U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Links from MedGen

    • Showing Current items.

    COL8A2 collagen type VIII alpha 2 chain [ Homo sapiens (human) ]

    Gene ID: 1296, updated on 5-Mar-2024

    Summary

    Go to the top of the page Help
    Official Symbol
    COL8A2provided by HGNC
    Official Full Name
    collagen type VIII alpha 2 chainprovided by HGNC
    Primary source
    HGNC:HGNC:2216
    See related
    Ensembl:ENSG00000171812 MIM:120252; AllianceGenome:HGNC:2216
    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
    FECD; PPCD; FECD1; PPCD2
    Summary
    This gene encodes the alpha 2 chain of type VIII collagen. This protein is a major component of the basement membrane of the corneal endothelium and forms homo- or heterotrimers with alpha 1 (VIII) type collagens. Defects in this gene are associated with Fuchs endothelial corneal dystrophy and posterior polymorphous corneal dystrophy type 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]
    Expression
    Broad expression in placenta (RPKM 6.6), spleen (RPKM 3.6) and 22 other tissues See more
    Orthologs
    mouse all
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    Go to the top of the page Help
    Location:
    1p34.3
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (36095239..36125222, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (35958119..35988102, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (36560840..36590823, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:36550265-36551063 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:36553996-36554581 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:36554582-36555166 Neighboring gene tektin 2 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:36563075-36563583 Neighboring gene ADP-ribosylserine hydrolase Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 654 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:36579590-36580530 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:36580531-36581471 Neighboring gene MPRA-validated peak176 silencer Neighboring gene trafficking protein particle complex subunit 3 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:36614757-36615417 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 655 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 656 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:36625977-36626754 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 745 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 746 Neighboring gene MAP7 domain containing 1 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr1:36638149-36639348 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 657 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:36643121-36643768 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:36643769-36644414 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:36644415-36645060

    Genomic regions, transcripts, and products

    Go to the top of the page Help

    Go to nucleotide: Graphics FASTA GenBank

    Expression

    Go to the top of the page Help
    • Project title: 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

    Go to the top of the pageHelp

    Related articles in PubMed

    1. Collagen type VIII alpha 2 chain (COL8A2), an important component of the basement membrane of the corneal endothelium, facilitates the malignant development of glioblastoma cells via inducing EMT. Cheng YX, et al. J Bioenerg Biomembr, 2021 Feb. PMID 33405048
    2. COL8A2 Regulates the Fate of Corneal Endothelial Cells. Hwang JS, et al. Invest Ophthalmol Vis Sci, 2020 Sep 1. PMID 32931574, Free PMC Article
    3. Distinct Clinical Phenotype of Corneal Dystrophy Predicts the p.(Leu450Trp) Substitution in COL8A2. Eghrari AO, et al. Cornea, 2016 May. PMID 26989952
    4. High prevalence of eosinophilic esophagitis in patients with inherited connective tissue disorders. Abonia JP, et al. J Allergy Clin Immunol, 2013 Aug. PMID 23608731, Free PMC Article
    5. Screening of the COL8A2 gene in an Australian family with early-onset Fuchs' endothelial corneal dystrophy. Kuot A, et al. Clin Exp Ophthalmol, 2014 Mar. PMID 23601356

