Affinage

COL4A2

Collagen alpha-2(IV) chain · UniProt P08572

Length
1712 aa
Mass
167.6 kDa
Annotated
2026-06-09
70 papers in source corpus 23 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COL4A2 encodes the α2(IV) chain of type IV collagen, which assembles with α1(IV) chains into the [α1(IV)]₂[α2(IV)] heterotrimer that is a ubiquitous structural component of basement membranes; missense mutations in the collagenous (conserved Gly-X-Y) and NC domains cause ocular, brain, kidney, and vascular defects in heterozygous mice, with homozygous lethality (PMID:17179069). Pathogenic missense mutations drive intracellular retention of both COL4A1 and COL4A2 in the endoplasmic reticulum, impairing secretion and triggering ER stress, unfolded protein response activation, proteasomal degradation of misfolded chains, reduced proliferation, and apoptosis—cellular defects partially reversed by reduced temperature or chemical chaperones such as 4-phenylbutyrate (PMID:22209247, PMID:24001601, PMID:24203695). COL4A1 and COL4A2 are transcribed divergently from a shared bidirectional promoter whose activity depends on cooperative and competitive interactions among CCAAT-binding proteins, Sp1, and gene-specific downstream activating elements, with an intronic silencer providing negative regulation (PMID:8334157, PMID:7744753, PMID:9094419); positive transcriptional input comes from SOX9 acting through a GAACAAT enhancer motif, WT1 (which additively transactivates with SOX9 and is required for testicular cord basement membrane integrity), and TGF-β1 signaling through canonical SMAD3/SMAD4 (PMID:17525254, PMID:23325811, PMID:26310581). As a basement-membrane and extracellular matrix component, COL4A2 turnover is spatially coupled to basement membrane expansion and epithelial progenitor proliferation during morphogenesis (PMID:39656438), and it modulates cell behavior across multiple contexts: it promotes ECM stiffness via collagen fiber crosslinking with downstream YAP1 activation (PMID:40714253), supports anoikis resistance downstream of Notch3 (PMID:25169943), and drives pro-angiogenic and pro-proliferative PI3K/AKT and MAPK-ERK signaling, in glioblastoma through direct binding to integrin α1β1 (ITGA1/ITGB1) (PMID:40993804, PMID:41308943). Mutant COL4A2 expressed in astrocytes activates JAK2/STAT3 neuroinflammatory signaling (PMID:39006838).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1987 High

    Establishing that COL4A2 encodes the α2(IV) chain with a triple-helical and carboxy-terminal NC1 domain and maps to 13q34 in synteny with COL4A1 defined the genomic basis for their coordinate regulation.

    Evidence cDNA cloning, human-rodent hybrid mapping, and in situ hybridization

    PMID:3674752 PMID:3692475

    Open questions at the time
    • Did not address how the two genes share regulatory elements
    • No functional protein assembly data
  2. 1993 Medium

    Identifying that COL4A1 and COL4A2 share a bidirectional promoter bound cooperatively by CCAAT-binding proteins, Sp1, and CTCBF answered how two divergent genes are coordinately yet differentially transcribed.

    Evidence Binding-site mutagenesis, reporter assays, and DNA-protein binding assays

    PMID:8334157

    Open questions at the time
    • CTCBF not molecularly identified
    • Tissue-specific contributions of each factor unresolved
  3. 1995 Medium

    Discovery of an intronic COL4 silencer element and its binding protein SILBF revealed a negative regulatory layer constraining transcription from the shared promoter.

    Evidence Deletion mapping, footprinting, and reporter assays with SILBF-site mutagenesis

    PMID:7744753

    Open questions at the time
    • SILBF not cloned/identified
    • Physiological contexts of silencing unknown
  4. 1997 Medium

    Showing that divergent transcription requires symmetric gene-specific downstream activating elements that compete for the shared promoter explained how output to each gene is balanced.

    Evidence Transient transfection with deletion/mutation of cis-elements and factor-binding assays

    PMID:9094419

    Open questions at the time
    • Identity of trans-acting factors not established
    • No endogenous-locus confirmation
  5. 2006 High

    An ENU allelic series in mouse established that the [α1(IV)]₂[α2(IV)] heterotrimer is essential, with collagenous/NC-domain mutations causing multi-organ basement membrane defects and homozygous lethality.

