Hyperlipidemia

Summary

Hyperlipidemia (MONDO:0021187) is a disease with 6 cohort genes (157 GWAS associations across 15 studies) and 616 clinical trials. Top therapeutic interventions include evolocumab, rosuvastatin, and pitavastatin.

At a glance

• Cohort genes: 6
• GWAS associations: 157
• ClinVar variants: 5
• Clinical trials: 616

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hyperlipidemia
Mondo ID	MONDO:0021187
MeSH	D006949
ICD-10-CM	E78.5
SNOMED CT	55822004
UMLS	C0020473
MedGen	5692
Is cancer (heuristic)	no

Also known as: hyperlipemia · hyperlipemias · hyperlipidemia · hyperlipidemia (disease) · lipemia · lipemias · lipidemia · lipidemias

Data availability: 5 ClinVar variants · 157 GWAS associations (15 studies) · 1 HPO phenotype.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › hyperlipidemia

Related subtypes (36): glutaric aciduria, mineral metabolism disease, xanthinuria, chondrocalcinosis, ochronosis disorder, glucose metabolism disease, diabetic kidney disease, xanthoma, diabetic retinopathy, hypertriglyceridemia, gout, lactic acidosis, acquired metabolic disease, lipodystrophy, developmental anomaly of metabolic origin, dopa-responsive dystonia, hypoalphalipoproteinemia, steroid dehydrogenase deficiency-dental anomalies syndrome, inborn errors of metabolism, vitamin B12 deficiency, proteostasis deficiencies, disorder of GPI anchor biosynthesis, bilirubin metabolism disease, hyperlipoproteinemia, carbohydrate metabolism disease, porphyrin metabolism disease, purine metabolism disease, amino acid metabolism disease, pyrimidine metabolism disease, disorder of acid-base balance, disorder of glutamate decarboxylase, tumor lysis syndrome, collagenous sprue, steroid metabolism disease, disorder of organic acid metabolism, skeletal fluorosis

Subtypes (3): familial hyperlipidemia, laminopathy type Decaudain-Vigouroux, hyperalphalipoproteinemia

Genetics & variants

GWAS landscape

157 GWAS associations across 15 studies. Top hits map to 24 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs7412	1e-323	APOE	C	0.42
rs7528419	8e-300	CELSR2	A	0.22
rs12740374	6e-259	CELSR2	G	0.21
rs138294113	3e-220	SMARCA4 - LDLR	C	0.24
rs73015020	1e-201	SMARCA4 - LDLR	G	0.23
rs964184	1e-194	ZPR1	G	0.22
rs28601761	2e-179	TRIB1AL	C	0.15
rs11591147	2e-159	PCSK9	G	0.58
rs668948	1e-145	APOB - TDRD15	G	0.16
rs563290	1e-130	APOB - TDRD15	G	0.15
rs58542926	1e-120	TM6SF2	C	0.21
rs28362286	5e-102	PCSK9	C	1.14
rs10455872	2e-100	LPA	A	0.22
rs142130958	8e-99	SMARCA4 - LDLR	G	0.3
rs662799	1e-76	APOA5	?	1.79
rs4299376	4e-76	ABCG8	G	0.1
rs651821	3e-72	APOA5	?
rs115478735	1e-66	ABO	A	0.11
rs4245791	7e-63	ABCG8	C	0.1
rs1260326	1e-54	GCKR	T	0.08
rs12916	1e-52	CERT1, HMGCR	T	0.08
rs12239736	2e-51	DOCK7	T	0.08
chr8:19859539	3e-45		G	0.08
rs3208305	5e-41	LPL	A	0.07
rs544187825	9e-39	ASGR2	G	0.68
chr5:156399950	1e-32		A	0.06
rs60201663	1e-31	PMFBP1	G	0.2
rs56156922	2e-29	HERPUD1 - CETP	T	0.06
rs1421085	3e-29	FTO	T	0.06
chr16:72097827	1e-28		C	0.07

