APOC4

Summary

APOC4 (apolipoprotein C4, HGNC:611) is a protein-coding gene on chromosome 19q13.32, encoding Apolipoprotein C-IV (P55056). May participate in lipoprotein metabolism.

This gene encodes a lipid-binding protein belonging to the apolipoprotein gene family. The protein is thought to play a role in lipid metabolism. Polymorphisms in this gene may influence circulating lipid levels and may be associated with coronary artery disease risk. 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 downstream apolipoprotein C-II (APOC2) gene.

Source: NCBI Gene 346 — RefSeq curated summary.

At a glance

• GWAS associations: 34
• Clinical variants (ClinVar): 26 total
• MANE Select transcript: NM_001646

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:611
Approved symbol	APOC4
Name	apolipoprotein C4
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000267467
Ensembl biotype	protein_coding
OMIM	600745
Entrez	346

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000591600, ENST00000592954, ENST00000896755, ENST00000896756, ENST00000896758, ENST00000896760

RefSeq mRNA: 1 — MANE Select: NM_001646 NM_001646

CCDS: CCDS12649

Canonical transcript exons

ENST00000592954 — 3 exons

Exon	Start	End
ENSE00002829107	44945140	44945496
ENSE00003705681	44944749	44944890
ENSE00003706149	44942237	44942353

Expression profiles

Bgee: expression breadth ubiquitous, 110 present calls, max score 99.22.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3584 / max 148.9042, expressed in 8 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176349	0.4724	9
176350	0.3584	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.22	gold quality
liver	UBERON:0002107	98.88	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.01	gold quality
mucosa of transverse colon	UBERON:0004991	59.38	gold quality
sural nerve	UBERON:0015488	54.69	gold quality
colonic epithelium	UBERON:0000397	49.66	gold quality
left adrenal gland cortex	UBERON:0035825	48.58	gold quality
right adrenal gland	UBERON:0001233	48.05	gold quality
left adrenal gland	UBERON:0001234	47.63	gold quality
right ovary	UBERON:0002118	47.47	gold quality
ventricular zone	UBERON:0003053	45.73	gold quality
right adrenal gland cortex	UBERON:0035827	45.23	gold quality
gall bladder	UBERON:0002110	45.19	gold quality
adrenal gland	UBERON:0002369	45.11	gold quality
skin of abdomen	UBERON:0001416	44.44	gold quality
apex of heart	UBERON:0002098	44.44	silver quality
esophagus mucosa	UBERON:0002469	43.63	gold quality
left testis	UBERON:0004533	43.62	gold quality
zone of skin	UBERON:0000014	42.84	gold quality
prostate gland	UBERON:0002367	42.77	gold quality
testis	UBERON:0000473	42.58	gold quality
right lung	UBERON:0002167	42.21	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	42.14	gold quality
skin of leg	UBERON:0001511	41.98	gold quality
ovary	UBERON:0000992	41.87	gold quality
right testis	UBERON:0004534	41.71	gold quality
left ovary	UBERON:0002119	41.27	gold quality
spleen	UBERON:0002106	40.92	gold quality
transverse colon	UBERON:0001157	40.76	gold quality
granulocyte	CL:0000094	40.08	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.54

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARG

miRNA regulators (miRDB)

8 targeting APOC4, 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-4531	99.99	69.70	3181
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-6798-3P	94.55	68.78	325

Literature-anchored findings (GeneRIF, showing 6)

• regulated expression of gene cluster in macrophages (PMID:12032151)
• ApoC-IV overexpression may perturb lipid metabolism leading to lipid accumulation. HCV core protein may modulate ApoC-IV expression through Ku antigen and PPARgamma/RXRalpha complex. (PMID:18809223)
• 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)
• variants in LPL, OASL and TOMM40/APOE-C1-C2-C4 genes are associated with multiple cardiovascular-related traits (PMID:21943158)
• APOC4 rs1132899 polymorphism was associated with an increased risk of premature coronary artery disease in Chinese subjects. (PMID:26129832)
• Includes the observation of APOC4-APOC2 read-through transcription (PMID:8530039)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Apoc4	ENSMUSG00000074336
rattus_norvegicus	Apoc4	ENSRNOG00000018405

Protein

Protein identifiers

Apolipoprotein C-IV — P55056 (reviewed: P55056)

Alternative names: Apolipoprotein C4

All UniProt accessions (2): P55056, K7EMC3

UniProt curated annotations — full annotation on UniProt →

Function. May participate in lipoprotein metabolism.

