Details for: CILP

Gene ID: 8483

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: CILP

Ensembl ID: ENSG00000138615

Description: cartilage intermediate layer protein

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

  • Signaling by receptor tyrosine kinases
    (R-HSA-9006934)
  • Signaling by type 1 insulin-like growth factor 1 receptor (igf1r)
    (R-HSA-2404192)
  • Signal transduction
    (R-HSA-162582)
  • Alkaline phosphatase activity
    (GO:0004035)
  • Collagen-containing extracellular matrix
    (GO:0062023)
  • Dinucleotide phosphatase activity
    (GO:0004551)
  • Extracellular exosome
    (GO:0070062)
  • Extracellular matrix structural constituent
    (GO:0005201)
  • Extracellular space
    (GO:0005615)
  • Negative regulation of gene expression
    (GO:0010629)
  • Negative regulation of insulin-like growth factor receptor signaling pathway
    (GO:0043569)
  • Negative regulation of smad protein signal transduction
    (GO:0060392)
  • Negative regulation of transforming growth factor beta receptor signaling pathway
    (GO:0030512)

Significant Cells

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

  • tendon cell CL0000388
    CSI 13.29
    rCSI 34.53%
    PRS 98.44
  • mesenchymal stem cell of adipose tissue CL0002570
    CSI 6.97
    rCSI 38.88%
    PRS 98.29
  • bronchus fibroblast of lung CL2000093
    CSI 6.77
    rCSI 5.5%
    PRS 97.7
  • adventitial cell CL0002503
    CSI 6.54
    rCSI 15.62%
    PRS 98.56
  • innate lymphoid cell CL0001065
    CSI 5.87
    rCSI 12.12%
    PRS 92.67
  • cytotoxic T cell CL0000910
    CSI 3.67
    rCSI 21.01%
    PRS 94.76
  • fibroblast of breast CL4006000
    CSI 2.78
    rCSI 11.68%
    PRS 98.58
  • basal cell of epidermis CL0002187
    CSI 2.09
    rCSI 3.71%
    PRS 78.69
  • helper T cell CL0000912
    CSI 2.06
    rCSI 2.92%
    PRS 93.25
  • alveolar adventitial fibroblast CL4028006
    CSI 1.91
    rCSI 3.01%
    PRS 98.31
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.21
    rCSI 1.47%
    PRS 84.39
  • suprabasal keratinocyte CL4033013
    CSI 1.12
    rCSI 1.82%
    PRS 80.43
  • pancreatic stellate cell CL0002410
    CSI 0.61
    rCSI 3.54%
    PRS 97.84

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)