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90475718	Verma A	2024	335,680	90,923	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90475717	Verma A	2024	82,035	32,046	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90479927	Verma A	2024	82,035	32,046	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90083754	Backman JD	2021	51,365	320,834	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90475716	Verma A	2024	39,936	15,904	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90435754	Zhou W	2018	35,844	373,034	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST010772	Bi W	2020	35,623	247,248	A Fast and Accurate Method for Genome-Wide Time-to-Event Data Analysis and Its Application to UK Biobank.
GCST90651132	Liu TY	2025	34,584	195,375	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90726738	Kim HI	2026	8,803	35,223	Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity.
GCST90255395	Nam K	2022	7,099	65,111	Genome-wide study on 72,298 individuals in Korean biobank data for 76 traits.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	6
Tier 2: splice/UTR	6
Tier 3: regulatory	3
Tier 4: intronic/intergenic	35

MAF distribution

Bucket	Variants
common (>=0.05)	45
low_freq (0.01-0.05)	2
rare (<0.01)	2
unknown	1

Functional consequences

Consequence	Count
intron_variant	15
intergenic_variant	10
unknown	10
3_prime_UTR_variant	5
missense_variant	4
regulatory_region_variant	3
stop_gained	2
splice_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs7412	19	44908822	C>T	0.08	missense_variant	APOE	1e-323	Tier 1: coding
rs7528419	1	109274570	A>G	0.218	3_prime_UTR_variant	CELSR2	8e-300	Tier 2: splice/UTR
rs12740374	1	109274968	G>T	0.222	3_prime_UTR_variant	CELSR2	6e-259	Tier 2: splice/UTR
rs138294113	19	11081053	C>T	0.118	intergenic_variant	SMARCA4 - LDLR	3e-220	Tier 4: intronic/intergenic
rs73015020	19	11081874	G>A,C	0.12	intergenic_variant	SMARCA4 - LDLR	1e-201	Tier 4: intronic/intergenic
rs964184	11	116778201	G>C	0.141	3_prime_UTR_variant	ZPR1	1e-194	Tier 2: splice/UTR
rs28601761	8	125487789	C>G	0.413	intron_variant	TRIB1AL	2e-179	Tier 4: intronic/intergenic
rs11591147	1	55039974	G>A,T	0.015	missense_variant	PCSK9	2e-159	Tier 1: coding
rs668948	2	21068657	G>A	0.204	intron_variant	APOB - TDRD15	1e-145	Tier 4: intronic/intergenic
rs563290	2	21065354	G>A,C	0.283	intron_variant	APOB - TDRD15	1e-130	Tier 4: intronic/intergenic
rs58542926	19	19268740	C>A,T	0.075	stop_gained	TM6SF2	1e-120	Tier 1: coding
rs28362286	1	55063542	C>A,T	0.007	stop_gained	PCSK9	5e-102	Tier 1: coding
rs10455872	6	160589086	A>G	0.069	intron_variant	LPA	2e-100	Tier 4: intronic/intergenic
rs142130958	19	11079976	G>A	0.134	intergenic_variant	SMARCA4 - LDLR	8e-99	Tier 4: intronic/intergenic
rs662799	11	116792991	G>A,C	0.05	regulatory_region_variant	APOA5	1e-76	Tier 3: regulatory
rs4299376	2	43845437	G>C,T	0.329	intron_variant	ABCG8	4e-76	Tier 4: intronic/intergenic
rs651821	11	116791863	C>A,T	0.05	splice_region_variant	APOA5	3e-72	Tier 2: splice/UTR
rs115478735	9	133274295	A>T	0.193	intron_variant	ABO	1e-66	Tier 4: intronic/intergenic
rs4245791	2	43847292	C>A,G,T	0.273	intron_variant	ABCG8	7e-63	Tier 4: intronic/intergenic
rs1260326	2	27508073	T>A,C,G	0.414	missense_variant	GCKR	1e-54	Tier 1: coding
rs12916	5	75360714	T>A,C,G	0.404	3_prime_UTR_variant	CERT1, HMGCR	1e-52	Tier 2: splice/UTR
rs12239736	1	62620326	T>A,C	0.367	intron_variant	DOCK7	2e-51	Tier 4: intronic/intergenic
chr8:19859539				0.289			3e-45	Tier 4: intronic/intergenic
rs3208305	8	19966137	A>T	0.333	3_prime_UTR_variant	LPL	5e-41	Tier 2: splice/UTR
rs544187825	17	7100610	G>A	0.003	intergenic_variant	ASGR2	9e-39	Tier 4: intronic/intergenic
chr5:156399950				0.372			1e-32	Tier 4: intronic/intergenic
rs60201663	16	72154990	G>A,C	0.112	intron_variant	PMFBP1	1e-31	Tier 4: intronic/intergenic
rs56156922	16	56953457	T>C	0.317	intergenic_variant	HERPUD1 - CETP	2e-29	Tier 4: intronic/intergenic
rs1421085	16	53767042	T>C	0.408	intron_variant	FTO	3e-29	Tier 4: intronic/intergenic
chr16:72097827				0.2			1e-28	Tier 4: intronic/intergenic

