Affinage

COL6A1

Collagen alpha-1(VI) chain · UniProt P12109

Length
1028 aa
Mass
108.5 kDa
Annotated
2026-04-28
85 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COL6A1 encodes the α1(VI) chain of type VI collagen, a structural extracellular matrix protein that assembles into microfibrils critical for the biomechanical integrity of pericellular matrices in skeletal muscle, cartilage, and connective tissue. Intracellularly, the α1(VI) chain forms anti-parallel dimers via a triple-helical cysteine residue and then tetramers with α2(VI) and α3(VI) chains; mutations that preserve this cysteine permit secretion of abnormal tetramers exerting dominant-negative effects on microfibrillar assembly, whereas mutations that remove it or truncate the C2 domain prevent secretion entirely (PMID:12840783, PMID:10329467, PMID:23738969). Loss of collagen VI in knockout mice causes mechanically deficient pericellular matrix in cartilage, sensitization of the mitochondrial permeability transition pore leading to muscle fiber apoptosis, and accelerated osteoarthritis (PMID:19248115, PMID:19519726). Dominant glycine substitutions and pseudoexon insertions in the triple-helical domain, as well as recessive loss-of-function mutations, cause the Bethlem myopathy–Ullrich congenital muscular dystrophy spectrum (PMID:9580662, PMID:16130093, PMID:30895940).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 High

    Establishing that COL6A1 haploinsufficiency—via nonsense-mediated mRNA decay of a premature stop codon allele—is sufficient to cause Bethlem myopathy resolved the question of whether quantitative reduction alone (without a structurally abnormal protein) can be pathogenic.

    Evidence RT-PCR and mRNA stability assays in patient fibroblasts and muscle, plus western blot of collagen VI output

    PMID:9580662

    Open questions at the time
    • Threshold of α1(VI) reduction needed for disease not defined
    • No rescue experiment to confirm causality
  2. 1999 High

    Demonstrating that deletion of a triple-helical cysteine prevents dimer formation and blocks mutant chain secretion established this residue as the gatekeeper for collagen VI assembly quality control.

    Evidence RT-PCR, western blot, and immunofluorescence of ECM in patient fibroblasts carrying a splice-site mutation deleting exon 14

    PMID:10329467

    Open questions at the time
    • Identity of the chaperone/ER retention machinery that detects misfolded chains unknown
    • Only one mutation analyzed
  3. 2000 High

    Mapping the minimal Col6a1 enhancer (E-L fragment) and showing that combinatorial binding of ubiquitous transcription factors—not tissue-restricted factors—drives tissue-specific expression answered how a widely expressed gene achieves restricted transcription in connective tissue and cartilage.

    Evidence Transgenic mice with deletion constructs and linker-scanning mutagenesis; EMSA with nuclear extracts from multiple tissues

    PMID:10747869

    Open questions at the time
    • Identity of the 22 ubiquitous factors not fully resolved
    • Chromatin context and epigenetic regulation not addressed
  4. 2001 Medium

    Showing that neuregulin signaling from neural crest cells initiates Col6a1 transcriptional competence in Schwann cells, which then becomes neuregulin-independent and cell-cycle-regulated, revealed a developmental switch coupling Col6a1 to myelination onset.

    Evidence lacZ transgenic reporter mice analyzed across development and in neuregulin-deficient backgrounds

    PMID:11287188

    Open questions at the time
    • Direct transcription factor mediating neuregulin-to-Col6a1 activation not identified
    • Biochemical pathway not dissected
  5. 2003 High

    By comparing two in-frame deletions—one preserving and one removing the dimerization cysteine—this study resolved why some triple-helical domain mutations exert dominant-negative effects while others do not, establishing that secretion competence of the mutant chain is the key determinant of phenotypic severity.

    Evidence In vitro fibroblast analysis of mutant chain synthesis, secretion, and ECM deposition across two contrasting mutations

    PMID:12840783

    Open questions at the time
    • Stoichiometry of mutant-to-wild-type chains in secreted tetramers not quantified
    • Fate of intracellularly retained chains not tracked
  6. 2004 Medium

    Systematic comparison of dominant glycine substitutions versus recessive truncating mutations across multiple patients established the general rule that triple-helical glycine substitutions act via dominant-negative poisoning of assembly while loss-of-function alleles cause the more severe Ullrich phenotype through biallelic depletion.

    Evidence Patient fibroblast analysis with RT-PCR, western blot, immunofluorescence, and parental genotyping

    PMID:16130093

    Open questions at the time
    • Some glycine substitutions produce intermediate phenotypes not explained by simple dominant-negative model
    • Modifier genes not explored
  7. 2008 High

    Genetic ablation of myogenic cells in limb buds (metD/D cross) abolished Col6a1 enhancer activation in mesenchymal cells, proving that muscle-derived paracrine signals are required for Col6a1 transcription in connective tissue.

