apolipoprotein c-III deficiency

Summary

apolipoprotein c-III deficiency (MONDO:0013534) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	apolipoprotein c-III deficiency
Mondo ID	MONDO:0013534
MeSH	C566270
OMIM	614028
DOID	DOID:0111370
UMLS	C3151467
MedGen	462817
GARD	0018076
Is cancer (heuristic)	no

Also known as: apolipoprotein c-III deficiency

Data availability: 9 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › apolipoprotein c-III deficiency

Related subtypes (92): thiopurine metabolic disease, hypercalcemia, infantile, hypermanganesemia with dystonia, abdominal obesity-metabolic syndrome, plasma protein metabolism disease, inherited lipid metabolism disorder, lysosomal storage disease, striatonigral degeneration, inborn metal metabolism disorder, inborn vitamin metabolic disorder, chondrocalcinosis 2, Ehlers-Danlos syndrome, spondylodysplastic type, fish eye disease, aromatase excess syndrome, spondyloepiphyseal dysplasia with congenital joint dislocations, hypertriglyceridemia 1, autosomal dominant myoglobinuria, diastrophic dysplasia, hemolytic anemia due to diphosphoglycerate mutase deficiency, multiple epiphyseal dysplasia type 4, atelosteogenesis type II, inherited threoninemia, inborn glycerol kinase deficiency, achondrogenesis type IB, diabetes mellitus, noninsulin-dependent, 1, diabetes mellitus, noninsulin-dependent, 2, renal tubular acidosis, distal, 3, with or without sensorineural hearing loss, diabetes mellitus, noninsulin-dependent, 3, hypercholesterolemia, familial, 4, hypoalphalipoproteinemia, primary, 1, autosomal recessive proximal renal tubular acidosis, diabetes mellitus, noninsulin-dependent, 4, normophosphatemic familial tumoral calcinosis, hypotonia-failure to thrive-microcephaly syndrome, chondrodysplasia with joint dislocations, gPAPP type, gluthathione peroxidase deficiency, congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome, diabetes mellitus, noninsulin-dependent, 5, congenital disorder of glycosylation, monogenic diabetes, 2-hydroxyglutaric aciduria, familial hypoparathyroidism, familial intrahepatic cholestasis, inborn aminoacylase deficiency, disorder of lysosomal-related organelles, inborn disorder of porphyrin metabolism, disorder of metabolite absorption and transport, autosomal dominant proximal renal tubular acidosis, neurodegeneration with brain iron accumulation, ferro-cerebro-cutaneous syndrome, familial hypocalciuric hypercalcemia, hypophosphatasia, hereditary amyloidosis, peroxisomal disease, inborn disorder of amino acid and other organic acid metabolism, inborn carbohydrate metabolic disorder, inborn disorder of energy metabolism, inborn disorder of biogenic amine metabolism and transport, inborn disorder of purine or pyrimidine metabolism, spondyloepimetaphyseal dysplasia, PAPSS2 type, hereditary lipodystrophy, hereditary recurrent myoglobinuria, DNA repair disease, 4-hydroxyphenylacetic aciduria, 5-nucleotidase syndrome, antigen-peptide-transporter 2 deficiency, APO A-i deficiency, cardiomyopathy hypogonadism metabolic anomalies, deficiency of coenzyme q cytochrome c reductase, defective apolipoprotein b-100, sulfide quinone oxidoreductase deficiency, congenital disorder of deglycosylation, hypoalphalipoproteinemia, primary, 2, uridine-cytidineuria, NAD(P)HX dehydratase deficiency, inborn disorder of aspartate family metabolism, weinstein kliman scully syndrome, glycoprotein metabolism disease, inherited thyroid metabolism disease, tumoral calcinosis, hyperphosphatemic, familial, 2, tumoral calcinosis, hyperphosphatemic, familial, 3, combined ApoA-I and ApoC-III deficiency, familial hyperphosphatemic tumoral calcinosis/hyperphosphatemic hyperostosis syndrome, tumoral calcinosis, hyperphosphatemic, familial, 1, Waldenstrom macroglobulinemia, mucopolysaccharidosis or mucopolysaccharidosis-like disorder, disorder of peptide and amine metabolism, CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis, Lane Hamilton syndrome, SQSTM1-related multisystem proteinopathy, hypertriglyceridemia 2, autosomal dominant dopa-responsive dystonia

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

9 retrieved; paginated sample, class counts are floors:

4 conflicting classifications of pathogenicity, 3 uncertain significance, 1 pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
17903	NM_000040.3(APOC3):c.232A>G (p.Lys78Glu)	APOC3	Pathogenic	no assertion criteria provided
139560	NM_000040.3(APOC3):c.55+1G>A	APOC3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
139561	NM_000040.3(APOC3):c.127G>A (p.Ala43Thr)	APOC3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
139562	NM_000040.3(APOC3):c.179+1G>T	APOC3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
17904	NM_000040.3(APOC3):c.55C>T (p.Arg19Ter)	APOC3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1803817	NM_000040.3(APOC3):c.148G>A (p.Val50Met)	APOC3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1803900	NM_000040.3(APOC3):c.161A>G (p.Gln54Arg)	APOC3	Uncertain significance	criteria provided, single submitter
2582727	NM_000040.3(APOC3):c.91T>G (p.Phe31Val)	APOC3	Uncertain significance	criteria provided, single submitter
518235	NM_000040.3(APOC3):c.102T>C (p.Gly34=)	APOC3	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
APOC3	Limited	Autosomal dominant	apolipoprotein c-III deficiency	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
APOC3	Orphanet:181428	Familial Hyperalphalipoproteinemia

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
APOC3	HGNC:610	ENSG00000110245	P02656	Apolipoprotein C-III	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
APOC3	Apolipoprotein C-III	Component of triglyceride-rich very low density lipoproteins (VLDL) and high density lipoproteins (HDL) in plasma.

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)
APOC3	Other/Unknown	no		Apo-CIII, Apo_CIII_sf

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
jejunal mucosa	1
liver	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
APOC3	156	tissue_specific	marker	jejunal mucosa, right lobe of liver, liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
APOC3	1,895

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
APOC3	P02656	1

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 assembly	1	1142.0×	0.004	APOC3
Chylomicron remodeling	1	1142.0×	0.004	APOC3
HDL remodeling	1	1142.0×	0.004	APOC3
Plasma lipoprotein assembly	1	713.8×	0.005	APOC3
Plasma lipoprotein remodeling	1	475.8×	0.005	APOC3
Metabolism of fat-soluble vitamins	1	380.7×	0.006	APOC3
Visual phototransduction	1	259.6×	0.006	APOC3
Retinoid metabolism and transport	1	248.3×	0.006	APOC3
Plasma lipoprotein assembly, remodeling, and clearance	1	228.4×	0.006	APOC3
Metabolism of vitamins and cofactors	1	116.5×	0.011	APOC3
Sensory Perception	1	95.2×	0.012	APOC3
Transport of small molecules	1	25.1×	0.043	APOC3
Metabolism	1	11.6×	0.086	APOC3

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
negative regulation of high-density lipoprotein particle clearance	1	16852.0×	0.001	APOC3
negative regulation of cholesterol import	1	5617.3×	0.001	APOC3
negative regulation of very-low-density lipoprotein particle clearance	1	4213.0×	0.001	APOC3
negative regulation of lipid metabolic process	1	3370.4×	0.001	APOC3
negative regulation of triglyceride catabolic process	1	2808.7×	0.001	APOC3
negative regulation of very-low-density lipoprotein particle remodeling	1	2808.7×	0.001	APOC3
chylomicron remnant clearance	1	2808.7×	0.001	APOC3
negative regulation of receptor-mediated endocytosis	1	1872.4×	0.002	APOC3
negative regulation of low-density lipoprotein particle clearance	1	1532.0×	0.002	APOC3
regulation of Cdc42 protein signal transduction	1	1404.3×	0.002	APOC3
very-low-density lipoprotein particle assembly	1	1203.7×	0.002	APOC3
phospholipid efflux	1	1123.5×	0.002	APOC3
lipoprotein metabolic process	1	936.2×	0.002	APOC3
reverse cholesterol transport	1	936.2×	0.002	APOC3
negative regulation of fatty acid biosynthetic process	1	887.0×	0.002	APOC3
negative regulation of lipid catabolic process	1	842.6×	0.002	APOC3
triglyceride catabolic process	1	802.5×	0.002	APOC3
high-density lipoprotein particle remodeling	1	802.5×	0.002	APOC3
cholesterol efflux	1	526.6×	0.002	APOC3
triglyceride homeostasis	1	481.5×	0.002	APOC3
triglyceride metabolic process	1	443.5×	0.002	APOC3
cholesterol homeostasis	1	156.0×	0.007	APOC3
G protein-coupled receptor signaling pathway	1	36.2×	0.028	APOC3

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
APOC3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
APOC3	1	Binding:1

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	APOC3

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)
APOC3	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.