ClinVar germline variants

5 retrieved; paginated sample, class counts are floors:

1 uncertain significance, 1 conflicting classifications of pathogenicity; risk factor, 1 conflicting classifications of pathogenicity, 1 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
523434	NM_019023.5(PRMT7):c.1713C>A (p.Cys571Ter)	PRMT7	Pathogenic	criteria provided, multiple submitters, no conflicts
523435	NM_019023.5(PRMT7):c.322G>T (p.Glu108Ter)	PRMT7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
199044	NM_000157.4(GBA1):c.1093G>A (p.Glu365Lys)	GBA1	Conflicting classifications of pathogenicity; risk factor	criteria provided, conflicting classifications
251662	NM_000527.5(LDLR):c.1097A>G (p.Gln366Arg)	LDLR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1338787	NM_173598.6(KSR2):c.2512C>T (p.Arg838Cys)	KSR2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 12 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PRMT7	Orphanet:464288	Short stature-brachydactyly-obesity-global developmental delay syndrome
DNM2	Orphanet:100044	Autosomal dominant intermediate Charcot-Marie-Tooth disease type B
DNM2	Orphanet:169189	Autosomal dominant centronuclear myopathy
DNM2	Orphanet:228179	Autosomal dominant Charcot-Marie-Tooth disease type 2M
DNM2	Orphanet:363409	Fetal akinesia-cerebral and retinal hemorrhage syndrome
GBA1	Orphanet:2072	Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome
GBA1	Orphanet:411602	Hereditary late-onset Parkinson disease
GBA1	Orphanet:77259	Gaucher disease type 1
GBA1	Orphanet:77260	Gaucher disease type 2
GBA1	Orphanet:77261	Gaucher disease type 3
GBA1	Orphanet:85212	Fetal Gaucher disease
LDLR	Orphanet:391665	Homozygous familial hypercholesterolemia

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	2
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KSR2	HGNC:18610	ENSG00000171435	Q6VAB6	Kinase suppressor of Ras 2	clinvar
PRMT7	HGNC:25557	ENSG00000132600	Q9NVM4	Protein arginine N-methyltransferase 7	clinvar
HCG22	HGNC:27780	ENSG00000228789	E2RYF7	Protein PBMUCL2	gwas
DNM2	HGNC:2974	ENSG00000079805	P50570	Dynamin-2	gwas
GBA1	HGNC:4177	ENSG00000177628	P04062	Lysosomal acid glucosylceramidase	clinvar
LDLR	HGNC:6547	ENSG00000130164	P01130	Low-density lipoprotein receptor	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KSR2	Kinase suppressor of Ras 2	Location-regulated scaffold connecting MEK to RAF.
PRMT7	Protein arginine N-methyltransferase 7	Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA.
DNM2	Dynamin-2	Catalyzes the hydrolysis of GTP and utilizes this energy to mediate vesicle scission at plasma membrane during endocytosis and filament remodeling at many actin structures during organization of the actin cytoskeleton.
GBA1	Lysosomal acid glucosylceramidase	Glucosylceramidase that catalyzes, within the lysosomal compartment, the hydrolysis of glucosylceramides/GlcCers (such as beta-D-glucosyl-(1<->1’)-N-acylsphing-4-enine) into free ceramides (such as N-acylsphing-4-enine) and glucose.
LDLR	Low-density lipoprotein receptor	Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis.

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.5

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
Enzyme (other)	2	4.0×	0.333
Kinase	1	4.6×	0.396
Scaffold/PPI	1	2.9×	0.401
Other/Unknown	2	0.6×	0.936

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KSR2	Kinase	yes	2.7.11.25	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
PRMT7	Enzyme (other)	yes	2.1.1.321	MeTrfase_PRMT7, Arg_MeTrfase, SAM-dependent_MTases_sf
HCG22	Other/Unknown	no		EZH_Inhibitor
DNM2	Scaffold/PPI	no	3.6.5.5	Dynamin_stalk, Dynamin_GTPase, PH_domain
GBA1	Enzyme (other)	yes	3.2.1.45	Glyco_hydro_30, GH_hydrolase_sf, GH30_C
LDLR	Other/Unknown	no		LDLR_classB_rpt, EGF-type_Asp/Asn_hydroxyl_site, EGF

Expression context

Cohort genes with no expression data: 0.

5 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	1
middle temporal gyrus	1
postcentral gyrus	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
esophagus mucosa	1
lower esophagus mucosa	1
male germ line stem cell (sensu Vertebrata) in testis	1
granulocyte	1
metanephros cortex	1
mucosa of transverse colon	1
islet of Langerhans	1
placenta	1
stromal cell of endometrium	1
adrenal tissue	1
lower lobe of lung	1
right adrenal gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KSR2	114	broad	marker	Brodmann (1909) area 23, middle temporal gyrus, postcentral gyrus
PRMT7	186	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
HCG22	107	tissue_specific	yes	lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis, esophagus mucosa
DNM2	234	ubiquitous	marker	metanephros cortex, granulocyte, mucosa of transverse colon
GBA1	134	ubiquitous	marker	stromal cell of endometrium, islet of Langerhans, placenta
LDLR	281	ubiquitous	marker	adrenal tissue, lower lobe of lung, right adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DNM2	4,715
GBA1	2,568
PRMT7	2,036
LDLR	1,426
KSR2	1,183
HCG22	0

Structural data

PDB: 4 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GBA1	P04062	58
LDLR	P01130	36
KSR2	Q6VAB6	9
DNM2	P50570	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PRMT7	Q9NVM4	93.19
HCG22	E2RYF7	69.41

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 46. Enrichment computed across 6 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
NOSTRIN mediated eNOS trafficking	1	456.8×	0.034	DNM2
Chylomicron clearance	1	456.8×	0.034	LDLR
Clathrin-mediated endocytosis	2	34.1×	0.034	DNM2, LDLR
Formation of annular gap junctions	1	207.6×	0.040	DNM2
Gap junction degradation	1	190.3×	0.040	DNM2
Retrograde neurotrophin signalling	1	163.1×	0.040	DNM2
LDL clearance	1	108.8×	0.040	LDLR
Plasma lipoprotein clearance	1	95.2×	0.040	LDLR
Signaling by RAS mutants	1	84.6×	0.040	KSR2
Metabolism of fat-soluble vitamins	1	76.1×	0.040	LDLR
Lysosome Vesicle Biogenesis	1	65.3×	0.040	DNM2
Signaling by high-kinase activity BRAF mutants	1	63.4×	0.040	KSR2
Association of TriC/CCT with target proteins during biosynthesis	1	58.6×	0.040	GBA1
Glycosphingolipid catabolism	1	58.6×	0.040	GBA1
MAP2K and MAPK activation	1	57.1×	0.040	KSR2
NGF-stimulated transcription	1	57.1×	0.040	DNM2
Signaling by RAF1 mutants	1	55.7×	0.040	KSR2
Visual phototransduction	1	51.9×	0.040	LDLR
Signaling by moderate kinase activity BRAF mutants	1	50.8×	0.040	KSR2
Paradoxical activation of RAF signaling by kinase inactive BRAF	1	50.8×	0.040	KSR2
Signaling downstream of RAS mutants	1	50.8×	0.040	KSR2
Oncogenic MAPK signaling	1	49.6×	0.040	KSR2
Retinoid metabolism and transport	1	49.6×	0.040	LDLR
Plasma lipoprotein assembly, remodeling, and clearance	1	45.7×	0.041	LDLR
Recycling pathway of L1	1	44.8×	0.041	DNM2
Golgi Associated Vesicle Biogenesis	1	40.1×	0.043	DNM2
Degradation of CDH1	1	39.4×	0.043	DNM2
Signaling by BRAF and RAF1 fusions	1	34.1×	0.048	KSR2
RMTs methylate histone arginines	1	29.3×	0.053	PRMT7
Toll Like Receptor 4 (TLR4) Cascade	1	26.2×	0.056	DNM2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of protein metabolic process	2	842.6×	2e-04	GBA1, LDLR
positive regulation of neuronal action potential	1	3370.4×	0.006	GBA1
regulation of phosphatidylcholine catabolic process	1	1685.2×	0.006	LDLR
cerebellar Purkinje cell layer formation	1	1685.2×	0.006	GBA1
receptor-mediated endocytosis involved in cholesterol transport	1	1685.2×	0.006	LDLR
vesicle scission	1	1685.2×	0.006	DNM2
beta-glucoside catabolic process	1	1685.2×	0.006	GBA1
negative regulation of membrane tubulation	1	1685.2×	0.006	DNM2
glucosylceramide catabolic process	1	1123.5×	0.006	GBA1
termination of signal transduction	1	1123.5×	0.006	GBA1
actin filament bundle organization	1	1123.5×	0.006	DNM2
negative regulation of astrocyte activation	1	1123.5×	0.006	LDLR
membrane tubulation	1	1123.5×	0.006	DNM2
regulation of lysosomal protein catabolic process	1	1123.5×	0.006	GBA1
phagocytosis	2	96.3×	0.006	DNM2, LDLR
receptor-mediated endocytosis	2	88.7×	0.006	DNM2, LDLR
cholesterol metabolic process	2	78.4×	0.006	GBA1, LDLR
autophagy	2	44.1×	0.006	DNM2, GBA1
peptidyl-arginine methylation	1	842.6×	0.007	PRMT7
plasma lipoprotein particle clearance	1	842.6×	0.007	LDLR
endocytosis	2	38.1×	0.007	DNM2, LDLR
negative regulation of receptor recycling	1	674.1×	0.007	LDLR
synaptic vesicle budding from presynaptic endocytic zone membrane	1	674.1×	0.007	DNM2
pyramidal neuron differentiation	1	674.1×	0.007	GBA1
autophagosome organization	1	674.1×	0.007	GBA1
positive regulation of lysosomal protein catabolic process	1	674.1×	0.007	LDLR
response to pH	1	561.7×	0.007	GBA1
cholesterol import	1	561.7×	0.007	LDLR
high-density lipoprotein particle clearance	1	481.5×	0.008	LDLR
lipoprotein catabolic process	1	481.5×	0.008	LDLR

