Affinage

COL3A1

Collagen alpha-1(III) chain · UniProt P02461

Length
1466 aa
Mass
138.6 kDa
Annotated
2026-04-28
100 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COL3A1 encodes the α1 chain of type III collagen, a major structural component of the extracellular matrix in skin, blood vessels, and hollow organs, where it regulates heterotypic collagen fibrillogenesis, ECM organization, and tissue mechanical integrity. Three α1(III) chains assemble into homotrimeric procollagen via C-terminal nucleation; glycine substitutions in the triple-helical domain reduce thermal stability, impair secretion with consequent ER retention and RER dilation, and produce small-diameter collagen fibrils, while haploinsufficiency through nonsense-mediated decay similarly reduces collagen output—both mechanisms cause vascular Ehlers–Danlos syndrome (vEDS) (PMID:2834369, PMID:2243125, PMID:11577371, PMID:9036918). Type III collagen organizes fibronectin and integrin receptors (α2β1, α5β1) in the ECM and serves as the extracellular ligand for GPR56 in the pial basement membrane, with Col3a1 loss in mice causing cobblestone-like cortical malformation due to pial BM breakdown, a phenotype recapitulated by biallelic COL3A1 mutations in humans (PMID:14970208, PMID:22235340, PMID:28258187). COL3A1 expression is regulated transcriptionally by YY1 and the NEDD9/NKX2-5 axis, and post-transcriptionally by METTL3-mediated m6A methylation and ELAVL1-dependent mRNA stabilization (PMID:29899023, PMID:32766145, PMID:38530094).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1988 High

    The first mechanistic insight into how COL3A1 mutations cause disease came from showing that internal deletions produce shortened pro-α1(III) chains that form thermally unstable, poorly secreted procollagen, establishing a dominant-negative paradigm.

    Evidence Biochemical analysis of cultured fibroblasts from an EDS IV patient with a multi-exon deletion

    PMID:2834369

    Open questions at the time
    • Only one mutation type examined
    • In vivo consequences of secretion impairment not tested
    • No quantification of ER retention
  2. 1990 High

    Systematic characterization of point mutations and splice-site mutations revealed that glycine substitutions directly destabilize the triple helix, while splice-site mutations produce context-dependent aberrant mRNAs—exon skipping, cryptic site use, or intron retention—depending on surrounding intron splicing kinetics.

    Evidence DNA sequencing, thermal unfolding assays, RNA splicing analysis across multiple COL3A1 mutations in patient fibroblasts

    PMID:2145268 PMID:2243125 PMID:2349939 PMID:2365710

    Open questions at the time
    • No crystal structure of mutant triple helix available
    • Quantitative relationship between thermal destabilization and clinical severity not established
  3. 1993 High

    Studies of C-terminal glycine substitutions (positions 1018–1021) showed that the C-terminal region of the triple helix is critical for secretion and protease resistance, with mutations there causing the most severe ultrastructural phenotype including extreme RER dilation and thin dermis with small collagen fibrils.

    Evidence Fibroblast secretion assays, trypsin digestion, TEM/SEM of skin biopsies from 22 genotyped EDS IV patients

    PMID:1496983 PMID:8098182 PMID:9036918

    Open questions at the time
    • Mechanism linking mutation position to severity of ER retention not defined at molecular level
    • No structural explanation for position-dependent effects
  4. 2001 High

    Demonstration that frameshift/nonsense COL3A1 mutations cause nonsense-mediated mRNA decay and haploinsufficiency—rather than a dominant-negative effect—established a second disease mechanism distinct from glycine substitutions, with truncated proteins from final-exon mutations failing to incorporate into trimers.

    Evidence RT-PCR, quantitative mRNA analysis, and protein incorporation assays in patient fibroblasts

    PMID:11577371

    Open questions at the time
    • Relative severity of haploinsufficiency versus dominant-negative mechanisms not quantitatively compared
    • Threshold of collagen reduction sufficient for disease not defined
  5. 2004 High

    Beyond structural scaffolding, type III collagen was shown to organize integrin receptors and fibronectin in the ECM: mutant fibroblasts lose α2β1 integrin and switch to αvβ3, while exogenous type III collagen rescues the phenotype, establishing collagen III as an instructive ECM signal.

    Evidence Antibody blocking and purified protein rescue experiments with immunofluorescence in cultured fibroblasts

    PMID:14970208

    Open questions at the time
    • Signaling pathways downstream of integrin switching not characterized
    • In vivo validation of integrin switch in vascular tissue not performed
  6. 2010 High

    In vivo haploinsufficiency models demonstrated that reduced type III collagen causes aortic dissection through aberrant collagen fibrillogenesis rather than aneurysm formation, and that this vulnerability is exacerbated by hemodynamic stress (angiotensin II).

