Affinage

COL6A3

Collagen alpha-3(VI) chain · UniProt P12111

Length
3177 aa
Mass
343.7 kDa
Annotated
2026-06-09
63 papers in source corpus 22 papers cited in narrative 24 extracted findings
Cross-family judge faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COL6A3 encodes the α3 chain of type VI collagen, an extracellular matrix component required for assembly of collagen VI microfibrils that organize the pericellular and interstitial matrix; loss of functional α3(VI) in vivo abolishes collagen VI microfibrils and produces decreased muscle mass, reduced contractile force, and tissue-specific defects in collagen I fibrillogenesis (PMID:23564457). Homozygous loss-of-function mutations cause Ullrich congenital muscular dystrophy with absence of collagen VI from muscle and fibroblasts (PMID:11992252), while glycine substitutions in the triple-helical domain and mutations in the N-terminal von Willebrand factor type A domain cause Bethlem myopathy (PMID:9536084, PMID:10399756); in-frame mutant chains act through a dominant-negative effect on microfibrillar assembly (PMID:24563484). Recessive mutations affecting exon 41 instead impair a neuronal extracellular matrix function, producing isolated dystonia (DYT27) with axonal outgrowth deficits, distinct from the muscle disease (PMID:26004199). The C-terminal C5 domain of α3(VI) is cleaved immediately after secretion and is absent from the mature matrix (PMID:11785962); this cleaved product, endotrophin, functions as a bioactive peptide that activates JNK-dependent hepatocyte apoptosis and drives inflammation and fibrosis, effects suppressed by neutralizing antibodies or by ETP-specific ablation (PMID:30246318), and links adiposity to coronary artery disease risk (PMID:39856218). In chondrocytes, COL6A3 binds fibronectin within the pericellular matrix and sets PCM elastic modulus, thereby governing mechanotransduction through osmotic calcium signaling and TRPV4-dependent anabolic responses, with damaging variants provoking an osteoarthritic state (PMID:39021299, PMID:41692747). In adipocytes, COL6A3 expression is driven by the transcription factor PRRX1 and negatively regulated by PPARγ-mediated differentiation and leptin, and COL6A3 acts upstream of inflammatory MCP1/CCL2 signaling and insulin/Akt responses (PMID:27312141, PMID:24719315, PMID:25337653, PMID:33214660).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1998 High

    Established that mutations in the N-terminal globular vWFA domain of α3(VI), not only the triple helix, are pathogenic, broadening the mutational basis of Bethlem myopathy.

    Evidence Linkage and segregation of a Gly→Glu vWFA missense mutation in a large pedigree, excluded in controls

    PMID:9536084

    Open questions at the time
    • Did not establish how the vWFA mutation perturbs microfibril assembly biochemically
    • No tissue-level collagen VI quantification
  2. 1999 Medium

    Confirmed that glycine substitutions disrupting the α3(VI) triple helix cause dominant Bethlem myopathy, anchoring the triple-helix structural mechanism.

    Evidence Sanger sequencing and domain analysis of a de novo Gly→Arg substitution

    PMID:10399756

    Open questions at the time
    • Single family
    • No functional assembly assay of the mutant chain
  3. 2002 Medium

    Demonstrated that the C5 domain is incorporated into nascent fibrils but cleaved off immediately after secretion, defining COL6A3 as the source of a secreted, post-assembly processing product later recognized as endotrophin.

    Evidence Confocal and immunoelectron microscopy with anti-C5 antiserum in articular cartilage

    PMID:11785962

    Open questions at the time
    • Did not identify the protease responsible for cleavage
    • Function of the cleaved C5 fragment not addressed
  4. 2002 High

    Established COL6A3 as a causal gene for Ullrich congenital muscular dystrophy via recessive loss-of-function alleles, tying disease to collagen VI absence.

