Affinage

COL4A5

Collagen alpha-5(IV) chain · UniProt P29400

Length
1685 aa
Mass
161.0 kDa
Annotated
2026-06-09
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COL4A5 encodes the alpha5(IV) collagen chain, a structural component of basement membranes whose disruption causes X-linked Alport syndrome with nephritis and deafness (PMID:2349482). The alpha5(IV) chain is required for assembly of the alpha3/alpha4/alpha5(IV) type IV collagen network of the glomerular basement membrane: loss of COL4A5 abolishes incorporation of the alpha3(IV) chain into the GBM (PMID:8196274), and Col4a5 deficiency in vivo disrupts both the alpha3/alpha4/alpha5(IV) and alpha5/alpha5/alpha6(IV) networks (PMID:34675305). Heterotrimer assembly capacity links genotype to phenotype: deletional and splice-site mutations cause complete absence of alpha3-alpha5(IV) chains while glycine missense substitutions permit residual antigenicity (PMID:8807602), and glycine missense mutations associated with early renal failure measurably reduce intracellular trimer formation or block secretion in a split-nanoluciferase trimer assay (PMID:32405592). A large proportion of pathogenic variants act through aberrant splicing — cryptic splice site use, exon skipping, and frameshift-driven premature stop codons (PMID:8004101, PMID:35005319). COL4A5 is arranged head-to-head with COL4A6 on Xq22 and shares a bidirectional, cell-type-specific bifunctional promoter, such that growth factors selectively enhance alpha5(IV) expression in glomerular cells while enhancing alpha6(IV) in tubular cells (PMID:7972123, PMID:15598179); contiguous deletions at this shared 5' region cause Alport syndrome with diffuse leiomyomatosis (PMID:1453602, PMID:28275241). Antisense-oligonucleotide exon skipping restores alpha345(IV) heterotrimer formation, GBM alpha5 expression, and survival in a truncating-variant Alport model, providing therapeutic proof of the assembly mechanism (PMID:32488001).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1990 High

    Established the disease gene: mutations in COL4A5 cause X-linked Alport syndrome, defining alpha5(IV) as a structural GBM component whose loss produces nephritis and deafness.

    Evidence Southern blotting and restriction/genomic analysis in Alport kindreds

    PMID:2349482

    Open questions at the time
    • Did not resolve how alpha5(IV) integrates into a multi-chain network
    • Mechanism linking chain loss to GBM failure not yet defined
  2. 1994 High

    Defined the genomic architecture and regulatory context: the 51-exon COL4A5 gene sits head-to-head with COL4A6 sharing a bidirectional, tissue-specific promoter, framing both single-gene and contiguous-gene-deletion disease.

    Evidence Genomic cloning/sequencing of the gene and RT-PCR of tissue-specific transcripts

    PMID:7972123 PMID:8120014

    Open questions at the time
    • Cell-type selectivity of the promoter not yet functionally dissected
    • Regulatory elements driving glomerulus-specific COL4A5 expression unmapped
  3. 1994 Medium

    Connected COL4A5 loss to network assembly failure: gene deletion abolishes alpha5(IV) and prevents alpha3(IV) incorporation into the GBM, showing alpha5 is needed for the alpha3-containing network.

    Evidence Alloantibody binding to recombinant NC1 domains in a deletion patient

    PMID:8196274

    Open questions at the time
    • Single patient
    • Did not directly measure trimer assembly biochemistry
  4. 1992 Medium

    Explained the Alport-diffuse leiomyomatosis association as a contiguous-gene phenomenon involving 5' COL4A5 deletions extending into an adjacent gene.

    Evidence Southern blotting with COL4A5 cDNA and 5' genomic probes in DL-AS patients

    PMID:1453602

    Open questions at the time
    • Adjacent gene (COL4A6) not yet directly implicated mechanistically
    • Three patients only
  5. 1995 High

    Mapped reciprocal tissue distribution of alpha5(IV) and alpha6(IV), showing alpha5 but not alpha6 in GBM and co-localization in skin/smooth muscle, explaining tissue-restricted disease consequences.

    Evidence Immunofluorescence and Western blot with NC1-specific monoclonal antibodies across tissues

    PMID:7657706

    Open questions at the time
    • Did not define which heterotrimers form in each tissue
    • Chain stoichiometry within networks not resolved
  6. 1996 Medium

    Established a genotype-protein correlation: mutation class predicts whether alpha3-alpha5(IV) chains are absent versus retained, linking chain integrity to network assembly.