    Evidence ENU mutagenesis screen with molecular and phenotypic characterization of multiple Col4a2 alleles

    PMID:17179069

    Open questions at the time
    • Did not define the cellular mechanism of dominance
    • Human disease relevance not yet linked
  6. 2007 High

    Identification of SOX9 binding a GAACAAT enhancer motif to activate Col4a2, downstream of TGF-β, connected matrix gene transcription to a defined signaling input in mesangial cells.

    Evidence EMSA, ChIP, luciferase reporters, enhancer point mutation, siRNA, and a nephrotoxic nephritis model

    PMID:17525254

    Open questions at the time
    • Generalizability beyond mesangial cells unaddressed
    • Interplay with the shared bidirectional promoter not integrated
  7. 2011 High

    Demonstrating that COL4A2 missense mutations cause ER retention of both chains with UPR/ER-stress cytotoxicity and a mouse ICH phenotype defined the gain-of-function/toxic misfolding disease mechanism.

    Evidence Secretion assays, ER-localization immunofluorescence, UPR assays, and a Col4a2 mutant mouse

    PMID:22209247

    Open questions at the time
    • Mutation-specific severity not fully explained
    • Therapeutic intervention not yet tested
  8. 2013 High

    Patient fibroblast and mouse allelic studies refined the mechanism by showing proteasomal degradation of mutant chains and rescue of ER stress and apoptosis by chemical chaperones and reduced temperature.

    Evidence Primary fibroblast/cell-line UPR assays, proteasome inhibition, and 4-PBA/temperature rescue

    PMID:24001601 PMID:24203695

    Open questions at the time
    • In vivo efficacy of chaperone therapy not established
    • Allelic heterogeneity in biosynthetic signatures not mechanistically resolved
  9. 2013 High

    Demonstrating that WT1 and SOX9 additively transactivate the promoters, with Wt1 loss causing basal lamina breakdown, extended transcriptional control to tissue-specific basement membrane maintenance.

    Evidence Sertoli-cell conditional Wt1 knockout with RT-PCR, Western blot, immunostaining, and luciferase assays

    PMID:23325811

    Open questions at the time
    • Direct WT1 promoter binding sites not fully mapped
    • Mechanism of additivity with SOX9 unresolved
  10. 2015 Medium

    Defining canonical SMAD3/SMAD4 as the mediator of TGF-β1-induced COL4A1/COL4A2 expression, without promoter activation, indicated a post-transcriptional or indirect regulatory route.

    Evidence ALK5 inhibitor, SMAD2/3/4 siRNA, qPCR/protein, and reporter assays in vascular smooth muscle cells and fibroblasts

    PMID:26310581

    Open questions at the time
    • The post-transcriptional mechanism not identified
    • Relationship to SOX9-dependent activation unclear
  11. 2016 High

    Functional dissection of the CAD-associated SNP rs4773144 linked an allele-specific transcriptional difference to SMC apoptosis and reduced plaque collagen IV, connecting COL4A2 regulation to vascular disease.

    Evidence Allelic-imbalance ChIP, EMSA, luciferase, genotyped primary SMC/EC, and ex vivo coronary IHC

    PMID:27389912

    Open questions at the time
    • The nuclear protein binding rs4773144 not identified
    • Causal link from SNP to plaque phenotype is correlative in tissue
  12. 2014 Medium

    Showing Notch3 promotes anoikis resistance via COL4A2 upregulation, rescuable by exogenous collagen IV, placed COL4A2 as an effector of survival signaling in ovarian cancer.

    Evidence Notch3 and COL4A2 siRNA, collagen IV supplementation rescue, and anoikis/anchorage-independent assays

    PMID:25169943

    Open questions at the time
    • Receptor mediating COL4A2 survival signal not defined here
    • Direct vs matrix-mediated effect not separated
  13. 2019 Medium

    Demonstrating COL4A2 promotes osteogenic differentiation of PDLSCs by inhibiting Wnt/β-catenin established a matrix-instructed differentiation role.

    Evidence siRNA/lentiviral COL4A2 modulation in ECM, in vitro/in vivo osteogenesis, and DKK-1/Wnt3a pathway tools

    PMID:31285761

    Open questions at the time
    • Mechanism linking COL4A2 to Wnt inhibition unknown
    • Receptor/signaling intermediary not identified
  14. 2019 Medium

    Identifying COL4A2 as a Tax-induced viral biofilm component required for Gag transfer added a role for the protein in HTLV-1 cell-to-cell transmission.