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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 [CILP](/details-gene/8483) (Cartilage Intermediate Layer Protein) is a protein-coding gene located on chromosome 15q22.31. Initially identified as a component of the extracellular matrix (ECM) in the intermediate layer of articular cartilage, its expression increases with age ([Link](https://doi.org/10.1074/jbc.273.36.23463)). Functionally, [CILP](/details-gene/8483) is an ECM structural constituent that also plays a significant regulatory role by negatively modulating key signaling pathways, including the transforming growth factor beta (TGF-beta) and insulin-like growth factor (IGF) receptor pathways ([GO:0030512](https://www.ebi.ac.uk/QuickGO/term/GO:0030512), [GO:0043569](https://www.ebi.ac.uk/QuickGO/term/GO:0043569)). While its name implies a cartilage-specific function, expression data reveals its significance extends to a broader range of connective tissue and mesenchymal cell types. **Overall**, it is most significant in '[tendon cell](/details-cell/CL0000388)', '[mesenchymal stem cell of adipose tissue](/details-cell/CL0002570)', and various fibroblast populations. Its role is implicated in several musculoskeletal pathologies, including osteoarthritis and lumbar disc disease ([Link](https://doi.org/10.1038/ng1557)). ## Cellular Roles and Expression Landscape The expression profile of [CILP](/details-gene/8483) highlights its primary role in mesenchymal and connective tissue cell types. **Overall**, the gene shows the highest significance in '[tendon cell](/details-cell/CL0000388)' (CSI: 13.29), underscoring its importance in the structural integrity and function of tendons. High significance is also observed in various progenitor and stromal cells, including '[mesenchymal stem cell of adipose tissue](/details-cell/CL0002570)' (CSI: 6.97), '[bronchus fibroblast of lung](/details-cell/CL2000093)' (CSI: 6.77), '[adventitial cell](/details-cell/CL0002503)' (CSI: 6.54), and '[fibroblast of breast](/details-cell/CL4006000)' (CSI: 2.78). This pattern suggests a broad function for [CILP](/details-gene/8483) in producing and maintaining the extracellular matrix across diverse tissues. Interestingly, [CILP](/details-gene/8483) also demonstrates moderate significance in several immune cell populations, including '[innate lymphoid cell](/details-cell/CL0001065)' (CSI: 5.87), '[cytotoxic T cell](/details-cell/CL0000910)' (CSI: 3.67), and '[helper T cell](/details-cell/CL0000912)' (CSI: 2.06). This suggests a potential secondary role for [CILP](/details-gene/8483) in modulating the tissue microenvironment inhabited by these immune cells or in direct immune cell function. Its presence in '[basal cell of epidermis](/details-cell/CL0002187)' and '[suprabasal keratinocyte](/details-cell/CL4033013)' points to a role in skin homeostasis as well. ## Pathways and Molecular Function [CILP](/details-gene/8483) functions primarily as an '[extracellular matrix structural constituent](/details-gene/GO:0005201)', consistent with its high expression in fibroblasts and tendon cells that actively secrete ECM components. It localizes to the '[extracellular space](/details-gene/GO:0005615)' and '[collagen-containing extracellular matrix](/details-gene/GO:0062023)'. Beyond its structural role, [CILP](/details-gene/8483) is a key signaling antagonist. It is involved in the negative regulation of the '[transforming growth factor beta receptor signaling pathway](/details-gene/GO:0030512)' and the '[negative regulation of smad protein signal transduction](/details-gene/GO:0060392)'. Furthermore, research has confirmed that one of its isoforms acts as a direct antagonist to insulin-like growth factor 1 ([Link](https://doi.org/10.1002/art.10927)), aligning with its annotated function in the '[negative regulation of insulin-like growth factor receptor signaling pathway](/details-gene/GO:0043569)'. These activities are part of broader signaling events, including '[Signaling by receptor tyrosine kinases](/details-pathway/R-HSA-9006934)'. The protein also possesses enzymatic activity, specifically '[alkaline phosphatase activity](/details-gene/GO:0004035)' and '[dinucleotide phosphatase activity](/details-gene/GO:0004551)', which was noted in its initial characterization ([Link](https://doi.org/10.1074/jbc.273.36.23469)). ## Research Directions The dual function of [CILP](/details-gene/8483) as both a structural ECM protein and a signaling modulator, combined with its association with degenerative diseases, presents several avenues for future research. Its upregulation has been observed in the cartilage of patients with osteoarthritis and calcium pyrophosphate dihydrate crystal deposition disease ([Link](https://doi.org/10.1002/art.10632)), and a functional SNP in the gene is linked to susceptibility to lumbar disc disease ([Link](https://doi.org/10.1038/ng1557)). Based on the available data, several testable hypotheses can be proposed: 1. **Hypothesis 1:** Given its high expression in various fibroblast populations and its role as a negative regulator of TGF-beta signaling, dysregulation of [CILP](/details-gene/8483) contributes to the pathogenesis of tissue fibrosis. In fibrotic conditions, reduced [CILP](/details-gene/8483) expression or function may lead to unchecked TGF-beta activity, promoting excessive ECM deposition by cells like '[bronchus fibroblast of lung](/details-cell/CL2000093)'. 2. **Hypothesis 2:** [CILP](/details-gene/8483) expressed in the tissue microenvironment directly modulates the behavior of resident or infiltrating immune cells, such as '[cytotoxic T cell](/details-cell/CL0000910)' and '[innate lymphoid cell](/details-cell/CL0001065)'. It may act as a barrier or signaling cue that influences immune cell trafficking, retention, or activation state during inflammation or tissue repair. To test the first hypothesis regarding fibrosis, a key experiment could be designed. To investigate the role of [CILP](/details-gene/8483) in lung fibrosis, a mouse model of bleomycin-induced pulmonary fibrosis could be utilized. CILP knockout mice and wild-type controls would be treated with bleomycin, and lung tissue would be analyzed at various time points for collagen deposition (Masson's trichrome staining), fibroblast activation marker expression (e.g., alpha-SMA), and levels of key TGF-beta signaling components via western blot or qPCR. As a therapeutic target, [CILP](/details-gene/8483) presents an intriguing profile. Since it is a secreted, extracellular protein, it is highly accessible to biologic drugs. In the context of arthropathies and disc degeneration, where its expression is often increased and appears to be pathogenic ([Link](https://doi.org/10.1136/ard.2003.008045)), therapeutic **inhibition** would be the logical strategy. A monoclonal antibody or a small molecule inhibitor designed to block its antagonistic effect on growth factor signaling or its enzymatic activity could potentially slow the progression of cartilage and intervertebral disc degradation.

Genular Protein ID: 4069158176

Symbol: CILP1_HUMAN

Name: Cartilage intermediate layer protein 1

UniProtKB Accession Codes:

O75339 B2R8F7 Q6UW99 Q8IYI5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 11 Ensembl 1 GO 7 Gene3D 2 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 10 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 1 SMART 3 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9722584

Title: Cloning and deduced amino acid sequence of a novel cartilage protein (CILP) identifies a proform including a nucleotide pyrophosphohydrolase.

PubMed ID: 9722584

DOI: 10.1074/jbc.273.36.23469

PubMed ID: 10319588

Title: Genomic organization, mapping, and polymorphisms of the gene encoding human cartilage intermediate layer protein (CILP).

PubMed ID: 10319588

DOI: 10.1007/s100380050143

PubMed ID: 10601732

Title: The human CILP gene: exon/intron organization and chromosomal mapping.