Therapeutics

Drugs indicated for this disease

3 approved, 15 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Ezetimibe	Approved (phase 4)
Niacin	Approved (phase 4)
Simvastatin	Approved (phase 4)
Atorvastatin	Phase 3 (in late-stage trials)
Bempedoic Acid	Phase 3 (in late-stage trials)
Bococizumab	Phase 3 (in late-stage trials)
Evacetrapib	Phase 3 (in late-stage trials)
Evolocumab	Phase 3 (in late-stage trials)
Fenofibrate	Phase 3 (in late-stage trials)
K-877	Phase 3 (in late-stage trials)
Laropiprant	Phase 3 (in late-stage trials)
Ongericimab	Phase 3 (in late-stage trials)
Pitavastatin	Phase 3 (in late-stage trials)
Pravastatin	Phase 3 (in late-stage trials)
Probucol	Phase 3 (in late-stage trials)
Rosuvastatin	Phase 3 (in late-stage trials)
Topiramate	Phase 3 (in late-stage trials)
Torcetrapib	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Anacetrapib, Dalcetrapib, Dextrose, Insulin Human, Insulin Pork, Lapaquistat Acetate, Seladelpar, Sitagliptin, Teduglutide, Tilarginine, Zinc Sulfate.

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 3

Druggability breadth: 5 of 6 evidence-associated genes (83%) 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
GBA1	MIGALASTAT
LDLR	NILOTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GBA1	12	4
PRMT7	1	3
LDLR	1	4
KSR2	0	0
HCG22	0	0
DNM2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MIGALASTAT	4	GBA1
GLUCONOLACTONE	4	GBA1
MIGLITOL	4	GBA1
MEXILETINE	4	GBA1
GENTIAN VIOLET	4	GBA1
CHLORHEXIDINE	4	GBA1
TAMOXIFEN	4	GBA1
NILOTINIB	4	LDLR
ADEMETIONINE	3	PRMT7
AMBROXOL	3	GBA1
AFEGOSTAT	2	GBA1
AFEGOSTAT TARTRATE	2	GBA1
DUVOGLUSTAT	2	GBA1
NIZUBAGLUSTAT	2	GBA1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

Symbol	Assays	Type breakdown
GBA1	436	Binding:403, Functional:33
PRMT7	100	Binding:98, Functional:2
LDLR	55	Binding:54, Functional:1
KSR2	28	Binding:28
DNM2	15	Binding:15