    Evidence Tax promoter assays, CRISPR COL4A2 knockout, co-localization, and cell-to-cell transfer assays in T-cells

    PMID:31708905

    Open questions at the time
    • Molecular basis of Gag-transfer dependence unclear
    • Whether heterotrimer or monomer functions in VB unknown
  15. 2024 High

    An endogenous eGFP-Col4a2 knock-in revealed spatially graded COL4A2 turnover, MMP-dependent, coupling basement membrane expansion to epithelial progenitor division orientation during morphogenesis.

    Evidence Live imaging of eGFP-Col4a2 mice, MMP inhibition, and division-orientation quantification in hair follicles

    PMID:39656438

    Open questions at the time
    • Which MMPs act on COL4A2 not specified
    • Signal coupling turnover to division orientation undefined
  16. 2024 Medium

    Showing a COL4A2 mutation activates JAK2/STAT3 in astrocytes with cytokine induction, reversed by WP1066, linked mutant COL4A2 to a neuroinflammatory mechanism.

    Evidence Mutant overexpression in astrocyte cell systems, ELISA, Western blot, immunofluorescence, and JAK/STAT inhibitor

    PMID:39006838

    Open questions at the time
    • How mutant COL4A2 activates JAK/STAT not defined
    • Overexpression rather than endogenous mutation
  17. 2025 Medium

    Defining a direct COL4A2-integrin α1β1 interaction driving PI3K-AKT/MAPK-ERK angiogenic signaling in GBM, with JMJD6-mediated upregulation, provided a receptor-level mechanism and therapeutic axis.

    Evidence Co-IP/pulldown, JMJD6 studies, obtustatin inhibition, and orthotopic GBM survival model

    PMID:40993804

    Open questions at the time
    • Reconstitution of direct binding not detailed
    • Contribution of heterotrimer vs free α2 chain unresolved
  18. 2025 Medium

    Demonstrating COL4A2-driven collagen crosslinking and ECM stiffness activates YAP1 to promote breast cancer migration and metastasis, and HES4-driven transcription in HCC, extended COL4A2's pro-tumor mechanotransduction and transcriptional control.

    Evidence dECM stiffness/migration/metastasis models with COL4A2 knockdown and YAP1 readout; ChIP and rescue for HES4 in HCC

    PMID:40714253 PMID:40715599

    Open questions at the time
    • Crosslinking enzymes mediating stiffness not identified
    • Direct vs indirect YAP1 activation not separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • The mechanistic link between extracellular COL4A2 matrix properties and the diverse intracellular signaling outputs (AKT, ERK, Wnt, YAP1, JAK/STAT) across cell types remains incompletely defined, as does the receptor logic distinguishing structural from signaling roles.
  • No unified receptor map across contexts
  • Heterotrimer vs monomer functional states not resolved
  • In vivo therapeutic translation of chaperone or integrin-axis interventions not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0098631 cell adhesion mediator activity 2
Localization
GO:0005783 endoplasmic reticulum 3 GO:0031012 extracellular matrix 3 GO:0005576 extracellular region 2 GO:0030312 external encapsulating structure 2
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-162582 Signal Transduction 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
COL4A1ITGA1ITGB1
Complex memberships
[α1(IV)]₂[α2(IV)] type IV collagen heterotrimer