Subcellular location. Secreted.

Tissue specificity. Expressed by the liver and secreted in plasma.

Similarity. Belongs to the apolipoprotein C4 family.

RefSeq proteins (1): NP_001637* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028120	APOC4	Family

Pfam: PF15119

UniProt features (8 total): sequence variant 5, signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55056-F1	77.09	0.30

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 63

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-8866423	VLDL assembly
R-HSA-8964046	VLDL clearance
R-HSA-9029569	NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux
R-HSA-162582	Signal Transduction
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-382551	Transport of small molecules
R-HSA-8963898	Plasma lipoprotein assembly
R-HSA-8964043	Plasma lipoprotein clearance
R-HSA-9006931	Signaling by Nuclear Receptors
R-HSA-9024446	NR1H2 and NR1H3-mediated signaling

MSigDB gene sets: 98 (showing top): GOBP_ACYLGLYCEROL_HOMEOSTASIS, GCM_GSPT1, GNF2_GSTM1, MODULE_45, GNF2_HPN, ROVERSI_GLIOMA_COPY_NUMBER_UP, HALMOS_CEBPA_TARGETS_UP, GOBP_LIPID_HOMEOSTASIS, MODULE_66, MODULE_118, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, GNF2_LCAT, GOBP_LIPID_METABOLIC_PROCESS, GNF2_HPX, MODULE_88

GO Biological Process (4): lipid metabolic process (GO:0006629), lipid storage (GO:0019915), triglyceride homeostasis (GO:0070328), lipid transport (GO:0006869)

GO Molecular Function (2): lipid carrier activity (GO:0005319), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), very-low-density lipoprotein particle (GO:0034361), high-density lipoprotein particle (GO:0034364)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Plasma lipoprotein assembly, remodeling, and clearance	2
Plasma lipoprotein assembly	1
Plasma lipoprotein clearance	1
NR1H2 and NR1H3-mediated signaling	1
Transport of small molecules	1
Signal Transduction	1
Signaling by Nuclear Receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary metabolic process	1
nutrient storage	1
acylglycerol homeostasis	1
transport	1
lipid localization	1
molecular carrier activity	1
binding	1
cellular anatomical structure	1
triglyceride-rich plasma lipoprotein particle	1
plasma lipoprotein particle	1

Protein interactions and networks

STRING

644 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOC4	APOC1	P02654	940
APOC4	APOC2	P02655	922
APOC4	APOE	P02649	841
APOC4	APOA2	P02652	744
APOC4	APOA5	Q6Q788	686
APOC4	APOC3	P02656	672
APOC4	PON1	P27169	646
APOC4	APOF	Q13790	602
APOC4	APOA1	P02647	591
APOC4	APOA4	P06727	583
APOC4	APOM	O95445	576
APOC4	C3	P01024	523
APOC4	APOD	P05090	521
APOC4	APOB	P04114	507
APOC4	APOL1	O14791	479

IntAct

72 interactions, top by confidence:

A	B	Type	Score
NFU1	APOC4	psi-mi:“MI:0915”(physical association)	0.560
TMEM14B	APOC4	psi-mi:“MI:0915”(physical association)	0.560
MICOS10	APOC4	psi-mi:“MI:0915”(physical association)	0.560
SYT16	APOC4	psi-mi:“MI:0915”(physical association)	0.560
RSAD2	APOC4	psi-mi:“MI:0915”(physical association)	0.560
MAIP1	APOC4	psi-mi:“MI:0915”(physical association)	0.560
GAD2	APOC4	psi-mi:“MI:0915”(physical association)	0.560
TPRG1	APOC4	psi-mi:“MI:0915”(physical association)	0.560
BCL2L2	APOC4	psi-mi:“MI:0915”(physical association)	0.560
GSDMA	APOC4	psi-mi:“MI:0915”(physical association)	0.560
SNAP47	APOC4	psi-mi:“MI:0915”(physical association)	0.560
APOC4	TPRG1	psi-mi:“MI:0915”(physical association)	0.560
APOC4	BCL2L2	psi-mi:“MI:0915”(physical association)	0.560
APOC4	GSDMA	psi-mi:“MI:0915”(physical association)	0.560
APOC4	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
APOC4	APOL2	psi-mi:“MI:0915”(physical association)	0.560
APOC4	NFU1	psi-mi:“MI:0915”(physical association)	0.560
APOC4	SENP2	psi-mi:“MI:0915”(physical association)	0.560
APOC4	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
APOC4	MICOS10	psi-mi:“MI:0915”(physical association)	0.560
APOC4	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
APOC4	SYT16	psi-mi:“MI:0915”(physical association)	0.560
APOC4	RSAD2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (26): APOC4 (Two-hybrid), APOC4 (Two-hybrid), APOC4 (Two-hybrid), APOC4 (Two-hybrid), APOC4 (Two-hybrid), APOC4 (Two-hybrid), APOC4 (Two-hybrid), APOC4 (Two-hybrid), APOC4 (Two-hybrid), APOC4 (Two-hybrid), APOC4 (Two-hybrid), APOC4 (Two-hybrid), APOC4 (Two-hybrid), APOC4 (Two-hybrid), APOC4 (Two-hybrid)