PubMed ID: 10601732

DOI: 10.1016/s0945-053x(99)00035-9

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16572171

Title: Analysis of the DNA sequence and duplication history of human chromosome 15.

PubMed ID: 16572171

DOI: 10.1038/nature04601

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: 9722583

Title: A novel cartilage protein (CILP) present in the mid-zone of human articular cartilage increases with age.

PubMed ID: 9722583

DOI: 10.1074/jbc.273.36.23463

PubMed ID: 12483726

Title: Up-regulated expression of cartilage intermediate-layer protein and ANK in articular hyaline cartilage from patients with calcium pyrophosphate dihydrate crystal deposition disease.

PubMed ID: 12483726

DOI: 10.1002/art.10632

PubMed ID: 11315923

Title: Implication of cartilage intermediate layer protein in cartilage destruction in subsets of patients with osteoarthritis and rheumatoid arthritis.

PubMed ID: 11315923

DOI: 10.1002/1529-0131(200104)44:4<838::aid-anr140>3.0.co;2-c

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: 14962958

Title: Characterisation of cartilage intermediate layer protein (CILP)-induced arthropathy in mice.

PubMed ID: 14962958

DOI: 10.1136/ard.2003.008045

PubMed ID: 15378262

Title: The prevalence of autoantibodies against cartilage intermediate layer protein, YKL-39, osteopontin, and cyclic citrullinated peptide in patients with early-stage knee osteoarthritis: evidence of a variety of autoimmune processes.

PubMed ID: 15378262

DOI: 10.1007/s00296-004-0497-2

PubMed ID: 15864306

Title: A functional SNP in CILP, encoding cartilage intermediate layer protein, is associated with susceptibility to lumbar disc disease.

PubMed ID: 15864306

DOI: 10.1038/ng1557

PubMed ID: 23033978

Title: Diagnostic exome sequencing in persons with severe intellectual disability.

PubMed ID: 23033978

DOI: 10.1056/nejmoa1206524

Sequence Information:

  • Length: 1184
  • Mass: 132565
  • Checksum: 190B0316404D3B84
  • Sequence:
    • MVGTKAWVFS FLVLEVTSVL GRQTMLTQSV RRVQPGKKNP SIFAKPADTL ESPGEWTTWF 
NIDYPGGKGD YERLDAIRFY YGDRVCARPL RLEARTTDWT PAGSTGQVVH GSPREGFWCL 
NREQRPGQNC SNYTVRFLCP PGSLRRDTER IWSPWSPWSK CSAACGQTGV QTRTRICLAE 
MVSLCSEASE EGQHCMGQDC TACDLTCPMG QVNADCDACM CQDFMLHGAV SLPGGAPASG 
AAIYLLTKTP KLLTQTDSDG RFRIPGLCPD GKSILKITKV KFAPIVLTMP KTSLKAATIK 
AEFVRAETPY MVMNPETKAR RAGQSVSLCC KATGKPRPDK YFWYHNDTLL DPSLYKHESK 
LVLRKLQQHQ AGEYFCKAQS DAGAVKSKVA QLIVIASDET PCNPVPESYL IRLPHDCFQN 
ATNSFYYDVG RCPVKTCAGQ QDNGIRCRDA VQNCCGISKT EEREIQCSGY TLPTKVAKEC 
SCQRCTETRS IVRGRVSAAD NGEPMRFGHV YMGNSRVSMT GYKGTFTLHV PQDTERLVLT 
FVDRLQKFVN TTKVLPFNKK GSAVFHEIKM LRRKKPITLE AMETNIIPLG EVVGEDPMAE 
LEIPSRSFYR QNGEPYIGKV KASVTFLDPR NISTATAAQT DLNFINDEGD TFPLRTYGMF 
SVDFRDEVTS EPLNAGKVKV HLDSTQVKMP EHISTVKLWS LNPDTGLWEE EGDFKFENQR 
RNKREDRTFL VGNLEIRERR LFNLDVPESR RCFVKVRAYR SERFLPSEQI QGVVISVINL 
EPRTGFLSNP RAWGRFDSVI TGPNGACVPA FCDDQSPDAY SAYVLASLAG EELQAVESSP 
KFNPNAIGVP QPYLNKLNYR RTDHEDPRVK KTAFQISMAK PRPNSAEESN GPIYAFENLR 
ACEEAPPSAA HFRFYQIEGD RYDYNTVPFN EDDPMSWTED YLAWWPKPME FRACYIKVKI 
VGPLEVNVRS RNMGGTHRQT VGKLYGIRDV RSTRDRDQPN VSAACLEFKC SGMLYDQDRV 
DRTLVKVIPQ GSCRRASVNP MLHEYLVNHL PLAVNNDTSE YTMLAPLDPL GHNYGIYTVT 
DQDPRTAKEI ALGRCFDGTS DGSSRIMKSN VGVALTFNCV ERQVGRQSAF QYLQSTPAQS 
PAAGTVQGRV PSRRQQRASR GGQRQGGVVA SLRFPRVAQQ PLIN