    Evidence lacZ transgenic reporter crossed with metD/D myogenic-cell-deficient mice; reporter expression and collagen VI immunostaining

    PMID:18761340

    Open questions at the time
    • Identity of the paracrine signal from myogenic cells unknown
    • Whether this regulation operates in adult muscle homeostasis not tested
  8. 2009 High

    Two concurrent studies using Col6a1−/− mice established that collagen VI deficiency causes both mechanically deficient pericellular matrix in cartilage (accelerating osteoarthritis) and mitochondrial permeability transition pore sensitization in skeletal muscle (driving apoptosis rescuable by cyclophilin D inhibition), defining the two major downstream pathological axes of COL6A1 loss.

    Evidence Col6a1 knockout mice; micropipette aspiration of PCM; mitochondrial Ca2+ retention and membrane potential assays; TUNEL; Debio 025 pharmacological rescue

    PMID:19248115 PMID:19519726

    Open questions at the time
    • Molecular link between absent pericellular collagen VI and mPTP sensitization not identified
    • Whether mPTP mechanism also operates in cartilage chondrocytes unknown
  9. 2013 Medium

    Identifying that truncations in the C-terminal C2 subdomain cause intracellular retention and also disrupt fibronectin network organization revealed a dual role for the C2 domain in both secretion competence and ECM network interactions.

    Evidence Patient fibroblast immunofluorescence, western blot, fibronectin staining

    PMID:23738969

    Open questions at the time
    • Only one patient studied
    • Direct binding interface between C2 domain and fibronectin not characterized
  10. 2019 High

    Discovery that a deep intronic variant (c.930+189C>T) creates a pseudoexon encoding an assembly-incompetent α1(VI) chain, correctable by ASO splice-switching and CRISPR deletion, established a new class of COL6A1 pathogenic mechanism and a therapeutic paradigm.

    Evidence Muscle RNA-seq; patient fibroblast culture; ASO and CRISPR/Cas9 correction with protein and matrix readouts

    PMID:30895940

    Open questions at the time
    • In vivo delivery and efficacy of ASOs not demonstrated
    • Long-term stability of correction unknown
  11. 2021 Medium

    Demonstration that COL6A1 interacts with SOCS5 to promote ubiquitin-dependent STAT1 degradation and that exosomal COL6A1 converts fibroblasts to cancer-associated fibroblasts revealed a non-structural signaling role for COL6A1 in osteosarcoma invasion.

    Evidence Co-immunoprecipitation; ubiquitination assay; exosome tracing; co-culture; in vivo xenograft

    PMID:33391546

    Open questions at the time
    • Structural basis of COL6A1–SOCS5 interaction unknown
    • Relevance outside osteosarcoma context not tested
    • Whether full-length or processed collagen VI mediates this effect unclear
  12. 2022 Medium

    Allele-specific CRISPR disruption of the dominant-negative G293R allele rescued collagen VI matrix assembly, providing proof-of-concept that selectively silencing the mutant allele is sufficient for phenotypic correction.

    Evidence CRISPR/Cas9 editing in patient fibroblasts; ddPCR allele quantification; immunofluorescence of matrix

    PMID:35457228

    Open questions at the time
    • Efficiency of editing (~40%) may be insufficient in vivo
    • Off-target analysis limited
  13. 2023 High

    Showing that the pseudoexon-containing mutant α1(VI) chain is secreted as a single chain (not incorporated into tetramers) and forms extracellular aggregates precisely defined why this mutation is dominant-negative: the mutant chain bypasses intracellular quality control but poisons the extracellular matrix.

    Evidence Mutation-specific antibody; patient fibroblasts; reconstitution of mutant chain in α1-deficient WI-26 VA4 cells

    PMID:40225172

    Open questions at the time
    • Nature and composition of extracellular aggregates not characterized at ultrastructural level
    • Whether aggregates actively damage surrounding matrix not tested
  14. 2024 High

    Allele-specific siRNA with an engineered mismatch selectively silenced the G293R mutant transcript and rescued collagen VI matrix, advancing therapeutic strategy beyond CRISPR by demonstrating reversible, tunable allele-selective knockdown.

    Evidence siRNA transfection in patient fibroblasts; allele-specific RT-qPCR; western blot; immunofluorescence

    PMID:38617974

    Open questions at the time
    • In vivo delivery to muscle not demonstrated
    • Duration of effect and dosing not established
  15. 2025 Medium

    ChIP-seq identification of direct thyroid hormone receptor α binding at the Col6a1 promoter, with functional validation by TRα knockdown, established a hormonal transcriptional input for COL6A1 expression relevant to myoblast proliferation and differentiation.