ESM2 similar proteins: A0A096P2H6, A0A0D9S1R4, A2APA5, A9CBA0, P06740, P06759, P0DKU6, P0DKW1, P0DKW2, P0DKW3, P0DKW4, P0DKY3, P0DML4, P0DML5, P0DML6, P0DMN8, P0DOC4, P0DP53, P0DTG9, P0DTH0, P0DTH1, P0DTH2, P0DTH3, P0DTH4, P0DUP5, P0DUP6, P22749, P33622, P35225, P55056, P55057, P55797, Q0VCT2, Q13790, Q3SYR5, Q3ZRW9, Q5HZE8, Q5JTB6, Q5JX69, Q5JX71

Diamond homologs: A0A096P2H6, A0A0D9S1R4, A0A2Y9GDB5, P0DKU6, P0DKW1, P0DKW2, P0DKW3, P0DKW4, P0DKY3, P0DML4, P0DML5, P0DML6, P0DMN8, P0DOC4, P0DP53, P0DTG9, P0DTH0, P0DTH1, P0DTH2, P0DTH3, P0DTH4, P0DUP5, P0DUP6, P55056, P55057, P55797, Q3SYR5, Q61268

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

321 predictions. Top by Δscore:

Variant	Effect	Δscore
19:44944747:A:AG	acceptor_gain	1.0000
19:44944748:G:GG	acceptor_gain	1.0000
19:44945137:TAG:T	acceptor_loss	1.0000
19:44942350:GGGG:G	donor_gain	0.9900
19:44942351:GGGG:G	donor_gain	0.9900
19:44944748:GC:G	acceptor_gain	0.9900
19:44944748:GCAT:G	acceptor_gain	0.9900
19:44944864:G:GT	donor_gain	0.9900
19:44944877:TGGCA:T	donor_gain	0.9900
19:44944878:G:GA	donor_gain	0.9900
19:44945138:A:AG	acceptor_gain	0.9900
19:44945138:AG:A	acceptor_gain	0.9900
19:44945139:G:GA	acceptor_gain	0.9900
19:44945139:GG:G	acceptor_gain	0.9900
19:44945139:GGA:G	acceptor_gain	0.9900
19:44942351:GGG:G	donor_gain	0.9800
19:44942352:GGG:G	donor_gain	0.9800
19:44944748:GCA:G	acceptor_gain	0.9800
19:44945135:T:TA	acceptor_gain	0.9800
19:44945139:GGAGC:G	acceptor_gain	0.9800
19:44942352:GG:G	donor_gain	0.9700
19:44942353:GG:G	donor_gain	0.9700
19:44942375:G:T	donor_gain	0.9700
19:44944743:A:AG	acceptor_gain	0.9700
19:44944746:TAGC:T	acceptor_loss	0.9700
19:44944747:A:T	acceptor_loss	0.9700
19:44944747:AGCAT:A	acceptor_gain	0.9700
19:44944748:G:C	acceptor_loss	0.9700
19:44944748:GCATG:G	acceptor_gain	0.9700
19:44944751:T:G	acceptor_gain	0.9700

