Details for: KERA

Gene ID: 11081

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: KERA

Ensembl ID: ENSG00000139330

Description: keratocan

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • tendon cell CL0000388
    CSI 4.58
    rCSI 11.89%
    PRS 100
  • mesenchymal stem cell CL0000134
    CSI 0.44
    rCSI 4.79%
    PRS 99.97

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.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • 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)

Loading network (please wait)...

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 [KERA](/details-gene/11081) (keratocan) is a protein-coding gene located on chromosome 12q21.33. It encodes a small leucine-rich proteoglycan that is a major component of the extracellular matrix ([GO:0031012](https://www.ebi.ac.uk/QuickGO/term/GO:0031012)), particularly in the cornea. Functionally, [KERA](/details-gene/11081) is essential for cornea development ([GO:0061303](https://www.ebi.ac.uk/QuickGO/term/GO:0061303)) and the maintenance of corneal transparency, which is critical for visual perception ([GO:0007601](https://www.ebi.ac.uk/QuickGO/term/GO:0007601)) [Link](https://doi.org/10.3109/10425179909033939). Mutations in this gene are causally linked to autosomal recessive cornea plana ([153245](https://omim.org/entry/217300)), a condition characterized by a flattened cornea [Link](https://doi.org/10.1038/75664), [Link](https://pubmed.ncbi.nlm.nih.gov/11726611/). While its role in the eye is well-established, expression data also indicates a highly significant presence in [tendon cells](/details-cell/CL0000388), suggesting a broader function in the organization of connective tissues. ## Cellular Roles and Expression Landscape The expression profile of [KERA](/details-gene/11081) highlights its specialized role in tissues rich in extracellular matrix. - **Primary Expression Context:** **Overall**, the gene shows its most significant expression in [tendon cells](/details-cell/CL0000388) (CSI: 4.58), indicating it may be a key structural or organizational protein in tendons. It also shows moderate significance in [mesenchymal stem cells](/details-cell/CL0000134) (CSI: 0.44), which are progenitors for various connective tissue cell types, including keratocytes of the cornea and tendon fibroblasts. - **Functional Specificity:** Although named for its role in the cornea (keratin), the high significance in [tendon cells](/details-cell/CL0000388) suggests a more general function in maintaining the structure of collagen-rich tissues. Its function as a keratan sulfate proteoglycan is critical for regulating collagen fibril spacing and diameter, a process essential for both corneal transparency and the tensile strength of tendons. Altered [KERA](/details-gene/11081) expression has been observed in pathological conditions, such as an increase in the stroma of keratoconus corneas [Link](https://doi.org/10.1007/bf03401852). ## Pathways and Molecular Function [KERA](/details-gene/11081) is centrally involved in glycosaminoglycan metabolism and extracellular matrix organization. - **GO Annotations:** The gene's primary biological process is annotated as cornea development ([GO:0061303](https://www.ebi.ac.uk/QuickGO/term/GO:0061303)). Its protein product is a component of the extracellular matrix ([GO:0031012](https://www.ebi.ac.uk/QuickGO/term/GO:0031012)) and is found in the extracellular space ([GO:0005615](https://www.ebi.ac.uk/QuickGO/term/GO:0005615)), consistent with its role as a secreted proteoglycan. - **Reactome Pathways:** [KERA](/details-gene/11081) is a key player in keratan sulfate biosynthesis ([R-HSA-2022854](https://reactome.org/content/detail/R-HSA-2022854)) and degradation ([R-HSA-2022857](https://reactome.org/content/detail/R-HSA-2022857)). Its involvement in broader pathways such as glycosaminoglycan metabolism ([R-HSA-1630316](https://reactome.org/content/detail/R-HSA-1630316)) and diseases associated with glycosaminoglycan metabolism ([R-HSA-3560782](https://reactome.org/content/detail/R-HSA-3560782)) underscores its importance in post-translational protein modification and matrix assembly. The link to pathways like 'Defective chst6 causes mcdc1' ([R-HSA-3656225](https://reactome.org/content/detail/R-HSA-3656225)) highlights the interconnectedness of keratan sulfate synthesis enzymes and substrates in maintaining tissue homeostasis. ## Research Directions The established role of [KERA](/details-gene/11081) in corneal disease and its high expression in other connective tissues suggest several avenues for future investigation. - **Proposed Hypotheses:** 1. Given that [KERA](/details-gene/11081) expression is reportedly increased in keratoconus [Link](https://doi.org/10.1007/bf03401852), we hypothesize that the overexpression of [KERA](/details-gene/11081) in corneal keratocytes disrupts the precise organization of collagen lamellae, leading to the stromal thinning and biomechanical instability characteristic of the disease. 2. Based on its high significance in [tendon cells](/details-cell/CL0000388), we hypothesize that [KERA](/details-gene/11081) is essential for proper tendon fibrillogenesis and that reduced [KERA](/details-gene/11081) function impairs tendon healing and increases susceptibility to tendinopathies by altering collagen fibril diameter and spacing. - **Experimental Approach:** To test the hypothesis regarding [KERA's](/details-gene/11081) role in tendon integrity (Hypothesis 2), a conditional knockout mouse model could be generated using a Scleraxis-Cre driver to specifically delete [KERA](/details-gene/11081) in tendon fibroblasts. The resulting phenotype could be assessed by a combination of transmission electron microscopy (TEM) to quantify collagen fibril diameter and organization in Achilles tendons, and biomechanical stress-strain testing to measure the ultimate tensile strength and stiffness of the tissue compared to wild-type littermates. - **Therapeutic Potential:** As loss-of-function mutations in [KERA](/details-gene/11081) cause cornea plana, therapeutic strategies would likely focus on functional restoration rather than inhibition. For this monogenic disorder, [KERA](/details-gene/11081) could be a candidate for gene replacement therapy, where a functional copy of the gene is delivered to corneal keratocytes via an adeno-associated virus (AAV) vector to restore normal proteoglycan synthesis and corneal curvature. For conditions like keratoconus where its expression may be elevated, targeted therapies to normalize its expression levels, such as siRNA-based approaches, could be explored, although this is more speculative.