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 COL4A2 missense mutations cause intracellular accumulation of both COL4A1 and COL4A2 proteins with retention in the endoplasmic reticulum (ER), impairing their secretion. Two of three identified mutations also trigger ER stress and activate the unfolded protein response, leading to cytotoxicity. Cellular secretion assay in transfected cells, immunofluorescence for ER localization, UPR/ER stress assays, Col4a2 mutant mouse model with ICH phenotype American journal of human genetics High 22209247
2006 Col4a2 and Col4a1 form the heterotrimer [α1(IV)]2[α2(IV)] ubiquitously expressed in basement membranes. Missense mutations in the collagenous domain (conserved Gly sites in Gly-X-Y repeats) or NC domain of Col4a2 cause ocular, brain, kidney, and vascular defects in heterozygous mice; homozygotes do not survive beyond the second trimester. ENU random mutagenesis screen in mouse, molecular characterization of mutations, phenotypic analysis of heterozygous and homozygous carriers Genetics High 17179069
2013 A dominant G702D mutation in the collagenous domain of COL4A2 causes ER retention of COL4A2, ER stress, unfolded protein response activation, reduced cell proliferation, and increased apoptosis in primary dermal fibroblasts. Mutant collagen IV is degraded via the proteasome. Chemical chaperone treatment decreases intracellular COL4A2 accumulation, ER stress, and apoptosis, ameliorating the cellular phenotype. Primary dermal fibroblast analysis, immunofluorescence for ER localization, UPR/ER stress assays, proteasome inhibition assay, chemical chaperone treatment Human molecular genetics High 24001601
2013 Allelic heterogeneity in Col4a1 and Col4a2 mutations produces distinct biosynthetic signatures: most mutations cause increased intracellular and decreased extracellular COL4A1/COL4A2, but three mutations have distinct profiles. Reduced temperature or 4-phenylbutyrate treatment ameliorated biosynthetic defects in mutant primary cell lines. Primary cell lines from mutant mice, COL4A1/COL4A2 intracellular/extracellular protein quantification, temperature reduction and 4-PBA chemical chaperone treatment Human molecular genetics Medium 24203695
1993 COL4A1 and COL4A2 are transcribed divergently from a shared bidirectional promoter. At least three nuclear proteins (a CCAAT-binding protein, Sp1, and a newly identified factor 'CTCBF') bind within this promoter and are essential for efficient transcription of both genes, but exert differential gene-specific effects. The shared promoter functions as two overlapping gene-specific promoters with shared elements. Mutagenesis of transcription factor binding sites, transient transfection reporter assays, DNA-protein binding assays Biochimica et biophysica acta Medium 8334157
1995 A transcriptional silencer ('COL4 silencer') was identified in the third intron of COL4A2 that inhibits transcription of both COL4A1 and COL4A2 from their shared promoter, as well as a heterologous promoter, in an orientation- and distance-independent manner. A specific nuclear protein ('SILBF') binds this element, and its interaction is both necessary and sufficient for silencing. Deletion mapping, transient transfection reporter assays, DNA footprinting assays, mutagenesis of SILBF binding site The Journal of biological chemistry Medium 7744753
1997 Divergent transcription of COL4A1 and COL4A2 from their shared promoter depends on cooperative interactions between the shared promoter and two symmetrically arranged, gene-specific downstream activating elements in each gene. Mutual inhibitory (competitive) effects between the two activating elements indicate competition for the shared promoter. Trans-acting factors bind cooperatively and competitively to promoter and activating elements. Transient transfection experiments, trans-acting factor binding assays, deletion and mutation analysis of cis-elements FEBS letters Medium 9094419