    Evidence Linkage mapping, mutation sequencing, and muscle/fibroblast collagen VI immunostaining across three families

    PMID:11992252

    Open questions at the time
    • Did not resolve the molecular consequence on microfibril architecture
    • Genotype–phenotype severity correlation not established
  5. 2013 High

    Showed in vivo that functional α3(VI) is required for collagen VI microfibril formation, muscle force, and tissue-specific collagen I fibrillogenesis, and that the C-terminal cleavage product is dispensable for normal development.

    Evidence Col6a3 mutant mouse with EM, contractile force, and fibrillogenesis readouts

    PMID:23564457

    Open questions at the time
    • Did not test pathological roles of the cleaved product under disease/stress
    • Mechanism of tendon-specific (not corneal) fibril defect unresolved
  6. 2014 High

    Defined the dominant-negative mechanism by which in-frame mutant α3(VI) chains poison microfibrillar assembly, explaining dominant UCMD.

    Evidence Exon-16-deletion mouse with biosynthetic pulse-chase, EM, and contractile assays

    PMID:24563484

    Open questions at the time
    • Did not quantify the stoichiometric threshold of mutant incorporation needed for dominance
  7. 2014 Medium

    Introduced allele-specific silencing as a strategy to rescue collagen VI matrix in UCMD by selectively knocking down the dominant-negative mutant transcript.

    Evidence Allele-specific siRNA in patient fibroblasts with reporter validation and confocal matrix readout

    PMID:24518369

    Open questions at the time
    • No in vivo efficacy
    • Single mutation context
  8. 2014 Medium

    Identified PPARγ-driven adipocyte differentiation as a negative regulator of COL6A3, embedding the gene in adipose ECM remodeling.

    Evidence PPARG siRNA knockdown and adipocyte size fractionation with RT-qPCR

    PMID:24719315

    Open questions at the time
    • Indirect regulation; no direct promoter binding shown
    • Single lab
  9. 2015 Medium

    Established leptin as a direct paracrine repressor of COL6A3 in adipose tissue, distinguishing it from glucose/insulin inputs.

    Evidence Dose-response leptin/insulin/glucose treatment of adipose explants with RT-qPCR

    PMID:25337653

    Open questions at the time
    • Mechanism of leptin-to-COL6A3 transcriptional repression not defined
    • Single method for the mechanistic claim
  10. 2015 High

    Revealed a tissue-specific neuronal function for COL6A3 distinct from muscle, with exon-41-dependent recessive mutations causing isolated dystonia (DYT27).

    Evidence Whole-exome sequencing in pedigrees, zebrafish axonal outgrowth assay, and mouse brain expression

    PMID:26004199

    Open questions at the time
    • Molecular role of exon 41 in neuronal ECM unresolved
    • No mammalian neuronal phenotype model
  11. 2017 Medium

    Extended allele-specific suppression with gapmer antisense oligonucleotides acting at the mRNA level via RNase H, restoring collagen VI deposition.

    Evidence Gapmer AON transfection in patient cells with allele-specific qPCR and matrix Western blot

    PMID:28918041

    Open questions at the time
    • No in vivo delivery
    • Mutation-specific design limits generalizability
  12. 2018 Medium

    Placed COL6A3 upstream of inflammatory MCP1/CCL2 signaling and metabolic regulation in adipocytes, linking the matrix protein to insulin sensitivity and lipid handling.

    Evidence Stable shRNA knockdown in human adipocytes with lipolysis/insulin assays, MMP-11 treatment, and macrophage co-culture

    PMID:27312141

    Open questions at the time
    • Whether the effect requires intact matrix versus the cleaved fragment not separated
    • Single lab
  13. 2018 Medium

    Defined endotrophin (cleaved C5) as a bioactive driver of hepatocyte apoptosis, inflammation, and fibrosis amenable to antibody neutralization, giving the post-secretion fragment a pathological function.

    Evidence Recombinant ETP treatment with JNK analysis and neutralizing antibody rescue in chronic liver disease models

    PMID:30246318

    Open questions at the time
    • ETP receptor/binding partner not identified
    • Single lab
  14. 2020 Medium

    Identified COL6A3 mutations causing intracellular retention and heightened ER/oxidative stress in Peters' anomaly, adding a proteostatic disease mechanism.

    Evidence Patient sequencing with mutant protein localization and ER/oxidative stress assays in cell lines

    PMID:33304895

    Open questions at the time
    • No animal model of the ocular phenotype
    • Causal chain from ER stress to malformation not established
  15. 2020 Medium

    Established PRRX1 as a direct transcriptional activator of COL6A3 integrating TGF-β and TNF-α inputs in adipose tissue.

    Evidence Promoter-reporter luciferase plus PRRX1 knockdown/overexpression and cytokine treatment in adipose cells

    PMID:33214660

    Open questions at the time
    • In vivo relevance of PRRX1–COL6A3 axis not tested
    • Single lab
  16. 2020 Medium

    Linked COL6A3 to mitophagy-dependent differentiation and anti-inflammatory effects in mesenchymal stem cells.

    Evidence Lentiviral overexpression with mitophagy markers and Mdivi-1 inhibitor rescue

    PMID:38270688

    Open questions at the time
    • Mechanism connecting an ECM protein to intracellular mitophagy unexplained
    • Overexpression-only, single lab
  17. 2023 Medium

    Identified COL6A3 as a functional inducer of cellular senescence acting through DREAM-complex-targeted cell-cycle genes.

    Evidence COL6A3 siRNA knockdown with RNA-seq comparison across 10 senescence models and DREAM gene-set analysis

    PMID:37938972

    Open questions at the time
    • Direct molecular link between COL6A3 and DREAM regulation not defined
    • Correlative transcriptomics
  18. 2024 High

    Showed via CRISPR organoid reconstitution that COL6A3 binds fibronectin in the pericellular matrix and is required for the inflammatory response to mechanical loading, with MIR31HG as an epigenetic regulator.

    Evidence CRISPR-edited iPSC neocartilage organoids with protein binding assay, mechanical loading, and multi-omics

    PMID:39021299

    Open questions at the time
    • Mechanistic role of MIR31HG downstream of COL6A3 not resolved
    • Loading-response signaling intermediates not fully mapped
  19. 2025 High

    Demonstrated that COL6A3 sets PCM elastic modulus to control chondrocyte mechanotransduction, calcium/TRPV4 signaling, circadian rhythm, and IL-1 catabolic responses.

    Evidence CRISPR-edited iPSC chondrocytes with AFM modulus measurement, calcium imaging, TRPV4 assays, RNA-seq, and IL-1 stimulation

    PMID:41692747

    Open questions at the time
    • How reduced PCM stiffness mechanistically couples to TRPV4 not fully defined
    • In vivo cartilage phenotype not tested
  20. 2025 Medium

    Provided ETP-specific genetic ablation showing endotrophin drives fibrosis independently of full-length COL6A3.

    Evidence Cre-lox ETP-specific knockout mice in renal ischemia-reperfusion model (preprint)

    Open questions at the time
    • Preprint, single lab
    • ETP downstream receptor/signaling in kidney not identified
  21. 2025 Medium

    Used genetic causal inference to position circulating endotrophin as a mediator linking obesity to coronary artery disease, suggesting therapeutic tractability.

    Evidence Two-step Mendelian randomization, colocalization, single-cell RNA-seq, and fat-loss intervention

    PMID:39856218

    Open questions at the time
    • No direct in vitro/in vivo ETP cardiovascular mechanism
    • Causal estimate, not experimental

Open questions

Synthesis pass · forward-looking unresolved questions
  • The protease(s) that cleave the C5/endotrophin domain and the receptor through which endotrophin signals remain unidentified, leaving the central bioactive axis mechanistically incomplete.
  • ETP receptor unknown
  • ETP-generating protease unknown
  • Direct molecular link between matrix loss and intracellular phenotypes (mitophagy, senescence) unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0048018 receptor ligand activity 3
Localization
GO:0031012 extracellular matrix 3 GO:0005576 extracellular region 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-1474244 Extracellular matrix organization 3 R-HSA-1643685 Disease 3
Partners
CSF1FN1
Complex memberships
collagen VI microfibril

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 The C5 domain of the COL6A3 α3(VI) chain is synthesized and incorporated into newly formed collagen VI fibrils but is cleaved off immediately after secretion and is absent from the mature pericellular type VI collagen matrix in adult articular cartilage, as shown by confocal laser-scanning microscopy and immunoelectron microscopy with a specific anti-C5 antiserum. Confocal laser-scanning microscopy, immunoelectron microscopy, double-labeling immunostaining Biochemical and biophysical research communications Medium 11785962
2002 Homozygous loss-of-function mutations in COL6A3 (splice-site 6930+5A>G causing exon 29 skipping, and nonsense R2342X) cause Ullrich congenital muscular dystrophy with partial or complete absence of collagen VI in muscle and fibroblasts, establishing COL6A3 as a causal gene for this muscular dystrophy. Microsatellite linkage mapping, Sanger sequencing of COL6A3 mutations, muscle biopsy immunostaining for collagen VI American journal of human genetics High 11992252
1998 A missense mutation (Gly→Glu) in the von Willebrand factor type A (vWFA/N2) domain of COL6A3 segregates with autosomal dominant Bethlem myopathy in a large pedigree, demonstrating that mutations in the N-terminal globular domain (as well as the triple-helical domain) of COL6A3 can cause Bethlem myopathy. Linkage analysis, Sanger sequencing, segregation analysis in 31 family members, exclusion from 338 control chromosomes Human molecular genetics High 9536084
1999 A de novo Gly→Arg substitution in the triple-helical coding region of COL6A3 disrupts triple helix structure and causes autosomal dominant Bethlem myopathy, confirming that glycine substitutions in the triple helix of α3(VI) collagen are pathogenic. Clinical description, Sanger sequencing, bioinformatic domain analysis Neuromuscular disorders Medium 10399756
2013 Mice expressing a non-functional α3(VI) collagen chain (Col6a3 mutant) lack extracellular collagen VI microfibrils, show decreased muscle mass and contractile force, and display ultrastructurally abnormal collagen fibrils in tendon but not cornea, indicating a tissue-specific role of COL6A3 in collagen I fibrillogenesis. The C-terminal cleavage product of α3(VI) is not required for normal growth and development. Transgenic mouse model, electron microscopy, muscle contractile force measurements, immunofluorescence, histopathology The Journal of biological chemistry High 23564457
2014 Heterozygous deletion of exon 16 in the Col6a3 gene produces a mutant α3(VI) protein that exerts a dominant-negative effect on collagen VI microfibrillar assembly in fibroblasts, recapitulating dominant Ullrich congenital muscular dystrophy; mutant mice develop myopathy with mitochondrial and sarcoplasmic reticulum ultrastructural alterations and compromised muscle contractile function. Targeted gene deletion (mouse model), biosynthetic pulse-chase studies, electron microscopy, muscle contractile function assays The Journal of biological chemistry High 24563484
2015 Recessive compound heterozygous mutations in COL6A3, with at least one allele affecting exon 41, cause early-onset isolated dystonia (DYT27) with underlying neurodevelopmental deficits (axonal outgrowth deficits) in zebrafish; Col6a3 is expressed in neurons of the adult mouse brain, placing COL6A3 in a neuronal extracellular matrix pathway distinct from its role in muscle. Whole-exome sequencing, zebrafish morpholino knockdown with in-frame deletions, axonal outgrowth assay, mouse brain in situ hybridization/RT-PCR American journal of human genetics High 26004199
2008 The t(1;2)(p13;q37) chromosomal translocation generates a COL6A3-CSF1 fusion transcript in tenosynovial giant cell tumors; in-frame fusion products were detected by RT-PCR, with CSF1 breakpoints downstream of exon 5 so the fusion does not encode the CSF1 receptor-binding amino-terminal domain. Cytogenetics, RT-PCR, sequence analysis of breakpoints Genes, chromosomes & cancer Medium 17918257
2011 COL6A3 undergoes tumor-specific alternative splicing in pancreatic ductal adenocarcinoma, with consistent inclusion of exons 3, 4, and 6 in tumor tissue but not adjacent normal tissue; exon 4 inclusion is exclusively tumor-specific, suggesting cancer-specific isoforms contribute to desmoplastic stroma. RT-PCR with isoform-specific primers, Western blot, immunohistochemistry in paired PDA vs. normal tissues and animal models Surgery Medium 21719059
2014 siRNA allele-specifically targeting a COL6A3 exon-16 skipping mutation in UCMD patient fibroblasts selectively suppresses mutant transcript expression without affecting the wild-type allele, and treatment considerably improves collagen VI matrix quantity and quality as assessed by confocal microscopy. siRNA allele-specific silencing, quantitative RT-PCR, reporter construct in HEK293T, confocal microscopy of collagen VI matrix Molecular therapy. Nucleic acids Medium 24518369
2017 Gapmer antisense oligonucleotides targeting a heterozygous 18-nt deletion mutation in COL6A3 exon 15 selectively suppress mutant transcripts at the mRNA level (more effectively than pre-mRNA targeting) via RNase H recruitment, resulting in increased deposition of collagen VI protein into the extracellular matrix in patient-derived cells. Gapmer AON transfection, RT-PCR/qPCR of allele-specific transcripts, Western blot of collagen VI matrix deposition Molecular therapy. Nucleic acids Medium 28918041
2018 COL6A3 knockdown in human adipocytes increases triglyceride content, lipolysis, insulin-induced Akt phosphorylation, and adipogenic gene expression, and abrogates TNF-α- and LPS-induced MCP1 (CCL2) mRNA expression and secretion; matrix metalloproteinase-11 treatment reduces COL6A3 protein and simultaneously suppresses MCP1 induction, placing COL6A3 upstream of inflammatory MCP1 signaling in adipocytes. Stable shRNA knockdown in immortalized human preadipocytes, MTT/lipolysis/insulin signaling assays, MMP-11 treatment, co-culture with THP1 macrophages, RT-PCR/ELISA Obesity (Silver Spring, Md.) Medium 27312141
2014 PPARG knockdown in developing human adipocytes increases COL6A3 mRNA ~1.5-fold, and COL6A3 mRNA is ~2.8-fold higher in small (less mature) compared to large adipocytes, demonstrating that PPARγ-mediated adipocyte differentiation negatively regulates COL6A3 expression. PPARG siRNA knockdown in primary human adipocytes (euglycemic clamp-phenotyped subjects), adipocyte size fractionation from surgical biopsies, RT-qPCR Obesity (Silver Spring, Md.) Medium 24719315
2015 Leptin treatment causes a dose-dependent decrease in COL6A3 expression in human adipose tissue, while insulin and glucose have no effect, demonstrating a direct paracrine regulatory pathway by which leptin modulates extracellular matrix composition through COL6A3. In vitro leptin/insulin/glucose treatment of adipose tissue explants, RT-qPCR, comparison across depot and obesity status Endocrinology Medium 25337653
2018 COL6A3-derived endotrophin (ETP, cleaved from the C5 domain) induces JNK-dependent hepatocyte apoptosis and activates non-parenchymal liver cells to promote hepatic inflammation and fibrosis; neutralizing anti-ETP antibodies suppress these pathological consequences in chronic liver disease models. Recombinant ETP treatment of hepatocytes, JNK pathway analysis, neutralizing antibody treatment in chronic liver disease mouse models, co-culture experiments The Journal of pathology Medium 30246318
2020 Two homozygous COL6A3 mutations (p.Val86Ala and p.Arg689Cys) identified in Peters' anomaly patients cause abnormal intracellular retention of mutant COL6A3 protein and reduce cellular resistance to oxidative stress through an enhanced endoplasmic reticulum stress response. Patient exome/panel sequencing, immunofluorescence for protein localization, ER stress markers, oxidative stress assays in cell lines expressing mutant protein Frontiers in cell and developmental biology Medium 33304895
2020 COL6A3 overexpression in bone marrow mesenchymal stem cells (BMSCs) promotes mitophagy (colocalization of mitochondria and lysosomes, restored mitochondrial membrane potential), enhances osteogenic and adipogenic differentiation, and reduces LPS-induced inflammatory mediator expression (iNOS, COX-2); blockade of mitophagy with Mdivi-1 abolishes these COL6A3-mediated effects. Lentiviral COL6A3 overexpression, Western blot, TUNEL apoptosis, JC-1 staining, immunofluorescence colocalization, mitophagy inhibitor (Mdivi-1) rescue experiment Molecular biology reports Medium 38270688
2023 Experimental knockdown of COL6A3 induces transcriptional changes overlapping with the majority of experimental senescence models, with cell-cycle arrest linked to modulation of DREAM complex-targeted genes, identifying COL6A3 as a functional inducer of cellular senescence. COL6A3 siRNA knockdown, RNA-seq transcriptome comparison across 10 senescence models, DREAM complex gene-set analysis Cell reports Medium 37938972
2020 PRRX1 transcription factor directly transactivates the human COL6A3 promoter (reporter assay), and PRRX1 knockdown reduces COL6A3 mRNA in human and mouse adipose cells; TGF-β1 upregulates Col6a3 mRNA while TNF-α decreases PRRX1-mediated transactivation, placing PRRX1 as a transcriptional regulator of COL6A3 in adipose tissue. PRRX1 knockdown and overexpression, COL6A3 promoter-reporter luciferase assay, qRT-PCR in human/mouse adipose cells, TGF-β1 and TNF-α treatment Scientific reports Medium 33214660
2024 A damaging COL6A3 variant introduced by CRISPR-Cas9 into iPSC-derived neocartilage organoids results in significantly lower binding between pericellular matrix proteins COL6A3 and fibronectin, provokes an osteoarthritic chondrocyte state, and abolishes the characteristic inflammatory signaling response (PTGS2, PECAM1, ADAMTS5) to hyperphysiological mechanical loading; the lncRNA MIR31HG is identified as a key epigenetic regulator of this loading response. CRISPR-Cas9 genome editing of iPSC-derived neocartilage organoids, multi-omics (mRNA and lncRNA), protein binding assay, mechanical loading Advanced science High 39021299
2026 A damaging COL6A3 variant in iPSC-derived chondrocytes reduces pericellular matrix (PCM) elastic modulus, reduces expression of key matrix proteins, causes heightened osmotically-induced calcium signaling (consistent with reduced PCM stiffness), reduces anabolic response to TRPV4 activation, disrupts circadian rhythms (increased BMAL1, phase shift), and exacerbates catabolic response to IL-1, demonstrating that COL6A3 regulates chondrocyte mechanotransduction via PCM mechanical properties. CRISPR-edited iPSC-derived chondrocytes, atomic force microscopy of PCM modulus, calcium imaging, TRPV4 activation assays, RNA-seq, circadian rhythm analysis, IL-1 stimulation Stem cell research & therapy High 41692747
2025 ETP-specific knockout mice (ETPKO), generated by inserting lox2272 sites into the Col6a3 locus to selectively ablate ETP while preserving Col6a3 expression, show that ETP depletion significantly attenuates kidney fibrosis progression in ischemia-reperfusion injury, establishing endotrophin as a key driver of fibrosis independently of the full COL6A3 protein. Cre-lox ETP-specific knockout mouse generation, genomic sequencing confirmation, mCherry reporter, renal ischemia-reperfusion injury model, fibrosis quantification bioRxiv (preprint)preprint Medium
2025 Integrative Mendelian randomization and colocalization identified COL6A3-derived endotrophin as mediating the effect of obesity (BMI) on coronary artery disease risk; body fat reduction decreases plasma endotrophin levels, implicating ETP as a tractable circulating mediator linking adiposity to cardiovascular disease. Two-step proteome-wide Mendelian randomization, Bayesian colocalization, single-cell RNA sequencing, epigenomics, clinical intervention (fat loss) studies Nature genetics Medium 39856218
2025 COL6A3 exon 4 inclusion is identified as one of a 5-ASE signature specifically associated with TGFβ-induced myofibroblast differentiation in primary skin fibroblasts, validated by ddPCR and AS-PCR and retrieved in multiple independent RNA-seq datasets of TGFβ-stimulated lung and skin fibroblasts. RNA-seq, ddPCR, AS-PCR in primary skin fibroblasts, validation in public lung/skin fibroblast datasets bioRxiv (preprint)preprint Low