    Evidence ChIP-seq and ChIP-qPCR in C2C12 myoblasts; siRNA knockdown of TRα; RT-qPCR; proliferation/differentiation assays

    PMID:40317420

    Open questions at the time
    • Whether TRα regulation operates in vivo in adult muscle not confirmed
    • Relationship to the upstream −5.4 kb enhancer not examined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular link between absence of pericellular collagen VI and sensitization of the mitochondrial permeability transition pore—the central pathogenic mechanism in collagen VI myopathies—remains undefined, as does the identity of the muscle-derived paracrine signal that activates COL6A1 transcription in connective tissue.
  • Transmembrane receptor mediating collagen VI signal to mitochondria unknown
  • Identity of muscle paracrine factor unknown
  • No structural model of collagen VI tetramer at atomic resolution

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 5
Localization
GO:0031012 extracellular matrix 6 GO:0005576 extracellular region 3
Pathway
R-HSA-1474244 Extracellular matrix organization 5 R-HSA-5357801 Programmed Cell Death 1
Partners
COL6A2COL6A3ITGA5SOCS5THRA
Complex memberships
Collagen VI tetramer (α1/α2/α3)

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 A heterozygous in-frame deletion near the amino-terminus of the COL6A1 triple-helical domain that preserves a unique cysteine required for dimer formation allows secretion of abnormal tetramers that exert a dominant-negative effect on microfibrillar assembly, causing loss of normal collagen VI localization in the basement membrane surrounding muscle fibers. In contrast, a deletion that removes this cysteine prevents dimer formation and secretion of the mutant chain, abrogating the dominant-negative effect and resulting in a milder phenotype. In vitro fibroblast analysis of mutant chain synthesis, secretion, and extracellular matrix deposition; genotype-phenotype correlation with active-site residue (cysteine) mutagenesis context American journal of human genetics High 12840783
1998 A heterozygous nonsense mutation in COL6A1 generates unstable mRNA subject to nonsense-mediated decay, causing haploinsufficiency of the α1(VI) subunit and reduced production of structurally normal collagen VI, leading to Bethlem myopathy. RT-PCR, mRNA stability analysis in patient fibroblasts and skeletal muscle, western blot of collagen VI production Human molecular genetics High 9580662
2009 Loss of COL6A1/type VI collagen in Col6a1−/− mice causes structurally intact but mechanically deficient pericellular matrix (PCM) in articular cartilage, altering the biomechanical environment of chondrocytes and accelerating osteoarthritis development. Col6a1 knockout mouse model; micropipette aspiration of PCM mechanical properties; histomorphometry; bone mineral density measurement Arthritis and rheumatism High 19248115
2009 Collagen VI deficiency in Col6a1−/− myopathic mice leads to mitochondrial dysfunction and increased apoptosis in skeletal muscle via sensitization of the mitochondrial permeability transition pore (mPTP); pharmacological inhibition of cyclophilin D with Debio 025 desensitizes the mPTP and normalizes mitochondrial function and ultrastructural defects without affecting calcineurin. Col6a1−/− mouse model; mitochondrial Ca2+ retention assay; membrane potential measurement; TUNEL apoptosis assay; electron microscopy; NFAT translocation assay for calcineurin activity British journal of pharmacology High 19519726
1999 A splice site mutation in COL6A1 intron 14 causes skipping of exon 14 and in-frame deletion of 18 amino acids including a cysteine residue in the triple-helical domain. The shortened α1(VI) chain is synthesized but not secreted by fibroblasts, resulting in reduced collagen VI microfibril deposition in the extracellular matrix. RT-PCR of patient fibroblast RNA; western blot; immunofluorescence of ECM Biochemical and biophysical research communications High 10329467
2019 A deep intronic c.930+189C>T variant in COL6A1 creates a cryptic donor splice site, inserting an in-frame 72-nt pseudoexon into COL6A1 mRNA. The encoded mutant α1(VI) chain exerts a dominant-negative effect on collagen VI matrix assembly. Antisense oligomers (ASOs) targeting the pseudoexon efficiently skip it in patient-derived fibroblasts, restoring wild-type matrix. CRISPR/Cas9 deletion of the intronic sequence containing the pseudoexon also abolishes its inclusion. Muscle RNA sequencing; patient fibroblast culture; ASO splice-switching; CRISPR/Cas9 deletion; western blot; immunofluorescence of collagen VI matrix JCI insight High 30895940
