hyperlipoproteinemia type V

Summary

hyperlipoproteinemia type V (MONDO:0007762) is a disease caused by APOA5 (GenCC Strong), with 1 cohort gene and 4 clinical trials. Top therapeutic interventions include rosuvastatin, anacetrapib, and recaticimab.

At a glance

• Causal gene: APOA5 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 12
• Clinical trials: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hyperlipoproteinemia type V
Mondo ID	MONDO:0007762
MeSH	D006954
OMIM	144650
Orphanet	530849, 70470
DOID	DOID:0111421, DOID:1171
SNOMED CT	34349009
UMLS	C0020481
MedGen	5693
GARD	0006704
MedDRA	10060755
Is cancer (heuristic)	no

Also known as: familial APOA5 deficiency · familial apolipoprotein A-V deficiency · familial apolipoprotein A5 deficiency · HLP type 5 · hyperchylomicronemia late onset · hyperlipemia combined fat and carbohydrate-induced · hyperlipemia mixed · hyperlipidemia type V · hyperlipoproteinemia type 5 · major hyperlipidemia · mixed hyperlipemia · type V hyperlipoproteinemia

Data availability: 12 ClinVar variants · 4 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 › hyperlipoproteinemia type V

Related subtypes (9): familial hypercholesterolemia, cholesterol-ester transfer protein deficiency, hyperlipidemia, familial combined, LPL related, 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

12 retrieved; paginated sample, class counts are floors:

3 conflicting classifications of pathogenicity, 3 uncertain significance, 3 pathogenic, 1 likely pathogenic, 1 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
381733	NM_001371904.1(APOA5):c.289C>T (p.Gln97Ter)	APOA5	Pathogenic	criteria provided, multiple submitters, no conflicts
4404	NM_001371904.1(APOA5):c.415C>T (p.Gln139Ter)	APOA5	Pathogenic	no assertion criteria provided
978324	NM_001371904.1(APOA5):c.990_993del (p.Asp332fs)	APOA5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
995944	NM_001371904.1(APOA5):c.579_592del (p.Tyr194fs)	APOA5	Pathogenic	criteria provided, single submitter
2434519	NM_001371904.1(APOA5):c.117_120del (p.Arg40fs)	APOA5	Likely pathogenic	criteria provided, single submitter
1204530	NM_001371904.1(APOA5):c.823C>T (p.Gln275Ter)	APOA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1678148	NM_001371904.1(APOA5):c.427del (p.Arg143fs)	APOA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2137252	NM_001371904.1(APOA5):c.644C>T (p.Pro215Leu)	APOA5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1803845	NM_001371904.1(APOA5):c.1081A>C (p.Ser361Arg)	APOA5	Uncertain significance	criteria provided, single submitter
3235173	NM_001371904.1(APOA5):c.334_399dup (p.Thr133_Met134insAlaGluAlaHisGluLeuValGlyTrpAsnLeuGluGlyLeuArgGlnGlnLeuLysProTyrThr)	APOA5	Uncertain significance	criteria provided, single submitter
2627073	NM_001371904.1(APOA5):c.16_39del (p.Ala6_Ala13del)	LOC108491825	Uncertain significance	criteria provided, multiple submitters, no conflicts
4403	NM_001371904.1(APOA5):c.56C>G (p.Ser19Trp)	APOA5	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
APOA5	Strong	Semidominant	hyperlipoproteinemia type V	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
APOA5	Orphanet:530849	Familial apolipoprotein A5 deficiency

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
APOA5	HGNC:17288	ENSG00000110243	Q6Q788	Apolipoprotein A-V	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
APOA5	Apolipoprotein A-V	Minor apolipoprotein mainly associated with HDL and to a lesser extent with VLDL.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
APOA5	Other/Unknown	no		ApoA_E, Apolipoprotein_A1/A4/E

Expression context

Cohort genes with no expression data: 0.

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
liver	1
right lobe of liver	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
APOA5	45	tissue_specific	yes	right lobe of liver, liver, skeletal muscle tissue of rectus abdominis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
APOA5	1,919

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
APOA5	Q6Q788	72.38

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
Chylomicron remodeling	1	1142.0×	0.009	APOA5
Assembly of active LPL and LIPC lipase complexes	1	601.0×	0.009	APOA5
Plasma lipoprotein remodeling	1	475.8×	0.009	APOA5
Plasma lipoprotein assembly, remodeling, and clearance	1	228.4×	0.014	APOA5
Regulation of lipid metabolism by PPARalpha	1	141.0×	0.018	APOA5
Post-translational protein phosphorylation	1	100.2×	0.019	APOA5
PPARA activates gene expression	1	94.4×	0.019	APOA5
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.019	APOA5
Metabolism of lipids	1	31.6×	0.046	APOA5
Transport of small molecules	1	25.1×	0.052	APOA5
Post-translational protein modification	1	19.2×	0.062	APOA5
Metabolism of proteins	1	12.4×	0.086	APOA5
Metabolism	1	11.6×	0.086	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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of very-low-density lipoprotein particle remodeling	1	8426.0×	0.001	APOA5
triglyceride-rich lipoprotein particle remodeling	1	5617.3×	0.001	APOA5
very-low-density lipoprotein particle clearance	1	3370.4×	0.001	APOA5
acylglycerol homeostasis	1	3370.4×	0.001	APOA5
positive regulation of triglyceride catabolic process	1	2106.5×	0.002	APOA5
positive regulation of lipid catabolic process	1	1872.4×	0.002	APOA5
positive regulation of fatty acid biosynthetic process	1	1296.3×	0.002	APOA5
phospholipid efflux	1	1123.5×	0.002	APOA5
lipoprotein metabolic process	1	936.2×	0.002	APOA5
triglyceride catabolic process	1	802.5×	0.002	APOA5
positive regulation of receptor-mediated endocytosis	1	802.5×	0.002	APOA5
tissue regeneration	1	766.0×	0.002	APOA5
cholesterol efflux	1	526.6×	0.003	APOA5
triglyceride homeostasis	1	481.5×	0.003	APOA5
triglyceride metabolic process	1	443.5×	0.003	APOA5
lipid transport	1	263.3×	0.004	APOA5
cholesterol metabolic process	1	195.9×	0.005	APOA5
cholesterol homeostasis	1	156.0×	0.006	APOA5

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
APOA5	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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)	0
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	1	APOA5

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)
APOA5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE4	1
PHASE3	1
PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00473655	PHASE4	COMPLETED	Effect of Rosuvastatin on Triglyceride Levels in Mexican Hypertriglyceridemic Patients
NCT04849000	PHASE3	COMPLETED	Study of SHR-1209 in the Treatment of Hypercholesterolemia and Hyperlipidemia Ⅲ Stage
NCT00325455	PHASE2	TERMINATED	MK0859 Dose-Ranging Study (0859-003)
NCT07491172	PHASE1	RECRUITING	A Safety and Tolerability Trial Evaluating CTX310 in Participants With Refractory Dyslipidemias

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ROSUVASTATIN	4	2
ANACETRAPIB	3	1
RECATICIMAB	3	1
CHEMBL1357356	0	1