Affinage

COL4A4

Collagen alpha-4(IV) chain · UniProt P53420

Length
1690 aa
Mass
164.0 kDa
Annotated
2026-06-09
79 papers in source corpus 13 papers cited in narrative 13 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COL4A4 encodes the α4 chain of type IV collagen, a structural component of the glomerular basement membrane (GBM) that assembles with the α3 and α5 chains into the α3α4α5(IV) heterotrimer (PMID:10534397, PMID:36514391). The gene is arranged head-to-head with COL4A3 on chromosome 2q36 under a shared bidirectional promoter, with two alternative transcripts—an epithelial-predominant exon 1 form and a ubiquitously expressed low-level exon 1' form—driving tissue-specific expression (PMID:9537506). Deletion of Col4a3/Col4a4 in mice eliminates both chains from the GBM and produces severe progressive glomerulonephritis with Alport-like ultrastructural changes, establishing the α4 chain as essential for GBM integrity and indicating that GBM-cell interactions govern glomerular cell maturation (PMID:10534397). Heterotrimer assembly is initiated at the chain N-termini, and a homozygous G394S missense variant impairs N-terminal trimer assembly and reduces secretion by ~50% while leaving C-terminal association intact, localizing the assembly defect to the N-terminus (PMID:36514391). In addition to complete loss of protein, in-frame mutations can yield dysfunctional trimers that are still secreted and incorporated into the GBM at reduced levels, recapitulating the abnormal collagen accumulation seen in a subset of Alport patients (PMID:24522496). A major share of pathogenic COL4A4 alleles act not by altering coding sequence directly but by disrupting pre-mRNA splicing: synonymous, intronic, and deep-intronic variants cause exon skipping (e.g. exons 27 and 38) or frameshifting truncations that impair α3α4α5(IV) heterotrimer formation and secretion (PMID:39190490, PMID:41050124, PMID:42204651). Intracellular retention of misfolded mutant collagen IV chains activates the unfolded protein response, a candidate modifier of disease severity (PMID:25514610). Collectively, COL4A4 loss-of-function and dominant-negative alleles produce a spectrum of glomerular disease ranging from thin basement membrane nephropathy to autosomal recessive Alport syndrome (PMID:9792860, PMID:10534397, PMID:41050124).

Mechanistic history

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

    Established the genomic architecture and regulation of COL4A4, showing it shares a bidirectional promoter with COL4A3 and uses alternative promoters to achieve tissue-specific versus ubiquitous expression.

    Evidence RACE, RNase protection, and genomic sequencing with tissue expression analysis

    PMID:9537506

    Open questions at the time
    • Does not establish which transcript predominates in glomerular podocytes/endothelium
    • Regulatory factors binding the GC/CCAAT boxes not identified
  2. 1998 High

    Defined the complete 48-exon structure of COL4A4 and linked loss-of-function mutations to autosomal recessive Alport syndrome, while showing not all glycine substitutions in collagen IV are pathogenic.

    Evidence Genomic structure characterization and comprehensive PCR/sequencing screen in patients and controls

    PMID:9792860

    Open questions at the time
    • Does not resolve the molecular basis distinguishing benign from pathogenic glycine substitutions
    • No protein-level assembly data
  3. 1999 High

    Demonstrated in vivo that loss of the α4 chain eliminates the α3α4α5(IV) network from the GBM and causes Alport-like progressive glomerulonephritis, establishing the chain as essential for GBM integrity.

    Evidence Col4a3/Col4a4 deletion mouse with immunohistochemistry, RT-PCR, and GBM electron microscopy

    PMID:10534397

    Open questions at the time
    • Deletion removes both Col4a3 and Col4a4, so chain-specific contributions are not separable
    • Mechanism of persistent cell proliferation not defined
  4. 2014 High

    Showed that in-frame mutations can produce dysfunctional trimers that are still secreted and incorporated into the GBM, distinguishing this mechanism from complete protein absence.

