Entrez Summary: Major alterations in the composition of the cartilage extracellular matrix occur in joint disease, such as osteoarthrosis. This gene encodes the cartilage intermediate layer protein (CILP), which increases in early osteoarthrosis cartilage. The encoded protein was thought to encode a protein precursor for two different proteins; an N-terminal CILP and a C-terminal homolog of NTPPHase, however, later studies identified no nucleotide pyrophosphatase phosphodiesterase (NPP) activity. The full-length and the N-terminal domain of this protein was shown to function as an IGF-1 antagonist. An allelic variant of this gene has been associated with lumbar disc disease. [provided by RefSeq, Sep 2010].
UniProt Summary: Probably plays a role in cartilage scaffolding. May act by antagonizing TGF-beta1 (TGFB1) and IGF1 functions. Has the ability to suppress IGF1-induced proliferation and sulfated proteoglycan synthesis, and inhibits ligand-induced IGF1R autophosphorylation. May inhibit TGFB1-mediated induction of cartilage matrix genes via its interaction with TGFB1. Overexpression may lead to impair chondrocyte growth and matrix repair and indirectly promote inorganic pyrophosphate (PPi) supersaturation in aging and osteoarthritis cartilage. {ECO:0000269|PubMed:12746903, ECO:0000269|PubMed:15864306}.
Pfam DomainsGO Terms
Pfam Domains
I-set
TSP 1
GO Terms
nucleotide diphosphatase activity
negative regulation of SMAD protein signal transduction
negative regulation of insulin-like growth factor receptor signaling pathway
alkaline phosphatase activity
regulation of SMAD protein signal transduction
regulation of insulin-like growth factor receptor signaling pathway
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway
extracellular matrix structural constituent
cellular response to transforming growth factor beta stimulus
response to transforming growth factor beta
regulation of transmembrane receptor protein serine/threonine kinase signaling pathway
dephosphorylation
collagen-containing extracellular matrix
cellular response to growth factor stimulus
response to growth factor
cellular response to endogenous stimulus
negative regulation of signal transduction
negative regulation of cell communication
negative regulation of signaling
response to endogenous stimulus
extracellular space
negative regulation of response to stimulus
negative regulation of gene expression
CRISPR Data
Compound HitMost Correlated Genes in ChemogenomicsTissues where Essential in the Avana Dataset (DepMap 20Q1)
Compound Hit
No hits were found.
Most Correlated Genes in Chemogenomics
No correlation found to any other genes in chemogenomics.
Tissues where Essential in the Avana Dataset (DepMap 20Q1)
Global Fraction of Cell Lines Where Essential: 0/739