    Evidence Col3a1 haploinsufficient mice, echocardiography, histology, and angiotensin II challenge

    PMID:21071432 PMID:23630948

    Open questions at the time
    • Molecular mechanism distinguishing dissection from aneurysm not identified
    • Whether collagen III quantity or quality is the proximate cause of aortic wall failure remains unresolved
  7. 2012 High

    Col3a1 knockout mice revealed a non-vascular role: type III collagen is a structural component of the pial basement membrane and the ligand for GPR56, required for cortical lamination, with loss causing cobblestone-like cortical malformation from E11.5.

    Evidence Histological and immunofluorescence analysis of Col3a1 knockout mouse brains with embryonic staging

    PMID:22235340

    Open questions at the time
    • Binding interface between collagen III and GPR56 not structurally defined
    • Cell-autonomous versus non-cell-autonomous effects on neuronal migration not resolved
  8. 2015 Medium

    X-ray crystallography of the COL3A1 C-propeptide provided the first structural framework for understanding how C-terminal variants disrupt chain recognition and trimerization initiation.

    Evidence X-ray crystallography and biochemical variant analysis

    PMID:25846194

    Open questions at the time
    • Full-length procollagen trimer structure not available
    • Functional mutagenesis of predicted critical residues not reported in detail
  9. 2017 High

    Biallelic COL3A1 mutations in humans were shown to cause brain malformations phenocopying GPR56 mutations, confirming the collagen III–GPR56 signaling axis as a requirement for human cortical development.

    Evidence Exome sequencing and brain MRI in affected families, fibroblast functional assays

    PMID:28258187

    Open questions at the time
    • Whether residual collagen III function modulates phenotypic severity not established
    • Downstream signaling from GPR56 activation by collagen III not fully elucidated
  10. 2018 High

    Transgenic mice expressing a glycine-substituted collagen III demonstrated that mutant chains disrupt heterotypic type III:I fibril formation, reducing total collagen content and altering the III:I ratio in vivo, while patient fibroblasts revealed broad ECM disassembly including loss of fibrillins, EMILINs, and the collagen chaperone FKBP22.

    Evidence Transgenic mouse model with EM and collagen analysis; transcriptome/proteome profiling of vEDS fibroblasts

    PMID:29346445 PMID:29551664

    Open questions at the time
    • Whether ECM disassembly is a direct consequence of mutant collagen secretion or an indirect ER stress response is unclear
    • Role of FKBP22 loss in disease pathology not tested
  11. 2018 High

    Transcriptional regulation of COL3A1 was linked to oxidant-stress signaling: NEDD9 Cys18 oxidation disrupts SMAD3 binding, stabilizes NEDD9, and enables NKX2-5-driven COL3A1 promoter activation in pulmonary artery endothelial cells.

    Evidence Microscale thermophoresis, ChIP-like assay, AFM, cell culture with aldosterone-induced oxidant stress

    PMID:29899023

    Open questions at the time
    • Whether this pathway operates in fibroblasts and vascular smooth muscle cells not tested
    • Contribution of this transcriptional axis to fibrotic disease not validated in vivo
  12. 2020 Medium

    Post-transcriptional regulation of COL3A1 was expanded to include METTL3-mediated m6A methylation that suppresses COL3A1 expression, and ELAVL1/YY1 that enhance mRNA stability and transcription respectively.

    Evidence m6A sequencing, luciferase reporters, siRNA knockdown, ChIP assays in cancer cell lines

    PMID:32766145 PMID:38530094

    Open questions at the time
    • Physiological relevance of m6A regulation of COL3A1 in non-cancer contexts unknown
    • Whether METTL3 and YY1 pathways intersect not examined
  13. 2023 High

    Patient-derived ECM from vEDS fibroblasts demonstrated that COL3A1 mutations directly alter ECM viscoelastic properties and impair endothelial cell migration, providing a biophysical mechanism linking COL3A1 to vascular dysfunction.

    Evidence Cell-derived ECM reconstitution, AFM viscoelastic testing, proteomics, endothelial migration assay

    PMID:37187299

    Open questions at the time
    • Whether altered viscoelasticity or specific ECM composition changes drive endothelial dysfunction is unresolved
    • In vivo relevance of viscoelastic changes to vascular rupture not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full-length procollagen trimer structure, the molecular basis of the collagen III–GPR56 binding interaction, the quantitative threshold of collagen III reduction sufficient for vascular rupture, and whether therapeutic supplementation with collagen III or chaperone-based approaches can rescue dominant-negative or haploinsufficient phenotypes.
  • No full-length type III procollagen trimer structure
  • Collagen III–GPR56 binding interface not structurally resolved
  • No established therapeutic rescue strategy for vEDS

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 5 GO:0048018 receptor ligand activity 2 GO:0098631 cell adhesion mediator activity 2
Localization
GO:0005576 extracellular region 4 GO:0031012 extracellular matrix 4 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-1643685 Disease 4 R-HSA-1474244 Extracellular matrix organization 3 R-HSA-1266738 Developmental Biology 2
Partners
ELAVL1FKBP22FN1GPR56ITGA2ITGB1NKX2-5
Complex memberships
heterotypic type I/III collagen fibriltype III procollagen homotrimer

