Familial lipoprotein lipase deficiency

Summary

Familial lipoprotein lipase deficiency (MONDO:0009387) is a disease caused by LPL (GenCC Definitive), with 3 cohort genes (56 GWAS associations across 7 studies) and 22 clinical trials. The dominant Reactome pathway is Chylomicron remodeling (3 cohort genes). Top therapeutic interventions include alipogene tiparvovec, mycophenolate mofetil, and volanesorsen.

At a glance

• Prevalence: 1-9 / 1 000 000 (United States) [Orphanet-validated]
• Causal gene: LPL (GenCC Definitive)
• Cohort genes: 3
• GWAS associations: 56
• ClinVar variants: 270
• Clinical trials: 22

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.1	United States	Validated
Point prevalence	1-9 / 1 000 000		Europe	Not yet validated

Identifiers

Disease identifiers

Field	Value
Canonical name	familial lipoprotein lipase deficiency
Mondo ID	MONDO:0009387
MeSH	D008072
OMIM	238600
Orphanet	309015
DOID	DOID:14118
ICD-11	1829539217
NCIT	C84771
SNOMED CT	275598004
UMLS	C0023817
MedGen	7352
GARD	0012241
NORD	1129
Is cancer (heuristic)	no

Also known as: Burger-Grutz syndrome · endogenous hypertriglyceridaemia · familial chylomicronemia syndrome · familial fat-induced hypertriglyceridemia · familial hyperchylomicronemia · familial lipoprotein lipase deficiency (disorder) [ambiguous] · familial lipoprotein lipase deficiency with type I phenotype · high density lipoprotein cholesterol level QTL 11 · hyperchylomicronemia · hyperlipoproteinemia type I · hyperlipoproteinemia, type 1 · hyperlipoproteinemia, type I · lipoprotein lipase deficiency, familial · LPL deficiency · type I hyperlipoproteinemia

Data availability: 270 ClinVar variants · 56 GWAS associations (7 studies) · 5 GenCC gene-disease records · 7 cell lines.

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 › familial lipoprotein lipase deficiency

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

Genetics & variants

GWAS landscape

56 GWAS associations across 7 studies. Top hits map to 25 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs964184	1e-323	ZPR1	G	0.56
chr19:45416178	8e-151		G	0.33
rs75627662	2e-138	APOE - APOC1	C	0.31
rs3208305	3e-129	LPL	A	0.27
rs1260326	3e-92	GCKR	T	0.21
rs651821	5e-90	APOA5	?
rs2980888	1e-65	TRIB1AL	T	0.19
rs2954038	6e-62	TRIB1AL	C	0.18
rs33951980	3e-48	MLXIPL	C	0.26
rs12740374	7e-45	CELSR2	G	0.16
rs10789118	1e-39	DOCK7	A	0.14
rs72836561	4e-38	CD300LG	C	0.36
rs174535	2e-36	TMEM258, MYRF	T	0.14
chr16:57000696	1e-34		T	0.16
rs174564	5e-34	FADS1, FADS2	A	0.13
rs11076175	5e-32	CETP	A	0.14
rs10889356	6e-32	DOCK7-DT	G	0.14
chr11:116662407	2e-30		G	0.54
rs116843064	2e-28	ANGPTL4	G	0.58
rs2144300	4e-27	GALNT2	C	0.11
chr1:230303150	2e-24		C	0.13
chr8:19823192	1e-22		T	0.45
rs11967262	2e-21	VEGFA - LINC02537	C	0.1
chr11:116663707	2e-18		G	0.83
chr8:19877461	8e-18		T	0.58
rs1801689	3e-17	APOH	A	0.29
rs138294113	3e-17	SMARCA4 - LDLR	C	0.13
chr8:18272881	4e-16		G	0.1
rs11787313	9e-15	NAT2 - PSD3	G	0.08
rs2972156	2e-13	NYAP2 - MIR5702	C	0.08

