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    COL4A4 collagen type IV alpha 4 chain [ Homo sapiens (human) ]

    Gene ID: 1286, updated on 3-Nov-2024

    Summary

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    Official Symbol
    COL4A4provided by HGNC
    Official Full Name
    collagen type IV alpha 4 chainprovided by HGNC
    Primary source
    HGNC:HGNC:2206
    See related
    Ensembl:ENSG00000081052 MIM:120131; AllianceGenome:HGNC:2206
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    BFH; ATS2; BFH1; CA44
    Summary
    This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. This particular collagen IV subunit, however, is only found in a subset of basement membranes. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. Mutations in this gene are associated with type II autosomal recessive Alport syndrome (hereditary glomerulonephropathy) and with familial benign hematuria (thin basement membrane disease). Two transcripts, differing only in their transcription start sites, have been identified for this gene and, as is common for collagen genes, multiple polyadenylation sites are found in the 3' UTR. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in kidney (RPKM 5.3), thyroid (RPKM 4.9) and 18 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See COL4A4 in Genome Data Viewer
    Location:
    2q36.3
    Exon count:
    57
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (226967360..227164488, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (227431447..227647252, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (227867430..228028921, complement)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene MPRA-validated peak4064 silencer Neighboring gene MPRA-validated peak4065 silencer Neighboring gene microRNA 5702 Neighboring gene Sharpr-MPRA regulatory region 3334 Neighboring gene MPRA-validated peak4066 silencer Neighboring gene Sharpr-MPRA regulatory region 11623 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12389 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:227661675-227662624 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12390 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12391 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12392 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12393 Neighboring gene insulin receptor substrate 1 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:227677874-227678445 Neighboring gene Sharpr-MPRA regulatory region 3963 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12394 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17195 Neighboring gene rhomboid domain containing 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12395 Neighboring gene MPRA-validated peak4067 silencer Neighboring gene small nucleolar RNA SNORA48 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17196 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr2:227859794-227860993 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:227929821-227930408 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:228028248-228029149 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12397 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:228050272-228050810 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr2:228055439-228056638 Neighboring gene collagen type IV alpha 3 chain Neighboring gene MFF divergent transcript Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:228185522-228186050 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17198 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12398 Neighboring gene stress induced phosphoprotein 1 pseudogene 2 Neighboring gene mitochondrial fission factor

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Benign familial hematuria due to mutation of the type IV collagen alpha4 gene. Lemmink HH, et al. J Clin Invest, 1996 Sep 1. PMID 8787673, Free PMC Article
    2. A novel heterozygous COL4A4 missense mutation in a Chinese family with focal segmental glomerulosclerosis. Wu Y, et al. J Cell Mol Med, 2016 Dec. PMID 27469977, Free PMC Article
    3. Three Novel Heterozygous COL4A4 Mutations Result in Three Different Collagen Type IV Kidney Disease Phenotypes. Li A, et al. Cytogenet Genome Res, 2018. PMID 29669314
    4. Mutations in the COL4A4 gene in thin basement membrane disease. Buzza M, et al. Kidney Int, 2003 Feb. PMID 12631110
    5. [Clinical and genetic diagnosis of a pedigree affected with autosomal recessive Alport syndrome]. Ge L, et al. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2019 Sep 10. PMID 31515789

