Details for: COL8A2

Gene ID: 1296

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: COL8A2

Ensembl ID: ENSG00000171812

Description: collagen type VIII alpha 2 chain

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • skin fibroblast CL0002620
    CSI 3.71
    rCSI 3.2%
    PRS 97.39
  • choroid plexus epithelial cell CL0000706
    CSI 2.78
    rCSI 4.55%
    PRS 94.71
  • chondrocyte CL0000138
    CSI 2.5
    rCSI 3.98%
    PRS 95.49
  • retinal pigment epithelial cell CL0002586
    CSI 1.9
    rCSI 3.77%
    PRS 95.66

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [COL8A2](/details-gene/1296) encodes the alpha-2 chain of type VIII collagen, a short-chain collagen that is a critical structural component of basement membranes in various tissues. Its primary function is to form homotrimeric molecules that assemble into hexagonal lattices, providing structural integrity and tensile strength to the extracellular matrix ([Link](https://doi.org/10.1016/s0945-053x(99)00053-0), [Link](https://doi.org/10.1074/jbc.m305805200)). **Overall**, expression data reveals that [COL8A2](/details-gene/1296) is a significant marker for specialized, matrix-secreting cells, including [skin fibroblast](/details-cell/CL0002620), [choroid plexus epithelial cell](/details-cell/CL0000706), and [retinal pigment epithelial cell](/details-cell/CL0002586). Clinically, mutations in [COL8A2](/details-gene/1296) are causally linked to corneal endothelial dystrophies, such as Fuchs' endothelial dystrophy and posterior polymorphous corneal dystrophy ([Link](https://doi.org/10.1093/hmg/10.21.2415), [Link](https://omim.org/entry/136800)). ## Cellular Roles and Expression Landscape The expression pattern of [COL8A2](/details-gene/1296) highlights its specialized role in the synthesis and maintenance of the extracellular matrix across diverse tissues. The **Overall** context shows its highest significance in two main functional categories of cells: 1. **Mesenchymal and Connective Tissue Cells:** [COL8A2](/details-gene/1296) is highly significant in [skin fibroblast](/details-cell/CL0002620) (CSI: 3.71) and [chondrocyte](/details-cell/CL0000138) (CSI: 2.50). These cells are fundamental producers of extracellular matrix components, and the high significance of [COL8A2](/details-gene/1296) suggests it is a key structural protein in the basement membranes associated with skin and cartilage. 2. **Specialized Epithelial and Endothelial Cells:** The gene also shows prominent significance in [choroid plexus epithelial cell](/details-cell/CL0000706) (CSI: 2.78) and [retinal pigment epithelial cell](/details-cell/CL0002586) (CSI: 1.90). These cells form critical biological barriers—the blood-cerebrospinal fluid barrier and the outer blood-retinal barrier, respectively. The high significance in these cell types indicates that type VIII collagen is a major constituent of their unique basement membranes, such as Bruch's membrane in the retina, which is essential for their barrier function and tissue homeostasis. The concentration of [COL8A2](/details-gene/1296) expression in these specific matrix-secreting cell types suggests a highly specialized structural function rather than a ubiquitous housekeeping role. ## Pathways and Molecular Function The functions of [COL8A2](/details-gene/1296) are intrinsically tied to the biology of the extracellular matrix (ECM). Its molecular function is defined as an 'Extracellular matrix structural constituent' ([GO:0005201](https://www.ebi.ac.uk/QuickGO/term/GO:0005201)) that confers 'tensile strength' ([GO:0030020](https://www.ebi.ac.uk/QuickGO/term/GO:0030020)). The protein product is a key component of the 'Basement membrane' ([GO:0005604](https://www.ebi.ac.uk/QuickGO/term/GO:0005604)) and assembles into a 'Collagen trimer' ([GO:0005581](https://www.ebi.ac.uk/QuickGO/term/GO:0005581)). At the process level, [COL8A2](/details-gene/1296) is involved in fundamental developmental and homeostatic pathways. Its role in 'Extracellular matrix organization' ([R-HSA-1474244](https://reactome.org/content/detail/R-HSA-1474244)) and 'Collagen formation' ([R-HSA-1474290](https://reactome.org/content/detail/R-HSA-1474290)) is consistent with its high expression in fibroblasts and chondrocytes. The annotation for 'Angiogenesis' ([GO:0001525](https://www.ebi.ac.uk/QuickGO/term/GO:0001525)) underscores its importance in the basement membranes of endothelial cells during blood vessel formation. Furthermore, its involvement in 'Camera-type eye morphogenesis' ([GO:0048593](https://www.ebi.ac.uk/QuickGO/term/GO:0048593)) provides a direct molecular link to its high expression in retinal cells and its established role in genetic disorders of the cornea ([Link](https://doi.org/10.1093/hmg/10.21.2415)). ## Research Directions The well-defined role of [COL8A2](/details-gene/1296) in matrix biology and its association with specific pathologies present several avenues for future investigation. While mutations are linked to corneal dystrophies, its broader role in other fibrotic or degenerative diseases warrants exploration. ### Testable Hypotheses 1. **Role in Neuro-Ocular Barrier Integrity:** Given its high significance in [choroid plexus epithelial cell](/details-cell/CL0000706) and [retinal pigment epithelial cell](/details-cell/CL0002586), it is hypothesized that age-related decline or dysfunction of [COL8A2](/details-gene/1296) contributes to the breakdown of the blood-CSF and blood-retinal barriers, potentially facilitating neuroinflammation or contributing to the pathology of age-related macular degeneration. 2. **Contribution to Renal Fibrosis:** Based on literature suggesting its expression is altered in diabetic nephropathy ([Link](https://doi.org/10.1111/j.1365-2362.2007.01864.x)), we hypothesize that hyperglycemia-induced stress in glomerular endothelial cells and podocytes leads to pathological overexpression and deposition of type VIII collagen, driving glomerular basement membrane thickening and contributing to the progression of renal fibrosis. ### Proposed Experiment To test the hypothesis regarding its role in diabetic nephropathy, a robust experimental approach would involve using a conditional knockout mouse model. *Col8a2* could be specifically deleted in kidney podocytes (e.g., using a Podocin-Cre driver) or endothelial cells in a mouse model of streptozotocin-induced diabetes. The functional consequences would be assessed by measuring key indicators of nephropathy, including albuminuria, and the structural impact would be evaluated through electron microscopy to quantify glomerular basement membrane thickness and histological staining (e.g., Masson's trichrome) to assess fibrosis. This would directly test the causal role of [COL8A2](/details-gene/1296) from specific cell types in the pathogenesis of the disease. ### Therapeutic Potential As a secreted structural protein, [COL8A2](/details-gene/1296) itself is a challenging direct therapeutic target for inhibition. However, in the context of fibrotic diseases like diabetic nephropathy, where its expression is pathologically increased, it serves as a valuable biomarker of disease progression. Therapeutic strategies would likely focus on the upstream regulatory pathways that control its transcription and deposition, such as the TGF-beta signaling pathway, rather than targeting the protein directly. Therefore, therapeutic intervention would likely be indirect, aiming to suppress the fibrotic response in which [COL8A2](/details-gene/1296) is a key downstream effector.

Genular Protein ID: 3812838396

Symbol: CO8A2_HUMAN

Name: Collagen alpha-2(VIII) chain

UniProtKB Accession Codes:

P25067 Q5JV31 Q8TEJ5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 ComplexPortal 2 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 2 ExpressionAtlas 1 GO 15 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 5 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PIR 1 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 5 RefSeq 2 SMART 1 SMR 1 STRING 1 SUPFAM 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 2019595

Title: The alpha 2(VIII) collagen gene. A novel member of the short chain collagen family located on the human chromosome 1.

PubMed ID: 2019595

DOI: 10.1016/s0021-9258(20)89508-8

PubMed ID: 1515454

Title: Cleavage of type VIII collagen by human neutrophil elastase.

PubMed ID: 1515454

DOI: 10.1016/0925-4439(92)90103-t

PubMed ID: 10686422

Title: The alpha1(VIII) and alpha2(VIII) collagen chains form two distinct homotrimeric proteins in vivo.

PubMed ID: 10686422

DOI: 10.1016/s0945-053x(99)00053-0

PubMed ID: 14990571

Title: Expression and supramolecular assembly of recombinant alpha1(viii) and alpha2(viii) collagen homotrimers.

PubMed ID: 14990571

DOI: 10.1074/jbc.m305805200

PubMed ID: 17888087

Title: Collagen type VIII expression in human diabetic nephropathy.

PubMed ID: 17888087

DOI: 10.1111/j.1365-2362.2007.01864.x

PubMed ID: 11689488

Title: Missense mutations in COL8A2, the gene encoding the alpha-2 chain of type VIII collagen, cause two forms of corneal endothelial dystrophy.