AlphaMissense

832 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:44945162:T:C	F81L	0.934
19:44945164:C:A	F81L	0.934
19:44945164:C:G	F81L	0.934
19:44944813:G:C	W47C	0.820
19:44944813:G:T	W47C	0.820
19:44945235:A:T	K105I	0.810
19:44944879:G:C	W69C	0.802
19:44944879:G:T	W69C	0.802
19:44945236:A:C	K105N	0.788
19:44945236:A:T	K105N	0.788
19:44945174:T:G	Y85D	0.767
19:44945267:T:A	C116S	0.755
19:44945268:G:C	C116S	0.755
19:44945267:T:C	C116R	0.752
19:44945188:C:A	H89Q	0.741
19:44945188:C:G	H89Q	0.741
19:44945186:C:G	H89D	0.734
19:44945282:T:A	C121S	0.732
19:44945283:G:C	C121S	0.732
19:44945163:T:C	F81S	0.730
19:44945163:T:G	F81C	0.729
19:44944877:T:A	W69R	0.712
19:44944877:T:C	W69R	0.712
19:44942320:T:C	C15R	0.689
19:44945282:T:C	C121R	0.684
19:44945174:T:A	Y85N	0.681
19:44945190:T:C	L90P	0.679
19:44942326:T:C	C17R	0.673
19:44945283:G:A	C121Y	0.660
19:44945174:T:C	Y85H	0.652

dbSNP variants (sampled 300 via entrez): RS1000679121 (19:44940346 G>A), RS1001298444 (19:44943164 G>A), RS1001772246 (19:44942988 C>A), RS1001925585 (19:44940301 G>A), RS1002018645 (19:44945002 G>A), RS1002709655 (19:44944356 A>G), RS1003832554 (19:44944429 A>G), RS1003837333 (19:44944914 G>A), RS1004079418 (19:44944635 T>A,C), RS1004667937 (19:44941190 A>C), RS1004829738 (19:44945400 C>A,T), RS1005482598 (19:44943890 C>T), RS1006430121 (19:44944642 G>A,C), RS1006752738 (19:44940287 G>A), RS1006763721 (19:44943361 G>A)

Disease associations

OMIM: gene MIM:600745 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

34 associations (top):

Study	Trait	p-value
GCST000132_2	LDL cholesterol	3.000000e-43
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
GCST000807_5	LDL cholesterol	2.000000e-40
GCST002690_17	Very long-chain saturated fatty acid levels (fatty acid 20:0)	4.000000e-06
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
GCST007001_15	Cerebrospinal AB1-42 levels in normal cognition	9.000000e-11
GCST007007_4	Cerebrospinal fluid t-tau levels	1.000000e-20
GCST007008_6	Cerebrospinal fluid p-tau levels	3.000000e-18
GCST007009_7	Hippocampal volume	2.000000e-19
GCST007010_3	Logical memory (delayed recall)	2.000000e-18
GCST007011_3	Logical memory (immediate recall)	2.000000e-13
GCST007012_6	Cerebrospinal fluid AB1-42 levels	1.000000e-51
GCST007827_13	Alzheimer’s disease or HDL levels (pleiotropy)	7.000000e-22
GCST007827_3	Alzheimer’s disease or HDL levels (pleiotropy)	1.000000e-97
GCST007827_5	Alzheimer’s disease or HDL levels (pleiotropy)	7.000000e-74
GCST007827_6	Alzheimer’s disease or HDL levels (pleiotropy)	7.000000e-54
GCST007827_7	Alzheimer’s disease or HDL levels (pleiotropy)	5.000000e-50
GCST007827_8	Alzheimer’s disease or HDL levels (pleiotropy)	3.000000e-36
GCST009496_15	Alzheimer’s disease (onset between ages 58 and 79)	2.000000e-09
GCST009496_24	Alzheimer’s disease (onset between ages 58 and 79)	1.000000e-11
GCST009738_3	Carotid intima media thickness (maximum)	7.000000e-14

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: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
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004614	apolipoprotein A 1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression	1
bisphenol A	increases expression	1
GW 4064	increases expression, affects cotreatment, decreases expression	1
GW 7647	affects cotreatment, decreases expression	1
6-(4-chlorophenyl)imidazo(2,1-b)(1,3)thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Chenodeoxycholic Acid	decreases expression	1
Chlorpromazine	affects cotreatment, affects expression	1
Cholic Acids	affects expression, affects cotreatment	1
Farnesol	decreases expression	1
Phenobarbital	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Progesterone	decreases expression	1
Sarin	increases expression	1
1-Naphthylisothiocyanate	affects cotreatment, affects expression	1
Cyclosporine	affects cotreatment, affects expression	1
Fenretinide	decreases expression	1
Oleic Acid	affects cotreatment, decreases expression	1
Okadaic Acid	decreases expression	1
Magnetite Nanoparticles	increases expression	1

Clinical trials (associated diseases)

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