    See all (124) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Four novel mutations identified in the COL4A3, COL4A4 and COL4A5 genes in 10 families with Alport syndrome.
      Title: Four novel mutations identified in the COL4A3, COL4A4 and COL4A5 genes in 10 families with Alport syndrome.
    2. The multifaceted roles of COL4A4 in lung adenocarcinoma: An integrated bioinformatics and experimental study.
      Title: The multifaceted roles of COL4A4 in lung adenocarcinoma: An integrated bioinformatics and experimental study.
    3. Genetic diagnosis of Alport syndrome in 16 Chinese families.
      Title: Genetic diagnosis of Alport syndrome in 16 Chinese families.
    4. Is there a dominant-negative effect in individuals with heterozygous disease-causing variants in COL4A3/COL4A4?
      Title: Is there a dominant-negative effect in individuals with heterozygous disease-causing variants in COL4A3/COL4A4?
    5. Potential Founder Variants in COL4A4 Identified in Bukharian Jews Linked to Autosomal Dominant and Autosomal Recessive Alport Syndrome.
      Title: Potential Founder Variants in COL4A4 Identified in Bukharian Jews Linked to Autosomal Dominant and Autosomal Recessive Alport Syndrome.
    6. COL4A gene variants are common in children with hematuria and a family history of kidney disease.
      Title: COL4A gene variants are common in children with hematuria and a family history of kidney disease.
    7. Genetic Variants of the COL4A3 , COL4A4 , and COL4A5 Genes Contribute to Thinned Glomerular Basement Membrane Lesions in Sporadic IgA Nephropathy Patients.
      Title: Genetic Variants of the COL4A3 , COL4A4 , and COL4A5 Genes Contribute to Thinned Glomerular Basement Membrane Lesions in Sporadic IgA Nephropathy Patients.
    8. A COL4A4-G394S Variant and Impaired Collagen IV Trimerization in a Patient with Mild Alport Syndrome.
      Title: A COL4A4-G394S Variant and Impaired Collagen IV Trimerization in a Patient with Mild Alport Syndrome.
    9. Heterozygous COL4A3/COL4A4 mutations: the hidden part of the iceberg?
      Title: Heterozygous COL4A3/COL4A4 mutations: the hidden part of the iceberg?
    10. COL4A4 variant recently identified: lessons learned in variant interpretation-a case report.
      Title: COL4A4 variant recently identified: lessons learned in variant interpretation-a case report.
    Submit: New GeneRIF Correction See all GeneRIFs (69)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Alport syndrome
    MedGen: C1567741 GeneReviews: Not available
    		not available
    Autosomal recessive Alport syndrome
    MedGen: C4746745 OMIM: 203780 GeneReviews: Alport Syndrome
    		not available
    Hematuria, benign familial, 1
    MedGen: CN376803 OMIM: 141200 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp160, precursor env HIV-1 gp160 and serum-free macrophage supernatant (MSP) enhance synthesis of type IV collagen by mesangial cells; anti-TGF-beta antibodies attenuate this gp160/MSP-induced collagen synthesis PubMed
    Tat tat HIV-1 Tat enhances adhesion of human U937 monocyte-like cells to proteins of the extracellular matrix, such as collagen IV, laminin, and ECM1 PubMed
    tat Treatment with cannabinoids inhibits HIV-1 Tat-enhanced attachment of U937 cells to collagen IV, laminin, or ECM1 proteins, which is linked to the cannabinoid receptor type 2 and the modulation of beta1-integrin and actin distribution PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables extracellular matrix structural constituent IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables extracellular matrix structural constituent conferring tensile strength IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables extracellular matrix structural constituent conferring tensile strength RCA
    inferred from Reviewed Computational Analysis
    more info
    		 PubMed 
    enables molecular adaptor activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in glomerular basement membrane development IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in glomerular basement membrane development IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in basement membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of collagen type IV trimer IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of collagen type IV trimer IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in collagen-containing extracellular matrix HDA PubMed 
    is_active_in collagen-containing extracellular matrix IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in endoplasmic reticulum lumen TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    collagen alpha-4(IV) chain
    Names
    Collagen IV, alpha-4 polypeptide
    collagen of basement membrane, alpha-4 chain
    collagen, type IV, alpha 4

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_011592.1 RefSeqGene

      Range
      5001..166849
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_231

    mRNA and Protein(s)

    1. NM_000092.5 → NP_000083.3  collagen alpha-4(IV) chain precursor

      See identical proteins and their annotated locations for NP_000083.3

      Status: REVIEWED

      Source sequence(s)
      AC073149, AC079235, BX094848, X81053
      Consensus CDS
      CCDS42828.1
      UniProtKB/Swiss-Prot
      A8MTZ1, P53420, Q53RW9, Q53S42, Q53WR1
      Related
      ENSP00000379866.3, ENST00000396625.5
      Conserved Domains (2) summary
      pfam01391
      Location:829 → 880
      Collagen; Collagen triple helix repeat (20 copies)
      pfam01413
      Location:1466 → 1570
      C4; C-terminal tandem repeated domain in type 4 procollagen

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      226967360..227164488 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011510565.3 → XP_011508867.1  collagen alpha-4(IV) chain isoform X10

      Conserved Domains (1) summary
      pfam01391
      Location:829 → 880
      Collagen; Collagen triple helix repeat (20 copies)

    2. XM_011510570.3 → XP_011508872.1  collagen alpha-4(IV) chain isoform X13

      See identical proteins and their annotated locations for XP_011508872.1

      Conserved Domains (1) summary
      pfam01391
      Location:829 → 880
      Collagen; Collagen triple helix repeat (20 copies)

    3. XM_011510562.3 → XP_011508864.1  collagen alpha-4(IV) chain isoform X7

      See identical proteins and their annotated locations for XP_011508864.1

      Conserved Domains (3) summary
      pfam01391
      Location:829 → 880
      Collagen; Collagen triple helix repeat (20 copies)
      pfam01413
      Location:1466 → 1570
      C4; C-terminal tandem repeated domain in type 4 procollagen
      cl02467
      Location:1574 → 1607
      C4; C-terminal tandem repeated domain in type 4 procollagen