2020 ASOs targeting the pseudoexon created by the COL6A1 c.930+189C>T deep intronic variant efficiently induce pseudoexon exclusion from mature transcripts in patient fibroblasts, restoring functional collagen VI microfibrillar matrix as assessed at RNA, protein, and structural levels. ASO transfection in patient-derived fibroblasts; qRT-PCR; western blot; immunofluorescence Molecular therapy. Nucleic acids High 32585628
2008 The Col6a1 gene enhancer region (−5.4 to −3.9 kb from transcription start) is required for activation of transcription in connective tissue cells associated with skeletal muscle. Using lacZ transgenic mice crossed with metD/D mutant mice (lacking myogenic cells in limb buds), the presence of myogenic-lineage cells was shown to be necessary for enhancer activation in mesenchymal cells, demonstrating that muscle cells signal to connective tissue cells to drive COL6A1 expression. Promoter-lacZ transgenic mice; genetic cross with metD/D (myogenic cell-deficient) mice; lacZ reporter expression analysis; collagen VI immunostaining Experimental cell research High 18761340
2000 The 383-bp E-L fragment (within the −5.4/−3.9 kb Col6a1 enhancer region) is the most active sequence for tissue-specific transcription; integrity of the entire E-J subfragment is required for enhancer activity in articular cartilage. EMSA showed at least 22 ubiquitous transcription factors bind this region, and their relative proportions (not tissue-specific factors) determine tissue-specific expression. Transgenic mice with deletion constructs; linker-scanning mutagenesis; electrophoretic mobility shift assay (EMSA) with nuclear extracts The Journal of biological chemistry High 10747869
2001 Activation of Col6a1 gene transcription in Schwann cells is part of their differentiation program induced by neuregulins from the neural crest; once competence to transcribe Col6a1 is established, transcriptional regulation becomes neuregulin-independent and is modulated by cell cycle status, correlating with myelination onset after birth. lacZ transgenic mouse reporter; developmental expression analysis; neuregulin-deficient genetic background Mechanisms of development Medium 11287188
2013 Truncating mutations within the COL6A1 C-terminal C2 subdomain result in intracellular retention of mutant collagen VI protein and severely decreased collagen VI matrix deposition; the absence of the α1(VI) C2 domain also leads to abnormal fibronectin network interactions, revealing a role for this domain in ECM organization. Patient fibroblast immunofluorescence; western blot; RNA analysis for NMD; fibronectin network staining BMC medical genetics Medium 23738969
2004 Dominant glycine substitutions in the triple-helical domain of COL6A1 cause disease via a dominant-negative mechanism, whereas recessive mutations (nonsense, frameshift) cause more severe phenotypes via loss of function, establishing that glycine substitutions in the triple helix act dominantly and missense/truncating mutations outside this region act recessively. Patient cell analysis; RT-PCR; western blot; immunofluorescence; parental DNA sequencing to confirm de novo status Annals of neurology Medium 16130093
2021 Upregulation of COL6A1 in osteosarcoma cells promotes migration and invasion by interacting with SOCS5 to suppress STAT1 expression via ubiquitination and proteasomal degradation. Exosomal COL6A1 derived from osteosarcoma cells converts normal fibroblasts to cancer-associated fibroblasts that secrete IL-6 and IL-8, promoting further invasion via TGF-β/COL6A1 signaling. Co-immunoprecipitation; ubiquitination assay; RNA sequencing; in vitro migration/invasion assays; exosome tracing; co-culture experiments; in vivo xenograft Theranostics Medium 33391546
2023 The COL6A1 c.930+189C>T mutation leads to secretion of the mutant α1(VI) chain as a single chain (not incorporated into tetramers) that forms large extracellular aggregates, while wild-type α1(VI) is assembled normally into tetramers. Expression of the mutant chain in α1-chain-deficient WI-26 VA4 cells confirms it cannot support tetramer assembly. Mutation-specific antibody; patient fibroblast cell culture; co-localization immunofluorescence; transfection of mutant/wild-type chains into WI-26 VA4 cells; protein secretion analysis Human mutation High 40225172
2024 COL6A1 interacts with ITGA5 (integrin alpha-5) and activates the FAK/Paxillin/AKT focal adhesion pathway in glioblastoma cells; tumor electric field therapy downregulates COL6A1, hindering its interaction with ITGA5 and suppressing this pathway. Co-immunoprecipitation; immunofluorescence co-localization; western blot of FAK/Paxillin/AKT pathway CNS neuroscience & therapeutics Low 38887185