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 A multi-exon deletion in one COL3A1 allele produces shortened pro-α1(III) chains that form triple helices of reduced length (~780 amino acids), with decreased thermal stability, impaired secretion, and defective processing of the mutant procollagen molecules. Biochemical analysis of cultured skin fibroblasts, protein gel analysis, thermal stability assays The Journal of biological chemistry High 2834369
1990 A glycine-to-arginine substitution at position 619 of the α1(III) chain (COL3A1 G619R) causes synthesis of type III procollagen with decreased thermal unfolding temperature, demonstrating that glycine substitutions in the triple-helical domain destabilize the collagen molecule. DNA sequencing of cultured skin fibroblast cDNA, thermal unfolding assay The Journal of clinical investigation High 2243125
1990 Identical G+1 splice-site mutations in three different introns of COL3A1 produce distinct aberrant splicing patterns (exon skipping, cryptic splice site use, intron retention), with the pattern determined by the relative rates of normal splicing of adjacent introns rather than the strength of cryptic splice sites. RNA sequencing, cDNA analysis, comparison of splicing outcomes across multiple mutation sites The Journal of biological chemistry High 2365710
1990 A G+1 to A mutation at intron 20 of COL3A1 causes aberrant RNA splicing (both cryptic splice site use and intron retention), producing abnormal type III procollagen and causing aortic aneurysms. DNA sequencing of PCR products from cultured skin fibroblasts, RNA splicing analysis American journal of human genetics High 2349939
1990 A single base mutation at the splice donor site of intron 41 of COL3A1 leads to exon 41 skipping, removing the mammalian collagenase cleavage site (Gly781-Ile782) and the cyanogen bromide cleavage site (Met797), rendering the mutant collagen resistant to both enzymes; fibroblasts produce normal homotrimers, mutant homotrimers, and mixed heterotrimers. cDNA sequencing, chemical cleavage of heteroduplexes, protein analysis, PCR of genomic DNA The Journal of biological chemistry High 2145268
1992 A glycine-1018-to-aspartate substitution in COL3A1 markedly decreases the amount of type III procollagen secreted into the medium by cultured skin fibroblasts, demonstrating that glycine substitutions near the C-terminus of the triple helix impair secretion. DNA sequencing of PCR products, fibroblast protein secretion assay American journal of human genetics High 1496983
1993 A glycine-1021-to-glutamic-acid substitution in COL3A1 produces type III procollagen that is poorly secreted, migrates more slowly on polyacrylamide gels, and is partially unstable at 25°C to trypsin digestion, placing the protein's C-terminal triple-helix region as critical for thermal stability and protease resistance. Fibroblast protein analysis, gel electrophoresis, trypsin digestion assay American journal of medical genetics High 8098182
1997 COL3A1 mutations causing glycine substitutions near the carboxyl-terminal end of the triple helix produce the most severe dermal phenotype: extreme dilation of rough endoplasmic reticulum (RER), thin dermis with reduced collagen, and small-diameter collagen fibrils (65–80 nm vs normal 95–110 nm), demonstrating a position-dependent effect of COL3A1 mutations on secretion, fibrillogenesis, and skin architecture. Transmission and scanning electron microscopy of skin biopsies from 22 genotyped EDS IV patients, light microscopy The Journal of investigative dermatology High 9036918
1997 Exon-skipping mutations in COL3A1 predominantly arise from mutations at the 5' (donor) splice site rather than the 3' (acceptor) splice site, because acceptor-site mutations preferentially lead to use of an alternative acceptor site creating a null allele with a premature termination codon rather than exon skipping. Mutation analysis of 33 unrelated EDS IV individuals, characterization of splicing outcomes American journal of human genetics High 9399899
2001 Frameshift mutations in COL3A1 that introduce premature termination codons lead to nonsense-mediated mRNA decay and functional haploinsufficiency; a mutation in the final exon produces a stable truncated protein not incorporated into mature type III procollagen trimers. Both mechanisms reduce overall type III collagen output and cause vascular EDS phenotype. RT-PCR, quantitative mRNA analysis, protein incorporation assay in cultured fibroblasts American journal of human genetics High 11577371
2004 COL3A1-mutant fibroblasts (EDS type IV) fail to organize type III collagen and fibronectin into the extracellular matrix, downregulate α2β1 integrin, and recruit αvβ3 integrin instead of α5β1 integrin. Treatment with purified type III collagen restores the normal phenotype; function-blocking antibodies to type III collagen or α2β1 integrin recapitulate the EDS phenotype in control fibroblasts, demonstrating that α2β1 integrin organization is controlled by its collagen ligand. Antibody blocking, purified protein rescue experiments, immunofluorescence, cell culture functional assays The Journal of biological chemistry High 14970208
2012 Loss of Col3a1 in mice causes cobblestone-like cortical malformation with breakdown of the pial basement membrane starting at E11.5 and neuronal overmigration, identifying type III collagen as a structural component of the pial BM required for cortical lamination and a ligand for GPR56. Histological analysis of Col3a1 knockout mice, immunofluorescence, embryonic staging PloS one High 22235340
2014 A gain-of-function missense point mutation in the PIIINP (N-terminal propeptide) segment of Col3a1 is the causal mutation in Tsk2/+ mice, producing a fibrotic phenotype with excessive ECM deposition—the first documented gain-of-function Col3a1 mutation—demonstrated by in vivo and in vitro genetic complementation tests. Linkage analysis, RNA sequencing, genome capture DNA sequencing, in vivo and in vitro genetic complementation The Journal of investigative dermatology High 25330296