    4. XM_047443250.1 → XP_047299206.1  collagen alpha-4(IV) chain isoform X13

    5. XM_047443245.1 → XP_047299201.1  collagen alpha-4(IV) chain isoform X7

    6. XM_011510569.3 → XP_011508871.1  collagen alpha-4(IV) chain isoform X13

      See identical proteins and their annotated locations for XP_011508871.1

      Conserved Domains (1) summary
      pfam01391
      Location:829 → 880
      Collagen; Collagen triple helix repeat (20 copies)

    7. XM_011510567.3 → XP_011508869.1  collagen alpha-4(IV) chain isoform X11

      See identical proteins and their annotated locations for XP_011508869.1

      Conserved Domains (1) summary
      pfam01391
      Location:829 → 880
      Collagen; Collagen triple helix repeat (20 copies)

    8. XM_047443249.1 → XP_047299205.1  collagen alpha-4(IV) chain isoform X11

    9. XM_011510566.3 → XP_011508868.1  collagen alpha-4(IV) chain isoform X11

      See identical proteins and their annotated locations for XP_011508868.1

      Conserved Domains (1) summary
      pfam01391
      Location:829 → 880
      Collagen; Collagen triple helix repeat (20 copies)

    10. XM_047443248.1 → XP_047299204.1  collagen alpha-4(IV) chain isoform X11

    11. XM_011510561.3 → XP_011508863.1  collagen alpha-4(IV) chain isoform X7

      See identical proteins and their annotated locations for XP_011508863.1

      Conserved Domains (3) summary
      pfam01391
      Location:829 → 880
      Collagen; Collagen triple helix repeat (20 copies)
      pfam01413
      Location:1466 → 1570
      C4; C-terminal tandem repeated domain in type 4 procollagen
      cl02467
      Location:1574 → 1607
      C4; C-terminal tandem repeated domain in type 4 procollagen

    12. XM_011510560.3 → XP_011508862.1  collagen alpha-4(IV) chain isoform X6

      See identical proteins and their annotated locations for XP_011508862.1

      Conserved Domains (3) summary
      pfam01391
      Location:829 → 880
      Collagen; Collagen triple helix repeat (20 copies)
      pfam01413
      Location:1466 → 1570
      C4; C-terminal tandem repeated domain in type 4 procollagen
      cl02467
      Location:1574 → 1605
      C4; C-terminal tandem repeated domain in type 4 procollagen

    13. XM_047443242.1 → XP_047299198.1  collagen alpha-4(IV) chain isoform X6

    14. XM_011510559.3 → XP_011508861.1  collagen alpha-4(IV) chain isoform X6

      See identical proteins and their annotated locations for XP_011508861.1

      Conserved Domains (3) summary
      pfam01391
      Location:829 → 880
      Collagen; Collagen triple helix repeat (20 copies)
      pfam01413
      Location:1466 → 1570
      C4; C-terminal tandem repeated domain in type 4 procollagen
      cl02467
      Location:1574 → 1605
      C4; C-terminal tandem repeated domain in type 4 procollagen

    15. XM_047443241.1 → XP_047299197.1  collagen alpha-4(IV) chain isoform X6

    16. XM_047443228.1 → XP_047299184.1  collagen alpha-4(IV) chain isoform X1

      UniProtKB/Swiss-Prot
      A8MTZ1, P53420, Q53RW9, Q53S42, Q53WR1

    17. XM_005246281.4 → XP_005246338.1  collagen alpha-4(IV) chain isoform X1

      See identical proteins and their annotated locations for XP_005246338.1

      UniProtKB/Swiss-Prot
      A8MTZ1, P53420, Q53RW9, Q53S42, Q53WR1
      Conserved Domains (2) summary
      pfam01391
      Location:829 → 880
      Collagen; Collagen triple helix repeat (20 copies)
      pfam01413
      Location:1466 → 1570
      C4; C-terminal tandem repeated domain in type 4 procollagen

    18. XM_005246282.4 → XP_005246339.1  collagen alpha-4(IV) chain isoform X8

      Conserved Domains (2) summary
      pfam01391
      Location:644 → 695
      Collagen; Collagen triple helix repeat (20 copies)
      pfam01413
      Location:1281 → 1385
      C4; C-terminal tandem repeated domain in type 4 procollagen

    19. XM_011510558.3 → XP_011508860.1  collagen alpha-4(IV) chain isoform X3

      Conserved Domains (2) summary
      pfam01391
      Location:793 → 844
      Collagen; Collagen triple helix repeat (20 copies)
      pfam01413
      Location:1430 → 1534
      C4; C-terminal tandem repeated domain in type 4 procollagen

    20. XM_011510557.3 → XP_011508859.1  collagen alpha-4(IV) chain isoform X2

      Conserved Domains (2) summary
      pfam01391
      Location:829 → 880
      Collagen; Collagen triple helix repeat (20 copies)
      pfam01413
      Location:1439 → 1543
      C4; C-terminal tandem repeated domain in type 4 procollagen

    21. XM_017003297.2 → XP_016858786.1  collagen alpha-4(IV) chain isoform X4

    22. XM_006712246.4 → XP_006712309.1  collagen alpha-4(IV) chain isoform X5

      Conserved Domains (3) summary
      pfam01391
      Location:829 → 880
      Collagen; Collagen triple helix repeat (20 copies)
      pfam01413
      Location:1511 → 1623
      C4; C-terminal tandem repeated domain in type 4 procollagen
      cl02467
      Location:1445 → 1507
      C4; C-terminal tandem repeated domain in type 4 procollagen

    23. XM_011510572.4 → XP_011508874.1  collagen alpha-4(IV) chain isoform X14

      Conserved Domains (2) summary
      pfam01391
      Location:271 → 322
      Collagen; Collagen triple helix repeat (20 copies)
      pfam01413
      Location:908 → 1012
      C4; C-terminal tandem repeated domain in type 4 procollagen

    24. XM_047443246.1 → XP_047299202.1  collagen alpha-4(IV) chain isoform X9

    25. XM_011510568.3 → XP_011508870.1  collagen alpha-4(IV) chain isoform X12

      Conserved Domains (1) summary
      pfam01391
      Location:829 → 880
      Collagen; Collagen triple helix repeat (20 copies)

    RNA

    1. XR_922837.3 RNA Sequence

    2. XR_001738602.2 RNA Sequence

    3. XR_007069255.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      227431447..227647252 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054340451.1 → XP_054196426.1  collagen alpha-4(IV) chain isoform X10

    2. XM_054340458.1 → XP_054196433.1  collagen alpha-4(IV) chain isoform X13

    3. XM_054340447.1 → XP_054196422.1  collagen alpha-4(IV) chain isoform X7

    4. XM_054340455.1 → XP_054196430.1  collagen alpha-4(IV) chain isoform X11

    5. XM_054340453.1 → XP_054196428.1  collagen alpha-4(IV) chain isoform X11

    6. XM_054340454.1 → XP_054196429.1  collagen alpha-4(IV) chain isoform X11

    7. XM_054340452.1 → XP_054196427.1  collagen alpha-4(IV) chain isoform X11

    8. XM_054340457.1 → XP_054196432.1  collagen alpha-4(IV) chain isoform X13

    9. XM_054340448.1 → XP_054196423.1  collagen alpha-4(IV) chain isoform X7

    10. XM_054340446.1 → XP_054196421.1  collagen alpha-4(IV) chain isoform X6

    11. XM_054340444.1 → XP_054196419.1  collagen alpha-4(IV) chain isoform X6

    12. XM_054340445.1 → XP_054196420.1  collagen alpha-4(IV) chain isoform X6

    13. XM_054340443.1 → XP_054196418.1  collagen alpha-4(IV) chain isoform X6

    14. XM_054340437.1 → XP_054196412.1  collagen alpha-4(IV) chain isoform X1

    15. XM_054340438.1 → XP_054196413.1  collagen alpha-4(IV) chain isoform X1

    16. XM_054340449.1 → XP_054196424.1  collagen alpha-4(IV) chain isoform X8

    17. XM_054340440.1 → XP_054196415.1  collagen alpha-4(IV) chain isoform X3

    18. XM_054340439.1 → XP_054196414.1  collagen alpha-4(IV) chain isoform X2

    19. XM_054340441.1 → XP_054196416.1  collagen alpha-4(IV) chain isoform X4

    20. XM_054340442.1 → XP_054196417.1  collagen alpha-4(IV) chain isoform X5

    21. XM_054340459.1 → XP_054196434.1  collagen alpha-4(IV) chain isoform X14

    22. XM_054340450.1 → XP_054196425.1  collagen alpha-4(IV) chain isoform X9

    23. XM_054340456.1 → XP_054196431.1  collagen alpha-4(IV) chain isoform X12

    RNA

    1. XR_008486265.1 RNA Sequence

    2. XR_008486264.1 RNA Sequence

    3. XR_008486263.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P53420.3 GenPept UniProtKB/Swiss-Prot:P53420

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