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90475724	Verma A	2024	17,425	419,299	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90475723	Verma A	2024	3,011	115,926	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90479925	Verma A	2024	3,011	115,926	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90475722	Verma A	2024	2,957	54,828	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90651128	Liu TY	2025	1,826	195,375	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90476483	Verma A	2024	254	6,420	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90435756	Zhou W	2018	58	373,034	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	7
Tier 2: splice/UTR	4
Tier 3: regulatory	0
Tier 4: intronic/intergenic	29

MAF distribution

Bucket	Variants
common (>=0.05)	36
low_freq (0.01-0.05)	4
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	14
unknown	9
missense_variant	7
intergenic_variant	5
3_prime_UTR_variant	3
non_coding_transcript_exon_variant	1
splice_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs964184	11	116778201	G>C	0.139	3_prime_UTR_variant	ZPR1	1e-323	Tier 2: splice/UTR
chr19:45416178				0.224			8e-151	Tier 4: intronic/intergenic
rs75627662	19	44910319	C>G,T	0.178	non_coding_transcript_exon_variant	APOE - APOC1	2e-138	Tier 4: intronic/intergenic
rs3208305	8	19966137	A>T	0.335	3_prime_UTR_variant	LPL	3e-129	Tier 2: splice/UTR
rs1260326	2	27508073	T>A,C,G	0.354	missense_variant	GCKR	3e-92	Tier 1: coding
rs651821	11	116791863	C>A,T	0.05	splice_region_variant	APOA5	5e-90	Tier 2: splice/UTR
rs2980888	8	125495066	T>C	0.276	intron_variant	TRIB1AL	1e-65	Tier 4: intronic/intergenic
rs2954038	8	125495147	C>A,G	0.305	intron_variant	TRIB1AL	6e-62	Tier 4: intronic/intergenic
rs33951980	7	73615107	C>G,T	0.126	intron_variant	MLXIPL	3e-48	Tier 4: intronic/intergenic
rs12740374	1	109274968	G>T	0.223	3_prime_UTR_variant	CELSR2	7e-45	Tier 2: splice/UTR
rs10789118	1	62629021	A>C,G	0.335	intron_variant	DOCK7	1e-39	Tier 4: intronic/intergenic
rs72836561	17	43848758	C>A,G,T	0.031	missense_variant	CD300LG	4e-38	Tier 1: coding
rs174535	11	61783884	T>A,C,G	0.336	missense_variant	TMEM258, MYRF	2e-36	Tier 1: coding
chr16:57000696				0.185			1e-34	Tier 4: intronic/intergenic
rs174564	11	61820833	A>C,G	0.316	intron_variant	FADS1, FADS2	5e-34	Tier 4: intronic/intergenic
rs11076175	16	56972466	A>G	0.193	intron_variant	CETP	5e-32	Tier 4: intronic/intergenic
rs10889356	1	62689678	G>A	0.327	intron_variant	DOCK7-DT	6e-32	Tier 4: intronic/intergenic
chr11:116662407				0.062			2e-30	Tier 4: intronic/intergenic
rs116843064	19	8364439	G>A	0.019	missense_variant	ANGPTL4	2e-28	Tier 1: coding
rs2144300	1	230159169	C>T	0.499	intron_variant	GALNT2	4e-27	Tier 4: intronic/intergenic
chr1:230303150				0.211			2e-24	Tier 4: intronic/intergenic
chr8:19823192				0.075			1e-22	Tier 4: intronic/intergenic
rs11967262	6	43792590	C>A,G,T	0.425	intergenic_variant	VEGFA - LINC02537	2e-21	Tier 4: intronic/intergenic
chr11:116663707				0.297			2e-18	Tier 4: intronic/intergenic
chr8:19877461				0.073			8e-18	Tier 4: intronic/intergenic
rs1801689	17	66214462	A>C,G,T	0.027	missense_variant	APOH	3e-17	Tier 1: coding
rs138294113	19	11081053	C>T	0.118	intergenic_variant	SMARCA4 - LDLR	3e-17	Tier 4: intronic/intergenic
chr8:18272881				0.225			4e-16	Tier 4: intronic/intergenic
rs11787313	8	18402516	G>C	0.333	intergenic_variant	NAT2 - PSD3	9e-15	Tier 4: intronic/intergenic
rs2972156	2	226253062	C>A,G,T	0.369	intergenic_variant	NYAP2 - MIR5702	2e-13	Tier 4: intronic/intergenic