2019 COL6A1 knockdown in PDGF-BB-stimulated vascular smooth muscle cells attenuates cell viability and invasive ability, partially reverses increased expression of fibronectin, MMP-2 and MMP-9, and inhibits AKT/mTOR pathway activation, placing COL6A1 upstream of AKT/mTOR signaling in VSMC migration. siRNA knockdown; CCK-8 viability assay; wound healing and Transwell invasion assay; western blot of pathway components Experimental and therapeutic medicine Low 31410158
2025 COL6A1 promotes osteoclast differentiation and formation in osteoarthritis by activating the EPAC/RAP1 signaling axis; COL6A1 knockdown in vivo reduces osteoclast-mediated subchondral bone remodeling and slows OA progression in DMM mouse models. WGCNA; in vitro perturbation and rescue experiments; in vivo DMM mouse model with COL6A1 knockdown; molecular docking FASEB journal Medium 40143596
2022 CRISPR/Cas9 allele-specific disruption of the dominant-negative COL6A1 c.877G>A (p.Gly293Arg) mutation in patient fibroblasts reduces mutant allele expression in >40% of reads with no effect on the wild-type allele, rescuing collagen VI extracellular matrix assembly. CRISPR/Cas9 genome editing; next-generation sequencing; droplet digital PCR with allele-specific probes; immunofluorescence of collagen VI matrix International journal of molecular sciences Medium 35457228
2024 An allele-specific siRNA with an intentional additional mismatch selectively silences the dominant-negative COL6A1 G293R (c.877G>A) mutant transcript while preserving wild-type transcript levels in patient fibroblasts, rescuing secretion and assembly of collagen VI matrix. siRNA transfection; allele-specific RT-qPCR; western blot; immunofluorescence of collagen VI matrix in patient fibroblasts Molecular therapy. Nucleic acids High 38617974
2018 A non-triple-helical polypeptide of type VI collagen α1 chain (NTH α1(VI), ~140 kDa) is encoded by COL6A1 and represents an alternative gene product with distinct glycosylation from the triple-helical form, detected in supernatants of several human cancer cell lines. Antibody characterization; western blot; lectin reactivity assays; expression in cancer cell supernatants Journal of biochemistry Low 29659864
2025 ANTXR2 (anthrax toxin receptor 2) expressed by fibro-adipogenic precursors controls COL6A1/collagen VI turnover via receptor-mediated endocytosis; Antxr2−/− mice accumulate collagen VI in intramuscular connective tissue, leading to tissue stiffening and myopathy, which is rescued in Antxr2−/−Col6a1−/− double knockout mice. Antxr2−/− and Antxr2−/−Col6a1−/− double knockout mouse models; proteomics; muscle histology; biomechanical testing; locomotion analysis bioRxivpreprint Medium bio_10.1101_2025.09.11.675515
2025 In a zebrafish col6a1 Δex14 model of Bethlem myopathy, Col6a1 deficiency leads to reduced dihydropyridine receptor (DHPR) charge movement density, a negative shift in DHPR voltage-dependence, elevated resting Ca2+ sparks (SR Ca2+ leak), and reduced twitch force, suggesting COL6A1 is required for proper DHPR function and Ca2+ homeostasis in skeletal muscle fibers. Zebrafish knockout model; electrophysiology (charge movement measurement); intracellular Ca2+ transient imaging; Ca2+ spark measurement; immunofluorescence of DHPR localization; muscle force measurement; swimming performance bioRxivpreprint Medium bio_10.1101_2025.06.02.657388
2025 In Col6a1−/− rats, absence of collagen VI reduces cardiac systolic function and paradoxically increases Ca2+ transient amplitude and SR Ca2+ load in isolated cardiomyocytes; β-adrenergic stimulation triggers diastolic Ca2+ release events in knockout cardiomyocytes, suggesting collagen VI contributes to cardiac Ca2+ regulation, potentially via linkage to the dystrophin-glycoprotein complex. Global Col6a1 knockout rat; echocardiography; cardiomyocyte Ca2+ transient imaging; SR Ca2+ load measurement; β-adrenergic stimulation protocol bioRxivpreprint Low bio_10.1101_2025.03.21.644665
2025 Thyroid hormone receptor α (TRα) directly binds the Col6a1 promoter region (identified by ChIP-seq) and positively regulates Col6a1 transcription; TRα knockdown in C2C12 myoblasts reduces Col6a1 expression and inhibits myoblast proliferation and differentiation. ChIP-seq; RNA-seq; ChIP-qPCR; siRNA knockdown of TRα; RT-qPCR; C2C12 proliferation/differentiation assays Journal of muscle research and cell motility Medium 40317420