    Evidence Spontaneous Col4a4 splice-donor mouse causing in-frame exon 30 skipping, with GBM protein analysis and electron microscopy

    PMID:24522496

    Open questions at the time
    • Does not define how the abnormal trimer alters GBM mechanics
    • Structural consequences of the missing exon 30 segment not resolved
  5. 2014 Medium

    Implicated the unfolded protein response as a candidate modifier of phenotypic severity, since mutant collagen IV chains are retained intracellularly and differentially activate the UPR.

    Evidence Podocyte transfection with wild-type/mutant chains and UPR pathway activation assays

    PMID:25514610

    Open questions at the time
    • Experiment used mutant COL4A3, not COL4A4, chains; COL4A4 context inferred
    • No in vivo demonstration that UPR modifies disease severity
  6. 2022 High

    Localized the assembly defect of a pathogenic missense variant to the heterotrimer N-terminus, showing G394S impairs N-terminal assembly and halves secretion while sparing C-terminal association.

    Evidence Split NanoLuciferase α3α4α5(IV) heterotrimer formation assays (N- and C-terminal tags) in HEK293T cells

    PMID:36514391

    Open questions at the time
    • Single variant tested; generality across missense variants not established
    • In vitro assay does not capture GBM incorporation
  7. 2022 Medium

    Began discriminating splicing-disrupting from neutral non-coding variants, with two tested COL4A4 variants showing no splicing effect while COL4A3 variants altered splicing.

    Evidence In vitro minigene splicing assays in HEK293T and HeLa cells

    PMID:35386907

    Open questions at the time
    • Tested COL4A4 variants were negative, providing no positive COL4A4 splicing mechanism
    • Minigene context may not reflect native splicing
  8. 2024 High

    Connected a common splicing event to glomerular phenotypes, showing exon 27 skipping impairs heterotrimer formation and secretion and associates with hematuria and albuminuria.

    Evidence TWAS (UK Biobank + GTEx), glomerular mRNA replication, and split NanoLuc heterotrimer assay

    PMID:39190490

    Open questions at the time
    • Effect of a common-allele splicing event on lifetime disease risk not quantified
    • Tissue regulation of the splicing event not detailed
  9. 2024 Medium

    Confirmed at the RNA level that a canonical splice-acceptor variant deletes exon 10 to yield a truncated protein, reinforcing splicing disruption as a recurrent pathogenic route.

    Evidence Whole-exome sequencing with RT-PCR cDNA analysis in a family

    PMID:36699462

    Open questions at the time
    • Single family; protein-level consequence predicted, not measured
    • No GBM analysis
  10. 2025 Medium

    Documented compound dual exon-skipping (exons 27 and 38) from deep intronic variants disrupting heterotrimer assembly, requiring RNA-based diagnostics to detect.

    Evidence Whole-transcriptome sequencing, exon-specific PCR, and immunofluorescence for the α3α4α5(IV) heterotrimer

    PMID:41050124

    Open questions at the time
    • Single case
    • Quantitative effect of dual skipping on residual trimer not measured
  11. 2025 Medium

    Confirmed at the RNA level a splice-acceptor variant producing a premature stop and severely truncated protein, extending the catalog of validated splicing-disrupting alleles.

    Evidence Whole-exome sequencing with in vivo RNA splicing validation from blood and urine

    PMID:40406358

    Open questions at the time
    • Single case
    • Functional GBM/heterotrimer consequence not directly assayed
  12. 2026 High

    Systematically established that synonymous and intronic COL4A4 variants are predominantly pathogenic through pre-mRNA splicing disruption rather than coding-sequence change.

    Evidence Quantitative minigene splicing assays in HEK293T and HeLa cells across 14 variants with ACMG/AMP reclassification

    PMID:42204651

    Open questions at the time
    • Minigene constructs may not reproduce all native splicing contexts
    • Direct protein-assembly consequences for each variant not measured

Open questions

Synthesis pass · forward-looking unresolved questions
  • How specific splicing/assembly defects quantitatively translate into the clinical spectrum from thin basement membrane nephropathy to Alport syndrome, and whether UPR activation causally modifies severity in vivo, remains unresolved.
  • No genotype-to-severity quantitative model
  • UPR modifier role not tested in vivo for COL4A4
  • Native-context splicing regulation incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3
Localization
GO:0005576 extracellular region 3 GO:0031012 extracellular matrix 2
Pathway
R-HSA-1474244 Extracellular matrix organization 2 R-HSA-8953854 Metabolism of RNA 2
Partners
COL4A3COL4A5
Complex memberships
α3α4α5(IV) collagen heterotrimer

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 COL4A3 and COL4A4 genes are arranged head-to-head on chromosome 2q36, sharing a bidirectional promoter region. COL4A4 has two alternative transcripts from two different promoters: one transcription start site (exon 1') is only 5 bp from the COL4A3 start site, while the other (exon 1) starts 373 nucleotides downstream. The exon 1 transcript is expressed predominantly in epithelial cells, while the exon 1' transcript shows ubiquitous low expression. The promoter region contains CpG dinucleotides, GC boxes, CTC boxes, and a CCAAT box but no TATA box. RACE, RNase protection assays, genomic DNA sequencing, tissue expression analysis FEBS letters High 9537506
1998 The COL4A4 gene contains 48 exons encoding the alpha4 type IV collagen chain. Loss-of-function mutations (nonsense, frameshift, missense in collagenous domain) cause autosomal recessive Alport syndrome. A glycine-to-alanine substitution in the collagenous domain found in ~11.5% of controls and in a homozygous control individual does not produce an obvious phenotype, indicating not all glycine substitutions in collagen IV are pathogenic. Complete genomic structure characterization, comprehensive gene screen by PCR/sequencing in patients and controls American journal of human genetics High 9792860
1999 Deletion of Col4a4 exons 1–12 (along with Col4a3 exons 1–2 and the intergenic promoter) in mice results in complete absence of both Col4a3 and Col4a4 transcripts and both proteins from the glomerular basement membrane, causing severe progressive glomerulonephritis with GBM ultrastructural changes resembling Alport syndrome. Persistent cellular proliferation in mutant kidneys suggests interaction with extracellular matrix is important for cell maturation. Transgenic insertional mutagenesis, FISH mapping, RT-PCR (transcript detection), immunohistochemistry/protein analysis, electron microscopy of GBM Genomics High 10534397
2014 A spontaneous Col4a4 splice-donor mutation (G-to-A in intron 30) causes skipping of exon 30 while maintaining the reading frame. The resulting mutant collagen α3α4α5(IV) trimers are secreted and incorporated into the GBM, but at reduced levels, and typical Alport GBM lesions develop. This is the only mouse model shown to accumulate abnormal collagen IV trimers in the GBM (as found in a subset of human Alport patients), demonstrating that missense/in-frame mutations can produce dysfunctional trimers rather than complete absence. Genetic mapping, DNA sequencing, protein analysis of GBM content, albuminuria measurement, electron microscopy Kidney international High 24522496
2014 Functional studies in cultured podocytes transfected with wild-type or mutant COL4A3 chains showed retention of mutant collagens intracellularly and differential activation of the unfolded protein response (UPR) cascade, indicating UPR activation as a potential modifier of phenotypic severity in collagen IV nephropathies caused by COL4A3/COL4A4 mutations. Cell transfection (podocytes), UPR pathway activation assays PloS one Medium 25514610