2018 Dominant-negative COL3A1 mutations (glycine substitutions and in-frame splice mutations) in vEDS fibroblasts cause disassembly of ECM structural proteins (fibrillins, EMILINs, elastin), reduction of proteoglycans (perlecan, decorin, versican), disturbed ER homeostasis with altered PDI distribution, and strong reduction of the collagen-modifying enzyme FKBP22, revealing broad post-translational and ECM organizational consequences. Transcriptome profiling (microarray), protein analysis by Western blot and immunofluorescence, cultured skin fibroblasts from three vEDS patients PloS one Medium 29346445
2018 Expression of mutant type III collagen with a glycine substitution (p.Gly182Ser) in transgenic mice disturbs heterotypic type III:I collagen fibril formation in dermal and arterial extracellular matrix, reducing total collagen content and altering the collagen III:I ratio, establishing a key role for type III collagen in collagen fibrillogenesis. Transgenic mouse model, collagen content analysis, electron microscopy of collagen fibrils Matrix biology : journal of the International Society for Matrix Biology High 29551664
2018 ALDO-induced oxidant stress causes oxidation of Cys18 in the SMAD3 docking region of NEDD9, impairing SMAD3-NEDD9 interaction, leading to impaired NEDD9 degradation, increased NEDD9 complex formation with NKX2-5, and increased NKX2-5 binding to the COL3A1 promoter, upregulating collagen III expression in pulmonary artery endothelial cells. Microscale thermophoresis for protein-protein interaction, atomic force microscopy for cell stiffness, ChIP-like binding assay, cell culture with oxidant stress Science translational medicine High 29899023
2010 Haploinsufficiency of the murine Col3a1 locus (185 kb deletion including promoter and exons 1–39) causes autosomal-dominant aortic dissection with incomplete penetrance, associated with aberrant collagen fibrillogenesis within the aortic wall but not elevated blood pressure or aneurysm formation. Spontaneous mouse mutant characterization, molecular genetic analysis, echocardiography, histology Cardiovascular research High 21071432
2013 Col3a1 haploinsufficient mice are hypersensitive to angiotensin II-induced thoracic aortic dissection and rupture, with deaths associated with low aortic collagen fibril content, demonstrating that type III collagen is required for aortic wall integrity under hemodynamic stress. Angiotensin II infusion in Col3a1+/- mice, echocardiography, histological analysis of collagen fibrils Hypertension (Dallas, Tex. : 1979) High 23630948
2017 Biallelic COL3A1 mutations cause a brain malformation phenotype similar to that of GPR56 (ADGRG1) mutations (cobblestone-like cortical malformation, white matter changes, cerebellar cysts), confirming the type III collagen–GPR56 axis as a regulator of cortical development and cortical lamination. Exome sequencing, brain MRI review, functional assays on dermal fibroblasts from affected individuals Journal of medical genetics High 28258187
2015 X-ray crystallographic analysis of the COL3A1 C-propeptide region provided structural evidence that variants in this region affect C-terminal assembly initiation of procollagen monomers, with pathogenicity correlating with structural disruption of the propeptide fold. X-ray crystallography, biochemical variant analysis, clinical phenotyping American journal of medical genetics. Part A Medium 25846194
2023 Patient-derived ECM synthesized from vEDS donor fibroblasts harboring COL3A1 glycine substitution mutations shows increased glycosaminoglycan content, unique viscoelastic mechanical properties (increased stress relaxation time constant), and reduces human aortic endothelial cell migration speed, establishing a direct role for COL3A1 in ECM mechanics and endothelial cell behavior. Cell-derived ECM from primary donor fibroblasts, atomic force microscopy/viscoelastic mechanical testing, proteomics, cell migration assay Acta biomaterialia High 37187299
2024 RNF185, a RING finger ubiquitin E3 ligase, negatively regulates COL3A1 availability; RNF185 depletion increases COL3A1 expression and enhances prostate cancer cell migration and metastasis, effects attenuated by co-inhibition of COL3A1, identifying COL3A1 as the primary downstream mediator of RNF185-controlled migration. RNA-sequencing, shRNA knockdown, subcutaneous xenograft mouse model, co-inhibition rescue experiments Molecular cancer research : MCR Medium 37831068
2020 METTL3-mediated m6A methylation of COL3A1 mRNA downregulates its expression; knockdown of METTL3 decreases m6A levels on COL3A1 mRNA and increases COL3A1 protein, enhancing TNBC cell migration, invasion, and adhesion, establishing COL3A1 as a direct m6A-regulated target of METTL3. siRNA knockdown, m6A sequencing, luciferase reporter, Western blot, migration/invasion assays Frontiers in oncology Medium 32766145
2024 ELAVL1 (HuR) enhances COL3A1 mRNA stability and expression, while transcription factor YY1 promotes COL3A1 transcription; both mechanisms contribute to COL3A1 upregulation in cisplatin-resistant NSCLC, and COL3A1 knockdown restores DDP sensitivity in vitro and in vivo. ChIP assay, luciferase reporter assay, RNA-binding protein knockdown, xenograft experiments Cancer biology & therapy Medium 38530094
2021 lnc-GULP1-2:1 regulates COL3A1 expression and promotes COL3A1 protein translocation into the nucleus in granulosa cells; overexpression of lnc-GULP1-2:1 increases COL3A1 expression and inhibits cell proliferation through CCND2 and p16, while COL3A1 silencing alone inhibits proliferation. Overexpression and silencing in KGN cells, immunofluorescence for nuclear localization, cell proliferation assays, RT-PCR Journal of ovarian research Low 33472700