    Evidence Immunohistochemistry with chain-specific antibodies in biopsies from genotyped patients

    PMID:8807602

    Open questions at the time
    • Nine patients, single center
    • Did not measure trimer assembly directly
  7. 2000 High

    Functionally dissected the bidirectional promoter, identifying minimal promoters and a positive regulatory element active in most cell types but not glomerular visceral epithelium, explaining selective COL4A5 transcription.

    Evidence RNase protection, reporter transfections, gel shift and footprinting in defined cell lines

    PMID:11096082

    Open questions at the time
    • Transcription factors conferring glomerular selectivity not identified
    • In vivo relevance of element not tested
  8. 2005 Medium

    Showed the bifunctional promoter responds to growth factors in a cell-type-directional manner (alpha5 in glomerular cells, alpha6 in tubular cells), establishing context-dependent regulation.

    Evidence Bidirectional reporter constructs with growth-factor stimulation in cell-type-specific lines

    PMID:15598179

    Open questions at the time
    • Signalling intermediates downstream of TGF-beta/EGF/VEGF/PDGF not defined
    • Reporter assay, single lab
  9. 2008 Medium

    Demonstrated that the ratio of normal to aberrant transcript governs disease severity, using somatic mosaicism for a splice mutation producing mosaic alpha5 staining and mild phenotype.

    Evidence Sequencing/restriction mosaicism detection, urinary-sediment RT-PCR, immunohistochemistry

    PMID:18332068

    Open questions at the time
    • Single patient
    • Quantitative threshold of transcript ratio not established
  10. 2010 Medium

    Revealed that non-collagenous interruption residues are functionally critical: an interruption-domain missense caused severe disease despite normal alpha5(IV) staining, expanding function beyond bulk network assembly.

    Evidence Exon sequencing, alpha5 immunostaining, and family segregation

    PMID:20881942

    Open questions at the time
    • Molecular basis of interruption-residue function unresolved
    • Single family
  11. 2017 Medium

    Defined the mutational mechanism of AS-DL contiguous deletions as homologous recombination between COL4A5/COL4A6 repetitive elements across the shared promoter, with leiomyomatosis requiring inactivation of both genes.

    Evidence Breakpoint sequencing and repetitive-element analysis in AS-DL patients

    PMID:28275241

    Open questions at the time
    • Five patients
    • How biallelic-region loss drives smooth muscle proliferation not mechanistically shown
  12. 2020 Medium

    Provided direct biochemical proof of the assembly mechanism: glycine missense mutations tied to early renal failure reduce secreted alpha345(IV) trimer, while benign-course mutations assemble normally.

    Evidence Split-nanoluciferase alpha3/alpha4/alpha5 co-transfection trimer assay across mutants

    PMID:32405592

    Open questions at the time
    • Single lab cell-based assay
    • Does not capture in vivo GBM incorporation kinetics
  13. 2020 High

    Delivered therapeutic validation of the assembly model: ASO exon-21 skipping restores trimer formation, GBM alpha5 expression, and survival in truncating-variant Alport mice.

    Evidence Triple-helix formation assay plus in vitro/in vivo ASO treatment with immunostaining and survival readouts

    PMID:32488001

    Open questions at the time
    • Limited to specific truncating-variant context
    • Long-term durability and human translation untested
  14. 2021 Medium

    Confirmed in vivo that Col4a5 is required for assembly of both the alpha3/alpha4/alpha5 and alpha5/alpha5/alpha6 networks via a genetic knockout.

    Evidence CRISPR/rGONAD Col4a5-knockout rat with chain-specific immunostaining and ultrastructural analysis

    PMID:34675305

    Open questions at the time
    • Single lab
    • Did not isolate tissue-specific contributions of each network to pathology
  15. 2021 High

    Systematically established splicing disruption as a major pathogenic mechanism, showing last-nucleotide and intronic variants cause exon skipping or cryptic splice activation.

    Evidence Hybrid minigene splicing assays with in vivo transcript confirmation

    PMID:31481700 PMID:35005319

    Open questions at the time
    • Minigene context may not fully recapitulate native splicing
    • Quantitative effect on residual protein not measured for all variants

Open questions

Synthesis pass · forward-looking unresolved questions
  • How cell-type-specific transcription factors select COL4A5 versus COL4A6 from the shared promoter, and the molecular basis by which non-collagenous interruption residues contribute to chain function, remain unresolved.
  • No transcription factor mediating glomerular COL4A5 selectivity identified
  • Structural basis of interruption-residue requirement unknown
  • Mechanism linking COL4A5/COL4A6 biallelic loss to leiomyomatosis undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3
Localization
GO:0031012 extracellular matrix 3 GO:0005576 extracellular region 1
Pathway
R-HSA-1474244 Extracellular matrix organization 4 R-HSA-1643685 Disease 3
Partners
COL4A3COL4A4COL4A6
Complex memberships
alpha3/alpha4/alpha5(IV) collagen heterotrimeralpha5/alpha5/alpha6(IV) collagen heterotrimer

