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 NT... See more...

Aliases for CILP Gene

Aliases for CILP Gene

  • Cartilage Intermediate Layer Protein 2 3 5
  • Cartilage Intermediate Layer Protein, Nucleotide Pyrophosphohydrolase 2 3
  • Cartilage Intermediate Layer Protein 1 3 4
  • CILP-1 3 4
  • Cartilage Intermediate Layer Protein 1 C1 3
  • Cartilage Intermediate Layer Protein 1 C2 3
  • Cartilage Intermediate-Layer Protein 4
  • HsT18872 3

External Ids for CILP Gene

Previous GeneCards Identifiers for CILP Gene

  • GC15M061331
  • GC15M058587
  • GC15M063068
  • GC15M063204
  • GC15M063275
  • GC15M065488
  • GC15M042312

Summaries for CILP Gene

Entrez Gene Summary for CILP Gene

  • 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]

GeneCards Summary for CILP Gene

CILP (Cartilage Intermediate Layer Protein) is a Protein Coding gene. Diseases associated with CILP include Intervertebral Disc Disease and Osteoarthritis. Among its related pathways are Signaling by GPCR and RET signaling. Gene Ontology (GO) annotations related to this gene include alkaline phosphatase activity and nucleotide diphosphatase activity. An important paralog of this gene is CILP2.

UniProtKB/Swiss-Prot Summary for CILP Gene

  • 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.

Gene Wiki entry for CILP Gene

Additional gene information for CILP Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CILP Gene

Genomics for CILP Gene

GeneHancer (GH) Regulatory Elements for CILP Gene

Promoters and enhancers for CILP Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH15J065209 Promoter/Enhancer 1.5 EPDnew Ensembl ENCODE CraniofacialAtlas 506.4 +0.4 401 3.4 CTCF MYC ZIC2 REST ZNF740 CTBP1 SMC3 MEF2A ZNF341 NCOR1 CILP PARP16 CLPX
GH15J065244 Promoter 0.5 EPDnew 512.2 -33.0 -32973 0.1 ZSCAN5C EHMT2 CILP CLPX lnc-CILP-1 RF00026-365 RNU6-686P PARP16
GH15J065303 Promoter/Enhancer 2.4 FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 20.5 -92.9 -92930 2.3 RXRA ZBTB40 ZNF217 EP300 CTCF ZSCAN5C TCF12 POLR2G SP1 BCLAF1 AB330788-002 RNU5B-1 lnc-PARP16-3 ZNF609 PARP16 CSNK1G1 INTS14 TRIP4 SLC24A1 PDCD7
GH15J065183 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas 12.2 +27.0 27001 3.8 RXRA EP300 FOXK2 HNRNPK ZBTB40 ZNF217 SIN3A NRF1 MYC TCF12 CLPX PARP16 INTS14 TRIP4 SNORA24B RNU5A-1 CILP RNU5B-1 RBPMS2 UBAP1L
GH15J065295 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 9.9 -87.0 -87030 6.5 RXRA ZNF217 CTCF TCF12 POLR2G USF1 SP1 NCOR1 BCLAF1 RBAK PARP16 INTS14 CSNK1G1 TRIP4 ZNF609 DENND4A ENSG00000265967 ENSG00000259924 MTFMT SLC24A1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CILP on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CILP

Top Transcription factor binding sites by QIAGEN in the CILP gene promoter:
  • E47
  • GR
  • GR-alpha
  • GR-beta
  • Ik-2
  • MyoD
  • Pax-2
  • Pax-2a
  • Pax-2b
  • Tal-1beta

Genomic Locations for CILP Gene

Genomic Locations for CILP Gene
chr15:65,194,760-65,211,502
(GRCh38/hg38)
Size:
16,743 bases
Orientation:
Minus strand
chr15:65,488,337-65,503,840
(GRCh37/hg19)
Size:
15,504 bases
Orientation:
Minus strand

Genomic View for CILP Gene

Genes around CILP on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CILP Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CILP Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CILP Gene

Proteins for CILP Gene

  • Protein details for CILP Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O75339-CILP1_HUMAN
    Recommended name:
    Cartilage intermediate layer protein 1
    Protein Accession:
    O75339
    Secondary Accessions:
    • B2R8F7
    • Q6UW99
    • Q8IYI5

    Protein attributes for CILP Gene

    Size:
    1184 amino acids
    Molecular mass:
    132565 Da
    Quaternary structure:
    • Monomer. Interacts with TGFB1.
    Miscellaneous:
    • Antibodies against CILP are detected in patients with early-stage knee osteoarthritis and rheumatoid arthritis.

neXtProt entry for CILP Gene

Post-translational modifications for CILP Gene

  • Cleaved into 2 chains possibly by a furin-like protease upon or preceding secretion.
  • Glycosylation at Thr96, Thr97, Thr105, Asn129, Asn132, Asn346, Asn420, Asn550, Asn631, Asn1000, Asn1056, Ser1135, Thr1136, Ser1140, and Thr1145
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • CILP1_HUMAN (1075)

Other Protein References for CILP Gene

ENSEMBL proteins:
REFSEQ proteins:

Assay Products

  • Boster Bio ELISA Kits for CILP
  • Signalway ELISA kits for CILP

No data available for DME Specific Peptides for CILP Gene

Domains & Families for CILP Gene

Gene Families for CILP Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted secreted proteins

Protein Domains for CILP Gene

Blocks:
  • Immunoglobulin C-2 type
  • Bacterial transferase hexapeptide repeat
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for CILP Gene

GenScript: Design optimal peptide antigens:
  • Cartilage intermediate-layer protein (CILP1_HUMAN)
genes like me logo Genes that share domains with CILP: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for CILP Gene

Function for CILP Gene

Molecular function for CILP Gene

UniProtKB/Swiss-Prot Function:
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.

Phenotypes From GWAS Catalog for CILP Gene

Gene Ontology (GO) - Molecular Function for CILP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004035 NOT alkaline phosphatase activity IDA 12746903
GO:0004551 NOT nucleotide diphosphatase activity IDA 12746903
GO:0005201 extracellular matrix structural constituent RCA 27068509
genes like me logo Genes that share ontologies with CILP: view
genes like me logo Genes that share phenotypes with CILP: view

Animal Models for CILP Gene

MGI Knock Outs for CILP:
  • Cilp Cilp<tm1b(EUCOMM)Wtsi>

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CILP

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for CILP Gene

Localization for CILP Gene

Subcellular locations from UniProtKB/Swiss-Prot for CILP Gene

Secreted, extracellular space, extracellular matrix.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CILP gene
Compartment Confidence
extracellular 4
plasma membrane 1
cytoskeleton 1
mitochondrion 1
nucleus 1
cytosol 1
lysosome 1

Gene Ontology (GO) - Cellular Components for CILP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IDA 9722584
GO:0062023 collagen-containing extracellular matrix IDA 9722583
GO:0070062 extracellular exosome HDA 23533145
genes like me logo Genes that share ontologies with CILP: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for CILP Gene

Pathways & Interactions for CILP Gene

genes like me logo Genes that share pathways with CILP: view

Pathways by source for CILP Gene

Interacting Proteins for CILP Gene

;

Gene Ontology (GO) - Biological Process for CILP Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0010629 negative regulation of gene expression IDA 29167509
GO:0016311 dephosphorylation IEA --
GO:0043569 negative regulation of insulin-like growth factor receptor signaling pathway IDA 12746903
GO:0060392 negative regulation of SMAD protein signal transduction IGI 29167509
GO:0071560 cellular response to transforming growth factor beta stimulus IDA 29167509
genes like me logo Genes that share ontologies with CILP: view

No data available for SIGNOR curated interactions for CILP Gene

Drugs & Compounds for CILP Gene

(1) Drugs for CILP Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Calcium Approved Nutra 7884

(1) Additional Compounds for CILP Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with CILP: view

Transcripts for CILP Gene

mRNA/cDNA for CILP Gene

1 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CILP

Alternative Splicing Database (ASD) splice patterns (SP) for CILP Gene

ExUns: 1 ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6 ^ 7 ^ 8 ^ 9a · 9b
SP1:
SP2:
SP3:

Relevant External Links for CILP Gene

GeneLoc Exon Structure for
CILP

Expression for CILP Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CILP Gene

mRNA differential expression in normal tissues according to GTEx for CILP Gene

This gene is overexpressed in Adipose - Visceral (Omentum) (x5.3) and Adipose - Subcutaneous (x5.2).

Protein differential expression in normal tissues from HIPED for CILP Gene

This gene is overexpressed in Cervix (21.0), Testis (15.0), Breast (10.6), and Lung (8.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for CILP Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CILP

SOURCE GeneReport for Unigene cluster for CILP Gene:

Hs.442180

mRNA Expression by UniProt/SwissProt for CILP Gene:

O75339-CILP1_HUMAN
Tissue specificity: Specifically expressed in cartilage. Localizes in the intermediates layer of articular cartilage but neither in the superficial nor in the deepest regions. Specifically and highly expressed in intervertebral disk tissue. Expression increases with aging in hip articular cartilage. Overexpressed in articular hyaline cartilage from patients with calcium pyrophosphate dihydrate crystal deposition disease (CPPD). Expression in intervertebral disk tissue from individuals with lumbar disk disease increases as disk degeneration progresses.
genes like me logo Genes that share expression patterns with CILP: view

No data available for Protein tissue co-expression partners , Evidence on tissue expression from TISSUES and Phenotype-based relationships between genes and organs from Gene ORGANizer for CILP Gene

Orthologs for CILP Gene

This gene was present in the common ancestor of chordates.

