familial apolipoprotein C-II deficiency

Summary

familial apolipoprotein C-II deficiency (MONDO:0008810) is a disease caused by APOC2 (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: APOC2 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 50

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		10	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	familial apolipoprotein C-II deficiency
Mondo ID	MONDO:0008810
OMIM	207750
Orphanet	309020
DOID	DOID:0111418
ICD-11	877401371
SNOMED CT	33513003
UMLS	C1720779
MedGen	328375
GARD	0000759
Is cancer (heuristic)	no

Also known as: familial apoC-II deficiency · familial apolipoprotein C-II deficiency · hyperlipoproteinemia, type IB

Data availability: 50 ClinVar variants · 6 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 › familial apolipoprotein C-II deficiency

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

50 retrieved; paginated sample, class counts are floors:

22 uncertain significance, 7 pathogenic, 5 conflicting classifications of pathogenicity, 4 benign/likely benign, 4 likely pathogenic, 3 pathogenic/likely pathogenic, 3 benign, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1685529	NM_000483.5(APOC2):c.274C>T (p.Gln92Ter)	APOC2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2576	NM_000483.5(APOC2):c.270del (p.Asp91fs)	APOC2	Pathogenic	no assertion criteria provided
2583	NM_000483.5(APOC2):c.142T>C (p.Trp48Arg)	APOC2	Pathogenic	no assertion criteria provided
3362701	NM_000483.5(APOC2):c.216-1G>A	APOC2	Pathogenic	criteria provided, single submitter
1284889	NM_000483.5(APOC2):c.118del (p.Gln39_Val40insTer)	APOC4-APOC2	Pathogenic	no assertion criteria provided
1374052	NM_000483.5(APOC2):c.10C>T (p.Arg4Ter)	APOC4-APOC2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2577	NM_000483.5(APOC2):c.55+1G>C	APOC4-APOC2	Pathogenic	no assertion criteria provided
2580	NM_000483.5(APOC2):c.177C>G (p.Tyr59Ter)	APOC4-APOC2	Pathogenic	no assertion criteria provided
2584	NM_000483.5(APOC2):c.255C>A (p.Tyr85Ter)	APOC4-APOC2	Pathogenic	no assertion criteria provided
634436	NM_000483.5(APOC2):c.189C>A (p.Tyr63Ter)	APOC4-APOC2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2579	NM_000483.5(APOC2):c.1A>G (p.Met1Val)	APOC2	Likely pathogenic	criteria provided, single submitter
2574	NM_000483.5(APOC2):c.177C>A (p.Tyr59Ter)	APOC4-APOC2	Likely pathogenic	criteria provided, single submitter
2575	NM_000483.5(APOC2):c.274dup (p.Gln92fs)	APOC4-APOC2	Likely pathogenic	criteria provided, single submitter
3583931	NM_000483.5(APOC2):c.79C>T (p.Gln27Ter)	APOC4-APOC2	Likely pathogenic	criteria provided, single submitter
2581	NM_000483.5(APOC2):c.122A>C (p.Lys41Thr)	APOC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
894241	NM_000483.5(APOC2):c.56-11T>C	APOC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
894637	NM_000483.5(APOC2):c.195C>A (p.Pro65=)	APOC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
329454	NM_000483.5(APOC2):c.102G>A (p.Pro34=)	APOC4-APOC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
894242	NM_000483.5(APOC2):c.85G>A (p.Asp29Asn)	APOC4-APOC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1756057	NM_000483.5(APOC2):c.68C>T (p.Thr23Ile)	APOC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1777009	NM_000483.5(APOC2):c.163G>A (p.Ala55Thr)	APOC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2447633	NM_000483.5(APOC2):c.257C>G (p.Thr86Arg)	APOC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2502228	NM_000483.5(APOC2):c.-14+8A>G	APOC2	Uncertain significance	criteria provided, single submitter
3064990	NM_000483.5(APOC2):c.55G>T (p.Glu19Ter)	APOC2	Uncertain significance	criteria provided, single submitter
329455	NM_000483.5(APOC2):c.301G>A (p.Glu101Lys)	APOC2	Uncertain significance	criteria provided, single submitter
329456	NM_000483.5(APOC2):c.*24C>T	APOC2	Uncertain significance	criteria provided, single submitter
3583928	NM_000483.5(APOC2):c.55+17G>A	APOC2	Uncertain significance	criteria provided, single submitter
3583930	NM_000483.5(APOC2):c.58G>A (p.Val20Ile)	APOC2	Uncertain significance	criteria provided, single submitter
3583932	NM_000483.5(APOC2):c.118G>T (p.Val40Leu)	APOC2	Uncertain significance	criteria provided, single submitter
3583935	NM_000483.5(APOC2):c.161C>A (p.Ala54Asp)	APOC2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
APOC2	Definitive	Autosomal recessive	familial apolipoprotein C-II deficiency	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
APOC2	Orphanet:309020	Familial apolipoprotein C-II deficiency

