Details for: CETP

Gene ID: 1071

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: CETP

Ensembl ID: ENSG00000087237

Description: cholesteryl ester transfer protein

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • Kupffer cell CL0000091
    CSI 5.08
    rCSI 11.61%
    PRS 99.89
  • myeloid leukocyte CL0000766
    CSI 5.07
    rCSI 4.68%
    PRS 99.9
  • macrophage CL0000235
    CSI 3.16
    rCSI 5.75%
    PRS 99.68
  • platelet CL0000233
    CSI 1.85
    rCSI 7.7%
    PRS 99.01

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

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  • Node Color (Target Cell CSI, relative to current network):
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  • 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 [CETP](/details-gene/1071) (Cholesteryl Ester Transfer Protein) encodes a secreted plasma glycoprotein that plays a central role in lipid metabolism. Its primary function is to facilitate the transfer of cholesteryl esters from high-density lipoproteins (HDL) to apolipoprotein B-containing particles, such as low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL), in exchange for triglycerides. This process is a key step in [reverse cholesterol transport](/details-go/GO0043691) and significantly influences plasma lipoprotein profiles. Mutations in the [CETP](/details-gene/1071) gene are associated with hyperalphalipoproteinemia ([118470](https://omim.org/entry/118470)), a condition characterized by elevated HDL cholesterol levels. Expression data indicates that [CETP](/details-gene/1071) is highly significant in myeloid lineage cells, particularly liver-resident [Kupffer cell](/details-cell/CL0000091)s and circulating [myeloid leukocyte](/details-cell/CL0000766)s, highlighting the importance of these cells in systemic lipid homeostasis. ## Cellular Roles and Expression Landscape **Overall**, expression analysis identifies [CETP](/details-gene/1071) as a gene of high significance in cells of the myeloid lineage, which are key players in both lipid metabolism and immunity. The highest significance is observed in [Kupffer cell](/details-cell/CL0000091)s (CSI: 5.08), the resident macrophages of the liver, which aligns with the liver's central role in producing and regulating circulating lipoproteins. High significance is also noted in the broader categories of [myeloid leukocyte](/details-cell/CL0000766) (CSI: 5.07) and [macrophage](/details-cell/CL0000235) (CSI: 3.16). This expression pattern suggests that beyond the liver's systemic contribution, macrophages may be a significant peripheral source of [CETP](/details-gene/1071), potentially influencing local lipid environments in tissues. This is particularly relevant in the context of atherosclerosis, where macrophage lipid accumulation leads to foam cell formation. Indeed, functional annotations link [CETP](/details-gene/1071) to the [negative regulation of macrophage derived foam cell differentiation](/details-go/GO0010745). Additionally, its notable significance in [platelet](/details-cell/CL0000233)s (CSI: 1.85) may suggest a role in the interplay between dyslipidemia and thrombosis. ## Pathways and Molecular Function [CETP](/details-gene/1071) functions as a lipid transporter that mediates the exchange of neutral lipids within the extracellular space, primarily in plasma. The crystal structure of the protein reveals a hydrophobic tunnel that accommodates lipid molecules, facilitating their transfer between lipoprotein particles ([Link](https://doi.org/10.1038/nsmb1197)). Its core molecular functions include [cholesterol transfer activity](/details-go/GO0120020), as well as binding to various lipids like [cholesterol](/details-go/GO0015485) and [triglyceride](/details-go/GO0017129). At the process level, [CETP](/details-gene/1071) is a critical component of [plasma lipoprotein assembly, remodeling, and clearance](/details-reactome/R-HSA-174824). Its activity directly contributes to [Hdl remodeling](/details-reactome/R-HSA-8964058) and [Ldl remodeling](/details-reactome/R-HSA-8964041). By transferring cholesteryl esters from HDL to LDL and VLDL particles, [CETP](/details-gene/1071) effectively lowers the concentration of cholesterol carried by HDL, a process often considered pro-atherogenic. Consequently, genetic variants that result in reduced [CETP](/details-gene/1071) function are associated with significantly increased plasma HDL levels and are considered protective against cardiovascular disease ([Link](https://doi.org/10.1056/nejm199011013231803)). ## Research Directions Given the central role of [CETP](/details-gene/1071) in lipoprotein metabolism and its high significance in macrophages, future research should focus on dissecting its cell-specific contributions to cardiometabolic diseases. 1. **Hypothesis 1:** Macrophage-secreted [CETP](/details-gene/1071) acts in a paracrine manner within atherosclerotic plaques to modulate the lipid composition and inflammatory state of neighboring immune and endothelial cells. This local effect may contribute to plaque instability independently of its systemic impact on plasma HDL levels. 2. **Hypothesis 2:** The expression of [CETP](/details-gene/1071) in [Kupffer cell](/details-cell/CL0000091)s is dynamically regulated by pro-inflammatory stimuli associated with metabolic syndrome (e.g., endotoxins, saturated fatty acids). This upregulation may represent a key mechanism linking liver inflammation (steatohepatitis) to systemic dyslipidemia. **Experimental Approach for Hypothesis 1:** To test the local role of macrophage-derived [CETP](/details-gene/1071), a mouse model with a myeloid-specific deletion of the *Cetp* gene (e.g., using a Lyz2-Cre driver) could be generated on an atherosclerosis-prone genetic background (e.g., *Ldlr* knockout). Following a high-fat diet challenge, detailed analysis of aortic root plaques via single-cell RNA sequencing and spatial transcriptomics would allow for a direct comparison of the cellular composition, lipid handling gene networks, and inflammatory signaling pathways between mice with and without macrophage-derived [CETP](/details-gene/1071). **Therapeutic Potential:** [CETP](/details-gene/1071) is a major therapeutic target for raising HDL cholesterol, and the primary strategy is **inhibition**. Several small-molecule inhibitors have been developed and tested in large-scale clinical trials. While these drugs successfully increase HDL-C levels, their clinical efficacy in reducing cardiovascular events has been inconsistent, with some trials showing benefit while others were halted due to off-target effects or lack of efficacy. The finding that [CETP](/details-gene/1071) is highly significant in macrophages suggests that future therapeutic strategies could focus on targeted delivery of inhibitors to these cells within atherosclerotic lesions, potentially maximizing local anti-atherogenic effects while minimizing systemic exposure and side effects.

Genular Protein ID: 2056490035

Symbol: CETP_HUMAN

Name: N/A

UniProtKB Accession Codes:

P11597 Q13987 Q13988 Q53YZ1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChEBI 3 ChEMBL 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EMBL 13 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 29 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 3 PDBsum 3 PIR 1 PIRSF 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 3 RefSeq 1 Rhea 3 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissLipids 1 SwissPalm 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 3600759

Title: Cloning and sequencing of human cholesteryl ester transfer protein cDNA.

PubMed ID: 3600759

DOI: 10.1038/327632a0

PubMed ID: 2334701

Title: Organization of the human cholesteryl ester transfer protein gene.

PubMed ID: 2334701

DOI: 10.1021/bi00458a004

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: 8943225

Title: Human cholesteryl ester transfer protein gene proximal promoter contains dietary cholesterol positive responsive elements and mediates expression in small intestine and periphery while predominant liver and spleen expression is controlled by 5'-distal sequences. Cis-acting sequences mapped in transgenic mice.

PubMed ID: 8943225

DOI: 10.1074/jbc.271.50.31831

PubMed ID: 9332354

Title: Sequencing of the cholesteryl ester transfer protein 5' regulatory region using artificial transposons.

PubMed ID: 9332354

DOI: 10.1016/s0378-1119(97)00247-3

PubMed ID: 3281933

Title: Monoclonal antibodies to the Mr 74,000 cholesteryl ester transfer protein neutralize all of the cholesteryl ester and triglyceride transfer activities in human plasma.

PubMed ID: 3281933

DOI: 10.1016/s0021-9258(18)60670-2

PubMed ID: 16335952

Title: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry.

PubMed ID: 16335952

DOI: 10.1021/pr0502065

PubMed ID: 17952847

Title: Common single-nucleotide polymorphisms act in concert to affect plasma levels of high-density lipoprotein cholesterol.

PubMed ID: 17952847

DOI: 10.1086/522497

PubMed ID: 19139490

Title: A strategy for precise and large scale identification of core fucosylated glycoproteins.

PubMed ID: 19139490

DOI: 10.1074/mcp.m800504-mcp200

PubMed ID: 24293641

Title: Cholesteryl ester transfer proteins from different species do not have equivalent activities.

PubMed ID: 24293641

DOI: 10.1194/jlr.m043646

PubMed ID: 17237796

Title: Crystal structure of cholesteryl ester transfer protein reveals a long tunnel and four bound lipid molecules.

PubMed ID: 17237796

DOI: 10.1038/nsmb1197

PubMed ID: 2215607

Title: Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation.

PubMed ID: 2215607

DOI: 10.1056/nejm199011013231803

PubMed ID: 8408659

Title: A missense mutation in the cholesteryl ester transfer protein gene with possible dominant effects on plasma high density lipoproteins.

PubMed ID: 8408659

DOI: 10.1172/jci116802

PubMed ID: 10391209

Title: Characterization of single-nucleotide polymorphisms in coding regions of human genes.

PubMed ID: 10391209

DOI: 10.1038/10290

PubMed ID: 12091484

Title: Two novel missense mutations in the CETP gene in Japanese hyperalphalipoproteinemic subjects: high-throughput assay by Invader assay.

PubMed ID: 12091484

DOI: 10.1194/jlr.m200024-jlr200

PubMed ID: 12966036

Title: Association of extreme blood lipid profile phenotypic variation with 11 reverse cholesterol transport genes and 10 non-genetic cardiovascular disease risk factors.

PubMed ID: 12966036

DOI: 10.1093/hmg/ddg314

Sequence Information:

  • Length: 493
  • Mass: 54756
  • Checksum: CD7762766A9B062E
  • Sequence:
    • MLAATVLTLA LLGNAHACSK GTSHEAGIVC RITKPALLVL NHETAKVIQT AFQRASYPDI 
TGEKAMMLLG QVKYGLHNIQ ISHLSIASSQ VELVEAKSID VSIQNVSVVF KGTLKYGYTT 
AWWLGIDQSI DFEIDSAIDL QINTQLTCDS GRVRTDAPDC YLSFHKLLLH LQGEREPGWI 
KQLFTNFISF TLKLVLKGQI CKEINVISNI MADFVQTRAA SILSDGDIGV DISLTGDPVI 
TASYLESHHK GHFIYKNVSE DLPLPTFSPT LLGDSRMLYF WFSERVFHSL AKVAFQDGRL 
MLSLMGDEFK AVLETWGFNT NQEIFQEVVG GFPSQAQVTV HCLKMPKISC QNKGVVVNSS 
VMVKFLFPRP DQQHSVAYTF EEDIVTTVQA SYSKKKLFLS LLDFQITPKT VSNLTESSSE 
SVQSFLQSMI TAVGIPEVMS RLEVVFTALM NSKGVSLFDI INPEIITRDG FLLLQMDFGF 
PEHLLVDFLQ SLS

Genular Protein ID: 1429060837

Symbol: B4DMZ5_HUMAN

Name: N/A

UniProtKB Accession Codes:

B4DMZ5

Database IDs:

ARBA 13 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChEBI 3 DNASU 1 DisGeNET 1 EMBL 2 GO 17 InterPro 5 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PIRNR 1 PIRSF 1 PIRSR 1 PROSITE 1 PeptideAtlas 1 Pfam 1 RefSeq 1 Rhea 3 SMART 4 SUPFAM 1

Sequence Information:

  • Length: 433
  • Mass: 47801
  • Checksum: 36C4476AE66F78E5
  • Sequence:
    • MLAATVLTLA LLGNAHACSK GTSHEAGIVC RITKPALLVL NHETAKVIQT AFQRASYPDI 
TGEKAMMLLG QVKYGLHNIQ ISHLSIASSQ VELVEAKSID VSIQNVSVVF KGTLKYGYTT 
AWWLGIDQSI DFEIDSAIDL QINTQLTCDS GRVRTDAPDC YLSFHKLLLH LQGEREPGWI 
KQLFTNFISF TLKLVLKGQI CKEINVISNI MADFVQTRAA SILSDGDIGV DISLTGDPVI 
TASYLESHHK AVLETWGFNT NQEIFQEVVG GFPSQAQVTV HCLKMPKISC QNKGVVVNSS 
VMVKFLFPRP DQQHSVAYTF EEDIVTTVQA SYSKKKLFLS LLDFQITPKT VSNLTESSSE 
SIQSFLQSMI TAVGIPEVMS RLEVVFTALM NSKGVSLFDI INPEIITRDG FLLLQMDFGF 
PEHLLVDFLQ SLS

Genular Protein ID: 971611158

Symbol: A0A0S2Z3I8_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A0S2Z3I8

Database IDs:

ARBA 15 AlphaFoldDB 1 Antibodypedia 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChEBI 3 DNASU 1 DisGeNET 1 EMBL 4 ExpressionAtlas 1 GO 17 InterPro 5 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PIRSF 1 PIRSR 1 PROSITE 1 Pfam 1 RefSeq 1 Rhea 3 SAM 1 SMART 4 SMR 1 SUPFAM 1 VEuPathDB 1

Citations:

PubMed ID: 11181995

Title: The sequence of the human genome.

PubMed ID: 11181995

DOI: 10.1126/science.1058040

PubMed ID: 26871637

Title: Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.

PubMed ID: 26871637

DOI: 10.1016/j.cell.2016.01.029

Sequence Information:

  • Length: 433
  • Mass: 47787
  • Checksum: ED675FD1456F78F7
  • Sequence:
    • MLAATVLTLA LLGNAHACSK GTSHEAGIVC RITKPALLVL NHETAKVIQT AFQRASYPDI 
TGEKAMMLLG QVKYGLHNIQ ISHLSIASSQ VELVEAKSID VSIQNVSVVF KGTLKYGYTT 
AWWLGIDQSI DFEIDSAIDL QINTQLTCDS GRVRTDAPDC YLSFHKLLLH LQGEREPGWI 
KQLFTNFISF TLKLVLKGQI CKEINVISNI MADFVQTRAA SILSDGDIGV DISLTGDPVI 
TASYLESHHK AVLETWGFNT NQEIFQEVVG GFPSQAQVTV HCLKMPKISC QNKGVVVNSS 
VMVKFLFPRP DQQHSVAYTF EEDIVTTVQA SYSKKKLFLS LLDFQITPKT VSNLTESSSE 
SVQSFLQSMI TAVGIPEVMS RLEVVFTALM NSKGVSLFDI INPEIITRDG FLLLQMDFGF 
PEHLLVDFLQ SLS