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 Mutations (intragenic deletion, Pst I site variant, uncharacterized abnormality) in COL4A5 were identified as causative for X-linked Alport syndrome, establishing that the alpha5(IV) collagen chain encoded by COL4A5 is a structural component of the glomerular basement membrane whose disruption causes nephritis and deafness. Southern blotting, restriction fragment analysis, direct genomic analysis in Alport syndrome kindreds Science High 2349482
1992 Deletions in the 5' end of COL4A5 extending beyond its 5' end are associated with Alport syndrome plus diffuse leiomyomatosis (DL), suggesting a contiguous gene deletion syndrome involving COL4A5 and an adjacent gene (later identified as COL4A6) responsible for smooth muscle proliferation. Southern blotting with cDNA probes spanning COL4A5 and 5' end genomic probe in patients with DL-AS association Kidney international Medium 1453602
1994 COL4A5 and COL4A6 genes are arranged head-to-head on chromosome Xq22 and share a bidirectional promoter region; COL4A6 is transcribed from two alternative promoters in a tissue-specific manner, with transcription start sites 442 bp and 1,492 bp from the COL4A5 transcription start site. Genomic sequencing, RT-PCR of tissue-specific transcripts, characterization of 5' flanking sequences Proceedings of the National Academy of Sciences of the United States of America High 7972123
1994 The COL4A5 gene contains 51 exons spanning ~140 kb of DNA, with exon size and distribution pattern highly homologous to COL4A1; the complete exon structure was determined from genomic lambda phage clones. Genomic cloning and sequencing of 17 lambda phage clones covering the COL4A5 gene The Journal of biological chemistry High 8120014
1994 COL4A5 gene deletion in an Alport patient leads to absence of alpha5(IV) chain in the glomerular basement membrane and production of post-transplant alloantibodies directed against the alpha3(IV) chain (not alpha5(IV)), establishing that COL4A5 mutations cause defective assembly of the alpha3(IV) chain into the GBM network. Circulating antibody binding assay to GBM constituents, recombinant NC1 domains of human type IV collagen chains, COL4A5 gene deletion analysis Kidney international Medium 8196274
1994 Splice site mutations in COL4A5 cause aberrant mRNA splicing including use of cryptic splice sites within exons, exon skipping, and incorporation of frameshift mutations leading to premature stop codons; female carriers show variable stability of mutated mRNA relative to normal transcript. RT-PCR and mRNA analysis of COL4A5 splice site mutations in patients and carriers Human molecular genetics Medium 8004101
1993 COL4A5 mRNA undergoes differential tissue-specific splicing: an 18 bp sequence (encoding two Gly-X-Y triplets) is present between exons 10 and 11 in kidney mRNA but absent in white blood cell mRNA, indicating a kidney-specific additional exon. A complex mutation deleting part of the triple helical domain and the entire NC1 domain was identified in an Alport patient. RT-PCR of COL4A5 cDNA from lymphoblasts and kidney tissue, direct sequencing Kidney international Medium 8301933
1995 The alpha5(IV) and alpha6(IV) chains encoded by COL4A5 and COL4A6 show distinct tissue-specific distribution: alpha5(IV) is present in glomerular basement membrane but alpha6(IV) is absent there, whereas both are co-localized in skin, smooth muscle cells, and adipocyte basement membranes. In Bowman's capsule and distal tubules, alpha6(IV) is present but its pattern differs from alpha5(IV). Immunofluorescence with peptide-specific rat monoclonal antibodies against NC1 domains of alpha5(IV) and alpha6(IV); Western blotting The Journal of cell biology High 7657706
1996 The type and severity of COL4A5 mutation determines the immunohistochemical expression pattern of alpha3(IV)-alpha5(IV) collagen chains in the glomerular basement membrane: deletional and splice site mutations cause complete absence of alpha3(IV)-alpha5(IV) chains, while glycine missense substitutions generally permit residual antigenicity of these chains, demonstrating that alpha5(IV) chain integrity is required for the assembly of the alpha3/alpha4/alpha5 network. Immunohistochemistry with monoclonal antibody series recognizing alpha1(IV)-alpha6(IV) chains in kidney biopsies from patients with identified COL4A5 mutations Kidney international Medium 8807602
1998 Deletions at the 5' end of COL4A5 extending into COL4A6 in diffuse leiomyomatosis/Alport syndrome involve breakpoints with topoisomerase I and II consensus sequences; immunohistochemical analysis confirms absence of alpha5(IV) and alpha6(IV) chains in most basement membranes of the smooth muscle tumor, with mosaic staining in one patient indicating somatic mosaicism. Characterization of deletion breakpoints by sequencing; immunohistochemistry with alpha-chain-specific monoclonal antibodies American journal of human genetics Medium 9463311
2000 The proximal bidirectional promoter between COL4A5 and COL4A6 contains minimal promoters within 100 bp of each transcription start site that are functionally distinct; a bidirectional positive regulatory element functions in multiple cell types but not in glomerular visceral epithelial cells (which selectively transcribe COL4A5). The intergenic region is 292 bp. RNase protection assays for transcription start site mapping; transient transfections with reporter gene constructs; gel shift and footprinting assays The Journal of biological chemistry High 11096082
2005 The bifunctional promoter between COL4A5 and COL4A6 regulates their expression in a cell-specific manner: in glomerular endothelial and mesangial cells, TGF-beta, EGF, VEGF, and PDGF enhance alpha5(IV) expression but not alpha6(IV); in tubular epithelial cells, the same growth factors enhance alpha6(IV) but not alpha5(IV) expression. Reporter gene constructs with bidirectional promoter, transient transfection in cell-type-specific lines, growth factor stimulation assays The Biochemical journal Medium 15598179