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
APOC2	HGNC:609	ENSG00000234906	P02655	Apolipoprotein C-II	gencc,clinvar
APOC4-APOC2	HGNC:44426	ENSG00000224916		APOC4-APOC2 readthrough (NMD candidate)	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
APOC2	Apolipoprotein C-II	Component of chylomicrons, very low-density lipoproteins (VLDL), low-density lipoproteins (LDL), 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)
APOC2	Other/Unknown	no		Apo-CII, ApoC-II_dom_sf
APOC4-APOC2	Other/Unknown	no

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
right lobe of liver	2
substantia nigra	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
APOC2	135	broad	marker	right lobe of liver, liver, substantia nigra
APOC4-APOC2	88	tissue_specific	marker	liver, right lobe of liver, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
APOC2	1,178
APOC4-APOC2	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
APOC2	P02655	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. Enrichment computed across 2 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 assembly	1	1142.0×	0.005	APOC2
Chylomicron remodeling	1	1142.0×	0.005	APOC2
HDL remodeling	1	1142.0×	0.005	APOC2
Plasma lipoprotein assembly	1	713.8×	0.006	APOC2
Assembly of active LPL and LIPC lipase complexes	1	601.0×	0.006	APOC2
Plasma lipoprotein remodeling	1	475.8×	0.006	APOC2
NR1H2 and NR1H3-mediated signaling	1	393.8×	0.006	APOC2
Metabolism of fat-soluble vitamins	1	380.7×	0.006	APOC2
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	1	308.6×	0.006	APOC2
Visual phototransduction	1	259.6×	0.007	APOC2
Retinoid metabolism and transport	1	248.3×	0.007	APOC2
Plasma lipoprotein assembly, remodeling, and clearance	1	228.4×	0.007	APOC2
Metabolism of vitamins and cofactors	1	116.5×	0.012	APOC2
Signaling by Nuclear Receptors	1	102.0×	0.013	APOC2
Sensory Perception	1	95.2×	0.013	APOC2
Transport of small molecules	1	25.1×	0.045	APOC2
Metabolism	1	11.6×	0.091	APOC2
Signal Transduction	1	10.2×	0.098	APOC2

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 phospholipid catabolic process	1	16852.0×	8e-04	APOC2
positive regulation of very-low-density lipoprotein particle remodeling	1	8426.0×	8e-04	APOC2
triglyceride-rich lipoprotein particle remodeling	1	5617.3×	8e-04	APOC2
negative regulation of very-low-density lipoprotein particle clearance	1	4213.0×	8e-04	APOC2
negative regulation of cholesterol transport	1	4213.0×	8e-04	APOC2
chylomicron remodeling	1	4213.0×	8e-04	APOC2
negative regulation of lipid metabolic process	1	3370.4×	8e-04	APOC2
chylomicron remnant clearance	1	2808.7×	8e-04	APOC2
high-density lipoprotein particle clearance	1	2407.4×	8e-04	APOC2
lipoprotein catabolic process	1	2407.4×	8e-04	APOC2
positive regulation of triglyceride catabolic process	1	2106.5×	8e-04	APOC2
very-low-density lipoprotein particle remodeling	1	2106.5×	8e-04	APOC2
negative regulation of receptor-mediated endocytosis	1	1872.4×	8e-04	APOC2
positive regulation of fatty acid biosynthetic process	1	1296.3×	0.001	APOC2
phospholipid efflux	1	1123.5×	0.001	APOC2
reverse cholesterol transport	1	936.2×	0.001	APOC2
cholesterol efflux	1	526.6×	0.002	APOC2
triglyceride homeostasis	1	481.5×	0.002	APOC2
lipid catabolic process	1	244.2×	0.004	APOC2
cholesterol homeostasis	1	156.0×	0.006	APOC2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
APOC2	0	0
APOC4-APOC2	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	2	APOC2, APOC4-APOC2

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)
APOC2	0	—
APOC4-APOC2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.