Source papers

Stage 0 corpus · 85 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Developmental and osteoarthritic changes in Col6a1-knockout mice: biomechanics of type VI collagen in the cartilage pericellular matrix. Arthritis and rheumatism 147 19248115
2021 H3K27 acetylation activated-COL6A1 promotes osteosarcoma lung metastasis by repressing STAT1 and activating pulmonary cancer-associated fibroblasts. Theranostics 133 33391546
2003 New molecular mechanism for Ullrich congenital muscular dystrophy: a heterozygous in-frame deletion in the COL6A1 gene causes a severe phenotype. American journal of human genetics 124 12840783
2003 Genomewide linkage and linkage disequilibrium analyses identify COL6A1, on chromosome 21, as the locus for ossification of the posterior longitudinal ligament of the spine. American journal of human genetics 124 12958705
2009 The cyclophilin inhibitor Debio 025 normalizes mitochondrial function, muscle apoptosis and ultrastructural defects in Col6a1-/- myopathic mice. British journal of pharmacology 105 19519726
2007 COL6A1 polymorphisms associated with ossification of the ligamentum flavum and ossification of the posterior longitudinal ligament. Spine 87 18246005
1998 Reduced collagen VI causes Bethlem myopathy: a heterozygous COL6A1 nonsense mutation results in mRNA decay and functional haploinsufficiency. Human molecular genetics 82 9580662
2005 COL6A1, the candidate gene for ossification of the posterior longitudinal ligament, is associated with diffuse idiopathic skeletal hyperostosis in Japanese. Spine 80 16227896
2011 Quantitative secretome analysis reveals that COL6A1 is a metastasis-associated protein using stacking gel-aided purification combined with iTRAQ labeling. Journal of proteome research 64 21186846
2005 Dominant and recessive COL6A1 mutations in Ullrich scleroatonic muscular dystrophy. Annals of neurology 60 16130093
2019 A recurrent COL6A1 pseudoexon insertion causes muscular dystrophy and is effectively targeted by splice-correction therapies. JCI insight 52 30895940
2005 Detection of common and private mutations in the COL6A1 gene of patients with Bethlem myopathy. Neurology 45 15955946
1999 A heterozygous splice site mutation in COL6A1 leading to an in-frame deletion of the alpha1(VI) collagen chain in an italian family affected by bethlem myopathy. Biochemical and biophysical research communications 45 10329467
1995 Genetic variation in the COL6A1 region is associated with congenital heart defects in trisomy 21 (Down's syndrome). Annals of human genetics 40 7486833
2014 Col6a1 null mice as a model to study skin phenotypes in patients with collagen VI related myopathies: expression of classical and novel collagen VI variants during wound healing. PloS one 36 25158062
1991 The COL6A1 and COL6A2 genes exist as a gene cluster and detect highly informative DNA polymorphisms in the telomeric region of human chromosome 21q. Human genetics 32 1676701
1995 Head to tail organization of the human COL6A1 and COL6A2 genes by fiber-FISH. Genomics 31 8575781
2020 Exon-Skipping Oligonucleotides Restore Functional Collagen VI by Correcting a Common COL6A1 Mutation in Ullrich CMD. Molecular therapy. Nucleic acids 29 32585628
2008 An enhancer required for transcription of the Col6a1 gene in muscle connective tissue is induced by signals released from muscle cells. Experimental cell research 29 18761340
2007 Variable penetrance of COL6A1 null mutations: implications for prenatal diagnosis and genetic counselling in Ullrich congenital muscular dystrophy families. Neuromuscular disorders : NMD 29 17537636
2020 Non-canonical Fzd7 signaling contributes to breast cancer mesenchymal-like stemness involving Col6a1. Cell communication and signaling : CCS 27 32894152
2008 Identification of COL6A1 as a differentially expressed gene in human astrocytomas. Genetics and molecular research : GMR 26 18551403
2002 Novel COL6A1 splicing mutation in a family affected by mild Bethlem myopathy. Muscle & nerve 26 11932968
2022 CRISPR/Cas9-Mediated Allele-Specific Disruption of a Dominant COL6A1 Pathogenic Variant Improves Collagen VI Network in Patient Fibroblasts. International journal of molecular sciences 23 35457228
2015 Reactive stroma component COL6A1 is upregulated in castration-resistant prostate cancer and promotes tumor growth. Oncotarget 23 25895032
2001 Mechanisms of transcriptional activation of the col6a1 gene during Schwann cell differentiation. Mechanisms of development 22 11287188
2014 Association between BMP-2 and COL6A1 gene polymorphisms with susceptibility to ossification of the posterior longitudinal ligament of the cervical spine in Korean patients and family members. Genetics and molecular research : GMR 21 24737472
