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Symbol CHI3L1 contributors: mct/npt/pgu - updated : 13-06-2015
HGNC name chitinase 3-like 1 (cartilage glycoprotein-39)
HGNC id 1932
Location 1q32.1      Physical location : 203.148.058 - 203.155.922
Synonym name
  • cartilage glycoprotein-39
  • 39 kDa synovial protein
  • Synonym symbol(s) CHIT, CRGP1, YKL40, GP39, YYL-40, DKFZp686N19119, FLJ38139, HC-gp39, HCGP-3P
    TYPE like-sequence
    STRUCTURE 7.86 kb     10 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    text structure a single Sp1 binding site having a predominant role in regulating promoter activity
    MAPPING cloned Y linked Y status confirmed
    Map cen - D1S196 - D1S191 - D1S306 ,CHI3L1 - D1S245 - qter
    TRANSCRIPTS type messenger
    text two initiation sites
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 1867 40 383 - 2009 19767768
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain   highly
    Respiratoryrespiratory tractbronchus    Homo sapiens
    Skin/Tegumentskin   highly
    Visualeye   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscular     Homo sapiens
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticneutrophil Homo sapiens
    Lymphoid/Immunemacrophage Homo sapiens
    Musculardifferentiated cell Homo sapiens
    Respiratoryepithelial cell Homo sapiens
    cell lineage
    cell lines
    at STAGE
  • N terminal sequence YKL, lacking the active site glutamate essential for chitinase activity, but first 22 AAs constitute the signal peptide that ensures the secretion of mature protein
  • putative arginine-lysine (RK)-rich domain(s), the motif that has been shown to be important for heparin binding
  • a chitin-binding motif (CBM) specifically associated with the CHI3L1-mediated activation of the Akt-signaling in colonic epithelial cells
  • conjugated GlycoP
    isoforms Precursor
    interspecies homolog to murine Chi3l1
    intraspecies homolog to CHIT1
  • glycosyl hydrolase 18 family
  • CATEGORY enzyme
    intracellular,cytoplasm,organelle,endoplasmic reticulum
  • specific granules of neutrophils
  • extra cellular matrix of cartilage
  • undifferentiated MSCs contain significant levels of CHI3L1 mRNA but do not synthesize detectable levels of CHI3L1 protein; MSCs induced to differentiate into chondrocytes and osteocytes soon began to express and secrete CHI3L1 protein, but in contrast, MSCs induced to trans-differentiate into neurons did not synthesize CHI3L1 protein
  • basic FUNCTION
  • may play a role in tissue remodeling and defense against pathogens
  • may be involved in the cellular response to various environmental events that are reported to increase the risk of schizophrenia
  • function in cells of epithelial origin may be related to cell motility and cell-cell adhesion, features associated with invasion and migration potential of tumor cells
  • can act as a fibroblast mitogen and can activate several signaling pathways
  • major protein secreted from stromal vascular fraction cells in human visceral adipose tissue
  • inhibited the degradation of type I collagen, a major extracellular matrix of AT, by matrix metalloproteinase MMP1 and increased rate of fibril formation of type I collagen
  • growth factor for connective tissue cells and a migration factor for endothelial cells
  • induces tumor angiogenesis and tumor development
  • is induced in astrocytes in a variety of neurological diseases but that it is most abundantly associated with astrocytes in regions of inflammatory cells
  • mechanical stress potently induces CHI3L1 expression leading to increased secretion of YCHI3L1 protein in an EGFR and MEK1/2-dependent pathway
  • may be important in initial cell differentiation from hESCs toward ectoderm and neuroectoderm, with retained epithelial morphology
  • promotes the growth of human synovial cells as well as skin and fetal lung fibroblasts similarly to insulin-like growth factor 1 (IGF1)
  • CHI3L1, CHI3L2 are involved in mediating the mitogenic response through the signal-regulated kinases ERK1/2
  • involved in hyperoxia-induced cell death, suggesting that CHI3L1 may be one of several cell death regulators influencing the MAPK and PI3K pathways during oxidative stress in human airway epithelial cells (pMID: 22554524)
  • role of CHI3L1 in the progression/prognosis of patients with peripheral arterial disease (PAD) and concomitant diabetes
  • secreted chitinase family protein that induces angiogenesis, cell survival, and cell proliferation, and plays roles in tissue remodeling and immune regulation
  • CHIA, CHIT1, CHI3L1, CHI3L2 and CHID1 exert important biological roles in the monocyte lineage and chronic inflammatory diseases
  • CHIA, CHI3L2 and CHID1 resulted unchanged during osteoclast differentiation, whereas CHIT1 and CHI3L1 increased significantly
  • novel and crucial role for both CHIT1 and CHI3L1 in promoting bone resorption
  • myokine CHI3L1, which is induced by pro-inflammatory cytokines, can counteract TNF-mediated inflammation and insulin resistance in human skeletal muscle cells, potentially involving an auto- and/or para-crine mechanism
  • may be important in the progression and angiogenesis of clear cell renal cell carcinoma
    metabolism carbohydrate
    a component
    small molecule
  • binds chitin tightly and heparin at lower affinity
  • cell & other
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in papillary thyroid carcinoma (PTC), and in hepatitis C virus
    tumoral     --over  
    in gastric cancers and significantly associated with tumor invasion and lymph node metastasis
    tumoral     --over  
    in human breast cancer is associated with blood vessel formation
    constitutional     --over  
    in cerebrospinal fluid (CSF) and serum CHI3L1 levels increased with the multiple sclerosis stage
    tumoral     --over  
    increased expression of CHI3L1 and microvessel density (MVD) is associated with metastasis and a worse prognosis in clear cell renal cell carcinoma
    constitutional     --over  
    serum levels of YKL-40 were elevated in patients with cerebrovascular disease in lesion subtype- and severity-dependent manners
    constitutional     --other  
    is dysregulated, in part, due to perturbation of VEGFA signaling, and may contribute to endothelial dysfunction and hypertension in Obstructive sleep apnea (OSA)
    Susceptibility to schizophrenia
    Variant & Polymorphism SNP SNP4 (rs4950928), the tagging SNP of CCC, impaired the MYC/MAX-regulated transcriptional activation of CHI3L1 and increasing the risk of schizophrenia
    Candidate gene
  • could be used as an independent molecular marker for the predicting poor prognosis of patients with gastric cancer
  • serum levels of CHI3L1 may serve as a cancer biomarker
  • Marker
  • potential for CHI3L1 as a diagnostic/prognostic biomarker for cerebrovascular disease
  • Therapy target
    CHI3L1 may be useful as new prognostic markers and new therapeutic targets in glioblastoma
    novel therapeutic agents targeting CHI3L1 that is overexpressed in a broad range of human cancers
    might be a novel strategy for therapy of the patients with renal cell carcinoma