2022 A novel homozygous COL4A4 missense variant G394S impairs assembly of the α3α4α5(IV) heterotrimer N-terminus and reduces secretion by approximately 50% compared to wild-type, as demonstrated by split NanoLuciferase-based heterotrimer formation assays in HEK293T cells. C-terminal tag assays showed comparable luminescence to WT, indicating the defect is specific to N-terminal trimer assembly and subsequent secretion. Split NanoLuciferase (N-terminal and C-terminal) α3α4α5(IV) heterotrimer formation assay in HEK293T cells, immunofluorescence, targeted DNA sequencing Kidney360 High 36514391
2024 Skipping of COL4A4 exon 27 (genetically predicted by intronic variant rs11898094, minor allele frequency 13%) is associated with hematuria and urinary albumin excretion. Functional assays using the split NanoLuc-based α3α4α5(IV) heterotrimer assay demonstrated that loss of exon 27 impairs type IV collagen heterotrimer formation and secretion. Transcriptome-wide association study (TWAS) using UK Biobank + GTEx kidney cortex data, independent replication in glomeruli-derived mRNA (n=245), split NanoLuc heterotrimer formation assay Journal of the American Society of Nephrology : JASN High 39190490
2022 Minigene assay in HEK293T/HeLa cells demonstrated that presumed missense variant COL4A3 c.4793T>G (p.Leu1598Arg) causes loss of an alternative full-length transcript during splicing, and synonymous variant COL4A3 c.765G>A (p.Thr255Thr) leads to in-frame deletion of exon 13. In contrast, COL4A4 variants c.3990G>A (p.Pro1330Pro) and c.4766C>T (p.Pro1589Leu) exhibited no deleterious effect on splicing. In vitro minigene splicing assay in HEK293T and HeLa cells Frontiers in medicine Medium 35386907
2025 Dual exon-skipping events at COL4A4 exons 27 and 38 (caused by compound heterozygous deep intronic variants) disrupt α3α4α5(IV) heterotrimer assembly, as confirmed by immunofluorescence analysis. This represents the first documented case of dual COL4A4 exon-skipping events contributing to autosomal recessive Alport syndrome severity. RNA-based diagnostics (whole-transcriptome sequencing) were required to detect these variants missed by DNA sequencing. Whole-transcriptome sequencing, exon-specific PCR, Sanger sequencing, immunofluorescence for α3α4α5(IV) heterotrimer Kidney medicine Medium 41050124
2026 Minigene assays in HEK293T and HeLa cells for 14 synonymous and intronic COL4A3/COL4A4 variants showed that 13 caused aberrant splicing (predominantly exon skipping), including frameshift transcripts with premature termination codons and in-frame exon skipping events. These results demonstrate that synonymous and intronic variants in COL4A4 cause pathogenic effects primarily through disruption of pre-mRNA splicing rather than direct coding-sequence alteration. In vitro minigene splicing assay in HEK293T and HeLa cells, quantitative splicing analysis, ACMG/AMP reclassification Human genomics High 42204651
2025 The COL4A4 c.817-1G>A splice acceptor site mutation disrupts mRNA splicing by affecting the splice acceptor site of intron 13 adjacent to exon 14, causing a 1-bp deletion before exon 14 and creating a premature stop codon. The resulting truncated protein is predicted to be 273 amino acids rather than the full-length 1,690 amino acids. Whole-exome sequencing, in vivo splicing validation using RNA from blood and urine (RT-PCR, Sanger sequencing) Frontiers in pediatrics Medium 40406358
2024 The COL4A4 splicing variant c.595-1G>A abolishes the canonical splice acceptor site of intron 9 and causes a single nucleotide deletion of exon 10, predicted to produce a truncated protein, as demonstrated by complementary DNA analysis. Whole exome sequencing, Sanger sequencing, RT-PCR cDNA analysis Frontiers in genetics Medium 36699462
2016 A COL4A4 splicing mutation (c.1459+1G>A) causes elimination of the entire exon 21 from COL4A4 cDNA, resulting in direct splicing of exons 20 and 22 and a frameshift mutation after exon 20 in the open reading frame, as demonstrated by RT-PCR and TA cloning of patient RNA. Direct sequencing, RT-PCR, TA cloning of cDNA Scientific reports Medium 26833262

