CILP (cartilage intermediate layer protein)

Gene

• Entrez ID: 8483
• Gene name: Cartilage intermediate layer protein
• Gene symbol: CILP
• Synonyms (NCBI Gene): CILP-1, CILP1, HsT18872
• Chromosome: 15
• Chromosome location: 15q22.31
• 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 pr

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs2073711	A>G	Risk-factor	Missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT2200869	hsa-miR-3125	CLIP-seq
MIRT2200870	hsa-miR-3180-5p	CLIP-seq
MIRT2200871	hsa-miR-3529	CLIP-seq
MIRT2200872	hsa-miR-379	CLIP-seq
MIRT2200873	hsa-miR-3916	CLIP-seq
MIRT2200874	hsa-miR-3928	CLIP-seq
MIRT2200875	hsa-miR-4451	CLIP-seq
MIRT2200876	hsa-miR-4650-3p	CLIP-seq
MIRT2200877	hsa-miR-499a-5p	CLIP-seq
MIRT2200878	hsa-miR-520a-5p	CLIP-seq
MIRT2200879	hsa-miR-525-5p	CLIP-seq
MIRT2200880	hsa-miR-877	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004035	Function	Alkaline phosphatase activity	IDA	12746903
GO:0004551	Function	Dinucleotide phosphatase activity	IDA	12746903
GO:0005201	Function	Extracellular matrix structural constituent	RCA	27068509, 27559042
GO:0005576	Component	Extracellular region	IEA
GO:0005615	Component	Extracellular space	IBA
GO:0005615	Component	Extracellular space	IDA	9722584, 12746903
GO:0010629	Process	Negative regulation of gene expression	IDA	29167509
GO:0030512	Process	Negative regulation of transforming growth factor beta receptor signaling pathway	IDA	29167509
GO:0031012	Component	Extracellular matrix	HDA	27068509, 27559042
GO:0031012	Component	Extracellular matrix	IBA
GO:0031012	Component	Extracellular matrix	IDA	9722583
GO:0043569	Process	Negative regulation of insulin-like growth factor receptor signaling pathway	IDA	12746903
GO:0060392	Process	Negative regulation of SMAD protein signal transduction	IGI	29167509
GO:0070062	Component	Extracellular exosome	HDA	23533145

Other IDs

• MIM: 603489
• HGNC: 1980
• e!Ensembl: ENSG00000138615

Protein

• UniProt ID: O75339
• Protein name: Cartilage intermediate layer protein 1 (CILP-1) (Cartilage intermediate-layer protein) [Cleaved into: Cartilage intermediate layer protein 1 C1; Cartilage intermediate layer protein 1 C2]
• Protein 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 autophosp
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF13330	Mucin2_WxxW	56 → 139	Mucin-2 protein WxxW repeating region	Family
  PF00090	TSP_1	153 → 200	Thrombospondin type 1 domain	Domain
  PF13927	Ig_3	308 → 380		Domain

• Tissue specificity: 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 inc
• Sequence:

  MVGTKAWVFSFLVLEVTSVLGRQTMLTQSVRRVQPGKKNPSIFAKPADTLESPGEWTTWF
  NIDYPGGKGDYERLDAIRFYYGDRVCARPLRLEARTTDWTPAGSTGQVVHGSPREGFWCL
  NREQRPGQNCSNYTVRFLCPPGSLRRDTERIWSPWSPWSKCSAACGQTGVQTRTRICLAE
  MVSLCSEASEEGQHCMGQDCTACDLTCPMGQVNADCDACMCQDFMLHGAVSLPGGAPASG
  AAIYLLTKTPKLLTQTDSDGRFRIPGLCPDGKSILKITKVKFAPIVLTMPKTSLKAATIK
  AEFVRAETPYMVMNPETKARRAGQSVSLCCKATGKPRPDKYFWYHNDTLLDPSLYKHESK
  LVLRKLQQHQAGEYFCKAQSDAGAVKSKVAQLIVIASDETPCNPVPESYLIRLPHDCFQN
  ATNSFYYDVGRCPVKTCAGQQDNGIRCRDAVQNCCGISKTEEREIQCSGYTLPTKVAKEC
  SCQRCTETRSIVRGRVSAADNGEPMRFGHVYMGNSRVSMTGYKGTFTLHVPQDTERLVLT
  FVDRLQKFVNTTKVLPFNKKGSAVFHEIKMLRRKKPITLEAMETNIIPLGEVVGEDPMAE
  LEIPSRSFYRQNGEPYIGKVKASVTFLDPRNISTATAAQTDLNFINDEGDTFPLRTYGMF
  SVDFRDEVTSEPLNAGKVKVHLDSTQVKMPEHISTVKLWSLNPDTGLWEEEGDFKFENQR
  RNKREDRTFLVGNLEIRERRLFNLDVPESRRCFVKVRAYRSERFLPSEQIQGVVISVINL
  EPRTGFLSNPRAWGRFDSVITGPNGACVPAFCDDQSPDAYSAYVLASLAGEELQAVESSP
  KFNPNAIGVPQPYLNKLNYRRTDHEDPRVKKTAFQISMAKPRPNSAEESNGPIYAFENLR
  ACEEAPPSAAHFRFYQIEGDRYDYNTVPFNEDDPMSWTEDYLAWWPKPMEFRACYIKVKI
  VGPLEVNVRSRNMGGTHRQTVGKLYGIRDVRSTRDRDQPNVSAACLEFKCSGMLYDQDRV
  DRTLVKVIPQGSCRRASVNPMLHEYLVNHLPLAVNNDTSEYTMLAPLDPLGHNYGIYTVT
  DQDPRTAKEIALGRCFDGTSDGSSRIMKSNVGVALTFNCVERQVGRQSAFQYLQSTPAQS
  PAAGTVQGRVPSRRQQRASRGGQRQGGVVASLRFPRVAQQPLIN