2004 A large tandem duplication of 35 COL4A5 exons (~65% increase in collagenous domain length) causes Alport syndrome with a founder effect in French Polynesia; the duplicated alpha5(IV) chain can still assemble into the type IV collagen network as demonstrated by immunofluorescence, yet uniformly produces thin GBM in males and variable severity of renal disease. Linkage analysis, mutation screening, immunofluorescence analysis of type IV collagen assembly Kidney international Medium 15149316
2006 Chromosomal translocation t(X;6)(q13-14;q22) in subungual exostosis rearranges both COL4A5 (at Xq22) and COL12A1 (at 6q13-14), with FISH showing these two collagen genes consistently co-localizing on derivative chromosomes, suggesting formation of a chimeric fusion gene or regulatory sequence exchange. Interphase and metaphase FISH on tumor cells from five subungual exostoses International journal of cancer Medium 16284948
2017 Contiguous deletions at the 5' ends of COL4A5 and COL4A6 that cause Alport syndrome-diffuse leiomyomatosis involve the bidirectional promoter region shared by both genes; eight of nine deletion alleles involve sequences homologous between COL4A5 and COL4A6, with breakpoints in transposed elements (LINEs, SINEs, DNA transposons, LTR retrotransposons), indicating homologous recombination as the mutational mechanism. Leiomyomatosis requires inactivation of both genes. Breakpoint characterization by sequencing in five AS-DL patients; analysis of repetitive element content at breakpoints Journal of human genetics Medium 28275241
2020 Exon skipping using antisense oligonucleotides (ASO) targeting exon 21 of COL4A5 in truncating variant Alport syndrome enables formation of the type IV collagen alpha3/alpha4/alpha5 heterotrimer (demonstrated by triple helix formation assay), restores alpha5 chain expression on glomerular and tubular basement membranes in vivo, and prolongs survival in treated mice. Type IV collagen alpha3/alpha4/alpha5 chain triple helix formation assay; in vitro and in vivo ASO treatment; immunostaining; survival analysis in mouse model Nature communications High 32488001
2020 A cell-based split nanoluciferase assay measuring alpha345(IV) heterotrimer formation showed that COL4A5 glycine missense mutations associated with early proteinuria and renal failure significantly reduce secreted trimer, either by reducing intracellular trimer formation or blocking secretion; mutations without early proteinuria showed trimer formation and secretion patterns similar to wild-type. Split nanoluciferase-fused alpha3/alpha5 mutant and alpha4 co-transfection assay measuring intracellular and secreted heterotrimer by luminescence Kidney international reports Medium 32405592
2021 Col4a5-deficient rats generated by CRISPR/rGONAD show disruption of both alpha3/alpha4/alpha5(IV) and alpha5/alpha5/alpha6(IV) type IV collagen networks in the kidney, demonstrating that Col4a5 is required for assembly of both collagen IV heterotrimeric networks in vivo. CRISPR-mediated Col4a5 knockout in rats; immunostaining for collagen IV alpha chain distribution; histological and ultrastructural analysis Scientific reports Medium 34675305
2018 A Col4a5 R471X nonsense mutation introduced into mice by CRISPR/Cas9 abolishes Col4a5 mRNA and protein expression in kidney, producing proteinuria, hematuria, glomerulosclerosis, interstitial fibrosis, and GBM irregular thickening with lamination consistent with Alport syndrome. CRISPR/Cas9 knock-in mouse model; RT-PCR and Western blot for Col4a5 expression; pathological and electron microscopy analysis Biochemistry and biophysics reports Medium 30582011
2010 A COL4A5 missense mutation (p.F222C) in a non-collagenous interruption of the collagenous domain causes severe glomerular disease with global/segmental glomerulosclerosis and rapid progression to ESRD in males despite normal alpha5(IV) immunostaining, demonstrating that non-collagenous interruption residues are functionally critical for COL4A5 function beyond its structural role in basement membrane network assembly. Exon sequencing of COL4A5 in affected family; immunostaining for alpha5(IV) collagen in renal biopsies; segregation analysis in family Kidney international Medium 20881942
2021 Single-base substitutions at the last nucleotide position of COL4A5 exons cause aberrant splicing (confirmed in 85% of 20 variants tested), resulting in exon skipping or cryptic splice site activation, as determined by hybrid minigene functional splicing assay; in vivo transcript analyses confirmed minigene results in all three cases tested. Hybrid minigene splicing assay; in vivo transcript analysis by RT-PCR of patient samples Kidney international reports High 35005319
2019 In vitro splicing assays using hybrid minigenes for seven COL4A5 intronic mutations revealed exon skipping in four variants, combined exon skipping and insertion in one, and no change (likely non-pathogenic) in one, providing mechanistic determination of pathogenicity for intronic COL4A5 variants. Hybrid minigene in vitro splicing assay; comparison to patient transcript data where available Scientific reports Medium 31481700
2008 Somatic mosaicism for a COL4A5 splice acceptor mutation (c.3998-2 a>t) causes mosaic alpha5(IV) staining in glomeruli and a mild phenotype; mRNA analysis from urinary sediments demonstrated both normal transcript and transcript with exon 44 skipping in the same patient, establishing that the ratio of normal to abnormal transcript determines disease severity. Direct sequencing showing two allele peaks; restriction enzyme analysis confirming mosaicism; RT-PCR of urinary sediment mRNA; immunohistochemistry Nephrology, dialysis, transplantation Medium 18332068

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Critical care medicine 4335 12682500
2003 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive care medicine 1678 12664219
1990 Identification of mutations in the COL4A5 collagen gene in Alport syndrome. Science (New York, N.Y.) 710 2349482
2010 An official ATS clinical policy statement: Congenital central hypoventilation syndrome: genetic basis, diagnosis, and management. American journal of respiratory and critical care medicine 340 20208042
1997 Mammalian homologues of the Polycomb-group gene Enhancer of zeste mediate gene silencing in Drosophila heterochromatin and at S. cerevisiae telomeres. The EMBO journal 249 9214638
1995 Differential expression of two basement membrane collagen genes, COL4A6 and COL4A5, demonstrated by immunofluorescence staining using peptide-specific monoclonal antibodies. The Journal of cell biology 239 7657706
1996 Casein kinase II phosphorylates I kappa B alpha at S-283, S-289, S-293, and T-291 and is required for its degradation. Molecular and cellular biology 175 8622692
2012 Ube3a-ATS is an atypical RNA polymerase II transcript that represses the paternal expression of Ube3a. Human molecular genetics 160 22493002
2020 Cas9 gene therapy for Angelman syndrome traps Ube3a-ATS long non-coding RNA. Nature 135 33087932
2013 Truncation of Ube3a-ATS unsilences paternal Ube3a and ameliorates behavioral defects in the Angelman syndrome mouse model. PLoS genetics 134 24385930
1996 Spectrum of mutations in the COL4A5 collagen gene in X-linked Alport syndrome. American journal of human genetics 133 8940267
1996 X-linked Alport syndrome: an SSCP-based mutation survey over all 51 exons of the COL4A5 gene. American journal of human genetics 119 8651296
2010 Anaplasma phagocytophilum Ats-1 is imported into host cell mitochondria and interferes with apoptosis induction. PLoS pathogens 116 20174550
2013 Correlation of mutation status and survival with predominant histologic subtype according to the new IASLC/ATS/ERS lung adenocarcinoma classification in stage III (N2) patients. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 104 23486266
1998 High mutation detection rate in the COL4A5 collagen gene in suspected Alport syndrome using PCR and direct DNA sequencing. Journal of the American Society of Nephrology : JASN 104 9848783
1992 Alport syndrome and diffuse leiomyomatosis: deletions in the 5' end of the COL4A5 collagen gene. Kidney international 96 1453602
1997 Collagen-binding heat shock protein (HSP) 47 expression in anti-thymocyte serum (ATS)-induced glomerulonephritis. The Journal of pathology 81 9370943
2018 ERS/ATS workshop report on respiratory health effects of household air pollution. The European respiratory journal 79 29301918
2007 Cell size at S phase initiation: an emergent property of the G1/S network. PLoS computational biology 79 17432928
1999 Detection of mutations in COL4A5 in patients with Alport syndrome. Human mutation 78 10094548
1994 Structure of the human type IV collagen COL4A5 gene. The Journal of biological chemistry 76 8120014
2016 Lung Adenocarcinoma Staging Using the 2011 IASLC/ATS/ERS Classification: A Pooled Analysis of Adenocarcinoma In Situ and Minimally Invasive Adenocarcinoma. Clinical lung cancer 73 27137345
2007 Management and treatment of Andersen-Tawil syndrome (ATS). Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 72 17395133
2020 Development of an exon skipping therapy for X-linked Alport syndrome with truncating variants in COL4A5. Nature communications 71 32488001
1994 The genes COL4A5 and COL4A6, coding for basement membrane collagen chains alpha 5(IV) and alpha 6(IV), are located head-to-head in close proximity on human chromosome Xq22 and COL4A6 is transcribed from two alternative promoters. Proceedings of the National Academy of Sciences of the United States of America 69 7972123
1996 Relationship between COL4A5 gene mutation and distribution of type IV collagen in male X-linked Alport syndrome. Japanese Alport Network. Kidney international 68 8807602