2007 SOX9 binds the GAACAAT motif in the Col4a2 enhancer in vitro and in vivo in mesangial cells, strongly activating Col4a2 enhancer-promoter constructs. Mutation of the GAACAAT motif eliminates SOX9-mediated activation. TGF-β treatment induces SOX9 and Col4a2 expression in mesangial cells, and siRNA against SOX9 reduces TGF-β-induced Col4a2 expression. Luciferase reporter assays, EMSA, ChIP, siRNA knockdown, point mutation analysis of enhancer, in vivo nephrotoxic nephritis model The American journal of pathology High 17525254
2013 WT1 (Wilms tumor gene) and SOX9 additively transactivate the Col4a1 and Col4a2 promoters in Sertoli cells. Loss of Wt1 in Sertoli cells leads to significant decrease in Col4a1 and Col4a2 mRNA and protein, breakdown of the testicular cord basal lamina, and subsequent testicular cord disruption. Conditional Wt1 knockout in Sertoli cells (Wt1-/flox; Amh-Cre), real-time RT-PCR, Western blot, immunostaining, luciferase assays, point mutation analysis of promoters Biology of reproduction High 23325811
2015 TGF-β1 stimulates COL4A1 and COL4A2 mRNA and protein expression via the canonical SMAD3/SMAD4 pathway (not SMAD2 or non-canonical pathways) in primary human aortic smooth muscle cells and HT1080 fibroblasts. ALK5 inhibitor or siRNA knockdown of SMAD3/SMAD4 abolishes TGF-β1-induced COL4A1/COL4A2 upregulation. Neither SMAD3 overexpression nor TGF-β1 treatment altered COL4A1 or COL4A2 promoter activity in reporter assays, suggesting post-transcriptional or indirect regulatory mechanisms. ALK5 inhibitor pharmacological blockade, siRNA knockdown of SMAD2/3/4, luciferase reporter assays, qPCR and protein expression analysis in primary human vascular smooth muscle cells Atherosclerosis Medium 26310581
2016 The CAD-associated SNP rs4773144 in COL4A2 affects COL4A1/COL4A2 transcription: the G allele shows lower transcriptional activity than the A allele in primary vascular smooth muscle cells and endothelial cells, as demonstrated by allelic imbalance in ChIP assays and a short DNA sequence encompassing rs4773144 interacting with a nuclear protein with lower efficiency for the G allele. The G/G genotype is associated with higher SMC apoptosis and lower collagen IV content in atherosclerotic plaques (thinner fibrous cap). Allelic imbalance ChIP assays, EMSA, luciferase reporter assays, primary SMC and EC cultures from different genotype individuals, immunohistochemistry of ex vivo coronary arteries PLoS genetics High 27389912
2019 COL4A2 in the extracellular matrix promotes osteogenic differentiation of periodontal ligament stem cells (PDLSCs) through negative regulation of the Wnt/β-catenin pathway. siRNA-mediated downregulation of COL4A2 in B-dECM reduced osteogenic differentiation, and this effect was confirmed in vivo. Wnt inhibitor DKK-1 and activator Wnt3a experiments confirmed the pathway involvement. siRNA knockdown and lentiviral overexpression of COL4A2 in ECM, in vitro osteogenic differentiation assays, in vivo subcutaneous implantation and alveolar bone defect model, Wnt pathway pharmacological modulation Theranostics Medium 31285761
2019 HTLV-1 oncoprotein Tax activates the COL4A2 promoter (and to a lesser extent COL4A1 promoter) in T-cells. COL4A2 protein is a component of the viral biofilm (VB) at the virological synapse and co-localizes with viral Gag protein. Knockout of COL4A2 in chronically infected T-cells impaired Gag transfer between infected and acceptor T-cells without affecting virus-like particle release. Luciferase promoter assays, Tax expression/repression, CRISPR knockout of COL4A2 in T-cell lines, immunofluorescence co-localization, cell-to-cell transfer assays Frontiers in microbiology Medium 31708905
2014 Notch3 overexpression in epithelial ovarian cancer promotes anoikis resistance through upregulation of COL4A2. Both mRNA and protein levels of COL4A2 are reduced when Notch3 levels are decreased. RNAi-mediated knockdown of COL4A2 induces cell death, and exogenous collagen IV supplementation reverses anoikis sensitivity caused by Notch3 reduction. Notch3 siRNA knockdown, COL4A2 siRNA knockdown, exogenous collagen IV supplementation rescue, anoikis/anchorage-independent growth assays Molecular cancer research : MCR Medium 25169943