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KSR2	2.7.11.25	mitogen-activated protein kinase kinase kinase
PRMT7	2.1.1.321	type III protein arginine methyltransferase
DNM2	3.6.5.5	dynamin GTPase
GBA1	3.2.1.45	glucosylceramidase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PRMT7	100
GBA1	436

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

14 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)
MIGALASTAT	4	GBA1
GLUCONOLACTONE	4	GBA1
MIGLITOL	4	GBA1
MEXILETINE	4	GBA1
GENTIAN VIOLET	4	GBA1
CHLORHEXIDINE	4	GBA1
TAMOXIFEN	4	GBA1
NILOTINIB	4	LDLR
ADEMETIONINE	3	PRMT7
AMBROXOL	3	GBA1
AFEGOSTAT	2	GBA1
AFEGOSTAT TARTRATE	2	GBA1
DUVOGLUSTAT	2	GBA1
NIZUBAGLUSTAT	2	GBA1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	GBA1, LDLR
B	Phased (≥1) drug, not yet approved	1	PRMT7
C	Druggable family + PDB, no drug	1	KSR2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	HCG22, DNM2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
KSR2	28	—
HCG22	0	—
DNM2	15	—

Clinical trials & evidence

Clinical trials

Clinical trials: 616.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	318
PHASE3	86
PHASE1	73
PHASE4	55
PHASE2	52
PHASE2/PHASE3	18
PHASE1/PHASE2	10
EARLY_PHASE1	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05537948	PHASE4	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Pitavastatin and PCSK9 Inhibitors in Liver Transplant Patients
NCT06586684	PHASE4	NOT_YET_RECRUITING	Effect of Small Interfering RNA Inclisiran on Carotid Plaques As Assessed by Carotid Ultrasound
NCT06789432	PHASE4	RECRUITING	Efficacy and Safety of Atorvastatin and Ezetimibe (10/10mg) Fixed Dose Combination Versus Atorvastatin (20mg) Monotherapy in Bangladeshi Population
NCT00117494	PHASE4	COMPLETED	Rosuvastatin Versus Pravastatin in HIV Patients Treated With Boosted Protease Inhibitors (PI) (ANRS126)
NCT00147251	PHASE4	COMPLETED	Stop Atherosclerosis in Native Diabetics Study
NCT00157638	PHASE4	COMPLETED	Integrating Family Medicine and Pharmacy to Advance Primary Care Therapeutics
NCT00174304	PHASE4	COMPLETED	Open Label Study To Assess The Effectiveness Of Amlodipine-Atorvastatin Combination In Hypertension And Dyslipidemia.
NCT00174330	PHASE4	COMPLETED	Comparing Amlodipine/Atorvastatin Co-Administration To Amlodipine Alone In Patients With Hypertension And Dyslipidemia
NCT00203476	PHASE4	COMPLETED	A Prospective, Open Label Comparison of Ezetimibe, Niacin, and Colestipol as Adjunct Therapy in Lipid Reduction
NCT00211705	PHASE4	COMPLETED	Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese(MEGA Study)
NCT00222833	PHASE4	COMPLETED	The Effect of Switching to Aripiprazole on Heart Health in Overweight and Obese Patients With Schizophrenia
NCT00225849	PHASE4	UNKNOWN	Japanese Primary Prevention Project With Aspirin
NCT00249938	PHASE4	COMPLETED	Evaluation of Combination Cholesterol Treatments in Patients With High Cholesterol.
NCT00299169	PHASE4	TERMINATED	Randomized Trial Comparing N of 1 Trials to Standard Practice to Improve Adherence to Statins in Patients With Diabetes
NCT00345657	PHASE4	COMPLETED	Efficacy Study of Extended-Release Niacin/Lovastatin Versus Usual Care
NCT00360074	PHASE4	COMPLETED	Phase 4 Study in Secondary Hypothyroidism: Body Weight Adapted Thyroxin Treatment and Triiodothyronine Supplementation
NCT00451828	PHASE4	COMPLETED	Cholesterol and Pharmacogenetic Study
NCT00473655	PHASE4	COMPLETED	Effect of Rosuvastatin on Triglyceride Levels in Mexican Hypertriglyceridemic Patients
NCT00490672	PHASE4	COMPLETED	Community Based Multiple Risk Factors Intervention Strategy
NCT00552747	PHASE4	COMPLETED	Effect of Fenofibrate on Endothelial Function and High-density Lipoproteins (HDL)in Patients With Coronary Heart Disease
NCT00603876	PHASE4	COMPLETED	Efficacy of Almonds Added to Chronic Statin Therapy
NCT00630734	PHASE4	COMPLETED	Genetic Predictors of Variability in the Drug-drug Interaction Between Darunavir/Ritonavir and Pravastatin
NCT00640549	PHASE4	TERMINATED	Atorvastatin and LDL Profile in Non-Insulin Dependent Diabetes Mellitus
NCT00645424	PHASE4	COMPLETED	A Study To Evaluate The Safety And Efficacy Of Atorvastatin In Patients With Diabetes And High Cholesterol
NCT00738985	PHASE4	WITHDRAWN	Efficacy of Ezetimibe/Simvastatin 10/20 mg and MK0524A (1-2 g/Day) in Mixed Hyperlipidemia and Two or More Risk Factors
NCT00753883	PHASE4	COMPLETED	Ezetrol Post-Marketing Study
NCT00843661	PHASE4	UNKNOWN	Coadministration of Ezetimibe With Fenofibrate Versus Pravastatin Monotherapy for the Treatment of Hyperlipidaemia in HIV-infected Patients
NCT00885872	PHASE4	UNKNOWN	Rosuvastatin Evaluation of Atherosclerotic Chinese Patients (REACH)
NCT00923676	PHASE4	UNKNOWN	Treatment of Hyperlipidemia and Sexual Dysfunction
NCT01023607	PHASE4	COMPLETED	Evaluation of Statin-induced Lipid-rich Plaque Progression by Optical Coherence Tomography (OCT) Combined With Intravascular Ultrasound (IVUS)
NCT01089231	PHASE4	COMPLETED	Effects of Omega-3 Fatty Acids on the Human Gene Expression
NCT01131832	PHASE4	COMPLETED	Genetic Basis for Heterogeneity in Response of Plasma Lipids to Plant Sterols
NCT01212159	PHASE4	COMPLETED	Telephone Based Management of Hyperlipidemia
NCT01239004	PHASE4	COMPLETED	Colesevelam Treatment for Impaired Fasting Glucose During Niacin Therapy
NCT01291641	PHASE4	COMPLETED	Effect of Probucol and/or Cilostazol on Mean IMT in Patients With Coronary Heart dIsease
NCT01382277	PHASE4	UNKNOWN	Rosuvastatin Effect on Reducing Coronary Atherosclerosis Plaques Volume
NCT01409434	PHASE4	COMPLETED	Long Term Antihypertensive Exposure and Adverse Metabolic Effects: PEAR Follow-Up Study
NCT01414803	PHASE4	COMPLETED	Tolerability and Efficacy of Rosuvastatin - Fenofibrate Combine Therapy in Korean Patients With Combined Hyperlipidemia
NCT01448174	PHASE4	COMPLETED	Salusin-alpha - a New Factor in the Pathogenesis of Lipid Abnormalities in Hemodialysis Patients
NCT01564875	PHASE4	UNKNOWN	Efficacy and Safety of Simvast Controlled Release (CR) and Zocor in Chronic Kidney Disease(CKD) Stage 3, 4 and 5 Patients With Hyperlipidemia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
EVOLOCUMAB	4	14
ROSUVASTATIN	4	14
PITAVASTATIN	4	13
FENOFIBRATE	4	10
MIPOMERSEN	4	8
COLESEVELAM	4	7
NIACIN	4	7
DARUNAVIR	4	6
PRAVASTATIN	4	6
ATORVASTATIN	4	5
EZETIMIBE	4	5
BEMPEDOIC ACID	4	4
ROSIGLITAZONE	4	4
SIMVASTATIN	4	4
LIOTHYRONINE	4	3
TEDUGLUTIDE	4	3
ALIROCUMAB	4	2
AMLODIPINE	4	2
ATAZANAVIR	4	2
FISH OIL	4	2
LEVOCARNITINE	4	2
METRELEPTIN	4	2
OMEGA-3-ACID ETHYL ESTERS	4	2
PROBUCOL	4	2
TELMISARTAN	4	2
ACETYLCHOLINE	4	1
ACIPIMOX	4	1
ARIPIPRAZOLE	4	1
ASPIRIN	4	1
BERBERINE	4	1