ClinVar germline variants

270 retrieved; paginated sample, class counts are floors:

96 uncertain significance, 38 pathogenic, 34 likely pathogenic, 28 conflicting classifications of pathogenicity, 23 benign, 21 pathogenic/likely pathogenic, 18 likely benign, 9 benign/likely benign, 2 not provided, 1 benign/likely benign; other

ClinVar	Variant (HGVS)	Gene	Classification	Review
144020	NM_178172.6(GPIHBP1):c.194G>A (p.Cys65Tyr)	GPIHBP1	Pathogenic	criteria provided, single submitter
1030690	NM_000237.3(LPL):c.991A>G (p.Lys331Glu)	LPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066635	NM_000237.3(LPL):c.547G>A (p.Asp183Asn)	LPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066636	NM_000237.3(LPL):c.805G>A (p.Glu269Lys)	LPL	Pathogenic	criteria provided, multiple submitters, no conflicts
1072728	NM_000237.3(LPL):c.541G>C (p.Gly181Arg)	LPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1203042	NM_000237.3(LPL):c.292G>A (p.Ala98Thr)	LPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1236167	NM_000237.3(LPL):c.721C>T (p.Pro241Ser)	LPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1366216	NM_000237.3(LPL):c.688del (p.Val230fs)	LPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1456311	NM_000237.3(LPL):c.541G>A (p.Gly181Ser)	LPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1457932	NM_000237.3(LPL):c.1019-3C>A	LPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1492400	NM_000237.3(LPL):c.89-1G>C	LPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1494261	NM_000237.3(LPL):c.89-1G>A	LPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1520	LPL, INS	LPL	Pathogenic	no assertion criteria provided
1521	NM_000237.3(LPL):c.898_1019-1234dup	LPL	Pathogenic	no assertion criteria provided
1522	NM_000237.3(LPL):c.644G>A (p.Gly215Glu)	LPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1523	NG_008855.2:g.(51625_55052)_(57638_59124)del	LPL	Pathogenic	no assertion criteria provided
1524	NM_000237.3(LPL):c.397C>T (p.Gln133Ter)	LPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1525	NM_000237.3(LPL):c.811T>A (p.Ser271Thr)	LPL	Pathogenic	no assertion criteria provided
1526	NM_000237.3(LPL):c.250-1G>A	LPL	Pathogenic	no assertion criteria provided
1527	NM_000237.3(LPL):c.701C>T (p.Pro234Leu)	LPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1528	NM_000237.3(LPL):c.693C>G (p.Asp231Glu)	LPL	Pathogenic	no assertion criteria provided
1530	NM_000237.3(LPL):c.809G>A (p.Arg270His)	LPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1531	NM_000237.3(LPL):c.300C>A (p.Tyr100Ter)	LPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1532	NM_000237.3(LPL):c.506G>A (p.Gly169Glu)	LPL	Pathogenic	criteria provided, single submitter
1533	NM_000237.3(LPL):c.548A>G (p.Asp183Gly)	LPL	Pathogenic	no assertion criteria provided
1535	NM_000237.3(LPL):c.249+1G>A	LPL	Pathogenic	criteria provided, multiple submitters, no conflicts
1536	NM_000237.3(LPL):c.264T>A (p.Tyr88Ter)	LPL	Pathogenic	criteria provided, single submitter
1537	NM_000237.3(LPL):c.1227G>A (p.Trp409Ter)	LPL	Pathogenic	criteria provided, multiple submitters, no conflicts
1538	NM_000237.3(LPL):c.742del (p.Ala248fs)	LPL	Pathogenic	no assertion criteria provided
1539	NM_000237.3(LPL):c.829G>A (p.Asp277Asn)	LPL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 3 · 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
LPL	Definitive	Autosomal recessive	familial lipoprotein lipase deficiency	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LPL	Orphanet:309015	Familial lipoprotein lipase deficiency
APOA5	Orphanet:530849	Familial apolipoprotein A5 deficiency
GPIHBP1	Orphanet:535458	Familial GPIHBP1 deficiency