2007 Sixteen novel mutations identified in COL4A3, COL4A4, and COL4A5 genes in Slovenian families with Alport syndrome and benign familial hematuria. Kidney international 58 17396119
1998 Ultrastructural and immunohistochemical findings in Alport's syndrome: a study of 108 patients from 97 Italian families with particular emphasis on COL4A5 gene mutation correlations. Journal of the American Society of Nephrology : JASN 53 9621285
2005 Distinct roles for p53 transactivation and repression in preventing UCN-01-mediated abrogation of DNA damage-induced arrest at S and G2 cell cycle checkpoints. Oncogene 51 15782134
2017 Dihydroorotate dehydrogenase Inhibitors Target c-Myc and Arrest Melanoma, Myeloma and Lymphoma cells at S-phase. Journal of Cancer 50 28928900
2014 The new IASLC/ATS/ERS lung adenocarcinoma classification from a clinical perspective: current concepts and future prospects. Journal of thoracic disease 50 25349703
1999 Identification of COL4A5 defects in Alport's syndrome by immunohistochemistry of skin. Kidney international 48 10200983
2022 Genotype-Phenotype Correlations for Pathogenic COL4A3-COL4A5 Variants in X-Linked, Autosomal Recessive, and Autosomal Dominant Alport Syndrome. Frontiers in medicine 46 35602506
2020 Isolation and structural characterization of a novel polysaccharide from Hericium erinaceus fruiting bodies and its arrest of cell cycle at S-phage in colon cancer cells. International journal of biological macromolecules 44 32339580
1994 COL4A5 gene deletion and production of post-transplant anti-alpha 3(IV) collagen alloantibodies in Alport syndrome. Kidney international 44 8196274
2005 Maternal disruption of Ube3a leads to increased expression of Ube3a-ATS in trans. Nucleic acids research 43 16027444
2012 miR-21 induces cell cycle at S phase and modulates cell proliferation by down-regulating hMSH2 in lung cancer. Journal of cancer research and clinical oncology 42 22806311
2005 Novel COL4A5, COL4A4, and COL4A3 mutations in Alport syndrome. Human mutation 42 15954103
1996 Identification of 17 mutations in ten exons in the COL4A5 collagen gene, but no mutations found in four exons in COL4A6: a study of 250 patients with hematuria and suspected of having Alport syndrome. Journal of the American Society of Nephrology : JASN 42 8738805
1992 Deletions of the COL4A5 gene in patients with Alport syndrome. Kidney international 42 1474765
2019 New frontiers to cure Alport syndrome: COL4A3 and COL4A5 gene editing in podocyte-lineage cells. European journal of human genetics : EJHG 41 31754267
2012 Snf1/AMPK regulates Gcn5 occupancy, H3 acetylation and chromatin remodelling at S. cerevisiae ADY2 promoter. Biochimica et biophysica acta 41 22306658
2006 Rearrangement of the COL12A1 and COL4A5 genes in subungual exostosis: molecular cytogenetic delineation of the tumor-specific translocation t(X;6)(q13-14;q22). International journal of cancer 41 16284948
1998 Topoisomerase I and II consensus sequences in a 17-kb deletion junction of the COL4A5 and COL4A6 genes and immunohistochemical analysis of esophageal leiomyomatosis associated with Alport syndrome. American journal of human genetics 40 9463311
2013 Adequacy of CT-guided biopsies with histomolecular subtyping of pulmonary adenocarcinomas: influence of ATS/ERS/IASLC guidelines. Lung cancer (Amsterdam, Netherlands) 39 23927885
1999 Detection of mutations in the COL4A5 gene in over 90% of male patients with X-linked Alport's syndrome by RT-PCR and direct sequencing. American journal of kidney diseases : the official journal of the National Kidney Foundation 39 10561141
2018 COL4A5 and LAMA5 variants co-inherited in familial hematuria: digenic inheritance or genetic modifier effect? BMC nephrology 37 29764427
2015 Coinheritance of COL4A5 and MYO1E mutations accentuate the severity of kidney disease. Pediatric nephrology (Berlin, Germany) 37 25739341
2013 Transmissible gastroenteritis virus infection induces cell cycle arrest at S and G2/M phases via p53-dependent pathway. Virus research 37 24095767