Orthologs for CILP Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CILP 31 30
  • 99.55 (n)
OneToOne
dog
(Canis familiaris)
Mammalia CILP 31 30
  • 89.44 (n)
OneToOne
cow
(Bos Taurus)
Mammalia CILP 31 30
  • 88.1 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Cilp 17 31 30
  • 87.32 (n)
rat
(Rattus norvegicus)
Mammalia Cilp 30
  • 86.63 (n)
oppossum
(Monodelphis domestica)
Mammalia CILP 31
  • 83 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CILP 31
  • 69 (a)
OneToOne
chicken
(Gallus gallus)
Aves CILP 31 30
  • 68.4 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia CILP 31
  • 67 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia cilp 30
  • 64.94 (n)
Str.12721 30
zebrafish
(Danio rerio)
Actinopterygii cilp 31 30
  • 63.79 (n)
OneToOne
Dr.27649 30
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.4324 30
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 36 (a)
OneToOne
Species where no ortholog for CILP was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for CILP Gene

ENSEMBL:
Gene Tree for CILP (if available)
TreeFam:
Gene Tree for CILP (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CILP: view image

Paralogs for CILP Gene

Paralogs for CILP Gene

(1) SIMAP similar genes for CILP Gene using alignment to 1 proteins:

  • CILP1_HUMAN
genes like me logo Genes that share paralogs with CILP: view

Variants for CILP Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CILP Gene

SNP ID Clinical significance and condition Chr 15 pos Variation AA Info Type
785496 Benign: not provided 65,197,096(-) G/A SYNONYMOUS_VARIANT
rs2073711 Risk Factor: Lumbar disc disease, susceptibility to. - 65,201,874(-) A/Gp.Ile395Thr MISSENSE_VARIANT
rs149286218 - p.Arg495His
rs2585033 - p.Trp59Leu
rs2679117 - p.Gln979Arg

Additional dbSNP identifiers (rs#s) for CILP Gene

Variation tolerance for CILP Gene

Residual Variation Intolerance Score: 17.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 12.73; 94.67% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CILP Gene

Human Gene Mutation Database (HGMD)
CILP
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CILP

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for CILP Gene

Disorders for CILP Gene

MalaCards: The human disease database

(9) MalaCards diseases for CILP Gene - From: OMIM, ClinVar, GTR, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
intervertebral disc disease
  • idd
osteoarthritis
  • kashin-beck disease
familial calcium pyrophosphate deposition
  • calcium pyrophosphate arthropathy
stapes ankylosis with broad thumbs and toes
  • ankylosis of stapes, hyperopia, broad thumbs, broad first toes, and syndactyly
back pain
- elite association - COSMIC cancer census association via MalaCards
Search CILP in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

CILP1_HUMAN
  • Intervertebral disc disease (IDD) [MIM:603932]: A common musculo-skeletal disorder caused by degeneration of intervertebral disks of the lumbar spine. It results in low-back pain and unilateral leg pain. {ECO:0000269 PubMed:15864306}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. {ECO:0000269 PubMed:15864306}.

Additional Disease Information for CILP

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with CILP: view

No data available for Genatlas for CILP Gene

Publications for CILP Gene

  1. A novel cartilage protein (CILP) present in the mid-zone of human articular cartilage increases with age. (PMID: 9722583) Lorenzo P … Heinegård D (The Journal of biological chemistry 1998) 2 3 4 23 54
  2. Cloning and deduced amino acid sequence of a novel cartilage protein (CILP) identifies a proform including a nucleotide pyrophosphohydrolase. (PMID: 9722584) Lorenzo P … Heinegård D (The Journal of biological chemistry 1998) 2 3 4 23 54
  3. The cartilage intermediate layer protein gene is associated with lumbar disc degeneration in collegiate judokas. (PMID: 19569011) Min SK … Hiranuma K (International journal of sports medicine 2009) 3 23 41 54
  4. Reproducible genetic associations between candidate genes and clinical knee osteoarthritis in men and women. (PMID: 16453284) Valdes AM … Spector TD (Arthritis and rheumatism 2006) 3 23 41 54
  5. 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. (PMID: 15378262) Du H … Kato T (Rheumatology international 2005) 3 4 23 54

Products for CILP Gene

  • Signalway ELISA kits for CILP
  • Signalway Proteins for CILP

Sources for CILP Gene