APOC2

Summary

APOC2 (apolipoprotein C2, HGNC:609) is a protein-coding gene on chromosome 19q13.32, encoding Apolipoprotein C-II (P02655). Component of chylomicrons, very low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL) in plasma.

This gene encodes a lipid-binding protein belonging to the apolipoprotein gene family. The protein is secreted in plasma where it is a component of very low density lipoprotein. This protein activates the enzyme lipoprotein lipase, which hydrolyzes triglycerides and thus provides free fatty acids for cells. Mutations in this gene cause hyperlipoproteinemia type IB, characterized by hypertriglyceridemia, xanthomas, and increased risk of pancreatitis and early atherosclerosis. This gene is present in a cluster with other related apolipoprotein genes on chromosome 19. Naturally occurring read-through transcription exists between this gene and the neighboring upstream apolipoprotein C-IV (APOC4) gene.

Source: NCBI Gene 344 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial apolipoprotein C-II deficiency (Definitive, GenCC)
• GWAS associations: 48
• Clinical variants (ClinVar): 102 total — 8 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 10
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_000483

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:609
Approved symbol	APOC2
Name	apolipoprotein C2
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000234906
Ensembl biotype	protein_coding
OMIM	608083
Entrez	344

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 21 protein_coding

ENST00000252490, ENST00000585786, ENST00000590360, ENST00000591597, ENST00000592257, ENST00000896546, ENST00000896547, ENST00000896548, ENST00000896549, ENST00000896550, ENST00000896551, ENST00000896552, ENST00000896553, ENST00000896554, ENST00000896555, ENST00000896556, ENST00000896557, ENST00000896558, ENST00000896559, ENST00000896560, ENST00000968228

RefSeq mRNA: 1 — MANE Select: NM_000483 NM_000483

CCDS: CCDS12650

Canonical transcript exons

ENST00000252490 — 4 exons

Exon	Start	End
ENSE00001735377	44946051	44946075
ENSE00003705148	44948701	44948860
ENSE00003804092	44948466	44948533
ENSE00003902855	44949159	44949565

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 99.91.

FANTOM5 (CAGE): breadth broad, TPM avg 19.8628 / max 3643.7863, expressed in 389 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176353	12.5476	312
176352	6.4000	313
176351	0.3266	116
176355	0.2336	66
176354	0.1767	95
176356	0.0752	16
176358	0.0583	15
176357	0.0448	12

Top tissues by expression

137 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.91	gold quality
liver	UBERON:0002107	99.88	gold quality
substantia nigra	UBERON:0002038	94.83	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.84	gold quality
duodenum	UBERON:0002114	92.72	gold quality
caudate nucleus	UBERON:0001873	92.32	gold quality
putamen	UBERON:0001874	91.45	gold quality
amygdala	UBERON:0001876	90.73	gold quality
temporal lobe	UBERON:0001871	90.71	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.67	gold quality
nucleus accumbens	UBERON:0001882	90.42	gold quality
hypothalamus	UBERON:0001898	89.53	gold quality
Ammon’s horn	UBERON:0001954	89.51	gold quality
prefrontal cortex	UBERON:0000451	84.68	gold quality
anterior cingulate cortex	UBERON:0009835	83.31	gold quality
cerebral cortex	UBERON:0000956	83.17	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.94	gold quality
frontal cortex	UBERON:0001870	82.84	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.82	gold quality
brain	UBERON:0000955	82.76	gold quality
right frontal lobe	UBERON:0002810	80.82	gold quality
adrenal tissue	UBERON:0018303	80.36	gold quality
primary visual cortex	UBERON:0002436	80.32	gold quality
upper lobe of left lung	UBERON:0008952	79.62	gold quality
colonic epithelium	UBERON:0000397	79.45	gold quality
lymph node	UBERON:0000029	79.13	gold quality
adult mammalian kidney	UBERON:0000082	78.55	gold quality
superior frontal gyrus	UBERON:0002661	78.46	gold quality
small intestine	UBERON:0002108	77.59	gold quality
right lung	UBERON:0002167	77.34	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-ENAD-20	yes	196.22
E-GEOD-125970	yes	7.38
E-HCAD-10	yes	6.84
E-ANND-3	yes	4.57

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF4A, NR1H3, NR1H4, NR2F2, NR2F6, PITX2, PPARA, RXRA, STAT1, THRB

miRNA regulators (miRDB)

32 targeting APOC2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-422A	99.18	65.83	550
HSA-MIR-10524-5P	99.05	66.08	963
HSA-MIR-219A-2-3P	98.62	68.78	797
HSA-MIR-378A-3P	98.43	66.10	548
HSA-MIR-378C	98.43	66.10	548
HSA-MIR-378D	98.43	66.10	548
HSA-MIR-378E	98.43	65.99	551
HSA-MIR-378H	98.43	66.16	545
HSA-MIR-378I	98.43	66.10	548
HSA-MIR-6509-3P	98.32	67.33	1343
HSA-MIR-3155A	98.16	66.09	965
HSA-MIR-3155B	98.16	66.09	965
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-3907	96.76	65.04	662
HSA-MIR-711	96.60	65.75	528

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Human apolipoprotein C-II (apoC-II) slowly forms amyloid fibers in lipid-free solutions at physiological pH and salt concentrations (PMID:11751863)
• regulated expression of gene cluster in macrophages (PMID:12032151)
• During amyloidosis under oxidizing conditions, cysteine-containing apolipoprotein C-II (apoC-II) derivatives form fibrils more rapidly and become extensively tangled compared to wild-type apoC-II. (PMID:12450397)
• Three categories of global constraints, together with the local classical NMR constraints, define the 3D structure of the apoCII-SDS micelle complex and give important clues toward a possible mechanism for the activation of lipoprotein lipase by apoCII. (PMID:12590574)
• regions of lipoprotein lipase that are responsive to activation by apoC-II (PMID:12682050)
• Hydrolysis activated by APOC2 was faster compared with the LPL-mediated lipolysis of emulsion triolein. The binding density of APOC2 was less for small emulsion surfaces than for large ones. (PMID:12782148)
• This protein, a non-fibrillar component, causes soluble fibrils to condense into localized fibrillar aggregates with a greatly enhanced local density of fibril entanglements. (PMID:15031287)
• Different levels of secreted apoC-II had little effect on LDL and HDL protein degradation by HepG2 cells. Compared to controls, cells under-expressing apoC-II showed a 160% higher capacity to selectively take up HDL-CE. (PMID:15778093)
• Results show that purified human HDL and recombinant apolipoprotein A-I lipid particles bind directly to amyloid beta and apolipoprotein C-II amyloid fibrils. (PMID:16432277)
• No relationship was found between ApoCII polymorphism and coronary disease in the Chinese Han population. (PMID:16459141)
• Decrease of LPL activity in the heart, along with the inhibitory effects of excess apolipoprotein C-II, may contribute to the hypertriglyceridemia observed in apolipoprotein c-ii transgenic mice. (PMID:17018885)
• Taken together these data demonstrate an interaction between antichymotrypsin and apolipoprotein C-II that accelerates fibrillogenesis and indicates a specific role for accessory proteins in protein aggregation. (PMID:17174330)
• These results suggested that T–>A substitution at position -190 in the apoC-II gene promoter only partly affected transcriptional activity of the apoC-II promoter, leading to decrease of apoC-II expression in quantity. (PMID:17222387)
• The ozone oxidation product of cholesterol, 3beta-hydroxy-5-oxo-5,6-secocholestan-6-al, rapidly promotes human apolipoprotein (apo) C-II amyloid fibril formation in vitro. (PMID:17429947)
• Both common and rare DNA variants of APOC2 gene were found in 10% patients with severe hypertriglyceridemia (PMID:17717288)
• Phospholipid interaction induces molecular-level polymorphism in APOC2 amyloid fibrils via alternative assembly pathways. (PMID:18005990)
• The concentration-dependent kinetics of apolipoprotein C-II amyloid fibril formation and correlated this with the final size distribution of the fibrils determined by sedimentation velocity experiments, is studied. (PMID:18206908)
• lipids promote on-pathway intermediates of apoC-II fibril assembly and the accumulation of a discrete tetrameric intermediate depends on the molecular state of the lipid (PMID:18852267)
• No significant differences were found between the acute hypertriglyceridaemic pancreatitis cases and controls with severe hypertriglyceridaemia in terms of LPL activity and mass, hepatic lipase activity, CII and CIII mass, or apo E polymorphisms. (PMID:19534808)
• Results describe the functional role of the secondary structure in the lipoprotein lipase-binding portion of apolipoprotein CII. (PMID:20042600)
• This study examines the association between APOE/C1/C4/C2 gene cluster variation using tagging single nucleotide polymorphisms and plasma lipid concentration along with risk of coronary heart disease in a prospective cohort. (PMID:20498921)
• Our structural model for apoC-II fibrils suggests that apoC-II monomers fold and self-assemble to form a stable cross-beta-scaffold containing relatively unstructured connecting loops. (PMID:21146539)
• These results support a predictive change in the ratio of plasma ApoCIII to ApoCII in pregnancies complicated by severe preeclampsia. (PMID:21321243)
• Physiological shear flow conditions and conditions experienced during apoC-II manufacturing exert significant effects on apoC-II conformation, leading to protein misfolding, aggregation, and amyloid fibril formation. (PMID:21476595)
• variants in LPL, OASL and TOMM40/APOE-C1-C2-C4 genes are associated with multiple cardiovascular-related traits (PMID:21943158)
• Activation of apoC-II fibrils by submicellar lipid (NBD-lyso-12-phosphocholine) is catalytic with release of monomer- and tetramer-bound lipid accompanying fibril elongation and growth. (PMID:21985034)
• Mutations in GPIHBP1 are rare but the associated clinical phenotype of hypertriglyceridaemia is severe (PMID:22239554)
• Substoichiometric concentrations of cyc[60-70] significantly delayed fibril formation by the fibrillogenic, linear peptides apoC-II[60-70] and apoC-II[56-76]. (PMID:22244853)
• STAT1 bound on multienhancer 2 cooperates with RXRalpha located on apoCII promoter and upregulates apoCII expression only in macrophages. (PMID:22808166)
• Six apolipoproteins (APOA1, APOA2, APOB, APOC2, APOC3, and APOE) were able to differentiate bladder cancer from hernia. SAA4 was significantly increased in bladder cancer subgroups, whereas ProEGF was significantly decreased in bladder cancer subgroups. (PMID:23631828)
• No APOC2 mutations were identified in a cohort of patients with diabetic lipemia. (PMID:25131724)
• Large deletion in APOC2 caused by Alu-Alu homologous recombination is associated with with apolipoprotein C-II deficiency. (PMID:25172036)
• Conformational rearrangement of apoC-II at lipoprotein surfaces promotes interaction with LPL. (PMID:26026161)
• The results highlight the importance of charge-pair interactions within the apoC-II fibril core (PMID:26196342)
• The results demonstrate the important role of both intra- and inter-subunit charge interactions in stabilizing apoC-II amyloid fibrils, a process that may be a key factor in determining the general ability of proteins to form amyloid fibrils. (PMID:28229588)
• Triglyceride-raising variant alleles of the APOC2 encoding apo C-II, associated with clinical Cardiovascular endpoints. (PMID:28534127)
• Results from this exploratory analysis suggest that regulatory element methylation levels within the larger TOMM40-APOE-APOC2 gene region correlate with AD-related biomarkers and TOMM40 or APOE gene expression in AD. (PMID:29371683)
• The effect of apolipoprotein C2 K30D-D69K mutations on rod-like apolipoprotein C2 fibril formation. (PMID:29791776)
• A case of patient with hereditary systemic amyloidosis caused by K19T apolipoprotein C-II variant is described. (PMID:30686043)
• Reduced serum levels apolipoprotein A2 and apolipoprotein C2 were significantly associated with the presence of aneurysm wall enhancement in MRI angiography. (PMID:31133485)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	apoc2	ENSDARG00000092155
mus_musculus	Apoc2	ENSMUSG00000002992
rattus_norvegicus	Apoc2	ENSRNOG00000018402

Protein

Protein identifiers

Apolipoprotein C-II — P02655 (reviewed: P02655)

Alternative names: Apolipoprotein C2

All UniProt accessions (6): A0A024R0T9, A0A0S2Z3C2, P02655, Q6P163, V9GYJ8, V9GZ01

UniProt curated annotations — full annotation on UniProt →

Function. Component of chylomicrons, very low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL) in plasma. Plays an important role in lipoprotein metabolism as an activator of lipoprotein lipase. Both proapolipoprotein C-II and apolipoprotein C-II can activate lipoprotein lipase. In normolipidemic individuals, it is mainly distributed in the HDL, whereas in hypertriglyceridemic individuals, predominantly found in the VLDL and LDL.

Subcellular location. Secreted.

Tissue specificity. Liver and intestine.

Post-translational modifications. Proapolipoprotein C-II is synthesized as a sialic acid containing glycoprotein which is subsequently desialylated prior to its proteolytic processing. Proapolipoprotein C-II, the major form found in plasma undergoes proteolytic cleavage of its N-terminal hexapeptide to generate apolipoprotein C-II, which occurs as the minor form in plasma.

Disease relevance. Hyperlipoproteinemia 1B (HLPP1B) [MIM:207750] Autosomal recessive trait characterized by hypertriglyceridemia, xanthomas, and increased risk of pancreatitis and early atherosclerosis. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the apolipoprotein C2 family.

RefSeq proteins (1): NP_000474* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008019	Apo-CII	Family
IPR023121	ApoC-II_dom_sf	Homologous_superfamily

Pfam: PF05355

UniProt features (22 total): strand 4, turn 4, sequence variant 4, helix 3, region of interest 3, chain 2, signal peptide 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1BY6	SOLUTION NMR
1I5J	SOLUTION NMR
1O8T	SOLUTION NMR
1SOH	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02655-F1	65.81	0.00

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-8963888	Chylomicron assembly
R-HSA-8963889	Assembly of active LPL and LIPC lipase complexes
R-HSA-8963901	Chylomicron remodeling
R-HSA-8964058	HDL remodeling
R-HSA-9029569	NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux
R-HSA-975634	Retinoid metabolism and transport
R-HSA-1430728	Metabolism
R-HSA-162582	Signal Transduction
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-196854	Metabolism of vitamins and cofactors
R-HSA-2187338	Visual phototransduction
R-HSA-382551	Transport of small molecules
R-HSA-6806667	Metabolism of fat-soluble vitamins
R-HSA-8963898	Plasma lipoprotein assembly
R-HSA-8963899	Plasma lipoprotein remodeling
R-HSA-9006931	Signaling by Nuclear Receptors
R-HSA-9024446	NR1H2 and NR1H3-mediated signaling
R-HSA-9709957	Sensory Perception

MSigDB gene sets: 307 (showing top): MODULE_172, GOBP_ACYLGLYCEROL_HOMEOSTASIS, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_TRIGLYCERIDE_METABOLIC_PROCESS, GOBP_STEROL_HOMEOSTASIS, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GNF2_GSTM1, GNF2_HPN, ROVERSI_GLIOMA_COPY_NUMBER_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_ENDOCYTOSIS, MCBRYAN_PUBERTAL_TGFB1_TARGETS_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (22): positive regulation of triglyceride catabolic process (GO:0010898), positive regulation of very-low-density lipoprotein particle remodeling (GO:0010902), negative regulation of very-low-density lipoprotein particle clearance (GO:0010916), lipid catabolic process (GO:0016042), negative regulation of cholesterol transport (GO:0032375), cholesterol efflux (GO:0033344), phospholipid efflux (GO:0033700), triglyceride-rich lipoprotein particle remodeling (GO:0034370), chylomicron remodeling (GO:0034371), very-low-density lipoprotein particle remodeling (GO:0034372), chylomicron remnant clearance (GO:0034382), high-density lipoprotein particle clearance (GO:0034384), lipoprotein catabolic process (GO:0042159), cholesterol homeostasis (GO:0042632), reverse cholesterol transport (GO:0043691), positive regulation of fatty acid biosynthetic process (GO:0045723), negative regulation of lipid metabolic process (GO:0045833), negative regulation of receptor-mediated endocytosis (GO:0048261), positive regulation of phospholipid catabolic process (GO:0060697), triglyceride homeostasis (GO:0070328), lipid metabolic process (GO:0006629), lipid transport (GO:0006869)

GO Molecular Function (8): lipid binding (GO:0008289), phospholipase activator activity (GO:0016004), phospholipase binding (GO:0043274), lipase inhibitor activity (GO:0055102), lipoprotein lipase activator activity (GO:0060230), molecular function activator activity (GO:0140677), protein binding (GO:0005515), enzyme activator activity (GO:0008047)

GO Cellular Component (9): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), early endosome (GO:0005769), very-low-density lipoprotein particle (GO:0034361), low-density lipoprotein particle (GO:0034362), intermediate-density lipoprotein particle (GO:0034363), spherical high-density lipoprotein particle (GO:0034366), chylomicron (GO:0042627), high-density lipoprotein particle (GO:0034364)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Plasma lipoprotein remodeling	3
Plasma lipoprotein assembly, remodeling, and clearance	2
Plasma lipoprotein assembly	1
NR1H2 and NR1H3-mediated signaling	1
Visual phototransduction	1
Metabolism of fat-soluble vitamins	1
Transport of small molecules	1
Metabolism	1
Sensory Perception	1
Metabolism of vitamins and cofactors	1
Signal Transduction	1
Signaling by Nuclear Receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cholesterol transport	3
plasma lipoprotein particle	3
positive regulation of lipid catabolic process	2
lipid metabolic process	2
triglyceride-rich lipoprotein particle remodeling	2
binding	2
lipase activator activity	2
triglyceride-rich plasma lipoprotein particle	2
regulation of triglyceride catabolic process	1
triglyceride catabolic process	1
positive regulation of triglyceride metabolic process	1
regulation of very-low-density lipoprotein particle remodeling	1
very-low-density lipoprotein particle remodeling	1
positive regulation of cellular component organization	1
positive regulation of multicellular organismal process	1
regulation of very-low-density lipoprotein particle clearance	1
negative regulation of lipoprotein particle clearance	1
very-low-density lipoprotein particle clearance	1
catabolic process	1
negative regulation of sterol transport	1
regulation of cholesterol transport	1
phospholipid transport	1
plasma lipoprotein particle remodeling	1
triglyceride-rich lipoprotein particle clearance	1
plasma lipoprotein particle clearance	1
protein catabolic process	1
lipoprotein metabolic process	1
sterol homeostasis	1
fatty acid biosynthetic process	1
regulation of fatty acid biosynthetic process	1
positive regulation of fatty acid metabolic process	1
positive regulation of lipid biosynthetic process	1
negative regulation of metabolic process	1
regulation of lipid metabolic process	1
receptor-mediated endocytosis	1
negative regulation of endocytosis	1
regulation of receptor-mediated endocytosis	1
phospholipid catabolic process	1
regulation of phospholipid catabolic process	1
positive regulation of phospholipid metabolic process	1

Protein interactions and networks

STRING

1118 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOC2	APOC1	P02654	999
APOC2	APOE	P02649	998
APOC2	APOC3	P02656	997
APOC2	APOA1	P02647	983
APOC2	LPL	P06858	983
APOC2	APOA5	Q6Q788	979
APOC2	APOA4	P06727	934
APOC2	APOA2	P02652	930
APOC2	LMF1	Q96S06	929
APOC2	APOB	P04114	928
APOC2	APOC4	P55056	922
APOC2	GPIHBP1	Q8IV16	871
APOC2	CLU	P10909	848
APOC2	LIPC	P11150	799
APOC2	PEPD	P12955	794

IntAct

17 interactions, top by confidence:

A	B	Type	Score
MED21	MED19	psi-mi:“MI:0914”(association)	0.880
APOC2	TTPA	psi-mi:“MI:0915”(physical association)	0.560
APOC2	APOE	psi-mi:“MI:0914”(association)	0.530
APOE	APOC2	psi-mi:“MI:0403”(colocalization)	0.530
APOC2	CFTR	psi-mi:“MI:0915”(physical association)	0.370
ALB	SH3BP5	psi-mi:“MI:0914”(association)	0.350
XAGE3	PSMG1	psi-mi:“MI:0914”(association)	0.350
DSCR4	GAST	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
SOX2	MYO1C	psi-mi:“MI:0914”(association)	0.350
APOB	APOC2	psi-mi:“MI:0403”(colocalization)	0.350
APOC2	APOA2	psi-mi:“MI:0403”(colocalization)	0.350
APOC2	APOC2	psi-mi:“MI:0403”(colocalization)	0.350
TTPA	APOC2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (43): APOC2 (Affinity Capture-MS), APOC2 (Two-hybrid), APOC2 (Two-hybrid), APOC2 (Two-hybrid), APOC2 (Two-hybrid), APOC2 (Two-hybrid), APOC2 (Two-hybrid), APOC2 (Two-hybrid), APOC2 (Two-hybrid), APOC2 (Two-hybrid), APOC2 (Two-hybrid), APOC2 (Two-hybrid), APOC2 (Two-hybrid), APOC2 (Two-hybrid), APOC2 (Two-hybrid)

ESM2 similar proteins: A0A096P2H4, A0A0D9S1R9, A0A1A6FVD4, A0A2U3Y4D7, A0A2Y9GHM8, A0A2Y9HRM2, G3HPD1, G3V8D4, G5BQH4, P02655, P02656, P0DKU5, P0DKV7, P0DKV9, P0DKW0, P0DKY1, P0DM92, P0DMN9, P0DMP9, P0DN28, P0DN40, P0DOC1, P0DP52, P0DP84, P0DSP0, P0DTQ5, P0DTQ6, P0DTR9, P0DTS4, P0DTS5, P0DUP3, P0DUP4, P0DUX6, P0DUX7, P0DUX8, P0DUX9, P0DUY0, P0DUY1, P12278, P12279

Diamond homologs: A0A096P2H4, A0A0D9S1R9, A0A1A6FVD4, A0A2U3Y4D7, A0A2Y9GHM8, G3HPD1, G3V8D4, P02655, P0DKU5, P0DKV7, P0DKV8, P0DKV9, P0DKW0, P0DKY1, P0DMN9, P0DMT9, P0DN40, P0DOC1, P0DP52, P0DTQ5, P0DTQ6, P0DTR9, P0DUP3, P0DUP4, P0DUX6, P0DUX7, P0DUX8, P0DUX9, P0DUY0, P0DUY1, P12278, P18658, P19034, P27916, Q05020, Q9BG58, T1W425

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
APOC2	“up-regulates activity”	LPL

Disease & clinical

Clinical variants and AI predictions

ClinVar

102 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	2
Uncertain significance	33
Likely benign	48
Benign	6

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
1937520	NM_000483.5(APOC2):c.10del (p.Arg4fs)	Pathogenic
2423146	NC_000019.9:g.(?45451736)(45452506_?)del	Pathogenic
2576	NM_000483.5(APOC2):c.270del (p.Asp91fs)	Pathogenic
2583	NM_000483.5(APOC2):c.142T>C (p.Trp48Arg)	Pathogenic
280159	NM_000483.5(APOC2):c.196_197del (p.Ala66fs)	Pathogenic
2992672	NM_000483.5(APOC2):c.25_26del (p.Leu9fs)	Pathogenic
3237335	Single allele	Pathogenic
3362701	NM_000483.5(APOC2):c.216-1G>A	Pathogenic
2579	NM_000483.5(APOC2):c.1A>G (p.Met1Val)	Likely pathogenic
4126902	NM_000483.5(APOC2):c.73C>T (p.Gln25Ter)	Likely pathogenic

SpliceAI

626 predictions. Top by Δscore:

Variant	Effect	Δscore
19:44946071:GTCTG:G	donor_gain	1.0000
19:44946076:G:GG	donor_gain	1.0000
19:44946077:T:A	donor_loss	1.0000
19:44948699:A:AG	acceptor_gain	1.0000
19:44948700:G:GG	acceptor_gain	1.0000
19:44947197:C:CA	acceptor_gain	0.9900
19:44947198:G:A	acceptor_gain	0.9900
19:44947307:AGCAG:A	donor_loss	0.9900
19:44947309:CAG:C	donor_loss	0.9900
19:44947310:AG:A	donor_loss	0.9900
19:44947311:GG:G	donor_loss	0.9900
19:44947312:G:GA	donor_loss	0.9900
19:44947313:T:G	donor_loss	0.9900
19:44948848:A:G	donor_gain	0.9900
19:44948922:G:GT	donor_gain	0.9900
19:44946072:TCTG:T	donor_gain	0.9800
19:44947308:GCAG:G	donor_gain	0.9800
19:44948700:GA:G	acceptor_gain	0.9800
19:44946073:CTG:C	donor_gain	0.9700
19:44947244:C:G	acceptor_gain	0.9700
19:44948697:GCA:G	acceptor_loss	0.9700
19:44948697:GCAG:G	acceptor_loss	0.9700
19:44948698:CA:C	acceptor_loss	0.9700
19:44948699:A:C	acceptor_loss	0.9700
19:44948700:G:GT	acceptor_loss	0.9700
19:44947314:GA:G	donor_loss	0.9600
19:44948531:TTGG:T	donor_loss	0.9600
19:44948534:GT:G	donor_loss	0.9600
19:44948535:TGAGT:T	donor_loss	0.9600
19:44948536:GAGTG:G	donor_loss	0.9600

AlphaMissense

648 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:44949206:T:C	I88T	0.989
19:44949175:A:C	S78R	0.984
19:44949177:C:A	S78R	0.984
19:44949177:C:G	S78R	0.984
19:44949221:T:A	V93D	0.974
19:44948796:G:C	A51P	0.970
19:44948809:C:A	A55D	0.970
19:44949206:T:G	I88S	0.968
19:44948808:G:C	A55P	0.966
19:44949196:T:G	Y85D	0.966
19:44949196:T:C	Y85H	0.963
19:44949184:G:C	A81P	0.962
19:44949196:T:A	Y85N	0.950
19:44949185:C:A	A81D	0.947
19:44949215:A:T	D91V	0.947
19:44949206:T:A	I88N	0.945
19:44949166:T:G	Y75D	0.944
19:44948797:C:A	A51E	0.938
19:44949209:T:C	F89S	0.927
19:44948857:T:A	L71H	0.926
19:44949188:T:A	M82K	0.922
19:44948789:G:C	W48C	0.915
19:44948789:G:T	W48C	0.915
19:44949214:G:C	D91H	0.914
19:44949188:T:G	M82R	0.911
19:44949181:G:C	A80P	0.904
19:44948818:T:C	L58P	0.903
19:44949218:A:C	Q92P	0.901
19:44948857:T:C	L71P	0.899
19:44948848:A:T	D68V	0.896

dbSNP variants (sampled 300 via entrez): RS1001285509 (19:44949243 G>A), RS1001483991 (19:44947688 C>A,T), RS1002018645 (19:44945002 G>A), RS1002708604 (19:44948279 G>C,T), RS1002709655 (19:44944356 A>G), RS1002947991 (19:44948104 C>T), RS1003723602 (19:44949488 C>G), RS1003832554 (19:44944429 A>G), RS1003837333 (19:44944914 G>A), RS1003986016 (19:44949331 CAGT>C), RS1004079418 (19:44944635 T>A,C), RS1004829738 (19:44945400 C>A,T), RS1004840895 (19:44946168 A>G), RS1006430121 (19:44944642 G>A,C), RS1007093998 (19:44948340 G>A)

Disease associations

OMIM: gene MIM:608083 | disease phenotypes: MIM:207750

GenCC curated gene-disease

Disease	Classification	Inheritance
familial apolipoprotein C-II deficiency	Definitive	Autosomal recessive

Mondo (1): familial apolipoprotein C-II deficiency (MONDO:0008810)

Orphanet (2): Familial apolipoprotein C-II deficiency (Orphanet:309020), Familial chylomicronemia syndrome (Orphanet:444490)

HPO phenotypes

10 total (10 of 10 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000660	Lipemia retinalis
HP:0001013	Eruptive xanthomas
HP:0001733	Pancreatitis
HP:0001744	Splenomegaly
HP:0002155	Hypertriglyceridemia
HP:0002240	Hepatomegaly
HP:0003124	Hypercholesterolemia
HP:0012238	Increased circulating chylomicron concentration
HP:0033983	Decreased circulating apolipoprotein C-II concentration

GWAS associations

48 associations (top):

Study	Trait	p-value
GCST000134_3	LDL cholesterol	1.000000e-60
GCST000234_2	LDL cholesterol	2.000000e-07
GCST000287_9	LDL cholesterol	4.000000e-27
GCST000337_15	Quantitative traits	5.000000e-06
GCST000337_19	Quantitative traits	3.000000e-07
GCST000337_29	Quantitative traits	2.000000e-06
GCST000755_36	HDL cholesterol	4.000000e-21
GCST000758_6	Triglycerides	1.000000e-30
GCST000759_24	LDL cholesterol	9.000000e-147
GCST000760_49	Cholesterol, total	5.000000e-111
GCST000807_5	LDL cholesterol	2.000000e-40
GCST001392_14	Lipid metabolism phenotypes	3.000000e-58
GCST002690_17	Very long-chain saturated fatty acid levels (fatty acid 20:0)	4.000000e-06
GCST004231_1	Total cholesterol levels	4.000000e-22
GCST004232_11	HDL cholesterol levels	6.000000e-34
GCST004232_31	HDL cholesterol levels	9.000000e-17
GCST004233_2	LDL cholesterol levels	2.000000e-286
GCST004233_4	LDL cholesterol levels	1.000000e-129
GCST004234_8	HDL cholesterol levels	5.000000e-12
GCST004235_17	Total cholesterol levels	1.000000e-51
GCST004235_6	Total cholesterol levels	8.000000e-315
GCST004236_1	LDL cholesterol levels	4.000000e-59
GCST004237_11	Triglyceride levels	2.000000e-10
GCST004541_1	Low density lipoprotein cholesterol levels	3.000000e-19
GCST004548_1	Total cholesterol levels	1.000000e-08
GCST006990_2	Cerebrospinal AB1-42 levels in Alzheimer’s disease dementia	3.000000e-07
GCST006993_15	Hippocampal volume in Alzheimer’s disease dementia	8.000000e-07
GCST006996_4	Cerebrospinal AB1-42 levels in mild cognitive impairment	6.000000e-27
GCST006997_3	Cerebrospinal fluid t-tau levels in mild cognitive impairment	1.000000e-13
GCST006998_7	Cerebrospinal fluid p-tau levels in mild cognitive impairment	2.000000e-11

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004574	total cholesterol measurement
EFO:0004458	C-reactive protein measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004529	lipid measurement
EFO:0006796	very long-chain saturated fatty acid measurement
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0005035	hippocampal volume
EFO:0004760	t-tau measurement
EFO:0004763	p-tau measurement
EFO:0004874	memory performance

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression, affects cotreatment, affects expression	2
bisphenol A	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
K 7174	decreases expression	1
obeticholic acid	increases expression	1
Pioglitazone	affects cotreatment, decreases expression	1
Amphotericin B	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects cotreatment, decreases expression	1
Cholic Acids	affects cotreatment, affects expression	1
Copper	affects binding	1
Succimer	affects cotreatment, decreases expression	1
Ephedrine	affects cotreatment, decreases expression	1
Nickel	affects binding	1
Phthalic Acids	decreases expression	1
Quercetin	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Valproic Acid	decreases expression, increases expression	1
1-Naphthylisothiocyanate	affects cotreatment, affects expression	1
Cadmium Chloride	increases abundance, decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Magnetite Nanoparticles	decreases expression, affects cotreatment	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.