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 Type III collagen (COL3A1): Gene and protein structure, tissue distribution, and associated diseases. Gene 296 31075413
2015 The type of variants at the COL3A1 gene associates with the phenotype and severity of vascular Ehlers-Danlos syndrome. European journal of human genetics : EJHG 178 25758994
1990 A mutation in the gene for type III procollagen (COL3A1) in a family with aortic aneurysms. The Journal of clinical investigation 167 2243125
1988 Ehlers-Danlos syndrome type IV: a multi-exon deletion in one of the two COL3A1 alleles affecting structure, stability, and processing of type III procollagen. The Journal of biological chemistry 161 2834369
2001 Haploinsufficiency for one COL3A1 allele of type III procollagen results in a phenotype similar to the vascular form of Ehlers-Danlos syndrome, Ehlers-Danlos syndrome type IV. American journal of human genetics 144 11577371
1993 Exclusion of mutations in the gene for type III collagen (COL3A1) as a common cause of intracranial aneurysms or cervical artery dissections: results from sequence analysis of the coding sequences of type III collagen from 55 unrelated patients. Neurology 118 8255472
2020 Reduced Expression of METTL3 Promotes Metastasis of Triple-Negative Breast Cancer by m6A Methylation-Mediated COL3A1 Up-Regulation. Frontiers in oncology 116 32766145
2018 NEDD9 targets COL3A1 to promote endothelial fibrosis and pulmonary arterial hypertension. Science translational medicine 116 29899023
2011 COL3A1 haploinsufficiency results in a variety of Ehlers-Danlos syndrome type IV with delayed onset of complications and longer life expectancy. Genetics in medicine : official journal of the American College of Medical Genetics 103 21637106
2004 Human fibroblasts with mutations in COL5A1 and COL3A1 genes do not organize collagens and fibronectin in the extracellular matrix, down-regulate alpha2beta1 integrin, and recruit alphavbeta3 Instead of alpha5beta1 integrin. The Journal of biological chemistry 94 14970208
1990 Inheritance of an RNA splicing mutation (G+ 1 IVS20) in the type III procollagen gene (COL3A1) in a family having aortic aneurysms and easy bruisability: phenotypic overlap between familial arterial aneurysms and Ehlers-Danlos syndrome type IV. American journal of human genetics 92 2349939
2014 Let-7d suppresses growth, metastasis, and tumor macrophage infiltration in renal cell carcinoma by targeting COL3A1 and CCL7. Molecular cancer 90 25193015
1990 Identical G+1 to A mutations in three different introns of the type III procollagen gene (COL3A1) produce different patterns of RNA splicing in three variants of Ehlers-Danlos syndrome. IV. An explanation for exon skipping some mutations and not others. The Journal of biological chemistry 84 2365710
1997 Mutations in the COL3A1 gene result in the Ehlers-Danlos syndrome type IV and alterations in the size and distribution of the major collagen fibrils of the dermis. The Journal of investigative dermatology 81 9036918
1986 Ehlers-Danlos syndrome type IV: cosegregation of the phenotype to a COL3A1 allele of type III procollagen. Human genetics 79 2875936
1990 Mapping of Col3a1 and Col6a3 to proximal murine chromosome 1 identifies conserved linkage of structural protein genes between murine chromosome 1 and human chromosome 2q. Genomics 78 1981051
1996 COL3A1 mutations cause variable clinical phenotypes including acrogeria and vascular rupture. The British journal of dermatology 75 8881656
2018 miR-29 Family Inhibits Resistance to Methotrexate and Promotes Cell Apoptosis by Targeting COL3A1 and MCL1 in Osteosarcoma. Medical science monitor : international medical journal of experimental and clinical research 69 30518744
1990 A base substitution at a splice site in the COL3A1 gene causes exon skipping and generates abnormal type III procollagen in a patient with Ehlers-Danlos syndrome type IV. The Journal of biological chemistry 64 2145268
2018 MicroRNA-29b-3p prevents Schistosoma japonicum-induced liver fibrosis by targeting COL1A1 and COL3A1. Journal of cellular biochemistry 63 29091295
1997 Splicing defects in the COL3A1 gene: marked preference for 5' (donor) spice-site mutations in patients with exon-skipping mutations and Ehlers-Danlos syndrome type IV. American journal of human genetics 59 9399899
2018 Type III collagen affects dermal and vascular collagen fibrillogenesis and tissue integrity in a mutant Col3a1 transgenic mouse model. Matrix biology : journal of the International Society for Matrix Biology 57 29551664