Genular Protein ID: 2173597130

Symbol: KERA_HUMAN

Name: Keratocan

UniProtKB Accession Codes:

O60938

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 GO 7 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 5 RefSeq 1 SMART 3 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10565548

Title: Structure and sequence of the gene encoding human keratocan.

PubMed ID: 10565548

DOI: 10.3109/10425179909033939

PubMed ID: 10802664

Title: Mutations in KERA, encoding keratocan, cause cornea plana.

PubMed ID: 10802664

DOI: 10.1038/75664

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 11683372

Title: Keratocan expression is increased in the stroma of keratoconus corneas.

PubMed ID: 11683372

DOI: 10.1007/bf03401852

PubMed ID: 16335952

Title: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry.

PubMed ID: 16335952

DOI: 10.1021/pr0502065

PubMed ID: 11726611

Title: A novel keratocan mutation causing autosomal recessive cornea plana.

PubMed ID: 11726611

Sequence Information:

  • Length: 352
  • Mass: 40509
  • Checksum: 0CF8DEC938852D28
  • Sequence:
    • MAGTICFIMW VLFITDTVWS RSVRQVYEVH DSDDWTIHDF ECPMECFCPP SFPTALYCEN 
RGLKEIPAIP SRIWYLYLQN NLIETIPEKP FENATQLRWI NLNKNKITNY GIEKGALSQL 
KKLLFLFLED NELEEVPSPL PRSLEQLQLA RNKVSRIPQG TFSNLENLTL LDLQNNKLVD 
NAFQRDTFKG LKNLMQLNMA KNALRNMPPR LPANTMQLFL DNNSIEGIPE NYFNVIPKVA 
FLRLNHNKLS DEGLPSRGFD VSSILDLQLS HNQLTKVPRI SAHLQHLHLD HNKIKSVNVS 
VICPSPSMLP AERDSFSYGP HLRYLRLDGN EIKPPIPMAL MTCFRLLQAV II