Affinage

COL6A3

Collagen alpha-3(VI) chain · UniProt P12111

Length
3177 aa
Mass
343.7 kDa
Annotated
2026-04-28
63 papers in source corpus 21 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COL6A3 encodes the α3(VI) chain of type VI collagen, a major structural component of pericellular and extracellular matrices whose assembly, secretion, and post-secretion proteolytic processing are essential for tissue integrity across muscle, tendon, cartilage, adipose, and vascular compartments. The α3(VI) chain is required for collagen VI microfibril formation; loss-of-function mutations cause Ullrich congenital muscular dystrophy and Bethlem myopathy through deficient or dominant-negatively disrupted collagen VI deposition (PMID:11992252, PMID:24563484), while exon 41-specific mutations cause recessive isolated dystonia (DYT27) via a distinct neuronal mechanism involving axonal outgrowth deficits (PMID:26004199). The C-terminal C5 domain is proteolytically cleaved after secretion to release endotrophin, a bioactive fragment that drives organ fibrosis through JNK-dependent apoptosis and inflammatory cell activation and contributes causally to cardiovascular disease risk (PMID:11785962, PMID:30246318, PMID:39856218). In chondrocytes, COL6A3 maintains pericellular matrix mechanical properties and is required for normal mechanotransduction, TRPV4-mediated anabolic signaling, and circadian rhythm regulation; its loss provokes an osteoarthritic cellular state with exaggerated catabolic and inflammatory responses to mechanical and cytokine stimuli (PMID:39021299, PMID:41692747).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1998 Medium

    Establishing that mutations in the α3(VI) globular domains cause Bethlem myopathy answered whether COL6A3 itself could be a disease gene for heritable myopathies and implicated the N-terminal vWFA domain as functionally critical.

    Evidence Missense mutation segregation in a large Bethlem myopathy pedigree

    PMID:9536084

    Open questions at the time
    • No biochemical demonstration of how the N2 domain mutation disrupts assembly
    • Single pedigree
  2. 2002 High

    Demonstrating that the C5 domain is proteolytically cleaved immediately after collagen VI secretion revealed a previously unknown post-secretion processing step and identified a bioactive fragment later termed endotrophin.

    Evidence Immunoelectron microscopy and double-label immunostaining in human articular cartilage

    PMID:11785962

    Open questions at the time
    • Protease responsible for C5 cleavage not identified
    • Biological function of the released C5 fragment not yet tested
  3. 2002 High

    Identifying homozygous loss-of-function COL6A3 mutations in Ullrich congenital muscular dystrophy families established the causal link between α3(VI) chain deficiency and severe congenital myopathy.

    Evidence Genome-wide linkage, mutation analysis, and collagen VI immunostaining in muscle biopsies from three UCMD families

    PMID:11992252

    Open questions at the time
    • Molecular mechanism by which collagen VI absence damages muscle fibers not defined
    • Genotype-phenotype correlation across mutation types incomplete
  4. 2013 High

    Characterization of a Col6a3-deficient mouse model demonstrated that α3(VI) is required for collagen VI microfibril deposition in vivo and revealed tissue-specific roles in muscle contractile function and tendon collagen I fibrillogenesis.

    Evidence Mouse knockout with ultrastructural analysis, immunofluorescence, and muscle contractile force measurement

    PMID:23564457

    Open questions at the time
    • Why corneal collagen fibrils are unaffected despite collagen VI expression not explained
    • Downstream signaling consequences of microfibril loss not characterized
  5. 2014 High

    A knock-in mouse carrying an in-frame triple-helical deletion in Col6a3 proved the dominant-negative mechanism of Bethlem myopathy mutations and showed that mutant α3(VI) chains are incorporated into defective trimers that poison microfibril assembly.

    Evidence Mouse knock-in model with fibroblast biosynthetic studies, histopathology, and electron microscopy

    PMID:24563484

    Open questions at the time
    • Stoichiometric threshold for dominant-negative poisoning not quantified
    • Whether all triple-helical glycine mutations act identically is unknown
  6. 2014 High

    Allele-specific siRNA silencing of a dominant COL6A3 mutation restored collagen VI matrix deposition in UCMD patient fibroblasts, providing proof-of-concept that selective knockdown of the mutant allele is a viable therapeutic strategy.

    Evidence siRNA targeting mutation-specific sequence in patient fibroblasts and HEK293T reporter assay

    PMID:24518369

    Open questions at the time
    • In vivo delivery and efficacy not tested
    • Long-term matrix quality restoration not assessed
  7. 2015 High

    Discovery that exon 41-specific COL6A3 mutations cause recessive isolated dystonia (DYT27) with axonal outgrowth deficits in zebrafish revealed a neuronal function of α3(VI) distinct from its structural role in the extracellular matrix.

    Evidence Whole-exome sequencing in dystonia pedigrees plus zebrafish morpholino knockdown of exon 41 versus other exons

    PMID:26004199

    Open questions at the time
    • Molecular mechanism linking exon 41 to axonal outgrowth unknown
    • Whether collagen VI is assembled in neurons or acts cell-non-autonomously not resolved
  8. 2018 Medium

    Showing that endotrophin (the C5 cleavage product) induces JNK-dependent hepatocyte apoptosis and drives hepatic fibrosis, suppressible by neutralizing antibodies, established endotrophin as an independent signaling molecule with pro-fibrotic and pro-inflammatory activity.

    Evidence In vitro endotrophin treatment of hepatocytes and neutralizing antibody intervention in chronic liver disease models

    PMID:30246318

    Open questions at the time
    • Receptor for endotrophin not identified
    • Whether endotrophin signals through TGF-β pathway components or an independent pathway not fully resolved
  9. 2020 High

    Identification of PRRX1 as a direct transcriptional activator of COL6A3 established a transcription factor–extracellular matrix axis controlling collagen VI levels in adipose tissue, modulated by inflammatory signals such as TNF-α.

    Evidence PRRX1 knockdown and overexpression with endogenous COL6A3 promoter reporter assay in human and mouse adipose cells

    PMID:33214660

    Open questions at the time
    • PRRX1 binding site on COL6A3 promoter not mapped at base-pair resolution
    • Whether PRRX1 regulation extends beyond adipose tissue not tested
  10. 2024 High

    CRISPR-engineered COL6A3 loss in iPSC-derived neocartilage organoids showed that collagen VI is required for fibronectin binding, mechanical load sensing, and suppression of an osteoarthritic chondrocyte state, placing COL6A3 as a central node in cartilage mechanotransduction.

    Evidence CRISPR-Cas9 in iPSC-derived organoids with multi-omics, protein binding assay, and mechanical loading

    PMID:39021299

    Open questions at the time
    • Whether COL6A3 loss-of-function is sufficient to initiate osteoarthritis in vivo not shown
    • Signaling intermediates between pericellular matrix disruption and inflammatory gene induction not fully mapped
  11. 2025 Medium

    Mendelian randomization provided causal genetic evidence that elevated COL6A3/endotrophin increases coronary artery disease risk through aortic wall expression, linking the pro-fibrotic endotrophin pathway to cardiovascular disease at the population level.

    Evidence Proteome-wide Mendelian randomization, Bayesian colocalization, plasma pQTL, and aortic eQTL analyses

    PMID:39856218

    Open questions at the time
    • No direct experimental intervention confirming the causal chain in vascular tissue
    • Endotrophin receptor and downstream vascular signaling cascade remain unidentified
  12. 2026 High

    Isogenic COL6A3-mutant iPSC-derived chondrocytes showed that α3(VI) is required for pericellular matrix stiffness, TRPV4-mediated anabolic responses, and circadian clock regulation, deepening the mechanotransduction model to include ion channel function and temporal gene regulation.

    Evidence CRISPR-edited hiPSC chondrocytes with AFM, calcium imaging, RNA-seq, and circadian rhythm analysis

    PMID:41692747

    Open questions at the time
    • Whether circadian disruption is primary or secondary to matrix softening not resolved
    • TRPV4 interaction with collagen VI pericellular matrix not structurally characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • The receptor and direct signaling pathway by which endotrophin exerts its pro-fibrotic and pro-apoptotic effects remain unidentified, and the molecular basis of the exon 41-specific neuronal function of α3(VI) is unexplained.
  • Endotrophin receptor unknown
  • Exon 41-encoded domain's neuronal interactors not identified
  • Protease responsible for C5 domain cleavage not identified

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:0031012 extracellular matrix 7 GO:0005576 extracellular region 3 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-1474244 Extracellular matrix organization 7 R-HSA-1643685 Disease 4 R-HSA-162582 Signal Transduction 3
Partners
COL6A1COL6A2FN1MIR31HGPRRX1
Complex memberships
type VI collagen heterotrimer (α1/α2/α3)

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 The C5 domain of the COL6A3-encoded α3(VI) collagen chain is cleaved off from type VI collagen fibrils immediately after secretion; immunostaining and immunoelectron microscopy in human articular cartilage showed C5 domain localization in the cytoplasm and immediate pericellular matrix but not in the mature pericellular type VI collagen matrix, demonstrating post-secretion proteolytic processing. Immunostaining, confocal laser-scanning microscopy, immunoelectron microscopy, double-labeling experiments in human articular cartilage Biochemical and biophysical research communications High 11785962
2002 Homozygous loss-of-function and splice-site mutations in COL6A3 cause Ullrich congenital muscular dystrophy (UCMD) with absence or partial reduction of collagen VI in muscle and fibroblasts, establishing COL6A3 as a disease-causing gene for UCMD via collagen VI deficiency. Genome-wide linkage mapping, mutation analysis, muscle biopsy immunostaining, mRNA transcript analysis American journal of human genetics High 11992252
1998 A missense mutation (Gly→Glu) in the N2 von Willebrand factor type A domain of the COL6A3-encoded α3(VI) collagen chain causes autosomal dominant Bethlem myopathy, demonstrating that the N-terminal globular domain of α3(VI) is functionally critical for collagen VI integrity in muscle. Genetic linkage, Sanger sequencing, segregation analysis in a large pedigree (19 affected members) Human molecular genetics Medium 9536084
1999 A de novo Gly→Arg substitution in the triple-helical domain of the COL6A3-encoded α3(VI) chain disrupts the collagen VI triple helix structure and causes Bethlem myopathy, establishing that glycine substitutions in the triple helix are pathogenic dominant-negative mutations. Clinical characterization, molecular mutation identification, Sanger sequencing in a two-generation family Neuromuscular disorders Medium 10399756
2008 The chromosomal translocation t(1;2)(p13;q37) generates COL6A3-CSF1 fusion transcripts in tenosynovial giant cell tumors, where the strong COL6A3 promoter drives overexpression of CSF1; RT-PCR identified in-frame and out-of-frame fusion transcripts, though the pathogenetic mechanism remains incompletely defined. RT-PCR on six TGCT cases with t(1;2) translocation Genes, chromosomes & cancer Medium 17918257
2013 Mice expressing a very low level of non-functional α3(VI) collagen chain (Col6a3 mutant) are deficient in extracellular collagen VI microfibrils, exhibit decreased muscle mass and contractile force, and display ultrastructurally abnormal collagen fibrils in tendon but not cornea, demonstrating a tissue-specific role of α3(VI) in collagen I fibrillogenesis and muscle function. Mouse knockout model characterization: ultrastructural analysis, muscle contractile force measurement, immunofluorescence, electron microscopy The Journal of biological chemistry High 23564457
2014 Heterozygous deletion of exon 16 in Col6a3 produces a mutant α3(VI) chain with an in-frame 54 bp triple-helical deletion that exerts a dominant-negative effect on collagen VI microfibrillar assembly in fibroblast biosynthetic studies, causing histopathologic myopathy, mitochondrial and sarcoplasmic reticulum ultrastructural alterations in muscle, and abnormal collagen fibrils in tendons. Mouse knock-in model, biosynthetic studies in mutant fibroblasts, histopathology, electron microscopy, muscle contractile function assays The Journal of biological chemistry High 24563484
2015 Recessive loss-of-function mutations in COL6A3, particularly affecting exon 41, cause early-onset isolated dystonia (DYT27) with neurodevelopmental deficits; suppression of the exon 41 ortholog in zebrafish caused deficits in axonal outgrowth, whereas suppression of other exons phenocopied collagen deposition mutants, indicating an exon 41-specific neuronal function of α3(VI) collagen. Whole-exome sequencing, genetic screening of dystonia cohort, zebrafish morpholino-based in-frame deletion experiments, mRNA expression analysis in mouse brain American journal of human genetics High 26004199
2011 COL6A3 undergoes tumor-specific alternative splicing in pancreatic ductal adenocarcinoma, with consistent inclusion of exons 3 and 6 in tumor versus adjacent tissue, and exclusive tumor-specific inclusion of exon 4; COL6A3 protein is upregulated in the desmoplastic stroma surrounding malignant ducts. RT-PCR with exon-specific primers on paired PDA-normal tissue (n=18), Western blot, immunohistochemistry, xenograft and transgenic PDA animal models Surgery Medium 21719059
2017 Gapmer antisense oligonucleotides selectively suppress the mutant COL6A3 allele (heterozygous 18-nt deletion in exon 15) at both pre-mRNA and mRNA levels via RNase H-mediated cleavage, and silencing the mutant allele increases deposition of collagen VI protein into the extracellular matrix in UCMD patient-derived fibroblasts, restoring functional protein production. Gapmer AON allele-specific silencing, RT-PCR transcript analysis, immunofluorescence of collagen VI matrix in patient fibroblasts Molecular therapy. Nucleic acids High 28918041
2014 siRNA targeting a dominant COL6A3 exon 16-skipping mutation selectively suppresses mutant allele expression and protein from a reporter construct without affecting the wild-type allele, and treatment of UCMD fibroblasts with these siRNAs considerably improved the quantity and quality of the collagen VI matrix. siRNA allele-specific silencing, semi-quantitative and quantitative RT-PCR, reporter assay in HEK293T cells, confocal microscopy of collagen VI matrix in patient fibroblasts Molecular therapy. Nucleic acids High 24518369
2018 COL6A3-derived endotrophin (ETP, cleavage product of the C5 domain) induces JNK-dependent hepatocyte apoptosis and activates nonparenchymal cells to drive hepatic inflammation and fibrosis in chronic liver disease; neutralizing antibodies against ETP suppressed these pathological consequences. In vitro ETP treatment of hepatocytes, JNK pathway analysis, neutralizing antibody treatment in chronic liver disease models The Journal of pathology Medium 30246318
2014 COL6A3 expression in adipocytes is regulated by PPARγ: PPARG knockdown in developing adipocytes increased COL6A3 mRNA 1.5-fold, and COL6A3 mRNA was 2.8-fold higher in small compared to large adipocytes, linking PPARγ-mediated adipocyte development to COL6A3 transcriptional control. PPARG knockdown in primary human adipocytes, qPCR, euglycemic-hyperinsulinemic clamp for insulin resistance phenotyping Obesity (Silver Spring, Md.) Medium 24719315
2015 Leptin treatment causes a dose-dependent decrease in COL6A3 expression in human adipose tissue, identifying a direct paracrine leptin signaling pathway that regulates extracellular matrix composition; insulin and glucose had no effect on COL6A3 expression. Leptin/insulin/glucose treatment of human adipose tissue explants, qPCR, comparison across depots and weight-loss conditions Endocrinology Medium 25337653
2016 COL6A3 knockdown in immortalized human preadipocytes increased triglyceride content, lipolysis, insulin-induced Akt phosphorylation, and adipogenic gene expression, while also decreasing basal MCP1 (CCL2) expression and abrogating TNF-α- and LPS-induced MCP1 induction; matrix metalloproteinase-11 treatment reduced COL6A3 protein and phenocopied MCP1 suppression, placing COL6A3 upstream of MCP1 inflammatory signaling in adipocytes. Stable shRNA knockdown in human adipocyte cell lines, MMP-11 treatment, flow cytometry, ELISA, THP1 macrophage co-culture assay Obesity (Silver Spring, Md.) Medium 27312141
2020 The homeobox transcription factor PRRX1 directly transactivates the endogenous human COL6A3 promoter; PRRX1 knockdown reduced COL6A3 mRNA in human and mouse adipose cells, and stable PRRX1 overexpression in 3T3-L1 cells induced Col6a3 mRNA threefold after adipogenic induction, while TNF-α decreased PRRX1-mediated Col6a3 transactivation. PRRX1 knockdown and overexpression in adipose cells, reporter construct with endogenous COL6A3 promoter, qPCR, transcriptome correlation across multiple clinical cohorts Scientific reports High 33214660
2023 COL6A3 knockdown induces transcriptional changes overlapping the majority of experimental senescence models, with cell-cycle arrest linked to modulation of DREAM complex-targeted genes, identifying COL6A3 as a candidate SASP factor and potential driver of senescence in human tissues. COL6A3 knockdown followed by transcriptomic analysis, integration with 10 senescence cell models and 224 multi-tissue gene co-expression network from ~600 CAD patients Cell reports Medium 37938972
2024 A damaging COL6A3 variant introduced by CRISPR-Cas9 into human iPSC-derived neocartilage organoids results in significantly lower binding between the pericellular matrix proteins collagen VI and fibronectin, provokes an osteoarthritic chondrocyte state, and abolishes the characteristic inflammatory signaling response (PTGS2, PECAM1, ADAMTS5) to hyperphysiological mechanical loading; the lncRNA MIR31HG was identified as a key regulator of this response. CRISPR-Cas9 genome engineering in iPSC-derived neocartilage organoids, multi-omics (mRNA and lncRNA), mechanical loading assay, protein binding assay (COLVI–FN interaction) Advanced science High 39021299
2020 Mutations in COL6A3 p.Val86Ala and p.Arg689Cys cause abnormal intracellular retention of the mutant COL6A3 protein and decrease cellular resistance to oxidative stress through an enhanced endoplasmic reticulum stress response, establishing a disease mechanism for COL6A3 mutation-associated Peters' anomaly. Panel and whole-exome sequencing, immunofluorescence of mutant protein localization, ER stress assay, oxidative stress resistance assay in patient-derived and transfected cells Frontiers in cell and developmental biology Medium 33304895
2025 ETP-specific knockout (ETPKO) mice, which selectively ablate the endotrophin cleavage product of COL6A3 while preserving Col6a3 expression, show significantly attenuated kidney fibrosis following ischemia-reperfusion injury, establishing endotrophin as a key driver of fibrosis independent of full-length COL6A3. CRISPR-based conditional ETP knockout mouse model with Cre-mediated recombination, unilateral/bilateral renal ischemia-reperfusion injury, mRNA quantification, fibrosis histopathology bioRxivpreprint High
2025 COL6A3 exon 4 alternative splicing is specifically induced by TGF-β in skin fibroblasts undergoing myofibroblast differentiation, constituting part of a 5-ASE signature validated by ddPCR/AS-PCR and retrieved in multiple independent TGF-β-stimulated lung and skin fibroblast RNA-seq datasets. RNA-seq, ddPCR, AS-PCR validation in primary skin fibroblasts with TGF-β treatment, replicated in publicly available datasets bioRxivpreprint Medium
2025 Mendelian randomization and colocalization analyses show that genetically elevated COL6A3 (particularly its endotrophin product) causally increases coronary artery disease risk, and that an aortic eQTL for COL6A3 colocalizes with plasma pQTL and AAA risk signals, suggesting a causal pathway from genetic variation in aortic wall COL6A3 expression to extracellular matrix remodeling and vascular disease. Two-step proteome-wide Mendelian randomization, Bayesian colocalization, epigenomics, single-cell RNA sequencing, plasma endotrophin measurement after fat reduction Nature genetics Medium 39856218
2026 A damaging COL6A3 variant in human iPSC-derived chondrocytes results in lower pericellular matrix elastic modulus, reduced key matrix protein expression, heightened osmotically-induced calcium signaling (consistent with reduced PCM modulus), reduced anabolic response to TRPV4 activation, disrupted circadian rhythms with increased BMAL1 expression, and exacerbated catabolic response to IL-1, demonstrating that COL6A3 is required for normal chondrocyte mechanotransduction via the pericellular matrix. CRISPR-Cas9 genome editing in hiPSC-derived chondrocytes, AFM for PCM elastic modulus, calcium imaging, RNA-sequencing, matrix biosynthesis assay, circadian rhythm analysis Stem cell research & therapy High 41692747

Source papers

Stage 0 corpus · 63 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Mutations in COL6A3 cause severe and mild phenotypes of Ullrich congenital muscular dystrophy. American journal of human genetics 125 11992252
2018 Silencing of COL1A2, COL6A3, and THBS2 inhibits gastric cancer cell proliferation, migration, and invasion while promoting apoptosis through the PI3k-Akt signaling pathway. Journal of cellular biochemistry 103 29143985
2008 Molecular identification of COL6A3-CSF1 fusion transcripts in tenosynovial giant cell tumors. Genes, chromosomes & cancer 82 17918257
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
2002 The C5 domain of Col6A3 is cleaved off from the Col6 fibrils immediately after secretion. Biochemical and biophysical research communications 75 11785962
2018 Dermatofibrosarcoma protuberans with a novel COL6A3-PDGFD fusion gene and apparent predilection for breast. Genes, chromosomes & cancer 73 30014607
1998 Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy. Human molecular genetics 73 9536084
2015 Recessive mutations in the α3 (VI) collagen gene COL6A3 cause early-onset isolated dystonia. American journal of human genetics 71 26004199
2014 COL6A3 expression in adipocytes associates with insulin resistance and depends on PPARγ and adipocyte size. Obesity (Silver Spring, Md.) 70 24719315
2015 COL6A3 is regulated by leptin in human adipose tissue and reduced in obesity. Endocrinology 64 25337653
2011 Tumor-specific expression and alternative splicing of the COL6A3 gene in pancreatic cancer. Surgery 62 21719059
2013 COL6A3 protein deficiency in mice leads to muscle and tendon defects similar to human collagen VI congenital muscular dystrophy. The Journal of biological chemistry 58 23564457
2018 Role of COL6A3 in colorectal cancer. Oncology reports 47 29620224
2013 Clinical significance of serum COL6A3 in pancreatic ductal adenocarcinoma. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 45 24002763
1999 A novel de novo mutation in the triple helix of the COL6A3 gene in a two-generation Italian family affected by Bethlem myopathy. A diagnostic approach in the mutations' screening of type VI collagen. Neuromuscular disorders : NMD 44 10399756
2017 Gapmer Antisense Oligonucleotides Suppress the Mutant Allele of COL6A3 and Restore Functional Protein in Ullrich Muscular Dystrophy. Molecular therapy. Nucleic acids 43 28918041
2014 A mouse model for dominant collagen VI disorders: heterozygous deletion of Col6a3 Exon 16. The Journal of biological chemistry 38 24563484
2018 COL6A3-derived endotrophin links reciprocal interactions among hepatic cells in the pathology of chronic liver disease. The Journal of pathology 33 30246318
2019 E2F1-induced upregulation of long non-coding RNA LMCD1-AS1 facilitates cholangiocarcinoma cell progression by regulating miR-345-5p/COL6A3 pathway. Biochemical and biophysical research communications 32 30876691
2013 Down Syndrome Related Muscle Hypotonia: Association with COL6A3 Functional SNP rs2270669. Frontiers in genetics 32 23626599
2016 Reduced expression of collagen VI alpha 3 (COL6A3) confers resistance to inflammation-induced MCP1 expression in adipocytes. Obesity (Silver Spring, Md.) 31 27312141
2014 siRNA-mediated Allele-specific Silencing of a COL6A3 Mutation in a Cellular Model of Dominant Ullrich Muscular Dystrophy. Molecular therapy. Nucleic acids 31 24518369
2020 COL6A3 expression in adipose tissue cells is associated with levels of the homeobox transcription factor PRRX1. Scientific reports 26 33214660
2019 A circular RNA derived from COL6A3 functions as a ceRNA in gastric cancer development. Biochemical and biophysical research communications 24 31122696
2025 Integrative proteogenomic analysis identifies COL6A3-derived endotrophin as a mediator of the effect of obesity on coronary artery disease. Nature genetics 21 39856218
2018 Two novel COL6A3 mutations disrupt extracellular matrix formation and lead to myopathy from Ullrich congenital muscular dystrophy and Bethlem myopathy spectrum. Gene 18 29894794
2013 Valproic acid substantially downregulated genes folr1, IGF2R, RGS2, COL6A3, EDNRB, KLF6, and pax-3, N-acetylcysteine alleviated most of the induced gene alterations in chicken embryo model. Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie 17 24398995
2024 COL6A3 enhances the osteogenic differentiation potential of BMSCs by promoting mitophagy in the osteoporotic microenvironment. Molecular biology reports 15 38270688
2024 A Damaging COL6A3 Variant Alters the MIR31HG-Regulated Response of Chondrocytes in Neocartilage Organoids to Hyperphysiologic Mechanical Loading. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 15 39021299
2016 The role of mutations in COL6A3 in isolated dystonia. Journal of neurology 15 26872670
2020 COL6A3 mutation associated early-onset isolated dystonia (DYT)-27: Report of a new case and review of published literature. Brain & development 13 32037012
2023 Integration of transcriptomes of senescent cell models with multi-tissue patient samples reveals reduced COL6A3 as an inducer of senescence. Cell reports 12 37938972
2020 COL6A3 promotes cellular malignancy of osteosarcoma by activating the PI3K/AKT pathway. Revista da Associacao Medica Brasileira (1992) 12 32696868
2015 The clinical phenotype of early-onset isolated dystonia caused by recessive COL6A3 mutations (DYT27). Movement disorders : official journal of the Movement Disorder Society 12 26687111
2017 Microstructural white matter abnormalities in patients with COL6A3 mutations (DYT27 dystonia). Parkinsonism & related disorders 11 29066004
2024 COL6A3 Exosomes Promote Tumor Dissemination and Metastasis in Epithelial Ovarian Cancer. International journal of molecular sciences 10 39125689
2021 Clinical and Molecular Spectrum Associated with COL6A3 c.7447A>G p.(Lys2483Glu) Variant: Elucidating its Role in Collagen VI-related Myopathies. Journal of neuromuscular diseases 9 33749658
2024 Integrative analysis of COL6A3 in lupus nephritis: insights from single-cell transcriptomics and proteomics. Frontiers in immunology 7 38855105
2020 Novel Mutations in COL6A3 That Associated With Peters' Anomaly Caused Abnormal Intracellular Protein Retention and Decreased Cellular Resistance to Oxidative Stress. Frontiers in cell and developmental biology 7 33304895
1998 CA repeat polymorphism of the COL6A3 gene on chromosome 2q37. Human heredity 7 9694257
2022 Everolimus combined with 5-aza-2-deoxycytidine generated potent anti-tumor effects on ovarian clear cell cancer stem-like/spheroid cells by inhibiting the COL6A3-AKT-mTOR pathway. American journal of cancer research 6 35530273
2021 Study of the collagen type VI alpha 3 (COL6A3) gene in Parkinson's disease. BMC neurology 6 33964895
1989 An NcoI RFLP associated with the gene encoding the alpha-3 chain of human type VI collagen (COL6A3). Nucleic acids research 5 2564183
2025 Spatial-reprogramming derived GPNMB+ macrophages interact with COL6A3+ fibroblasts to enhance vascular fibrosis in glioblastoma. Genome medicine 4 41174767
2024 Corrigendum: Integrative analysis of COL6A3 in lupus nephritis: insights from single-cell transcriptomics and proteomics. Frontiers in immunology 4 39497818
2020 Coexistence of digenic mutations in the collagen VI genes (COL6A1 and COL6A3) leads to Bethlem myopathy. Clinica chimica acta; international journal of clinical chemistry 4 32389683
2020 Collagen VI-related limb-girdle syndrome caused by frequent mutation in COL6A3 gene with conflicting reports of pathogenicity. Neuromuscular disorders : NMD 4 32448721
2019 DNA methylation and mRNA expression of COL6A3 in antler mesenchyme of female and male reindeer. Genes & genomics 4 31134592
2019 Variants in COL6A3 gene influence susceptibility to esophageal cancer in the Chinese population. Cancer genetics 4 31425922
2021 Collagen VI-Related Myopathy Caused by Compound Heterozygous Mutations of COL6A3 in a Consanguineous Kurdish Family. Journal of clinical neuromuscular disease 3 33596003
2023 A novel variant of COL6A3 c.6817-2(IVS27)A>G causing Bethlem myopathy: A case report. Frontiers in neurology 2 36779064
2023 A novel compound heterozygous mutation of COL6A3 in Chinese patients with isolated cervical dystonia. Frontiers in neurology 2 37082441
2023 Novel COL6A3 frameshift variant in American Staffordshire Terrier dogs with Ullrich-like congenital muscular dystrophy. Journal of veterinary internal medicine 2 37706358
2022 Autosomal dominant Ullrich congenital muscular dystrophy due to a de novo mutation in COL6A3 gene. A case report. Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology 2 35832501
2025 Development, validation, and preliminary phenotypic characterization of a Col6a3 knockout mouse model targeting exon 3. Animal models and experimental medicine 1 40792431
2025 The Role of COL6A3 in Tumorigenesis, Metastasis, Diagnosis, and Disease Management. Cancers 1 41228242
2023 Genetic Analysis of HIBM Myopathy-Specific GNE V727M Hotspot Mutation Identifies a Novel COL6A3 Allied Gene Signature That Is Also Deregulated in Multiple Neuromuscular Diseases and Myopathies. Genes 1 36980840
2022 Prmt7 Downregulation in Mouse Spermatogonia Functions through miR-877-3p/Col6a3. Life (Basel, Switzerland) 1 36013373
2019 [Clinical manifestations and genetics analysis of collagen type Ⅵ-related myopathy caused by variants in COL6A3 gene]. Zhonghua er ke za zhi = Chinese journal of pediatrics 1 30695889
2014 [Study of a Bethlem myopathy pedigree resulted from a novel mutation of COL6A3 gene]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 1 25449070
2026 A damaging mutation in COL6A3 alters the mechanobiologic response of chondrocytes derived from human induced pluripotent stem cells. Stem cell research & therapy 0 41692747
2026 Artificial intelligence driven multi-omics framework identifies COL6A3 as a diagnostic biomarker and a putative gene target modulated by Embelin in Colorectal cancer. Frontiers in oncology 0 41704606
2025 Landscape Analysis of COL6A1, COL6A2, and COL6A3 Pathogenic Variants in a Large Italian Cohort Presenting with Collagen VI-Related Myopathies: A Nationwide Report. Biomolecules 0 41154655