2010 Haploinsufficiency of the murine Col3a1 locus causes aortic dissection: a novel model of the vascular type of Ehlers-Danlos syndrome. Cardiovascular research 57 21071432
1989 Cloning and analysis of the 5' portion of the human type-III procollagen gene (COL3A1). Gene 56 2777083
2014 Identification of COL3A1 and RAB2A as novel translocation partner genes of PLAG1 in lipoblastoma. Genes, chromosomes & cancer 53 24700772
1992 Substitution of aspartate for glycine 1018 in the type III procollagen (COL3A1) gene causes type IV Ehlers-Danlos syndrome: the mutated allele is present in most blood leukocytes of the asymptomatic and mosaic mother. American journal of human genetics 48 1496983
1991 Characterization of a large deletion associated with a polymorphic block of repeated dinucleotides in the type III procollagen gene (COL3A1) of a patient with Ehlers-Danlos syndrome type IV. American journal of human genetics 47 1998337
1989 Genetic evidence that mutations in the COL1A1, COL1A2, COL3A1, or COL5A2 collagen genes are not responsible for mitral valve prolapse. British heart journal 47 2930668
1988 Linkage of a polymorphic marker for the type III collagen gene (COL3A1) to atypical autosomal dominant Ehlers-Danlos syndrome type IV in a large Belgian pedigree. Human genetics 46 3162228
1993 Parental somatic and germ-line mosaicism for a multiexon deletion with unusual endpoints in a type III collagen (COL3A1) allele produces Ehlers-Danlos syndrome type IV in the heterozygous offspring. American journal of human genetics 43 8317500
2009 COL3A1 2209G>A is a predictor of pelvic organ prolapse. International urogynecology journal and pelvic floor dysfunction 42 19444361
2021 COL3A1 and MMP9 Serve as Potential Diagnostic Biomarkers of Osteoarthritis and Are Associated With Immune Cell Infiltration. Frontiers in genetics 40 34512730
2012 Loss of Col3a1, the gene for Ehlers-Danlos syndrome type IV, results in neocortical dyslamination. PloS one 38 22235340
2009 Homozygosity for a null allele of COL3A1 results in recessive Ehlers-Danlos syndrome. European journal of human genetics : EJHG 37 19455184
2018 Transcriptome analysis of skin fibroblasts with dominant negative COL3A1 mutations provides molecular insights into the etiopathology of vascular Ehlers-Danlos syndrome. PloS one 36 29346445
1992 A single base mutation in the gene for type III collagen (COL3A1) converts glycine 847 to glutamic acid in a family with Ehlers-Danlos syndrome type IV. An unaffected family member is mosaic for the mutation. Human genetics 35 1352273
2019 Long noncoding RNA DNM3OS promotes prostate stromal cells transformation via the miR-29a/29b/COL3A1 and miR-361/TGFβ1 axes. Aging 33 31694982
2021 miR-29a-3p-dependent COL3A1 and COL5A1 expression reduction assists sulforaphane to inhibit gastric cancer progression. Biochemical pharmacology 32 33819468
1991 Exclusion of COL1A1, COL1A2, and COL3A1 genes as candidate genes for Ehlers-Danlos syndrome type I in one large family. Human genetics 32 1684560
2017 Bi-allelic variants in COL3A1 encoding the ligand to GPR56 are associated with cobblestone-like cortical malformation, white matter changes and cerebellar cysts. Journal of medical genetics 31 28258187
2010 Hemizygous deletion of COL3A1, COL5A2, and MSTN causes a complex phenotype with aortic dissection: a lesson for and from true haploinsufficiency. European journal of human genetics : EJHG 31 20648054
2002 Analysis of the COL3A1 gene in patients with spontaneous cervical artery dissections. Journal of neurology 31 12140670
1995 Ehlers-Danlos syndrome type IV: a single base substitution of the last nucleotide of exon 34 in COL3A1 leads to exon skipping. The Journal of investigative dermatology 31 7665911
1992 A 27-bp deletion from one allele of the type III collagen gene (COL3A1) in a large family with Ehlers-Danlos syndrome type IV. Human genetics 30 1370809
2004 Association between COL3A1 collagen gene exon 31 polymorphism and risk of floppy mitral valve/mitral valve prolapse. International journal of cardiology 29 15193836
1993 Single base mutation that substitutes glutamic acid for glycine 1021 in the COL3A1 gene and causes Ehlers-Danlos syndrome type IV. American journal of medical genetics 29 8098182
2015 Overrepresentation of the COL3A1 AA genotype in Polish skiers with anterior cruciate ligament injury. Biology of sport 28 26060338