• Sequence length: 1184

Pathways

Reactome:

Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CILP-related disorder	Benign; risk factor; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTERVERTEBRAL DISC DISEASE	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTERVERTEBRAL DISC DISORDER	—	ClinVar, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lumbar disc disease, susceptibility to	Benign; risk factor	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Aortic Valve Stenosis	Aortic Valve Sclerosis	BEFREE	29167509		★☆☆☆☆ Found in Text Mining only
Arthritis Rheumatoid	Rheumatoid arthritis	Pubtator	15146421	Associate	★☆☆☆☆ Found in Text Mining only
Autoimmune Diseases	Autoimmune Diseases	BEFREE	15146421		★☆☆☆☆ Found in Text Mining only
Cardiomyopathies	Cardiomyopathy	Pubtator	33016206	Associate	★☆☆☆☆ Found in Text Mining only
Chondrocalcinosis	Chondrocalcinosis	Pubtator	10524685	Associate	★☆☆☆☆ Found in Text Mining only
Chondrocalcinosis 2	Chondrocalcinosis	Pubtator	12483726	Associate	★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	BEFREE	15146421, 29233086, 31352363		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Insulin-Dependent	Diabetes Mellitus	BEFREE	29436660		★☆☆☆☆ Found in Text Mining only
Esophageal Squamous Cell Carcinoma	Esophageal squamous cell carcinoma	Pubtator	35899307	Associate	★☆☆☆☆ Found in Text Mining only
Heart Failure	Heart failure	Pubtator	33016206	Associate	★☆☆☆☆ Found in Text Mining only
Intervertebral Disc Degeneration	Intervertebral Disc Degeneration	BEFREE	15864306, 22107760, 24631904, 27359356		★☆☆☆☆ Found in Text Mining only
Intervertebral Disc Degeneration	Intervertebral disc disease	Pubtator	22107760	Associate	★☆☆☆☆ Found in Text Mining only
Intervertebral Disc Degeneration	Intervertebral disc disease	Pubtator	34233701	Stimulate	★☆☆☆☆ Found in Text Mining only
Intervertebral disc disorder	Intervertebral Disc Disorder	BEFREE	29436660		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intervertebral disc disorder	Intervertebral Disc Disorder	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lhermitte-Duclos disease	Lhermitte-Duclos disease	BEFREE	30288688		★☆☆☆☆ Found in Text Mining only
Lumbar disc disease	Lumbar Disc Disease	BEFREE	15864306, 17220213, 24631904, 30288688		★☆☆☆☆ Found in Text Mining only
Lumbar disc disease	Lumbar Disc Disease	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Narcolepsy	Narcolepsy	GWASDB_DG	19629137		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	31746390	Associate	★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	Pubtator	21947364	Associate	★☆☆☆☆ Found in Text Mining only
Osteoarthritis	Osteoarthritis	Pubtator	15146421, 15334463	Associate	★☆☆☆☆ Found in Text Mining only
Osteoarthritis Knee	Osteoarthritis	Pubtator	31352363	Associate	★☆☆☆☆ Found in Text Mining only
Rheumatoid Arthritis	Rheumatoid arthritis	BEFREE	15146421		★☆☆☆☆ Found in Text Mining only
Thyroid Neoplasms	Thyroid cancer	Pubtator	29321030	Associate	★☆☆☆☆ Found in Text Mining only