Source papers

Stage 0 corpus · 79 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 COL4A3/COL4A4 mutations: from familial hematuria to autosomal-dominant or recessive Alport syndrome. Kidney international 167 12028435
2013 COL4A3/COL4A4 mutations and features in individuals with autosomal recessive Alport syndrome. Journal of the American Society of Nephrology : JASN 134 24052634
2009 Clinico-pathological correlations in 127 patients in 11 large pedigrees, segregating one of three heterozygous mutations in the COL4A3/ COL4A4 genes associated with familial haematuria and significant late progression to proteinuria and chronic kidney disease from focal segmental glomerulosclerosis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 124 19357112
1998 Determination of the genomic structure of the COL4A4 gene and of novel mutations causing autosomal recessive Alport syndrome. American journal of human genetics 114 9792860
2004 Autosomal-dominant Alport syndrome: natural history of a disease due to COL4A3 or COL4A4 gene. Kidney international 112 15086897
1997 Autosomal dominant Alport syndrome linked to the type IV collage alpha 3 and alpha 4 genes (COL4A3 and COL4A4). Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 106 9269635
2020 Prevalence of clinical, pathological and molecular features of glomerular basement membrane nephropathy caused by COL4A3 or COL4A4 mutations: a systematic review. Clinical kidney journal 76 33391746
2009 Autosomal dominant Alport syndrome: molecular analysis of the COL4A4 gene and clinical outcome. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 74 19129241
2009 Polymorphisms in COL4A3 and COL4A4 genes associated with keratoconus. Molecular vision 66 20029656
2003 Mutations in the COL4A4 gene in thin basement membrane disease. Kidney international 59 12631110
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
2001 COL4A4 mutation in thin basement membrane disease previously described in Alport syndrome. Kidney international 56 11473630
2014 Frequency of COL4A3/COL4A4 mutations amongst families segregating glomerular microscopic hematuria and evidence for activation of the unfolded protein response. Focal and segmental glomerulosclerosis is a frequent development during ageing. PloS one 55 25514610
1999 Insertional mutation of the collagen genes Col4a3 and Col4a4 in a mouse model of Alport syndrome. Genomics 54 10534397
2005 Novel COL4A5, COL4A4, and COL4A3 mutations in Alport syndrome. Human mutation 42 15954103
2014 A mouse Col4a4 mutation causing Alport glomerulosclerosis with abnormal collagen α3α4α5(IV) trimers. Kidney international 41 24522496
1998 Two genes, COL4A3 and COL4A4 coding for the human alpha3(IV) and alpha4(IV) collagen chains are arranged head-to-head on chromosome 2q36. FEBS letters 38 9537506
2003 Novel COL4A4 splice defect and in-frame deletion in a large consanguine family as a genetic link between benign familial haematuria and autosomal Alport syndrome. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 36 12748344
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
2008 COL4A3/COL4A4 mutations link familial hematuria and focal segmental glomerulosclerosis. glomerular epithelium destruction via basement membrane thinning? Connective tissue research 28 18661361
2007 Nine novel COL4A3 and COL4A4 mutations and polymorphisms identified in inherited membrane diseases. Pediatric nephrology (Berlin, Germany) 28 17216251
2015 Evaluation of possible relationship between COL4A4 gene polymorphisms and risk of keratoconus. Cornea 24 25651396
2014 Whole exome sequencing reveals novel COL4A3 and COL4A4 mutations and resolves diagnosis in Chinese families with kidney disease. BMC nephrology 23 25381091
2014 Polymorphism analysis of COL4A3 and COL4A4 genes in Greek patients with keratoconus. Ophthalmic genetics 22 25083577
2016 A novel heterozygous COL4A4 missense mutation in a Chinese family with focal segmental glomerulosclerosis. Journal of cellular and molecular medicine 21 27469977
2017 Novel mutations in COL4A3, COL4A4, and COL4A5 in Chinese patients with Alport Syndrome. PloS one 20 28542346