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LPL	HGNC:6677	ENSG00000175445	P06858	Lipoprotein lipase	gencc,clinvar
APOA5	HGNC:17288	ENSG00000110243	Q6Q788	Apolipoprotein A-V	clinvar
GPIHBP1	HGNC:24945	ENSG00000277494	Q8IV16	Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LPL	Lipoprotein lipase	Key enzyme in triglyceride metabolism.
APOA5	Apolipoprotein A-V	Minor apolipoprotein mainly associated with HDL and to a lesser extent with VLDL.
GPIHBP1	Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1	Mediates the transport of lipoprotein lipase LPL from the basolateral to the apical surface of endothelial cells in capillaries.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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)	1	4.0×	0.460
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LPL	Enzyme (other)	yes	3.1.1.34	TAG_lipase, PLAT/LH2_dom, Lipo_Lipase
APOA5	Other/Unknown	no		ApoA_E, Apolipoprotein_A1/A4/E
GPIHBP1	Other/Unknown	no		Toxin/TOLIP, Snake_toxin-like_sf, Ly-6/neurotoxin-like_GPI-ap

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
dorsal root ganglion	1
olfactory bulb	1
trigeminal ganglion	1
liver	1
right lobe of liver	1
skeletal muscle tissue of rectus abdominis	1
C1 segment of cervical spinal cord	1
apex of heart	1
spinal cord	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LPL	272	broad	marker	olfactory bulb, trigeminal ganglion, dorsal root ganglion
APOA5	45	tissue_specific	yes	right lobe of liver, liver, skeletal muscle tissue of rectus abdominis
GPIHBP1	193	broad	marker	apex of heart, C1 segment of cervical spinal cord, spinal cord

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LPL	2,149
APOA5	1,919
GPIHBP1	1,006

Intra-cohort edges

A	B	Sources
APOA5	GPIHBP1	string_interaction
APOA5	LPL	intact, string_interaction
GPIHBP1	LPL	intact, string_interaction

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LPL	P06858	5
GPIHBP1	Q8IV16	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
APOA5	Q6Q788	72.38