2021 Col6a1+/CD201+ mesenchymal cells regulate intestinal morphogenesis and homeostasis. Cellular and molecular life sciences : CMLS 19 34910257
2019 COL6A1 knockdown suppresses cell proliferation and migration in human aortic vascular smooth muscle cells. Experimental and therapeutic medicine 16 31410158
2015 A Nonsense Variant in COL6A1 in Landseer Dogs with Muscular Dystrophy. G3 (Bethesda, Md.) 16 26438297
2024 Identification and validation of COL6A1 as a novel target for tumor electric field therapy in glioblastoma. CNS neuroscience & therapeutics 15 38887185
2018 Association of IL17RC and COL6A1 genetic polymorphisms with susceptibility to ossification of the thoracic posterior longitudinal ligament in Chinese patients. Journal of orthopaedic surgery and research 15 29764467
2022 P4HA1 Regulates CD31 via COL6A1 in the Transition of Glioblastoma Stem-Like Cells to Tumor Endothelioid Cells. Frontiers in oncology 14 35494018
2020 The impact of COL1A1 and COL6A1 expression on hypospadias and penile curvature severity. BMC urology 14 33261612
1993 Polymorphisms and linkage disequilibrium in the COL6A1 and COL6A2 gene cluster: novel DNA polymorphisms in the region of a candidate gene for congenital heart defects in Down's syndrome. Human genetics 14 8094066
2017 Targeted deletion of RANKL in M cell inducer cells by the Col6a1-Cre driver. Biochemical and biophysical research communications 13 28882590
2013 Characterization of a rare case of Ullrich congenital muscular dystrophy due to truncating mutations within the COL6A1 gene C-terminal domain: a case report. BMC medical genetics 12 23738969
2011 COL6A1 gene and Ironman triathlon performance. International journal of sports medicine 12 22012643
1994 Unusual genotypes in the COL6A1 gene in parents of children with trisomy 21 and major congenital heart defects. Human genetics 12 7909528
2009 Lentiviral-mediated RNAi in vivo silencing of Col6a1, a gene with complex tissue specific expression pattern. Journal of biotechnology 11 19428725
2024 Optimized allele-specific silencing of the dominant-negative COL6A1 G293R substitution causing collagen VI-related dystrophy. Molecular therapy. Nucleic acids 10 38617974
2021 Identification of COL6A1 as the Key Gene Associated with Antivascular Endothelial Growth Factor Therapy in Glioblastoma Multiforme. Genetic testing and molecular biomarkers 10 33970702
2018 Type VI collagen α1 chain polypeptide in non-triple helical form is an alternative gene product of COL6A1. Journal of biochemistry 10 29659864
2021 Association analysis and functional study of COL6A1 single nucleotide polymorphisms in thoracic ossification of the ligamentum flavum in the Chinese Han population. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 8 34287704
2019 COL6A1 mutation leading to Bethlem myopathy with recurrent hematuria: a case report. BMC neurology 8 30808312
2014 Molecular Genetic Diagnosis of a Bethlem Myopathy Family with an Autosomal-Dominant COL6A1 Mutation, as Evidenced by Exome Sequencing. Journal of clinical neurology (Seoul, Korea) 8 25749816
2000 Analysis of transcription of the Col6a1 gene in a specific set of tissues suggests a new variant of enhancer region. The Journal of biological chemistry 8 10747869
2021 Intrafamilial Phenotypic Variability of Collagen VI-Related Myopathy Due to a New Mutation in the COL6A1 Gene. Journal of neuromuscular diseases 7 33337382
2021 Effect of Glucose Variability on Pancreatic Cancer Through Regulation of COL6A1. Cancer management and research 7 33603474
2007 Faithful tissue-specific expression of the human chromosome 21-linked COL6A1 gene in BAC-transgenic mice. Mammalian genome : official journal of the International Mammalian Genome Society 7 17334655
1997 Human COL6A1: genomic characterization of the globular domains, structural and evolutionary comparison with COL6A2. Mammalian genome : official journal of the International Mammalian Genome Society 7 9107679
2025 COL6A1 Promotes Milk Production and Fat Synthesis Through the PI3K-Akt/Insulin/AMPK/PPAR Signaling Pathways in Dairy Cattle. International journal of molecular sciences 6 40076877
2025 Mechanistic study of COL6A1-mediated subchondral bone remodeling in osteoarthritis via the EPAC/RAP1 axis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 6 40143596
2023 Activation and Functions of Col6a1+ Fibroblasts in Colitis-Associated Cancer. International journal of molecular sciences 6 38203319
2021 COL6A1 related muscular dystrophy in Landseer dogs: A canine model for Ullrich congenital muscular dystrophy. Muscle & nerve 6 33382107
2019 The COL6A1 rs201153092 single nucleotide polymorphism, associates with thoracic ossification of the posterior longitudinal ligament. Molecular medicine reports 6 31939624
2014 Ullrich Congenital Muscular Dystrophy Possibly Related With COL6A1 p.Gly302Arg Variant. Annals of rehabilitation medicine 5 24855628