2019 Effect of heterozygous pathogenic COL4A3 or COL4A4 variants on patients with X-linked Alport syndrome. Molecular genetics & genomic medicine 19 30883042
2014 Collagen type IV-related nephropathies in Portugal: pathogenic COL4A3 and COL4A4 mutations and clinical characterization of 25 families. Clinical genetics 19 25307543
2002 Three novel COL4A4 mutations resulting in stop codons and their clinical effects in autosomal recessive Alport syndrome. Human mutation 19 12325029
2001 Benign familial hematuria associated with a novel COL4A4 mutation. Pediatric nephrology (Berlin, Germany) 18 11685592
2022 Presumed COL4A3/COL4A4 Missense/Synonymous Variants Induce Aberrant Splicing. Frontiers in medicine 15 35386907
2024 Increased prevalence of kidney cysts in individuals carrying heterozygous COL4A3 or COL4A4 pathogenic variants. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 12 38317457
2020 How to resolve confusion in the clinical setting for the diagnosis of heterozygous COL4A3 or COL4A4 gene variants? Discussion and suggestions from nephrologists. Clinical and experimental nephrology 12 32232700
2012 Common variants in the COL4A4 gene confer susceptibility to lattice degeneration of the retina. PloS one 11 22723992
2022 Heterozygous COL4A3/COL4A4 mutations: the hidden part of the iceberg? Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 9 35090027
2014 COL4A4 gene study of a European population: description of new mutations causing autosomal dominant Alport syndrome. International journal of molecular epidemiology and genetics 9 25755845
2023 A Deeper Insight into COL4A3, COL4A4, and COL4A5 Variants and Genotype-Phenotype Correlation of a Turkish Cohort with Alport Syndrome. Molecular syndromology 8 38357258
2016 Identification of a novel collagen type IV alpha-4 (COL4A4) mutation in a Chinese family with autosomal dominant Alport syndrome using exome sequencing. The Indian journal of medical research 8 27934798
2022 Analysis of the association of ANO3/MUC15, COL4A4, RRBP1, and KLK1 polymorphisms with COPD susceptibility in the Kashi population. BMC pulmonary medicine 7 35513865
2020 Association of TIMP-1 and COL4A4 Gene Polymorphisms with Keratoconus in an Iranian Population. Journal of ophthalmic & vision research 7 32864060
2019 Identification of a Novel COL4A4 Variant in Compound-Heterozygous State in a Patient With Alport Syndrome and Histological Findings Similar to Focal Segmental Glomerulosclerosis (FSGS). Frontiers in genetics 7 30745910
2016 A Novel COL4A4 Mutation Identified in a Chinese Family with Thin Basement Membrane Nephropathy. Scientific reports 7 26833262
2013 COL4A4-related nephropathy caused by a novel mutation in a large consanguineous Saudi family. International journal of pediatric otorhinolaryngology 7 24398087
2009 Identification of novel variants in the COL4A4 gene in Korean patients with thin basement membrane nephropathy. The Indian journal of medical research 7 19675380
2023 The multifaceted roles of COL4A4 in lung adenocarcinoma: An integrated bioinformatics and experimental study. Computers in biology and medicine 6 38217972
2022 A COL4A4-G394S Variant and Impaired Collagen IV Trimerization in a Patient with Mild Alport Syndrome. Kidney360 6 36514391
2019 A Nonsense Mutation in COL4A4 Gene Causing Isolated Hematuria in Either Heterozygous or Homozygous State. Frontiers in genetics 6 31312213
2017 Mutation analysis of COL4A3 and COL4A4 genes in a Chinese autosomal-dominant Alport syndrome family. Journal of genetics 6 28674241
2024 Four novel mutations identified in the COL4A3, COL4A4 and COL4A5 genes in 10 families with Alport syndrome. BMC medical genomics 5 38978054
2024 Association of Genetically Predicted Skipping of COL4A4 Exon 27 with Hematuria and Albuminuria. Journal of the American Society of Nephrology : JASN 5 39190490
2020 A novel heterozygous variant of the COL4A4 gene in a Chinese family with hematuria and proteinuria leads to focal segmental glomerulosclerosis and chronic kidney disease. Molecular genetics & genomic medicine 5 33159707
2020 Heterozygous Urinary Abnormality-Causing Variants of COL4A3 and COL4A4 Affect Severity of Autosomal Recessive Alport Syndrome. Kidney360 5 35369551