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 28. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Chylomicron remodeling	3	1142.0×	1e-08	LPL, APOA5, GPIHBP1
Assembly of active LPL and LIPC lipase complexes	3	601.0×	5e-08	LPL, APOA5, GPIHBP1
Plasma lipoprotein remodeling	2	317.2×	1e-04	LPL, APOA5
Retinoid metabolism and transport	2	165.5×	3e-04	LPL, GPIHBP1
Plasma lipoprotein assembly, remodeling, and clearance	2	152.3×	3e-04	LPL, APOA5
Transport of small molecules	2	16.8×	0.021	LPL, APOA5
Metabolism of fat-soluble vitamins	1	126.9×	0.031	LPL
Visual phototransduction	1	86.5×	0.039	LPL
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1	71.8×	0.039	LPL
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	1	65.6×	0.039	LPL
Post-translational modification: synthesis of GPI-anchored proteins	1	56.0×	0.039	GPIHBP1
Adipogenesis	1	52.1×	0.039	LPL
Epigenetic regulation by WDR5-containing histone modifying complexes	1	51.4×	0.039	LPL
Regulation of lipid metabolism by PPARalpha	1	47.0×	0.039	APOA5
Metabolism	2	7.7×	0.039	LPL, APOA5
Transcriptional regulation of white adipocyte differentiation	1	43.3×	0.040	LPL
Metabolism of vitamins and cofactors	1	38.8×	0.042	LPL
Post-translational protein phosphorylation	1	33.4×	0.044	APOA5
Sensory Perception	1	31.7×	0.044	LPL
PPARA activates gene expression	1	31.5×	0.044	APOA5
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	28.8×	0.046	APOA5
MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	1	27.6×	0.046	LPL
Epigenetic regulation of gene expression	1	23.8×	0.050	LPL
Metabolism of lipids	1	10.5×	0.107	APOA5
Post-translational protein modification	1	6.4×	0.166	APOA5
Gene expression (Transcription)	1	6.0×	0.171	LPL
Developmental Biology	1	4.8×	0.201	LPL
Metabolism of proteins	1	4.1×	0.223	APOA5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
triglyceride catabolic process	3	802.5×	8e-08	LPL, APOA5, GPIHBP1
triglyceride homeostasis	3	481.5×	2e-07	LPL, APOA5, GPIHBP1
very-low-density lipoprotein particle clearance	2	2246.9×	3e-06	LPL, APOA5
cholesterol homeostasis	3	156.0×	3e-06	LPL, APOA5, GPIHBP1
positive regulation of fatty acid biosynthetic process	2	864.2×	2e-05	APOA5, GPIHBP1
triglyceride metabolic process	2	295.6×	1e-04	LPL, APOA5
positive regulation of chylomicron remodeling	1	5617.3×	0.001	GPIHBP1
positive regulation of chylomicron remnant clearance	1	5617.3×	0.001	GPIHBP1
positive regulation of very-low-density lipoprotein particle remodeling	1	2808.7×	0.002	APOA5
triglyceride-rich lipoprotein particle remodeling	1	1872.4×	0.002	APOA5
low-density lipoprotein particle mediated signaling	1	1872.4×	0.002	LPL
response to heparin	1	1872.4×	0.002	GPIHBP1
chylomicron remodeling	1	1404.3×	0.003	LPL
acylglycerol homeostasis	1	1123.5×	0.003	APOA5
positive regulation of cholesterol storage	1	802.5×	0.004	LPL
positive regulation of triglyceride catabolic process	1	702.2×	0.004	APOA5
cellular response to nutrient	1	702.2×	0.004	LPL
very-low-density lipoprotein particle remodeling	1	702.2×	0.004	LPL
positive regulation of lipid catabolic process	1	624.1×	0.004	APOA5
protein import	1	561.7×	0.004	GPIHBP1
transcytosis	1	561.7×	0.004	GPIHBP1
positive regulation of chemokine (C-X-C motif) ligand 2 production	1	510.7×	0.004	LPL
positive regulation of lipid storage	1	468.1×	0.005	LPL
phospholipid efflux	1	374.5×	0.005	APOA5
positive regulation of adipose tissue development	1	351.1×	0.006	LPL
lipoprotein metabolic process	1	312.1×	0.006	APOA5
positive regulation of macrophage derived foam cell differentiation	1	280.9×	0.006	LPL
high-density lipoprotein particle remodeling	1	267.5×	0.006	LPL
positive regulation of receptor-mediated endocytosis	1	267.5×	0.006	APOA5
tissue regeneration	1	255.3×	0.006	APOA5

Therapeutics

Drugs indicated for this disease

1 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Alipogene Tiparvovec	Approved (phase 4)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Cyclosporine, Methylprednisolone, Mycophenolate Mofetil, Orlistat, Prednisolone.

