Details for: CILP2

Gene ID: 148113

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: CILP2

Ensembl ID: ENSG00000160161

Description: cartilage intermediate layer protein 2

Cell Significance Landscape

Associated with

Significant Cells

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

  • chondrocyte CL0000138
    CSI 3.58
    rCSI 5.69%
    PRS 99.83

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

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  • Node Color (Target Cell CSI, relative to current network):
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    • 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 Cartilage intermediate layer protein 2, encoded by the [CILP2](/details-gene/148113) gene, is an extracellular protein with a highly specialized role in cartilage biology. Expression data indicates its function is almost exclusively confined to [chondrocytes](/details-cell/CL0000138), the primary cells responsible for producing and maintaining the cartilaginous matrix. Functionally, [CILP2](/details-gene/148113) has been shown to possess enzymatic activities, including alkaline phosphatase and dinucleotide phosphatase functions ([GO:0004035](https://www.ebi.ac.uk/QuickGO/term/GO:0004035), [GO:0004551](https://www.ebi.ac.uk/QuickGO/term/GO:0004551)). Notably, research suggests it acts as an antagonist to insulin-like growth factor 1 (IGF-1), a key regulator of cartilage homeostasis, and its expression is altered in pathological conditions such as osteoarthritis ([Link](https://doi.org/10.1002/art.10927), [Link](https://doi.org/10.1074/jbc.m111.248039)). ## Cellular Roles and Expression Landscape The expression profile of [CILP2](/details-gene/148113) demonstrates remarkable cell-type specificity. **Overall**, the gene's significance is overwhelmingly concentrated in [chondrocytes](/details-cell/CL0000138) (CSI: 3.58), positioning it as a key marker for this cell lineage. This restricted expression pattern is consistent with its annotated function in the extracellular space ([GO:0005615](https://www.ebi.ac.uk/QuickGO/term/GO:0005615)) of cartilage tissue. Studies have confirmed its expression in both articular and meniscal cartilage, further underscoring its specific role in joint tissues ([Link](https://doi.org/10.1074/jbc.m111.248039)). The lack of significant expression in other cell types suggests a highly specialized function related to the maintenance and regulation of the cartilage extracellular matrix. ## Pathways and Molecular Function [CILP2](/details-gene/148113) is an extracellular protein, found in the extracellular space and exosomes ([GO:0005615](https://www.ebi.ac.uk/QuickGO/term/GO:0005615), [GO:0070062](https://www.ebi.ac.uk/QuickGO/term/GO:0070062)), where it performs key regulatory and enzymatic functions. Its annotated molecular functions include alkaline phosphatase activity and dinucleotide phosphatase activity, suggesting a role in modulating the local concentration of phosphate-containing molecules within the cartilage matrix. Perhaps its most critical function is its role as an antagonist of IGF-1 signaling ([Link](https://doi.org/10.1002/art.10927)). By opposing the anabolic and anti-catabolic effects of IGF-1, [CILP2](/details-gene/148113) likely plays a crucial role in balancing cartilage tissue turnover and maintaining homeostasis. ## Research Directions Evidence that [CILP2](/details-gene/148113) is down-regulated in experimental osteoarthritis provides a strong foundation for investigating its role in joint pathology ([Link](https://doi.org/10.1074/jbc.m111.248039)). This down-regulation in a disease state, coupled with its known function as an IGF-1 antagonist, suggests that its loss could disrupt the delicate balance of anabolic and catabolic signaling in [chondrocytes](/details-cell/CL0000138), contributing to cartilage degradation. Based on these findings, several testable hypotheses can be proposed: 1. The down-regulation of [CILP2](/details-gene/148113) expression during the onset of osteoarthritis leads to excessive IGF-1 signaling in [chondrocytes](/details-cell/CL0000138), promoting a pathological cellular phenotype and accelerating cartilage matrix breakdown. 2. The enzymatic phosphatase activity of [CILP2](/details-gene/148113) is critical for preventing pathological calcification of articular cartilage, and its loss in osteoarthritis contributes to the formation of osteophytes and joint stiffening. To directly test the first hypothesis, a compelling experimental approach would be to utilize a mouse model of surgically induced osteoarthritis, such as destabilization of the medial meniscus (DMM). One cohort of mice would receive weekly intra-articular injections of recombinant [CILP2](/details-gene/148113) protein to restore its physiological levels, while a control group receives a vehicle. The therapeutic effect could be evaluated after several weeks by histological analysis of cartilage integrity (e.g., Safranin-O staining) and immunohistochemical staining for markers of cartilage degradation (e.g., MMP13 and ADAMTS5). Given that [CILP2](/details-gene/148113) expression is reduced in osteoarthritis, it represents a potential therapeutic agent rather than a target for inhibition. Its high specificity for [chondrocytes](/details-cell/CL0000138) and extracellular location make it an attractive candidate for protein-based replacement therapy. A strategy involving the delivery of recombinant [CILP2](/details-gene/148113) directly to the joint could potentially restore normal homeostatic signaling and slow or reverse cartilage degradation, suggesting a role in disease modification for osteoarthritis.