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 126 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 104 29143985
2008 Molecular identification of COL6A3-CSF1 fusion transcripts in tenosynovial giant cell tumors. Genes, chromosomes & cancer 83 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 74 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.) 71 24719315
2015 COL6A3 is regulated by leptin in human adipose tissue and reduced in obesity. Endocrinology 65 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 59 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
2017 Gapmer Antisense Oligonucleotides Suppress the Mutant Allele of COL6A3 and Restore Functional Protein in Ullrich Muscular Dystrophy. Molecular therapy. Nucleic acids 44 28918041
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
2014 A mouse model for dominant collagen VI disorders: heterozygous deletion of Col6a3 Exon 16. The Journal of biological chemistry 38 24563484
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 33 30876691
2018 COL6A3-derived endotrophin links reciprocal interactions among hepatic cells in the pathology of chronic liver disease. The Journal of pathology 33 30246318
2016 Reduced expression of collagen VI alpha 3 (COL6A3) confers resistance to inflammation-induced MCP1 expression in adipocytes. Obesity (Silver Spring, Md.) 32 27312141
2013 Down Syndrome Related Muscle Hypotonia: Association with COL6A3 Functional SNP rs2270669. Frontiers in genetics 32 23626599
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 27 33214660
2025 Integrative proteogenomic analysis identifies COL6A3-derived endotrophin as a mediator of the effect of obesity on coronary artery disease. Nature genetics 25 39856218
2019 A circular RNA derived from COL6A3 functions as a ceRNA in gastric cancer development. Biochemical and biophysical research communications 24 31122696
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 18 24398995
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) 16 39021299
2024 COL6A3 enhances the osteogenic differentiation potential of BMSCs by promoting mitophagy in the osteoporotic microenvironment. Molecular biology reports 15 38270688
2016 The role of mutations in COL6A3 in isolated dystonia. Journal of neurology 15 26872670
2023 Integration of transcriptomes of senescent cell models with multi-tissue patient samples reveals reduced COL6A3 as an inducer of senescence. Cell reports 13 37938972
2020 COL6A3 mutation associated early-onset isolated dystonia (DYT)-27: Report of a new case and review of published literature. Brain & development 13 32037012
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 8 38855105
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 7 35530273
2021 Study of the collagen type VI alpha 3 (COL6A3) gene in Parkinson's disease. BMC neurology 7 33964895
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
2025 Spatial-reprogramming derived GPNMB+ macrophages interact with COL6A3+ fibroblasts to enhance vascular fibrosis in glioblastoma. Genome medicine 5 41174767
1989 An NcoI RFLP associated with the gene encoding the alpha-3 chain of human type VI collagen (COL6A3). Nucleic acids research 5 2564183
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

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