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) 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
LPL	ORLISTAT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LPL	1	4
APOA5	0	0
GPIHBP1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ORLISTAT	4	LPL

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
LPL	16	Binding:16

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
LPL	3.1.1.34	lipoprotein lipase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	LPL
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	2	APOA5, GPIHBP1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GPIHBP1	0	LPL
APOA5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 22.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	8
Not specified	5
PHASE2	4
PHASE2/PHASE3	2
EARLY_PHASE1	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05130450	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) in Participants With Familial Chylomicronemia Syndrome (FCS)
NCT05185843	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRX) Administered to Adults With Familial Chylomicronemia Syndrome (FCS) Previously Treated With Volanesorsen
NCT00891306	PHASE2/PHASE3	COMPLETED	Efficacy and Safety of Human Lipoprotein Lipase (LPL)[S447X] Expressed by an Adeno-Associated Viral Vector in LPL-deficient Subjects
NCT01109498	PHASE2/PHASE3	UNKNOWN	Safety and Efficacy in LPL-Deficient Subjects of AMT-011, an Adeno-Associated Viral Vector Expressing Human Lipoprotein Lipase [S447X]
NCT01514461	PHASE3	COMPLETED	A Randomized, Double-blind, Placebo Controlled Study to Assess Efficacy, Safety and Tolerability of LCQ908 in Subjects With Familial Chylomicronemia Syndrome
NCT01589237	PHASE3	TERMINATED	Extension to a Randomized, Double-blind, Placebo Controlled Study of LCQ908 in Subjects With Familial Chylomicronemia Syndrome.
NCT02211209	PHASE3	COMPLETED	The APPROACH Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Patients With Familial Chylomicronemia Syndrome
NCT02658175	PHASE3	COMPLETED	The Approach Open Label Study: A Study of Volanesorsen (Formerly IONIS-APOCIIIRx) in Participants With Familial Chylomicronemia Syndrome
NCT04568434	PHASE3	COMPLETED	A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRx) Administered to Patients With Familial Chylomicronemia Syndrome (FCS)
NCT05902598	PHASE3	COMPLETED	A Phase 3 Study of ARO-APOC3 / VSA001 / SAR449124 (Plozasiran) in Chinese Adults With Familial Chylomicronemia Syndrome
NCT06471543	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study of RN0361in Adult Healthy Subjects and Adult Hypertriglyceridemic Subjects
NCT02098278	PHASE2	COMPLETED	Pilot Study To Assess CAT-2003 in Patients With Chylomicronemia
NCT02767531	PHASE2	COMPLETED	Orlistat for the Treatment of Type I Hyperlipoproteinemia
NCT02904772	PHASE2	WITHDRAWN	Alipogene Tiparvovec for the Treatment of LPLD Patients
NCT03360747	PHASE2	COMPLETED	Phase 2 Study of AKCEA-ANGPTL3-LRx (ISIS 703802) in Participants With Familial Chylomicronemia Syndrome (FCS)
NCT07176923	EARLY_PHASE1	RECRUITING	CS-121 APOC3 Base Editing in FCS
NCT07371767	EARLY_PHASE1	RECRUITING	CS-121 APOC3 Base Editing in Children and Adolescents With Hyperchylomicronemia
NCT01447901	Not specified	TERMINATED	Duration of Effect of Alipogene Tiparvovec Treatment, Which Was Administered in Other Studies
NCT03293810	Not specified	COMPLETED	Glybera Registry, Lipoprotein Lipase Deficient (LPLD) Patients
NCT03912181	Not specified	COMPLETED	Medical Complications in Familial and Multifactorial Chylomicronaemia Syndromes
NCT04223908	Not specified	COMPLETED	InFocus France Epidemiological Study of Health Burden in Major Hypertriglyceridemia
NCT06360237	Not specified	APPROVED_FOR_MARKETING	Olezarsen Early Access Program for Patients With Familial Chylomicronemia Syndrome (FCS)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ALIPOGENE TIPARVOVEC	4	3
MYCOPHENOLATE MOFETIL	4	3
VOLANESORSEN	4	2
ORLISTAT	4	1
OLEZARSEN	3	4
PLOZASIRAN	3	1
VUPANORSEN	2	1
CHEMBL406352	0	2
CHEMBL2354678	0	1
CHEMBL365190	0	1
CHEMBL458622	0	1