CETP
protein-codingcholesteryl ester transfer protein, the group of BPI fold containing
Gene summary
The protein encoded by this gene is found in plasma, where it is involved in the transfer of cholesteryl ester from high density lipoprotein (HDL) to other lipoproteins. Defects in this gene are a cause of hyperalphalipoproteinemia 1 (HALP1). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~21.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0007744
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Cardiovascular
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CETP variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000078.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 6 | 49 | 8 | 63 | ||
| missense | 147 | 25 | 1 | 173 | ||
| nonsense | 1 | 4 | 2 | 7 | ||
| start loss | 0 | |||||
| frameshift | 1 | 3 | 2 | 6 | ||
| splice donor/acceptor (+/-2bp) | 1 | 2 | 4 | 7 | ||
| Total | 3 | 9 | 161 | 74 | 9 | 256 |
Highest pathogenic variant AF is 0.0001016099
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000069.2 | 16 | MANE Select | |
| Ensembl | ENSP00000200676.3 | 16 | MANE Select | |
| RefSeq | NP_001273014.1 | 15 | Standard | |
| Ensembl | ENSP00000369106.2 | 15 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cholesterol metabolism - Homo sapiens (human)
- Composition of Lipid Particles
- Statin Pathway
- LDL remodeling
- HDL remodeling
Biological Process
- triglyceride metabolic process
- lipid transport
- cholesterol metabolic process
- negative regulation of macrophage derived foam cell differentiation
- regulation of cholesterol efflux
Molecular Function
- lipid transporter activity
- phospholipid transporter activity
- lipid binding
- cholesterol binding
- cholesterol transporter activity
Cellular Component
- extracellular region
- extracellular space
- vesicle
- high-density lipoprotein particle
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000200676
- Coding exons
- 16
- Length
- 21996
- Individuals with no LoFs
- 125640
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 107
- Defined
- 125748
- p
- 0.000430
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.526 | 290 | 266 | 1.09 | 0.0000153 | 3240 |
| Missense (PolyPhen) | 56 | 62.346 | 0.89821 | 827 | ||
| Synonymous | -0.735 | 125 | 115 | 1.09 | 0.00000768 | 962 |
| Loss of Function | -0.612 | 33 | 29.4 | 1.12 | 0.00000166 | 315 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00068 | 0.00068 | rare |
| Latino/Admixed American | 0.00038 | 0.00038 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00049 | 0.00049 | rare |
| Finnish | 0.0014 | 0.0014 | notable |
| European (Non-Finnish) | 0.00024 | 0.00024 | rare |
| South Asian | 0.00049 | 0.00046 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in the transfer of neutral lipids, including cholesteryl ester and triglyceride, among lipoprotein particles. Allows the net movement of cholesteryl ester from high density lipoproteins/HDL to triglyceride-rich very low density lipoproteins/VLDL, and the equimolar transport of triglyceride from VLDL to HDL (PubMed:3600759, PubMed:24293641). Regulates the reverse cholesterol transport, by which excess cholesterol is removed from peripheral tissues and returned to the liver for elimination (PubMed:17237796). {ECO:0000269|PubMed:24293641, ECO:0000303|PubMed:17237796, ECO:0000305|PubMed:3600759}.;
- Disease
- DISEASE: Hyperalphalipoproteinemia 1 (HALP1) [MIM:143470]: A condition characterized by high levels of high density lipoprotein (HDL) and increased HDL cholesterol levels. {ECO:0000269|PubMed:12091484, ECO:0000269|PubMed:2215607, ECO:0000269|PubMed:8408659}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.370
Intolerance Scores
- LoFtool
- 0.970
- RVIS EVS
- -0.06
- RVIS percentile EVS
- 48.84
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.681
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |