Cholesterol-ester transfer protein deficiency

Summary

Cholesterol-ester transfer protein deficiency (MONDO:0007744) is a disease caused by CETP (GenCC Strong), with 2 cohort genes and 1 clinical trial.

At a glance

• Causal gene: CETP (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 3
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cholesterol-ester transfer protein deficiency
Mondo ID	MONDO:0007744
OMIM	143470
Orphanet	79506
DOID	DOID:0111369
SNOMED CT	15771000119109
UMLS	C3875011
MedGen	840020
GARD	0016724
Is cancer (heuristic)	no

Also known as: CEPT deficiency · familial hyperalphalipoproteinemia · HALP1 · high density lipoprotein cholesterol level QTL 10 · hyperalphalipoproteinemia · hyperalphalipoproteinemia 1 · hyperalphalipoproteinemia type 1

Data availability: 3 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inherited lipid metabolism disorder › familial hyperlipidemia › cholesterol-ester transfer protein deficiency

Related subtypes (9): familial hypercholesterolemia, hyperlipidemia, familial combined, LPL related, hyperlipoproteinemia type V, familial apolipoprotein C-II deficiency, familial lipoprotein lipase deficiency, hyperlipidemia, combined, 2, hyperlipidemia due to hepatic triglyceride lipase deficiency, hyperlipoproteinemia, type 1D, hyperlipoproteinemia type 3

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity, 1 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3779056	NM_000078.3(CETP):c.976C>T (p.Gln326Ter)	CETP	Likely pathogenic	criteria provided, single submitter
17904	NM_000040.3(APOC3):c.55C>T (p.Arg19Ter)	APOC3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3779055	NM_000078.3(CETP):c.799T>C (p.Phe267Leu)	CETP	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CETP	Strong	Autosomal dominant	cholesterol-ester transfer protein deficiency	2
APOC3	Supportive	Autosomal dominant	cholesterol-ester transfer protein deficiency	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CETP	Orphanet:181428	Familial Hyperalphalipoproteinemia
APOC3	Orphanet:181428	Familial Hyperalphalipoproteinemia

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CETP	HGNC:1869	ENSG00000087237	P11597	Cholesteryl ester transfer protein	gencc,clinvar
APOC3	HGNC:610	ENSG00000110245	P02656	Apolipoprotein C-III	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CETP	Cholesteryl ester transfer protein	Involved in the transfer of neutral lipids, including cholesteryl ester and triglyceride, among lipoprotein particles.
APOC3	Apolipoprotein C-III	Component of triglyceride-rich very low density lipoproteins (VLDL) and high density lipoproteins (HDL) in plasma.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CETP	Other/Unknown	no		Lipid-bd_serum_glycop_C, Cholesteryl_ester_transfer, Lipid-bd_serum_glycop_N
APOC3	Other/Unknown	no		Apo-CIII, Apo_CIII_sf

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
liver	2
lymph node	1
spleen	1
jejunal mucosa	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CETP	165	broad	marker	lymph node, spleen, liver
APOC3	156	tissue_specific	marker	jejunal mucosa, right lobe of liver, liver

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
APOC3	1,895
CETP	1,391

Intra-cohort edges

A	B	Sources
APOC3	CETP	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CETP	P11597	3
APOC3	P02656	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
HDL remodeling	2	1142.0×	1e-05	CETP, APOC3
LDL remodeling	1	951.7×	0.007	CETP
Chylomicron assembly	1	571.0×	0.007	APOC3
Chylomicron remodeling	1	571.0×	0.007	APOC3
Plasma lipoprotein assembly	1	356.9×	0.008	APOC3
Plasma lipoprotein remodeling	1	237.9×	0.010	APOC3
Metabolism of fat-soluble vitamins	1	190.3×	0.011	APOC3
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	1	154.3×	0.012	CETP
Visual phototransduction	1	129.8×	0.012	APOC3
Retinoid metabolism and transport	1	124.1×	0.012	APOC3
Plasma lipoprotein assembly, remodeling, and clearance	1	114.2×	0.012	APOC3
Metabolism of vitamins and cofactors	1	58.3×	0.021	APOC3
Sensory Perception	1	47.6×	0.024	APOC3
Transport of small molecules	1	12.6×	0.083	APOC3
Metabolism	1	5.8×	0.165	APOC3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
reverse cholesterol transport	2	936.2×	3e-05	CETP, APOC3
high-density lipoprotein particle remodeling	2	802.5×	3e-05	CETP, APOC3
triglyceride homeostasis	2	481.5×	4e-05	CETP, APOC3
triglyceride metabolic process	2	443.5×	4e-05	CETP, APOC3
cholesterol homeostasis	2	156.0×	3e-04	CETP, APOC3
negative regulation of high-density lipoprotein particle clearance	1	8426.0×	7e-04	APOC3
negative regulation of cholesterol import	1	2808.7×	0.002	APOC3
negative regulation of very-low-density lipoprotein particle clearance	1	2106.5×	0.002	APOC3
triglyceride transport	1	2106.5×	0.002	CETP
negative regulation of lipid metabolic process	1	1685.2×	0.002	APOC3
negative regulation of triglyceride catabolic process	1	1404.3×	0.002	APOC3
negative regulation of very-low-density lipoprotein particle remodeling	1	1404.3×	0.002	APOC3
chylomicron remnant clearance	1	1404.3×	0.002	APOC3
regulation of cholesterol efflux	1	1203.7×	0.002	CETP
positive regulation of cholesterol transport	1	1203.7×	0.002	CETP
positive regulation of phospholipid transport	1	1203.7×	0.002	CETP
very-low-density lipoprotein particle remodeling	1	1053.2×	0.002	CETP
negative regulation of receptor-mediated endocytosis	1	936.2×	0.002	APOC3
negative regulation of low-density lipoprotein particle clearance	1	766.0×	0.002	APOC3
regulation of Cdc42 protein signal transduction	1	702.2×	0.003	APOC3
negative regulation of macrophage derived foam cell differentiation	1	648.1×	0.003	CETP
very-low-density lipoprotein particle assembly	1	601.9×	0.003	APOC3
phospholipid efflux	1	561.7×	0.003	APOC3
low-density lipoprotein particle remodeling	1	526.6×	0.003	CETP
phospholipid homeostasis	1	495.6×	0.003	CETP
lipoprotein metabolic process	1	468.1×	0.003	APOC3
negative regulation of fatty acid biosynthetic process	1	443.5×	0.003	APOC3
negative regulation of lipid catabolic process	1	421.3×	0.003	APOC3
triglyceride catabolic process	1	401.2×	0.003	APOC3
phosphatidylcholine metabolic process	1	401.2×	0.003	CETP

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CETP	5	3
APOC3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ANACETRAPIB	3	CETP
EVACETRAPIB	3	CETP
DALCETRAPIB	3	CETP
TORCETRAPIB	3	CETP
URSOLIC ACID	2	CETP

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CETP	132	Binding:127, Functional:5
APOC3	1	Binding:1

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CETP	132

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

5 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
ANACETRAPIB	3	CETP
EVACETRAPIB	3	CETP
DALCETRAPIB	3	CETP
TORCETRAPIB	3	CETP
URSOLIC ACID	2	CETP

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	CETP
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	APOC3

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
APOC3	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01916512	Not specified	UNKNOWN	Relationship Between CETP Deficiency and Atherosclerosis in Patients With Hyperalphalipoproteinemia