2024 An eGFP-Col4a2 knock-in mouse revealed a spatial gradient in COL4A2 turnover rate during hair follicle morphogenesis that is coupled with basement membrane expansion rate and epithelial progenitor proliferation rate. Matrix metalloproteinase inhibition delays COL4A2 turnover, restrains BM expansion, and increases perpendicular divisions of epithelial progenitors, altering hair follicle morphology. Endogenous eGFP-Col4a2 fusion mouse line, live imaging of developing hair follicles, MMP inhibitor treatment, quantification of cell division orientation The Journal of cell biology High 39656438
2024 A COL4A2 mutation (c.1838G>T) expressed in astrocytes activates the JAK/STAT signaling pathway, leading to increased phosphorylation of JAK2 and STAT3, astrocyte activation, and elevated inflammatory cytokines (IL-1β, IL-6, TNF-α, iNOS, COX-2). JAK/STAT inhibitor WP1066 counteracts these effects. COL4A2 mutant overexpression in CTX-TNA cells and primary astrocytes, ELISA, Western blot, immunofluorescence for astrocyte activation markers, JAK/STAT inhibitor treatment International journal of medical sciences Medium 39006838
2025 COL4A2 promotes GBM vascularization by activating PI3K-AKT and MAPK-ERK signaling through direct interaction with ITGA1/ITGB1 (integrin α1β1) receptors on tumor-associated endothelial cells. JMJD6, an anti-pause enhancer, mediates epigenetic upregulation of COL4A2 in GBM. Pharmacological inhibition of the COL4A2-ITGA1/ITGB1 axis suppresses pro-angiogenic signaling and prolongs survival in orthotopic GBM models. Multi-omics profiling, Co-IP/pulldown for COL4A2-ITGA1/ITGB1 interaction, JMJD6 functional studies, pharmacological inhibition with obtustatin, orthotopic GBM mouse model survival assay Acta neuropathologica communications Medium 40993804
2025 COL4A2 promotes ECM stiffness through increased crosslinking of collagen fibers in metastatic breast cancer. Reduced COL4A2 in decellularized ECM decreases stiffness and inhibits cell migration in vitro and metastasis in vivo. Elevated COL4A2-driven stiffness activates YAP1 expression in tumor cells. dECM models from metastatic/non-metastatic breast cancer, virus-mediated COL4A2 knockdown, ECM stiffness measurement, in vitro migration assays, in vivo metastasis model, YAP1 expression analysis Biomaterials advances Medium 40714253
2024 COL4A2 overexpression enhances proliferation, migration, and angiogenesis of human retinal capillary endothelial cells under high glucose conditions via activation of AKT signaling. AKT inhibitor treatment blocks these COL4A2-driven proliferative effects. COL4A2 knockdown and overexpression in HRCECs, CCK-8, Annexin V/PI, scratch, tube formation assays, AKT inhibitor treatment, Western blot Experimental eye research Medium 41308943
2025 Hypoxia-induced transcription factor HES4 binds to the COL4A2 promoter to enhance its transcription in hepatocellular carcinoma cells. HES4 knockdown reduces COL4A2 expression, and COL4A2 overexpression reverses the inhibitory effects of HES4 silencing on HCC cell proliferation and motility. ChIP assay for HES4 binding to COL4A2 promoter, HES4 siRNA knockdown, COL4A2 overexpression rescue, CCK-8, EdU, wound healing, Transwell assays Discover oncology Medium 40715599
1987 The COL4A2 gene (encoding part of the α2 chain of collagen IV including the triple-helical domain and the carboxy-terminal globular NC1 domain) was mapped to chromosome 13q34, syntenic with COL4A1, indicating both type IV collagen chains are encoded in the same chromosomal cluster. cDNA cloning from human placental library, DNA sequence analysis, human-rodent hybrid cell line mapping, in situ hybridization Human genetics High 3674752 3692475
2020 COL4A2 activates the RhoA/ROCK pathway to promote chicken hepatocellular carcinoma (LMH) cell invasion and migration. miR-29a-3p targets COL4A2 as a direct target gene, and selenium downregulates miR-29a-3p to maintain COL4A2 expression and RhoA/ROCK activity. Luciferase reporter assay for miR-29a-3p targeting of COL4A2 3'UTR, COL4A2 knockdown/overexpression, RhoA/ROCK pathway assessment, Transwell invasion/migration assays Metallomics : integrated biometal science Low 32039426

Source papers

Stage 0 corpus · 70 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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
2011 COL4A2 mutations impair COL4A1 and COL4A2 secretion and cause hemorrhagic stroke. American journal of human genetics 169 22209247
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
2012 COL4A2 mutation associated with familial porencephaly and small-vessel disease. European journal of human genetics : EJHG 96 22333902
2011 De novo and inherited mutations in COL4A2, encoding the type IV collagen α2 chain cause porencephaly. American journal of human genetics 81 22209246
2013 Allelic heterogeneity contributes to variability in ocular dysgenesis, myopathy and brain malformations caused by Col4a1 and Col4a2 mutations. Human molecular genetics 72 24203695
2019 COL4A2 in the tissue-specific extracellular matrix plays important role on osteogenic differentiation of periodontal ligament stem cells. Theranostics 68 31285761
2013 Chemical chaperone treatment reduces intracellular accumulation of mutant collagen IV and ameliorates the cellular phenotype of a COL4A2 mutation that causes haemorrhagic stroke. Human molecular genetics 62 24001601
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
2018 Alpha-synuclein deregulates the expression of COL4A2 and impairs ER-Golgi function. Neurobiology of disease 49 30092270
2014 Notch3 overexpression promotes anoikis resistance in epithelial ovarian cancer via upregulation of COL4A2. Molecular cancer research : MCR 48 25169943
2022 Main features of COL4A1-COL4A2 related cerebral microangiopathies. Cerebral circulation - cognition and behavior 46 36324412
2017 siRNA-mediated suppression of collagen type iv alpha 2 (COL4A2) mRNA inhibits triple-negative breast cancer cell proliferation and migration. Oncotarget 46 27906681
2020 The correlation and role analysis of COL4A1 and COL4A2 in hepatocarcinogenesis. Aging 42 31905170
2015 Functional interaction between COL4A1/COL4A2 and SMAD3 risk loci for coronary artery disease. Atherosclerosis 41 26310581
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
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 COL4A2 mutation causing adult onset recurrent intracerebral hemorrhage and leukoencephalopathy. Journal of neurology 34 24390199
2007 SRY-related HMG box 9 regulates the expression of Col4a2 through transactivating its enhancer element in mesangial cells. The American journal of pathology 34 17525254
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
1995 Identification and characterization of a novel transcriptional silencer in the human collagen type IV gene COL4A2. The Journal of biological chemistry 32 7744753
1987 Partial structure of the human alpha 2(IV) collagen chain and chromosomal localization of the gene (COL4A2). Human genetics 32 3692475
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
2011 Sequence variants in COL4A1 and COL4A2 genes in Ecuadorian families with keratoconus. Molecular vision 25 21527998
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
2021 Long non-coding RNA COL4A2-AS1 facilitates cell proliferation and glycolysis of colorectal cancer cells via miR-20b-5p/hypoxia inducible factor 1 alpha subunit axis. Bioengineered 21 34477476
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
2022 COL4A1/COL4A2 and inherited platelet disorder gene variants in fetuses showing intracranial hemorrhage. Prenatal diagnosis 18 35150448
2020 Selenium-mediated gga-miR-29a-3p regulates LMH cell proliferation, invasion, and migration by targeting COL4A2. Metallomics : integrated biometal science 17 32039426
2015 A mutation in COL4A2 causes autosomal dominant porencephaly with cataracts. American journal of medical genetics. Part A 16 26708157
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
2024 An eGFP-Col4a2 mouse model reveals basement membrane dynamics underlying hair follicle morphogenesis. The Journal of cell biology 13 39656438
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 Secretome analysis reveals reduced expression of COL4A2 in hypoxic cancer-associated fibroblasts with a tumor-promoting function in gastric cancer. Journal of cancer research and clinical oncology 9 36125535
2021 A Study of Associations Between rs9349379 (PHACTR1), rs2891168 (CDKN2B-AS), rs11838776 (COL4A2) and rs4880 (SOD2) Polymorphic Variants and Coronary Artery Disease in Iranian Population. Biochemical genetics 9 34109516
2022 The ETS1-LINC00278 negative feedback loop plays a role in COL4A1/COL4A2 regulation in laryngeal squamous cell carcinoma. Neoplasma 8 35532293
2021 Novel COL4A2 mutation causing familial malformations of cortical development. European review for medical and pharmacological sciences 8 33577044
2022 PECAM1, COL4A2, PHACTR1, and LMOD1 Gene Polymorphisms in Patients with Unstable Angina. Journal of clinical medicine 6 35054067
2007 Do mutations in COL4A1 or COL4A2 cause thin basement membrane nephropathy (TBMN)? Pediatric nephrology (Berlin, Germany) 6 17216253
2025 COL4A2 drives ECM remodeling and stiffness increasing to promote breast cancer metastasis via YAP signaling pathway in dECM induced models. Biomaterials advances 5 40714253
2025 JMJD6-driven epigenetic activation of COL4A2 reprograms glioblastoma vascularization via integrin α1β1-dependent PI3K/MAPK signaling. Acta neuropathologica communications 4 40993804
2022 Rare metabolic disease mimicking COL4A1/COL4A2 fetal brain phenotype. Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology 4 35943828
2024 COL4A2 enhances thyroid cancer cell proliferation through the AKT pathway. Oncology research 3 39220121
2021 Coexistence of RASA1 and COL4A2 variants caused pial arteriovenous fistula (AVF) in a patient with capillary malformation-arteriovenous malformation. Clinical neurology and neurosurgery 3 33799089
2021 Next-generation sequencing in a large pedigree segregating visceral artery aneurysms suggests potential role of COL4A1/COL4A2 in disease etiology. Vascular 3 34281442
2019 Association of COL4A2 Gene Polymorphisms with Lacunar Stroke in Xinjiang Han Populations. Journal of molecular neuroscience : MN 3 31214923
2026 COL4A1 and COL4A2 Gene Duplication or Triplication as a Genetic Cause of Cerebral Small Vessel Disease in Adults. Stroke 2 41480674
2025 Cerebral small vessel disease associated with COL4A1 and COL4A2 duplication: clinical and MRI features resembling CADASIL. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 2 40261521
2025 Integrated machine learning and single-cell RNA sequencing reveal COL4A2 and CXCL6 as oxidative stress-associated biomarkers in periodontitis. Frontiers in immunology 2 40539067
2021 Are COL4A1 and COL4A2 gene polymorphisms associated with cerebral palsy? Turkish journal of physical medicine and rehabilitation 2 34396076
2020 A Novel COL4A2 Mutation Associated with Recurrent Strokes. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 2 32912510
2025 Hypoxia-mediated HES4 promotes the proliferation and motility of hepatocellular carcinoma cell by enhancing COL4A2 transcription. Discover oncology 1 40715599
2025 Biallelic COL4A2 Variants Associated With Brain Small Vessel Disease and Brain Malformations. Clinical genetics 1 41499643
2024 Col4a2 Mutations Contribute to Infantile Epileptic Spasm Syndrome and Neuroinflammation. International journal of medical sciences 1 39006838
2024 COL4A2 -Related Disorder Presenting in Adulthood With Rhabdomyolysis. American journal of medical genetics. Part A 1 39679724
2026 COL4A1/COL4A2 gene duplication causing hereditary cerebral small vessel disease in a Chinese patient. Acta neurologica Belgica 0 41784710
2026 Identification of COL4A2 as a Biomarker of Extracellular Matrix Remodeling and Vascular Scaffold in Choroid for Myopia. Investigative ophthalmology & visual science 0 41823499
2025 ASSESSMENT OF RETINAL ARTERIOLAR TORTUOSITY IN PATIENTS WITH COL4A1 OR COL4A2 MUTATIONS. Retina (Philadelphia, Pa.) 0 39405554
2025 miR-29a-3p participates in the pathogenesis of spontaneous abortion by inhibiting trophoblast function targeting COL4A2/COL5A1. Biochemical pharmacology 0 40562119
2025 Contiguous Gene Deletion Involving <italic>COL4A1</italic> and <italic>COL4A2</italic> in a Patient with Thin Basement Membrane Nephropathy: A Case Report. Nephron 0 41269897
2025 COL4A2 activation of AKT signaling drives endothelial cell proliferation, migration, and angiogenesis in diabetic retinopathy. Experimental eye research 0 41308943
2025 Late-onset dementia with leukoencephalopathy and a COL4A2 gene variant, causal link or fortuitous association: a case report. Cerebral circulation - cognition and behavior 0 41312509
2024 Association of the COL4A2 Gene Polymorphisms with Primary Intracerebral Hemorrhage Risk and Outcome in Chinese Han Population. Molecular neurobiology 0 38565785
2024 Association of COL4A2 indel polymorphism with the development of stomach adenocarcinoma in Chinese populations. Nucleosides, nucleotides & nucleic acids 0 39340310
2024 Identification of a novel intronic variant in COL4A2 gene associated with fetal severe cerebral encephalomalacia and subdural hemorrhage. BMC medical genomics 0 39350129
2021 Erratum: Recessive COL4A2 Mutation Leads to Intellectual Disability, Epilepsy, and Spastic Cerebral Palsy. Neurology. Genetics 0 34250229
2021 Bilateral Non-Arteritic Anterior Ischaemic Optic Neuropathy in a Patient with a COL4A2 Mutation. Neuro-ophthalmology (Aeolus Press) 0 35574169

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