2012 No association between COL3A1, COL6A1 or COL12A1 gene variants and range of motion. Journal of sports sciences 5 23013106
2025 Insufficient expression of COL6A1 promotes the development of early-onset severe preeclampsia by inhibiting the APJ/AKT signaling pathway. Cell death discovery 4 40025063
2025 RNA-seq and ChIP-seq unveils thyroid hormone receptor α deficiency affects skeletal muscle myoblast proliferation and differentiation via Col6a1 during aging. Journal of muscle research and cell motility 4 40317420
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
2017 A novel de novo COL6A1 mutation emphasizes the role of intron 14 donor splice site defects as a cause of moderate-progressive form of ColVI myopathy - a case report and review of the genotype-phenotype correlation. Folia neuropathologica 4 28984114
2011 Molecular mining of alleles in water buffalo Bubalus bubalis and characterization of the TSPY1 and COL6A1 genes. PloS one 4 21949806
2023 Exon-Skipping for a Pathogenic COL6A1 Variant in Ullrich Congenital Muscular Dystrophy. Methods in molecular biology (Clifton, N.J.) 3 36401040
2023 The UCMD-Causing COL6A1 (c.930 + 189C > T) Intron Mutation Leads to the Secretion and Aggregation of Single Mutated Collagen VI α1 Chains. Human mutation 3 40225172
2008 Single nucleotide polymorphism of COL6A1 in patients with ankylosing spondylitis. The Journal of rheumatology 3 18634150
2026 Col6a1 knock-in mice provide a promising pre-clinical model for collagen VI-related dystrophies. Disease models & mechanisms 2 41287928
2024 The recurrent deep intronic pseudoexon-inducing variant COL6A1 c.930+189C>T results in a consistently severe phenotype of COL6-related dystrophy: Towards clinical trial readiness for splice-modulating therapy. medRxiv : the preprint server for health sciences 2 38585825
2025 Characterization of severe COL6-related dystrophy due to the recurrent variant COL6A1 c.930+189C>T. Brain : a journal of neurology 1 40177858
2025 Substitutions of nucleotides at the 3' ends of COL6A1/2/3 exons induce exon skipping associated with collagen VI-related muscular dystrophies and therapeutic strategies. Genetics in medicine : official journal of the American College of Medical Genetics 1 40219784
2025 COL6A1, LAPTM5, and ZFAND2A as Crucial Biomolecules Driving Immunoregulation in Human Nucleus Pulposus Degeneration. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1 41124083
2024 Exome sequencing in extreme altitude mountaineers identifies pathogenic variants in RTEL1 and COL6A1 previously associated with respiratory failure. Physiological reports 1 38653581
2024 COL6A1 Inhibits the Malignant Development of Bladder Cancer by Regulating FBN1. Cell biochemistry and biophysics 1 39365515
2024 A Novel Splice Site Variant in COL6A1 Causes Ullrich Congenital Muscular Dystrophy in a Consanguineous Malian Family. Molecular genetics & genomic medicine 1 39523858
2024 Generation of a human induced pluripotent stem cell line (CRICKi021-A) from a patient with Ullrich congenital muscular dystrophy carrying a pathogenic mutation in the COL6A1 gene. Stem cell research 1 39764974
2021 A novel variant in the COL6A1 gene causing Ullrich congenital muscular dystrophy in a consanguineous family: a case report. BMC neurology 1 33750322
2026 Megakaryocyte and platelet thrombospondin-1 regulates matrix remodeling by stabilizing basement membrane COL6A1 in lung injury. Nature communications 0 41820365
2025 Generation of an iPSC line (with isogenic control) from the PBMCs of a COL6A1 (c.1056 + 2T > A) Bethlem myopathy patient. Stem cell research 0 39954549
2025 Multimodal Evaluation of Bethlem Myopathy with the c.788G > A Variant in the COL6A1 Gene: a case report with genetic, ultrasonographic, and structural-functional discordance correlations. Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology 0 40626679
2025 Inhibition of lnc-COL6A1-6-Alleviated Osteogenic Differentiation of Valvular Interstitial Cells During Aortic Valve Calcification. Cardiovascular therapeutics 0 40937116
2025 TGF-βI/FERMT2/COL6A1 Reciprocal Loop Drives Tumor-Stroma Crosstalk and Promotes Peritoneal Metastasis in Gastric Cancer. International journal of biological sciences 0 41079932
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
2025 Synergistic Anticancer Effects of COL6A1 Downregulation and the PD1 Inhibitor Pembrolizumab in Bladder Cancer. Journal of biochemical and molecular toxicology 0 41276784
2024 A humanized knock-in Col6a1 mouse recapitulates a deep-intronic splice-activating variant. bioRxiv : the preprint server for biology 0 38585878
2023 Homozygous splice variant (c.1741-6G>A) of the COL6A1 gene in three patients with Ullrich congenital muscular dystrophy. Neuromuscular disorders : NMD 0 37315421