Genular Protein ID: 3810237274

Symbol: CILP2_HUMAN

Name: Cartilage intermediate layer protein 2

UniProtKB Accession Codes:

Q8IUL8 Q6NV88 Q8N4A6 Q8WV21

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 1 ExpressionAtlas 1 GO 2 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 10 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 4 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SMART 3 STRING 1 SUPFAM 3 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12746903

Title: One of two chondrocyte-expressed isoforms of cartilage intermediate-layer protein functions as an insulin-like growth factor 1 antagonist.

PubMed ID: 12746903

DOI: 10.1002/art.10927

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: 21880736

Title: Cartilage intermediate layer protein 2 (CILP-2) is expressed in articular and meniscal cartilage and down-regulated in experimental osteoarthritis.

PubMed ID: 21880736

DOI: 10.1074/jbc.m111.248039

Sequence Information:

  • Length: 1156
  • Mass: 126291
  • Checksum: CE4AAB47841C07F9
  • Sequence:
    • MASLLPLLCL CVVAAHLAGA RDATPTEEPM ATALGLERRS VYTGQPSPAL EDWEEASEWT 
SWFNVDHPGG DGDFESLAAI RFYYGPARVC PRPLALEART TDWALPSAVG ERVHLNPTRG 
FWCLNREQPR GRRCSNYHVR FRCPLEASWG AWGPWGPCSG SCGPGRRLRR RHCPSPAGDA 
CPGRPLEAQK CVRPRCPGCS LDTCECPDHI LLGSVVTPSG QPLLGARVSL RDQPGTVATS 
DAHGTFRVPG VCADSRANIR AQMDGFSAGE AQAQANGSIS VVTIILDKLE KPYLVKHPES 
RVREAGQNVT FCCKASGTPM PKKYSWFHNG TLLDRRAHGY GAHLELRGLR PDQAGIYHCK 
AWNEAGAVRS GTARLTVLAP GQPACDPRPR EYLIKLPEDC GQPGSGPAYL DVGLCPDTRC 
PSLAGSSPRC GDASSRCCSV RRLERREIHC PGYVLPVKVV AECGCQKCLP PRGLVRGRVV 
AADSGEPLRF ARILLGQEPI GFTAYQGDFT IEVPPSTQRL VVTFVDPSGE FMDAVRVLPF 
DPRGAGVYHE VKAMRKKAPV ILHTSQSNTI PLGELEDEAP LGELVLPSGA FRRADGKPYS 
GPVEARVTFV DPRDLTSAAS APSDLRFVDS DGELAPLRTY GMFSVDLRAP GSAEQLQVGP 
VAVRVAASQI HMPGHVEALK LWSLNPETGL WEEESGFRRE GSSGPRVRRE ERVFLVGNVE 
IRERRLFNLD VPERRRCFVK VRAYANDKFT PSEQVEGVVV TLVNLEPAPG FSANPRAWGR 
FDSAVTGPNG ACLPAFCDAD RPDAYTALVT ATLGGEELEP APSLPRPLPA TVGVTQPYLD 
RLGYRRTDHD DPAFKRNGFR INLAKPRPGD PAEANGPVYP WRSLRECQGA PVTASHFRFA 
RVEADKYEYN VVPFREGTPA SWTGDLLAWW PNPQEFRACF LKVKIQGPQE YMVRSHNAGG 
SHPRTRGQLY GLRDARSVRD PERPGTSAAC VEFKCSGMLF DQRQVDRTLV TIMPQGSCRR 
VAVNGLLRDY LTRHPPPVPA EDPAAFSMLA PLDPLGHNYG VYTVTDQSPR LAKEIAIGRC 
FDGSSDGFSR EMKADAGTAV TFQCREPPAG RPSLFQRLLE SPATALGDIR REMSEAAQAQ 
ARASGPLRTR RGRVRQ