29 binding site leading to COL4A1 upregulation causes pontine autosomal dominant microangiopathy with leukoencephalopathy. Annals of neurology 78 27666438
2010 Novel COL4A1 mutations associated with HANAC syndrome: a role for the triple helical CB3[IV] domain. American journal of medical genetics. Part A 78 20818663
2013 Allelic heterogeneity contributes to variability in ocular dysgenesis, myopathy and brain malformations caused by Col4a1 and Col4a2 mutations. Human molecular genetics 72 24203695
2012 Childhood presentation of COL4A1 mutations. Developmental medicine and child neurology 69 22574627
2007 Clinical and brain MRI follow-up study of a family with COL4A1 mutation. Neurology 66 17938367
2010 Col4a1 mutation in mice causes defects in vascular function and low blood pressure associated with reduced red blood cell volume. Human molecular genetics 65 20056676
2009 COL4A1 mutation in preterm intraventricular hemorrhage. The Journal of pediatrics 59 19840616
2016 Coronary-Heart-Disease-Associated Genetic Variant at the COL4A1/COL4A2 Locus Affects COL4A1/COL4A2 Expression, Vascular Cell Survival, Atherosclerotic Plaque Stability and Risk of Myocardial Infarction. PLoS genetics 58 27389912
2009 A dominantly inherited mutation in collagen IV A1 (COL4A1) causing childhood onset stroke without porencephaly. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 58 19477666
2010 Ophthalmological features associated with COL4A1 mutations. Archives of ophthalmology (Chicago, Ill. : 1960) 57 20385946
2011 Fetal origin of brain damage in 2 infants with a COL4A1 mutation: fetal and neonatal MRI. Neuropediatrics 50 21500141
2014 Whole exome analysis identifies dominant COL4A1 mutations in patients with complex ocular phenotypes involving microphthalmia. Clinical genetics 49 24628545
2019 COL4A1 Mutations Cause Neuromuscular Disease with Tissue-Specific Mechanistic Heterogeneity. American journal of human genetics 48 31051113
2015 HANAC Syndrome Col4a1 Mutation Causes Neonate Glomerular Hyperpermeability and Adult Glomerulocystic Kidney Disease. Journal of the American Society of Nephrology : JASN 48 26260163
2012 Novel COL4A1 mutations cause cerebral small vessel disease by haploinsufficiency. Human molecular genetics 47 23065703
2022 Main features of COL4A1-COL4A2 related cerebral microangiopathies. Cerebral circulation - cognition and behavior 46 36324412
2017 The highly expressed COL4A1 genes contributes to the proliferation and migration of the invasive ductal carcinomas. Oncotarget 45 28938546
2016 Col4a1 mutations cause progressive retinal neovascular defects and retinopathy. Scientific reports 44 26813606
2010 Role of COL4A1 in basement-membrane integrity and cerebral small-vessel disease. The COL4A1 stroke syndrome. Current medicinal chemistry 43 20166936
2020 The correlation and role analysis of COL4A1 and COL4A2 in hepatocarcinogenesis. Aging 42 31905170
2016 ER stress and basement membrane defects combine to cause glomerular and tubular renal disease resulting from Col4a1 mutations in mice. Disease models & mechanisms 42 26839400
2011 COL4A1 mutations associated with a characteristic pattern of intracranial calcification. Neuropediatrics 42 22134833
2015 Functional interaction between COL4A1/COL4A2 and SMAD3 risk loci for coronary artery disease. Atherosclerosis 41 26310581
2018 Severity of arterial defects in the retina correlates with the burden of intracerebral haemorrhage in COL4A1-related stroke. The Journal of pathology 37 29266233
1993 Differential effects of DNA-binding proteins on bidirectional transcription from the common promoter region of human collagen type IV genes COL4A1 and COL4A2. Biochimica et biophysica acta 37 8334157
2011 Drosophila basement membrane collagen col4a1 mutations cause severe myopathy. Matrix biology : journal of the International Society for Matrix Biology 36 22037604
2024 A distinct subset of urothelial cells with enhanced EMT features promotes chemotherapy resistance and cancer recurrence by increasing COL4A1-ITGB1 mediated angiogenesis. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 35 38968684
2021 miR-543 in human mesenchymal stem cell-derived exosomes promotes cardiac microvascular endothelial cell angiogenesis after myocardial infarction through COL4A1. IUBMB life 35 33890394
2021 Prevalence of COL4A1 and COL4A2 mutations in severe fetal multifocal hemorrhagic and/or ischemic cerebral lesions. Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology 34 32515830
2014 Next generation sequencing uncovers a missense mutation in COL4A1 as the cause of familial retinal arteriolar tortuosity. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 34 25228067
2018 The Value of Genetic Testing in Polycystic Kidney Diseases Illustrated by a Family With PKD2 and COL4A1 Mutations. American journal of kidney diseases : the official journal of the National Kidney Foundation 33 29395486
2019 4-Sodium phenyl butyric acid has both efficacy and counter-indicative effects in the treatment of Col4a1 disease. Human molecular genetics 32 30351356
2018 Further refinement of COL4A1 and COL4A2 related cortical malformations. European journal of medical genetics 32 30315939
2013 The Wilms tumor gene, Wt1, maintains testicular cord integrity by regulating the expression of Col4a1 and Col4a2. Biology of reproduction 32 23325811
2020 Prenatal clinical manifestations in individuals with COL4A1/2 variants. Journal of medical genetics 31 32732225
1997 Cooperative and competitive interactions of regulatory elements are involved in the control of divergent transcription of human Col4A1 and Col4A2 genes. FEBS letters 31 9094419
2017 HANAC Col4a1 Mutation in Mice Leads to Skeletal Muscle Alterations due to a Primary Vascular Defect. The American journal of pathology 29 28056338
2021 COL4A1, negatively regulated by XPD and miR-29a-3p, promotes cell proliferation, migration, invasion and epithelial-mesenchymal transition in liver cancer cells. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 28 33891266
2022 LncRNA SND1-IT1 facilitates TGF-β1-induced epithelial-to-mesenchymal transition via miR-124/COL4A1 axis in gastric cancer. Cell death discovery 26 35184134
2022 Collagen type IV alpha 1 (COL4A1) silence hampers the invasion, migration and epithelial-mesenchymal transition (EMT) of gastric cancer cells through blocking Hedgehog signaling pathway. Bioengineered 26 35297303
2019 miR-29c overexpression and COL4A1 downregulation in infertile human endometrium reduces endometrial epithelial cell adhesive capacity in vitro implying roles in receptivity. Scientific reports 26 31201347
2015 Strain-Dependent Anterior Segment Dysgenesis and Progression to Glaucoma in Col4a1 Mutant Mice. Investigative ophthalmology & visual science 26 26567795
2014 Fetal intracerebral hemorrhage and cataract: think COL4A1. Journal of perinatology : official journal of the California Perinatal Association 26 24374867
2011 Sequence variants in COL4A1 and COL4A2 genes in Ecuadorian families with keratoconus. Molecular vision 25 21527998
2013 Variants of anterior segment dysgenesis and cerebral involvement in a large family with a novel COL4A1 mutation. American journal of ophthalmology 24 23394911
1988 Macrorestriction mapping of COL4A1 and COL4A2 collagen genes on human chromosome 13q34. Genomics 24 3224982
2019 Collagen IV (COL4A1, COL4A2), a Component of the Viral Biofilm, Is Induced by the HTLV-1 Oncoprotein Tax and Impacts Virus Transmission. Frontiers in microbiology 23 31708905
2017 Genetic dissection of anterior segment dysgenesis caused by a Col4a1 mutation in mouse. Disease models & mechanisms 23 28237965
2016 A novel COL4A1 frameshift mutation in familial kidney disease: the importance of the C-terminal NC1 domain of type IV collagen. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 23 27190376
2014 A novel COL4A1 gene mutation results in autosomal dominant non-syndromic congenital cataract in a Chinese family. BMC medical genetics 22 25124159
2021 Identification of fibronectin 1 as a candidate genetic modifier in a Col4a1 mutant mouse model of Gould syndrome. Disease models & mechanisms 21 34424299
2014 Porencephaly in a fetus and HANAC in her father: variable expression of COL4A1 mutation. American journal of medical genetics. Part A 21 25425218
2020 miR‑29 mediates exercise‑induced skeletal muscle angiogenesis by targeting VEGFA, COL4A1 and COL4A2 via the PI3K/Akt signaling pathway. Molecular medicine reports 20 32467996
2012 MiR-21 is enriched in the RNA-induced silencing complex and targets COL4A1 in human granulosa cell lines. Reproductive sciences (Thousand Oaks, Calif.) 20 22573493
2023 Impaired intracellular Ca2+ signaling contributes to age-related cerebral small vessel disease in Col4a1 mutant mice. Science signaling 19 37963192
2023 A novel human iPSC model of COL4A1/A2 small vessel disease unveils a key pathogenic role of matrix metalloproteinases. Stem cell reports 19 37977146
2016 COL4A1 Mutation in a Neonate With Intrauterine Stroke and Anterior Segment Dysgenesis. Pediatric neurology 19 28043398
2012 COL4A1-related disease: raised creatine kinase and cerebral calcification as useful pointers. Neuropediatrics 19 22932948
2022 COL4A1/COL4A2 and inherited platelet disorder gene variants in fetuses showing intracranial hemorrhage. Prenatal diagnosis 18 35150448
2020 Overexpression of DDR1 Promotes Migration, Invasion, Though EMT-Related Molecule Expression and COL4A1/DDR1/MMP-2 Signaling Axis. Technology in cancer research & treatment 18 33234027
2020 Role of the XIST-miR-181a-COL4A1 axis in the development and progression of keratoconus. Molecular vision 17 32165822
2021 Novel COL4A1-VEGFD gene fusion in myofibroma. Journal of cellular and molecular medicine 16 33830670
2015 Two families with novel missense mutations in COL4A1: When diagnosis can be missed. Journal of the neurological sciences 16 25873210
1987 The human alpha 2(IV) collagen gene, COL4A2, is syntenic with the alpha 1(IV) gene, COL4A1, on chromosome 13. Annals of human genetics 16 3674752
2022 Elevated TGFβ signaling contributes to ocular anterior segment dysgenesis in Col4a1 mutant mice. Matrix biology : journal of the International Society for Matrix Biology 15 35525525
2019 Cervical Spinal Involvement in a Chinese Pedigree With Pontine Autosomal Dominant Microangiopathy and Leukoencephalopathy Caused by a 3' Untranslated Region Mutation of COL4A1 Gene. Stroke 15 31366314
2024 Integrating single-cell and spatial transcriptomes reveals COL4A1/2 facilitates the spatial organisation of stromal cells differentiation in breast phyllodes tumours. Clinical and translational medicine 14 38481388
2023 An mTurq2-Col4a1 mouse model allows for live visualization of mammalian basement membrane development. The Journal of cell biology 14 38051393
2020 Effect of COL4A1 Expression on the Survival of Neoadjuvant Chemotherapy Breast Cancer Patients. Journal of oncology 14 32565804
2018 Novel COL4A1 mutation in a fetus with early prenatal onset of schizencephaly. Human genome variation 14 29760938
2023 COL4A1 promotes the proliferation and migration of oral squamous cell carcinoma cells by binding to NID1. Experimental and therapeutic medicine 13 37006878
2021 A Novel Mutation in COL4A1 Gene in a Chinese Family with Pontine Autosomal Dominant Microangiopathy and Leukoencephalopathy. Translational stroke research 13 34415564
2019 Cerebral small vessel disease with hemorrhagic stroke related to COL4A1 mutation: A case report. Neuropathology : official journal of the Japanese Society of Neuropathology 12 31808207
2016 Association of COL4A1 gene polymorphisms with cerebral palsy in a Chinese Han population. Clinical genetics 12 26748532
2016 A severe pulmonary complication in a patient with COL4A1-related disorder: A case report. European journal of medical genetics 12 28017902
2015 Case of Small Vessel Disease Associated with COL4A1 Mutations following Trauma. Case reports in neurology 12 26120313
2025 COL4A1 and COL4A2-related disorders: Clinical features, diagnostic guidelines, and management. Genetics in medicine : official journal of the American College of Medical Genetics 11 40616396
2022 FOXL2 regulates the expression of the Col4a1 collagen gene in chicken granulosa cells. Molecular reproduction and development 11 35122350
2021 METTL3 participates in glioma development by regulating the methylation level of COL4A1. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 11 34565019

Missed literature

Know a paper Affinage missed for COL4A1? Flag it for the maintainers and the community.

No submissions yet.