    See all (46) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Collagen type VIII alpha 2 chain (COL8A2), an important component of the basement membrane of the corneal endothelium, facilitates the malignant development of glioblastoma cells via inducing EMT.
      Title: Collagen type VIII alpha 2 chain (COL8A2), an important component of the basement membrane of the corneal endothelium, facilitates the malignant development of glioblastoma cells via inducing EMT.
    2. COL8A2 Regulates the Fate of Corneal Endothelial Cells.
      Title: COL8A2 Regulates the Fate of Corneal Endothelial Cells.
    3. Analysis of SLC4A11, ZEB1, LOXHD1, COL8A2 and TCF4 gene sequences in a multi-generational family with late-onset Fuchs corneal dystrophy found no evidence for found polymorophisms causing the disease in this specific pedigree.
      Title: Analysis of SLC4A11, ZEB1, LOXHD1, COL8A2 and TCF4 gene sequences in a multi-generational family with late-onset Fuchs corneal dystrophy.
    4. Peripheral, anterior microcystic corneal edema represents a characteristic aspect of the phenotype associated with the p.(Leu450Trp) substitution in COL8A2, in at least 2 of 3 known affected families worldwide.
      Title: Distinct Clinical Phenotype of Corneal Dystrophy Predicts the p.(Leu450Trp) Substitution in COL8A2.
    5. No mutations were identified in COL8A2, in neither the late-onset cohort nor the early-onset family, suggesting genetic heterogeneity in this Late-onset Fuchs endothelial corneal dystrophy (FECD) family.
      Title: Biosynthetic and functional defects in newly identified SLC4A11 mutants and absence of COL8A2 mutations in Fuchs endothelial corneal dystrophy.
    6. mutations in the COL8A2 gene do not contribute to all cases of early-onset early-onset Fuchs' endothelial corneal dystrophy .
      Title: Screening of the COL8A2 gene in an Australian family with early-onset Fuchs' endothelial corneal dystrophy.
    7. Variation in the COL8A2, SLC4A11, and ZEB1 genes is present in only a small fraction of African American cases and as such does not appear to significantly contribute to the genetic risk of Fuchs endothelial corneal dystrophy.
      Title: Genetic screen of African Americans with Fuchs endothelial corneal dystrophy.
    8. Esophageal transcript profiling identified a distinct subset of genes, including COL8A2, in patients with Eosionophilic esophagitis and inherited connective tissue disorders.
      Title: High prevalence of eosinophilic esophagitis in patients with inherited connective tissue disorders.
    9. Association of central corneal thickness with TCF4 was also significant (p = 6.1x10(-7)), but was abolished with adjustment for FECD grade (p = 0.92).
      Title: Differing roles for TCF4 and COL8A2 in central corneal thickness and fuchs endothelial corneal dystrophy.
    10. Single nucleotide polymorphisms in COL8A2 gene is not associated with central corneal thickness in glaucoma.
      Title: Population-based meta-analysis in Caucasians confirms association with COL5A1 and ZNF469 but not COL8A2 with central corneal thickness.
    Submit: New GeneRIF Correction See all GeneRIFs (25)

    Phenotypes

    Go to the top of the page Help

    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Corneal dystrophy, Fuchs endothelial, 1
    MedGen: C1850959 OMIM: 136800 GeneReviews: Not available
    		Compare labs
    Posterior polymorphous corneal dystrophy 2
    MedGen: C1852795 OMIM: 609140 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus.
    EBI GWAS Catalog

    Variation

    Go to the top of the page Help

    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Interactions

    Go to the top of the page Help
    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Go to the top of the page Help

    Markers

    Homology

    Clone Names

    • FLJ00201, MGC116970, MGC116972

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables extracellular matrix structural constituent NAS
    Non-traceable Author Statement
    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 protein-macromolecule adaptor activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in angiogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in camera-type eye morphogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cell-cell adhesion NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in endothelial cell proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in extracellular matrix organization IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in extracellular matrix organization NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in basement membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in basement membrane NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    part_of collagen trimer IEA
    Inferred from Electronic Annotation
    more info
    		  
    colocalizes_with collagen-containing extracellular matrix HDA PubMed 
    located_in collagen-containing extracellular matrix HDA PubMed 
    located_in endoplasmic reticulum lumen TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular matrix NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    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

    Go to the top of the page Help
    Preferred Names
    collagen alpha-2(VIII) chain
    Names
    collagen VIII, alpha-2 polypeptide
    collagen, type VIII, alpha 2
    endothelial collagen

    NCBI Reference Sequences (RefSeq)

    Go to the top of the page Help

    NEW Try the new Transcript table

    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_016245.2 RefSeqGene

      Range
      4863..34846
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001294347.2 → NP_001281276.1  collagen alpha-2(VIII) chain isoform 2

      See identical proteins and their annotated locations for NP_001281276.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate splice site in the 5' region and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus than isoform 1.
      Source sequence(s)
      AI084614, AK074129, AL138787, HY025990
      Consensus CDS
      CCDS72756.1
      UniProtKB/TrEMBL
      E9PP49
      Related
      ENSP00000436433.1, ENST00000481785.1
      Conserved Domains (2) summary
      smart00110
      Location:503 → 638
      C1Q; Complement component C1q domain
      pfam01391
      Location:368 → 417
      Collagen; Collagen triple helix repeat (20 copies)

    2. NM_005202.4 → NP_005193.1  collagen alpha-2(VIII) chain isoform 1 precursor

      See identical proteins and their annotated locations for NP_005193.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AI084614, AK074129, AL138787, HY025990
      Consensus CDS
      CCDS403.1
      UniProtKB/Swiss-Prot
      P25067, Q5JV31, Q8TEJ5
      Related
      ENSP00000380901.1, ENST00000397799.2
      Conserved Domains (2) summary
      smart00110
      Location:568 → 703
      C1Q; Complement component C1q domain
      pfam01391
      Location:433 → 482
      Collagen; Collagen triple helix repeat (20 copies)

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      36095239..36125222 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      35958119..35988102 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P25067.2 GenPept UniProtKB/Swiss-Prot:P25067

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous