Cholesterol metabolism disease

Summary

Cholesterol metabolism disease (MONDO:0045008) is a disease with 1 cohort gene and 2 clinical trials. Top therapeutic interventions include ezetimibe.

At a glance

• Cohort genes: 1
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cholesterol metabolism disease
Mondo ID	MONDO:0045008
SNOMED CT	123963007
UMLS	C0342877
MedGen	575263
GARD	0025928
Is cancer (heuristic)	no

Also known as: cholesterol metabolic process disease · cholesterol metabolism disease · disorder of cholesterol metabolic process · disorder of cholesterol metabolism

Data availability: 1 GenCC gene-disease record.

Disease family

An umbrella term covering 2 Mondo subtypes.

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 › sterol metabolism disorder › cholesterol metabolism disease

Related subtypes (3): recessive X-linked ichthyosis, inborn disorder of bile acid synthesis, sterol biosynthesis disorder

Subtypes (2): cholesterol catabolic process disease, cholesterol biosynthetic process disease

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 0 · 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
PPARA	Limited	Autosomal dominant	cholesterol metabolism disease

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PPARA	HGNC:9232	ENSG00000186951	Q07869	Peroxisome proliferator-activated receptor alpha	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PPARA	Peroxisome proliferator-activated receptor alpha	Ligand-activated transcription factor.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Nuclear receptor	1	385.9×	0.003

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PPARA	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
biceps brachii	1
jejunal mucosa	1
renal medulla	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PPARA	265	ubiquitous	marker	renal medulla, jejunal mucosa, biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PPARA	4,803

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PPARA	Q07869	79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
BMAL1:CLOCK,NPAS2 activates circadian expression	1	423.0×	0.007	PPARA
RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression	1	407.9×	0.007	PPARA
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	1	380.7×	0.007	PPARA
SUMOylation of intracellular receptors	1	335.9×	0.007	PPARA
Expression of BMAL (ARNTL), CLOCK, and NPAS2	1	292.8×	0.007	PPARA
Activation of gene expression by SREBF (SREBP)	1	259.6×	0.007	PPARA
Heme signaling	1	215.5×	0.007	PPARA
Transcriptional activation of mitochondrial biogenesis	1	203.9×	0.007	PPARA
Nuclear Receptor transcription pathway	1	200.3×	0.007	PPARA
Cytoprotection by HMOX1	1	184.2×	0.007	PPARA
Regulation of lipid metabolism by PPARalpha	1	141.0×	0.008	PPARA
Transcriptional regulation of white adipocyte differentiation	1	129.8×	0.008	PPARA
PPARA activates gene expression	1	94.4×	0.011	PPARA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of fatty acid transport	1	8426.0×	0.002	PPARA
regulation of ketone metabolic process	1	4213.0×	0.002	PPARA
cellular response to fructose stimulus	1	4213.0×	0.002	PPARA
positive regulation of fatty acid metabolic process	1	3370.4×	0.002	PPARA
negative regulation of leukocyte cell-cell adhesion	1	2808.7×	0.002	PPARA
negative regulation of hepatocyte apoptotic process	1	2808.7×	0.002	PPARA
positive regulation of fatty acid oxidation	1	2407.4×	0.002	PPARA
regulation of fatty acid metabolic process	1	1872.4×	0.002	PPARA
behavioral response to nicotine	1	1872.4×	0.002	PPARA
negative regulation of cholesterol storage	1	1532.0×	0.002	PPARA
positive regulation of fatty acid beta-oxidation	1	1532.0×	0.002	PPARA
negative regulation of appetite	1	1532.0×	0.002	PPARA
peroxisome proliferator activated receptor signaling pathway	1	1532.0×	0.002	PPARA
nitric oxide metabolic process	1	1404.3×	0.002	PPARA
negative regulation of cell growth involved in cardiac muscle cell development	1	1404.3×	0.002	PPARA
negative regulation of macrophage derived foam cell differentiation	1	1296.3×	0.002	PPARA
enamel mineralization	1	1203.7×	0.002	PPARA
positive regulation of ATP biosynthetic process	1	1203.7×	0.002	PPARA
negative regulation of glycolytic process	1	1053.2×	0.002	PPARA
intracellular receptor signaling pathway	1	991.3×	0.002	PPARA
negative regulation of reactive oxygen species biosynthetic process	1	991.3×	0.002	PPARA
lipoprotein metabolic process	1	936.2×	0.002	PPARA
positive regulation of lipid biosynthetic process	1	887.0×	0.003	PPARA
positive regulation of gluconeogenesis	1	766.0×	0.003	PPARA
negative regulation of blood pressure	1	648.1×	0.003	PPARA
negative regulation of miRNA transcription	1	624.1×	0.003	PPARA
lactation	1	421.3×	0.004	PPARA
negative regulation of cytokine production involved in inflammatory response	1	421.3×	0.004	PPARA
hormone-mediated signaling pathway	1	401.2×	0.004	PPARA
gluconeogenesis	1	324.1×	0.005	PPARA

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
PPARA	ROSIGLITAZONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PPARA	39	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ROSIGLITAZONE	4	PPARA
CYCLOSPORINE	4	PPARA
RACECADOTRIL	4	PPARA
SELADELPAR	4	PPARA
PEMAFIBRATE	4	PPARA
BERBERINE	4	PPARA
ELAFIBRANOR	4	PPARA
GEMFIBROZIL	4	PPARA
CIPROFIBRATE	4	PPARA
CLOFIBRATE	4	PPARA
PIOGLITAZONE	4	PPARA
FENOFIBRATE	4	PPARA
FENOFIBRIC ACID	4	PPARA
MURAGLITAZAR	3	PPARA
BEZAFIBRATE	3	PPARA
TESAGLITAZAR	3	PPARA
LOBEGLITAZONE	3	PPARA
LOBEGLITAZONE SULFATE	3	PPARA
LANIFIBRANOR	3	PPARA
ICOSAPENT	3	PPARA
GAMOLENIC ACID	3	PPARA
ALEGLITAZAR	3	PPARA
IMIGLITAZAR	3	PPARA
FARGLITAZAR	2	PPARA
INDEGLITAZAR	2	PPARA
URSOLIC ACID	2	PPARA
NAVEGLITAZAR	2	PPARA
GW590735	2	PPARA
RAGAGLITAZAR	2	PPARA
LINOLEIC ACID	2	PPARA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PPARA	1,232	Binding:928, Functional:263, ADMET:41

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PPARA	1,232

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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)
ROSIGLITAZONE	4	PPARA
CYCLOSPORINE	4	PPARA
RACECADOTRIL	4	PPARA
SELADELPAR	4	PPARA
PEMAFIBRATE	4	PPARA
BERBERINE	4	PPARA
ELAFIBRANOR	4	PPARA
GEMFIBROZIL	4	PPARA
CIPROFIBRATE	4	PPARA
CLOFIBRATE	4	PPARA
PIOGLITAZONE	4	PPARA
FENOFIBRATE	4	PPARA
FENOFIBRIC ACID	4	PPARA
MURAGLITAZAR	3	PPARA
BEZAFIBRATE	3	PPARA
TESAGLITAZAR	3	PPARA
LOBEGLITAZONE	3	PPARA
LOBEGLITAZONE SULFATE	3	PPARA
LANIFIBRANOR	3	PPARA
ICOSAPENT	3	PPARA
GAMOLENIC ACID	3	PPARA
ALEGLITAZAR	3	PPARA
IMIGLITAZAR	3	PPARA
FARGLITAZAR	2	PPARA
INDEGLITAZAR	2	PPARA
URSOLIC ACID	2	PPARA
NAVEGLITAZAR	2	PPARA
GW590735	2	PPARA
RAGAGLITAZAR	2	PPARA
LINOLEIC ACID	2	PPARA

Druggability pyramid

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

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

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01603758	PHASE1	COMPLETED	Physiological Study of Human Cholesterol Metabolism and Excretion
NCT02854475	Not specified	COMPLETED	Confocal Raman Spectroscopy: in Vivo Measurement of Physiological Skin Parameters

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
EZETIMIBE	4	1