2013 Angiotensin II promotes thoracic aortic dissections and ruptures in Col3a1 haploinsufficient mice. Hypertension (Dallas, Tex. : 1979) 28 23630948
2010 Traumatic subarachnoid hemorrhage and the COL3A1 gene: emergence of a potential causal link. Forensic science, medicine, and pathology 28 21086191
1988 Genetic distance of two fibrillar collagen loci, COL3A1 and COL5A2, located on the long arm of human chromosome 2. Genomics 26 3224983
2014 The Tsk2/+ mouse fibrotic phenotype is due to a gain-of-function mutation in the PIIINP segment of the Col3a1 gene. The Journal of investigative dermatology 24 25330296
2002 Ehlers-Danlos syndrome type IV with few extrathoracic findings: a newly recognized point mutation in the COL3A1 gene. The European respiratory journal 24 11843319
2002 Genetic variability in the extracellular matrix as a determinant of cardiovascular risk: association of type III collagen COL3A1 polymorphisms with coronary artery disease. Blood 24 12149201
2022 Radiation increases COL1A1, COL3A1, and COL1A2 expression in breast cancer. Open medicine (Warsaw, Poland) 23 35274048
2021 COL3A1 rs1800255 polymorphism is associated with pelvic organ prolapse susceptibility in Caucasian individuals: Evidence from a meta-analysis. PloS one 23 33930075
2017 Biallelic COL3A1 mutations result in a clinical spectrum of specific structural brain anomalies and connective tissue abnormalities. American journal of medical genetics. Part A 22 28742248
2021 Lnc-GULP1-2:1 affects granulosa cell proliferation by regulating COL3A1 expression and localization. Journal of ovarian research 21 33472700
2009 The relationship between COL3A1 exon 31 polymorphism and pelvic organ prolapse. The Journal of urology 21 19152942
2006 Extracellular matrix containing mutated fibrillin-1 (Fbn1) down regulates Col1a1, Col1a2, Col3a1, Col5a1, and Col5a2 mRNA levels in Tsk/+ and Tsk/Tsk embryonic fibroblasts. Amino acids 21 16583319
2001 Genomic organization of the human COL3A1 and COL5A2 genes: COL5A2 has evolved differently than the other minor fibrillar collagen genes. Matrix biology : journal of the International Society for Matrix Biology 21 11566270
2022 Silencing of COL3A1 represses proliferation, migration, invasion, and immune escape of triple negative breast cancer cells via down-regulating PD-L1 expression. Cell biology international 20 35930601
2017 Dexmedetomidine Protects PC12 Cells from Lidocaine-Induced Cytotoxicity Through Downregulation of COL3A1 Mediated by miR-let-7b. DNA and cell biology 20 28436683
2000 Characterization of 11 new mutations in COL3A1 of individuals with Ehlers-Danlos syndrome type IV: preliminary comparison of RNase cleavage, EMC and DHPLC assays. Human mutation 20 10923041
1990 Physical mapping by PFGE localizes the COL3A1 and COL5A2 genes to a 35-kb region on human chromosome 2. Genomics 20 1979060
1986 The pro alpha 2(V) collagen gene (COL5A2) maps to 2q14----2q32, syntenic to the pro alpha 1 (III) collagen locus (COL3A1). Human genetics 20 3011647
2007 RNAi-mediated inhibition of COL1A1 and COL3A1 in human skin fibroblasts. Experimental dermatology 19 17576241
2003 Ehlers-Danlos syndrome type IV: unusual congenital anomalies in a mother and son with a COL3A1 mutation and a normal collagen III protein profile. Clinical genetics 19 12694234
2020 Role of COL3A1 and POSTN on Pathologic Stages of Esophageal Cancer. Technology in cancer research & treatment 18 33280513
2019 Atypical COL3A1 variants (glutamic acid to lysine) cause vascular Ehlers-Danlos syndrome with a consistent phenotype of tissue fragility and skin hyperextensibility. Genetics in medicine : official journal of the American College of Medical Genetics 18 30837697
1993 A T+6 to C+6 mutation in the donor splice site of COL3A1 IVS7 causes exon skipping and results in Ehlers-Danlos syndrome type IV. Journal of medical genetics 17 8320698
2022 Atypical variants in COL1A1 and COL3A1 associated with classical and vascular Ehlers-Danlos syndrome overlap phenotypes: expanding the clinical phenotype based on additional case reports. Clinical and experimental rheumatology 16 35587586
2001 Ehlers-Danlos syndrome type IV with a unique point mutation in COL3A1 and familial phenotype of myocardial infarction without organic coronary stenosis. Journal of internal medicine 16 11168790
1999 Large kindred with Ehlers-Danlos syndrome type IV due to a point mutation (G571S) in the COL3A1 gene of type III procollagen: low risk of pregnancy complications and unexpected longevity in some affected relatives. American journal of medical genetics 16 10051163