PubMed ID: 11689488

DOI: 10.1093/hmg/10.21.2415

PubMed ID: 15175909

Title: Analysis of COL8A2 gene mutation in Japanese patients with Fuchs' endothelial dystrophy and posterior polymorphous dystrophy.

PubMed ID: 15175909

DOI: 10.1007/s10384-003-0063-6

Sequence Information:

  • Length: 703
  • Mass: 67244
  • Checksum: 84BD7CBDBDECD466
  • Sequence:
    • MLGTLTPLSS LLLLLLVLVL GCGPRASSGG GAGGAAGYAP VKYIQPMQKG PVGPPFREGK 
GQYLEMPLPL LPMDLKGEPG PPGKPGPRGP PGPPGFPGKP GMGKPGLHGQ PGPAGPPGFS 
RMGKAGPPGL PGKVGPPGQP GLRGEPGIRG DQGLRGPPGP PGLPGPSGIT IPGKPGAQGV 
PGPPGFQGEP GPQGEPGPPG DRGLKGDNGV GQPGLPGAPG QGGAPGPPGL PGPAGLGKPG 
LDGLPGAPGD KGESGPPGVP GPRGEPGAVG PKGPPGVDGV GVPGAAGLPG PQGPSGAKGE 
PGTRGPPGLI GPTGYGMPGL PGPKGDRGPA GVPGLLGDRG EPGEDGEPGE QGPQGLGGPP 
GLPGSAGLPG RRGPPGPKGE AGPGGPPGVP GIRGDQGPSG LAGKPGVPGE RGLPGAHGPP 
GPTGPKGEPG FTGRPGGPGV AGALGQKGDL GLPGQPGLRG PSGIPGLQGP AGPIGPQGLP 
GLKGEPGLPG PPGEGRAGEP GTAGPTGPPG VPGSPGITGP PGPPGPPGPP GAPGAFDETG 
IAGLHLPNGG VEGAVLGKGG KPQFGLGELS AHATPAFTAV LTSPFPASGM PVKFDRTLYN 
GHSGYNPATG IFTCPVGGVY YFAYHVHVKG TNVWVALYKN NVPATYTYDE YKKGYLDQAS 
GGAVLQLRPN DQVWVQMPSD QANGLYSTEY IHSSFSGFLL CPT

Genular Protein ID: 3602165902

Symbol: E9PP49_HUMAN

Name: N/A

UniProtKB Accession Codes:

E9PP49

Database IDs:

ARBA 2 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 2 GO 2 Gene3D 1 GeneTree 1 HGNC 1 HOGENOM 1 InterPro 4 NCBI Taxonomy 1 OMA 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 2 PeptideAtlas 1 Pfam 2 Proteomes 2 ProteomicsDB 2 RefSeq 1 SAM 1 SMART 1 SUPFAM 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

Sequence Information:

  • Length: 638
  • Mass: 60707
  • Checksum: EA6328BCD8888E45
  • Sequence:
    • MPLPLLPMDL KGEPGPPGKP GPRGPPGPPG FPGKPGMGKP GLHGQPGPAG PPGFSRMGKA 
GPPGLPGKVG PPGQPGLRGE PGIRGDQGLR GPPGPPGLPG PSGITIPGKP GAQGVPGPPG 
FQGEPGPQGE PGPPGDRGLK GDNGVGQPGL PGAPGQGGAP GPPGLPGPAG LGKPGLDGLP 
GAPGDKGESG PPGVPGPRGE PGAVGPKGPP GVDGVGVPGA AGLPGPQGPS GAKGEPGTRG 
PPGLIGPTGY GMPGLPGPKG DRGPAGVPGL LGDRGEPGED GEPGEQGPQG LGGPPGLPGS 
AGLPGRRGPP GPKGEAGPGG PPGVPGIRGD QGPSGLAGKP GVPGERGLPG AHGPPGPTGP 
KGEPGFTGRP GGPGVAGALG QKGDLGLPGQ PGLRGPSGIP GLQGPAGPIG PQGLPGLKGE 
PGLPGPPGEG RAGEPGTAGP TGPPGVPGSP GITGPPGPPG PPGPPGAPGA FDETGIAGLH 
LPNGGVEGAV LGKGGKPQFG LGELSAHATP AFTAVLTSPF PASGMPVKFD RTLYNGHSGY 
NPATGIFTCP VGGVYYFAYH VHVKGTNVWV ALYKNNVPAT YTYDEYKKGY LDQASGGAVL 
QLRPNDQVWV QMPSDQANGL YSTEYIHSSF SGFLLCPT