2019 Association of KIF26B and COL4A4 gene polymorphisms with the risk of keratoconus in a sample of Iranian population. International ophthalmology 5 31077021
2018 Novel variants in COL4A4 and COL4A5 are rare causes of FSGS in two unrelated families. Human genome variation 5 30002862
2022 A Novel Homozygous Mutation in the COL4A4 Gene (Gly1436del) Causing Alport Syndrome Exposed by Pregnancy: A Case Report and Review of the Literature. Case reports in nephrology 3 35028164
2018 The COL4A3 and COL4A4 Digenic Mutations in cis Result in Benign Familial Hematuria in a Large Chinese Family. Cytogenetic and genome research 3 29742505
2023 Identification of COL4A4 variants in Chinese patients with familial hematuria. Frontiers in genetics 2 36699462
2022 Novel heterozygous mutation in COL4A4 responsible for Alport syndrome in a Chinese family. Frontiers in genetics 2 36159970
2021 Clinical and pathohistological characteristics of Alport spectrum disorder caused by COL4A4 mutation c.193-2A>C: a case series. Croatian medical journal 2 34212557
2021 Autosomal recessive Alport syndrome caused by a novel COL4A4 compound heterozygous mutation: A case report. Clinical nephrology 2 34448697
2019 Autosomal dominant Alport syndrome due to a COL4A4 mutation with an additional ESPN variant detected by whole-exome analysis. CEN case reports 2 31677115
2005 Evaluation of canine COL4A3 and COL4A4 as candidates for familial renal disease in the Norwegian elkhound. The Journal of heredity 2 16014809
2025 Whole exome sequencing shows novel COL4A3 and COL4A4 variants as causes of Alport syndrome in Rio Grande do Norte, Brazil. BMC genomics 1 40169949
2025 Lithuanian Study on COL4A3 and COL4A4 Genetic Variants in Alport Syndrome: Clinical Characterization of 52 Individuals from 38 Families. International journal of molecular sciences 1 40806767
2024 Alport Syndrome With a Rare Collagen Type IV Alpha-4 (COL4A4) Gene Mutation: A Case Report. Cureus 1 39398663
2021 Establishment of the induced pluripotent stem cell line (NCKDi005-A) from a male patient with Alport syndrome carrying a homozygous frameshift mutation in the COL4A4 gene. Stem cell research 1 34942480
2021 A novel compound heterozygous COL4A4 mutation in a Chinese family with Alport syndrome: A care case report. Medicine 1 34964757
2019 Autosomal recessive Alport syndrome caused by a novel COL4A4 splice site mutation: a case report. Croatian medical journal 1 31686460
2026 Functional validation of spliceogenic COL4A3 and COL4A4 variants by minigene assays refines molecular diagnosis of Alport syndrome. Human genomics 0 42204651
2025 The heterozygous mutation COL4A4 c.817-1G>A causes Alport syndrome in a Chinese family: a case report. Frontiers in pediatrics 0 40406358
2025 Severe Clinical Phenotype in Alport Syndrome Due to 2 COL4A4 Exon-Skipping Events. Kidney medicine 0 41050124
2025 Expanding the COL4A4 variant spectrum: genotype-phenotype correlation in 19 Chinese children using updated Alport kidney disease classification. Renal failure 0 41087309
2025 Case Report: A novel TTN gene variant and a concurrent rare COL4A4 gene variant in a Chinese patient with dilated cardiomyopathy. Frontiers in cardiovascular medicine 0 41306271
2024 Novel Digenic Variants in COL4A4 and COL4A5 Causing X-Linked Alport Syndrome: A Case Report. Case reports in nephrology and dialysis 0 38179179
2024 A case report: Alport syndrome and growth hormone deficiency associated with a new COL4A4 mutation. Translational pediatrics 0 38840691
2023 The same heterozygous Col4A4 mutation triggered different renal pathological changes in Chinese family members. Frontiers in genetics 0 37323683
2023 [Genetic analysis of a patient with Alport syndrome due to compound heterozygous variants of COL4A4 gene]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 37643964
2023 Potential Founder Variants in COL4A4 Identified in Bukharian Jews Linked to Autosomal Dominant and Autosomal Recessive Alport Syndrome. Genes 0 37895203
2022 COL4A4 variant recently identified: lessons learned in variant interpretation-a case report. BMC nephrology 0 35842573

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