2014 Collagen type III alpha 1 polymorphism (rs1800255, COL3A1 2209 G>A) assessed with high-resolution melting analysis is not associated with pelvic organ prolapse in the Dutch population. International urogynecology journal 15 24760181
2019 Polymorphism rs1800255 from COL3A1 gene and the risk for pelvic organ prolapse. International urogynecology journal 14 31041498
2007 Developmental changes of Col3a1 mRNA expression in muscle and their association with intramuscular collagen in pigs. Journal of genetics and genomics = Yi chuan xue bao 14 17498619
2021 A novel mutation in COL3A1 associates to vascular Ehlers-Danlos syndrome with predominant musculoskeletal involvement. Molecular genetics & genomic medicine 13 34318601
2015 Dysregulated COL3A1 and RPL8, RPS16, and RPS23 in Disc Degeneration Revealed by Bioinformatics Methods. Spine 13 25893343
2015 A 19-year-old man with relapsing bilateral pneumothorax, hemoptysis, and intrapulmonary cavitary lesions diagnosed with vascular Ehlers-Danlos syndrome and a novel missense mutation in COL3A1. Chest 12 25940258
1996 A dimorphic Alu Sb-like insertion in COL3A1 is ethnic-specific. Journal of molecular evolution 12 8919863
1992 A 15 base-pair AT-rich variable number tandem repeat in the type III procollagen gene (COL3A1) as an informative marker for 2q31-2q32.3. Matrix (Stuttgart, Germany) 12 1560789
2022 Knockdown of lncRNA-NEAT1 expression inhibits hypoxia-induced scar fibroblast proliferation through regulation of the miR-488-3p/COL3A1 axis. Experimental and therapeutic medicine 11 35720634
2019 Vascular Ehlers-Danlos Syndrome with a Novel Missense Mutation in COL3A1: A Man in His 50s with Aortic Dissection after Interventional Treatment for Hemothorax as the First Manifestation. Internal medicine (Tokyo, Japan) 11 31391389
1994 Linkage mapping of the gene for type III collagen (COL3A1) to human chromosome 2q using a VNTR polymorphism. Genomics 11 8020975
2021 COL3A1 and Its Related Molecules as Potential Biomarkers in the Development of Human Ewing's Sarcoma. BioMed research international 10 35047627
2017 A New COL3A1 Mutation in Ehlers-Danlos Syndrome Vascular Type With Different Phenotypes in the Same Family. Vascular and endovascular surgery 10 28183226
2010 Ehlers-Danlos syndrome type IV, vascular type, which demonstrated a novel point mutation in the COL3A1 gene. Internal medicine (Tokyo, Japan) 10 20720362
2008 A novel COL3A1 gene mutation in patient with aortic dissected aneurysm and cervical artery dissections. Heart and vessels 10 18389341
1994 Single-strand conformation polymorphism (SSCP) analysis of the COL3A1 gene detects a mutation that results in the substitution of glycine 1009 to valine and causes severe Ehlers-Danlos syndrome type IV. Human mutation 10 8019562
2024 Role and mechanism of COL3A1 in regulating the growth, metastasis, and drug sensitivity in cisplatin-resistant non-small cell lung cancer cells. Cancer biology & therapy 9 38530094
2016 Next-generation sequencing and a novel COL3A1 mutation associated with vascular Ehlers-Danlos syndrome with severe intestinal involvement: a case report. Journal of medical case reports 9 27799058
2013 A new COL3A1 mutation in Ehlers-Danlos syndrome type IV. Experimental dermatology 9 23489429
1991 Ehlers-Danlos syndrome type IV: phenotypic consequences of a splicing mutation in one COL3A1 allele. Journal of medical genetics 9 1757960
2023 Patient-derived extracellular matrix demonstrates role of COL3A1 in blood vessel mechanics. Acta biomaterialia 8 37187299
2022 Nonsyndromic arteriopathy and aortopathy and vascular Ehlers-Danlos syndrome causing COL3A1 variants. American journal of medical genetics. Part A 8 35543214
2018 Retracted: microRNA-129-5p involved in the neuroprotective effect of dexmedetomidine on hypoxic-ischemic brain injury by targeting COL3A1 through the Wnt/β-catenin signaling pathway in neonatal rats. Journal of cellular biochemistry 8 29377229
2016 miRNA-29a targets COL3A1 to regulate the level of type III collagen in pig. Gene 8 27476968
2015 Clinical, structural, biochemical and X-ray crystallographic correlates of pathogenicity for variants in the C-propeptide region of the COL3A1 gene. American journal of medical genetics. Part A 8 25846194
2024 RNF185 Control of COL3A1 Expression Limits Prostate Cancer Migration and Metastatic Potential. Molecular cancer research : MCR 7 37831068
2022 Phenotype of COL3A1/COL5A2 deletion patients. European journal of medical genetics 7 35964930