2013 X-linked, COL4A5 hypomorphic Alport mutations such as G624D and P628L may only exhibit thin basement membrane nephropathy with microhematuria and late onset kidney failure. Hippokratia 37 24470729
2010 The Alport syndrome COL4A5 variant database. Human mutation 37 20574986
1994 Aberrant splicing of the COL4A5 gene in patients with Alport syndrome. Human molecular genetics 36 8004101
2016 Association between the histological subtype of lung adenocarcinoma, EGFR/KRAS mutation status and the ALK rearrangement according to the novel IASLC/ATS/ERS classification. Oncology letters 35 27073516
2016 Gibberellins Regulate Ovule Integument Development by Interfering with the Transcription Factor ATS. Plant physiology 35 27794102
2014 X-linked Alport syndrome caused by splicing mutations in COL4A5. Clinical journal of the American Society of Nephrology : CJASN 34 25183659
2014 Correlation of EGFR mutation and histological subtype according to the IASLC/ATS/ERS classification of lung adenocarcinoma. International journal of clinical and experimental pathology 34 25550848
2009 Alport retinopathy results from "severe" COL4A5 mutations and predicts early renal failure. Clinical journal of the American Society of Nephrology : CJASN 34 19965530
2005 Detection of mutations in the COL4A5 gene by analyzing cDNA of skin fibroblasts. Kidney international 34 15780079
2001 Detection of mutations in the COL4A5 gene by SSCP in X-linked Alport syndrome. Human mutation 33 11462238
2021 Last Nucleotide Substitutions of COL4A5 Exons Cause Aberrant Splicing. Kidney international reports 32 35005319
2015 Porcine epidemic diarrhea virus M protein blocks cell cycle progression at S-phase and its subcellular localization in the porcine intestinal epithelial cells. Acta virologica 31 26435150
2014 Disialoganglioside GD3-synthase over expression inhibits survival and angiogenesis of pancreatic cancer cells through cell cycle arrest at S-phase and disruption of integrin-β1-mediated anchorage. The international journal of biochemistry & cell biology 31 24842107
2019 Novel mutations of COL4A3, COL4A4, and COL4A5 genes in Chinese patients with Alport Syndrome using next generation sequence technique. Molecular genetics & genomic medicine 30 30968591
2010 Classic swine fever virus NS2 protein leads to the induction of cell cycle arrest at S-phase and endoplasmic reticulum stress. Virology journal 27 20064240
2004 A large tandem duplication within the COL4A5 gene is responsible for the high prevalence of Alport syndrome in French Polynesia. Kidney international 27 15149316
1993 Differential splicing of COL4A5 mRNA in kidney and white blood cells: a complex mutation in the COL4A5 gene of an Alport patient deletes the NC1 domain. Kidney international 27 8301933
2008 Somatic mosaicism for a mutation of the COL4A5 gene is a cause of mild phenotype male Alport syndrome. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 25 18332068
2022 The Contribution of COL4A5 Splicing Variants to the Pathogenesis of X-Linked Alport Syndrome. Frontiers in medicine 23 35211492
2016 R-Phycoerythrin Induces SGC-7901 Apoptosis by Arresting Cell Cycle at S Phase. Marine drugs 23 27626431
2015 Novel Pactamycin Analogs Induce p53 Dependent Cell-Cycle Arrest at S-Phase in Human Head and Neck Squamous Cell Carcinoma (HNSCC) Cells. PloS one 23 25938491
2017 Chalepin: A Compound from Ruta angustifolia L. Pers Exhibits Cell Cycle Arrest at S phase, Suppresses Nuclear Factor-Kappa B (NF-κB) Pathway, Signal Transducer and Activation of Transcription 3 (STAT3) Phosphorylation and Extrinsic Apoptotic Pathway in Non-small Cell Lung Cancer Carcinoma (A549). Pharmacognosy magazine 22 29142404
2020 Trimerization and Genotype-Phenotype Correlation of COL4A5 Mutants in Alport Syndrome. Kidney international reports 21 32405592
2018 Establishment of X-linked Alport syndrome model mice with a Col4a5 R471X mutation. Biochemistry and biophysics reports 21 30582011
1995 Major COL4A5 gene rearrangements in patients with juvenile type Alport syndrome. American journal of medical genetics 21 8599366
2017 Characterization of contiguous gene deletions in COL4A6 and COL4A5 in Alport syndrome-diffuse leiomyomatosis. Journal of human genetics 20 28275241
2017 Novel mutations in COL4A3, COL4A4, and COL4A5 in Chinese patients with Alport Syndrome. PloS one 20 28542346
2005 Bifunctional promoter of type IV collagen COL4A5 and COL4A6 genes regulates the expression of alpha5 and alpha6 chains in a distinct cell-specific fashion. The Biochemical journal 20 15598179
2019 Determination of the pathogenicity of known COL4A5 intronic variants by in vitro splicing assay. Scientific reports 19 31481700
2018 Molecular signatures in IASLC/ATS/ERS classified growth patterns of lung adenocarcinoma. PloS one 19 30352093
2014 A novel COL4A5 mutation identified in a Chinese Han family using exome sequencing. BioMed research international 19 25110662
2015 Transition from two to one integument in Prunus species: expression pattern of INNER NO OUTER (INO), ABERRANT TESTA SHAPE (ATS) and ETTIN (ETT). The New phytologist 18 25991552
2005 Inhibition of the herpes simplex virus type 1 DNA polymerase induces hyperphosphorylation of replication protein A and its accumulation at S-phase-specific sites of DNA damage during infection. Journal of virology 18 15890955
2000 Mutational analysis of COL4A5 gene in Korean Alport syndrome. Pediatric nephrology (Berlin, Germany) 17 10684360
2019 Identification of a novel COL4A5 mutation in the proband initially diagnosed as IgAN from a Chinese family with X-linked Alport syndrome. Science China. Life sciences 16 31209800
2006 A two-tier approach to mutation detection in the COL4A5 gene for Alport syndrome. Human mutation 16 16941480
2022 Dissecting the genotype-phenotype correlation of COL4A5 gene mutation and its response to renin-angiotensin-aldosterone system blockers in Chinese male patients with Alport syndrome. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 15 35020912
2013 Clinical relevance of the new IASLC/ERS/ATS adenocarcinoma classification. Journal of clinical pathology 15 23564952
1994 Mutations in the COL4A5 gene in Alport syndrome: a possible mutation in primordial germ cells. Kidney international 15 7853788
2025 The UBE3A-ATS antisense oligonucleotide rugonersen in children with Angelman syndrome: a phase 1 trial. Nature medicine 14 40646322
2021 Creation of X-linked Alport syndrome rat model with Col4a5 deficiency. Scientific reports 14 34675305
2017 Associations between epidermal growth factor receptor mutations and histological subtypes of lung adenocarcinoma according to the IASLC/ATS/ERS classification in Chinese patients. Thoracic cancer 14 28940943
2010 Novel X-linked glomerulopathy is associated with a COL4A5 missense mutation in a non-collagenous interruption. Kidney international 14 20881942
2008 MLPA and cDNA analysis improves COL4A5 mutation detection in X-linked Alport syndrome. Clinical genetics 14 18616531
2015 A COL4A5 mutation with glomerular disease and signs of chronic thrombotic microangiopathy. Clinical kidney journal 13 26613025
2015 Associations between the IASLC/ATS/ERS lung adenocarcinoma classification and EGFR and KRAS mutations. Pathology 13 27020204
2000 Regulation of the paired type IV collagen genes COL4A5 and COL4A6. Role of the proximal promoter region. The Journal of biological chemistry 13 11096082
1997 Ammonia inhibits proliferation and cell cycle progression at S-phase in human gastric cells. Digestive diseases and sciences 13 9246035
1992 Construction of a yeast artificial chromosome contig encompassing the human alpha 5(IV) collagen gene (COL4A5). Genomics 13 1427889
2014 Pulmonary adenocarcinoma: implications of the recent advances in molecular biology, treatment and the IASLC/ATS/ERS classification. Journal of thoracic disease 12 25349702
1995 A nonsense mutation in the COL4A5 collagen gene in a family with X-linked juvenile Alport syndrome. Kidney international 12 7731166

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