APOC1

Summary

APOC1 (apolipoprotein C1, HGNC:607) is a protein-coding gene on chromosome 19q13.32, encoding Apolipoprotein C-I (P02654). Inhibitor of lipoprotein binding to the low density lipoprotein (LDL) receptor, LDL receptor-related protein, and very low density lipoprotein (VLDL) receptor.

This gene encodes a member of the apolipoprotein C1 family. This gene is expressed primarily in the liver, and it is activated when monocytes differentiate into macrophages. The encoded protein plays a central role in high density lipoprotein (HDL) and very low density lipoprotein (VLDL) metabolism. This protein has also been shown to inhibit cholesteryl ester transfer protein in plasma. A pseudogene of this gene is located 4 kb downstream in the same orientation, on the same chromosome. This gene is mapped to chromosome 19, where it resides within a apolipoprotein gene cluster. Alternative splicing and the use of alternative promoters results in multiple transcript variants.

Source: NCBI Gene 341 — RefSeq curated summary.

At a glance

• GWAS associations: 242
• Clinical variants (ClinVar): 24 total — 1 pathogenic
• MANE Select transcript: NM_001645

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:607
Approved symbol	APOC1
Name	apolipoprotein C1
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	Apo-CI, ApoC-I, apo-CIB, apoC-IB, APOC1B
Ensembl gene	ENSG00000130208
Ensembl biotype	protein_coding
OMIM	107710
Entrez	341

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 13 protein_coding, 2 nonsense_mediated_decay

ENST00000586638, ENST00000588750, ENST00000588802, ENST00000589078, ENST00000589781, ENST00000590334, ENST00000592176, ENST00000592535, ENST00000592885, ENST00000876409, ENST00000876410, ENST00000876411, ENST00000876412, ENST00000876413, ENST00000928314

RefSeq mRNA: 4 — MANE Select: NM_001645 NM_001321065, NM_001321066, NM_001379687, NM_001645

CCDS: CCDS12648, CCDS92639

Canonical transcript exons

ENST00000592535 — 4 exons

Exon	Start	End
ENSE00000893956	44914872	44914949
ENSE00002961329	44914608	44914733
ENSE00003462718	44916190	44916325
ENSE00003499864	44919173	44919346

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 99.94.

FANTOM5 (CAGE): breadth broad, TPM avg 4.9859 / max 289.9119, expressed in 459 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176341	2.3029	340
176346	0.8134	129
176345	0.7960	111
176342	0.5874	171
176344	0.3946	184
176343	0.0916	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.94	gold quality
liver	UBERON:0002107	99.92	gold quality
left adrenal gland cortex	UBERON:0035825	99.84	gold quality
adrenal cortex	UBERON:0001235	99.83	gold quality
left adrenal gland	UBERON:0001234	99.81	gold quality
right adrenal gland cortex	UBERON:0035827	99.80	gold quality
right adrenal gland	UBERON:0001233	99.78	gold quality
adrenal gland	UBERON:0002369	99.66	gold quality
adrenal tissue	UBERON:0018303	99.25	gold quality
nucleus accumbens	UBERON:0001882	99.18	gold quality
putamen	UBERON:0001874	98.98	gold quality
caudate nucleus	UBERON:0001873	98.92	gold quality
right lung	UBERON:0002167	98.91	gold quality
spleen	UBERON:0002106	98.23	gold quality
substantia nigra	UBERON:0002038	97.98	gold quality
hypothalamus	UBERON:0001898	97.88	gold quality
lymph node	UBERON:0000029	97.79	gold quality
upper lobe of left lung	UBERON:0008952	97.54	gold quality
upper lobe of lung	UBERON:0008948	97.42	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.40	gold quality
midbrain	UBERON:0001891	97.30	gold quality
amygdala	UBERON:0001876	97.29	gold quality
medial globus pallidus	UBERON:0002477	97.07	gold quality
globus pallidus	UBERON:0001875	96.82	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.82	gold quality
lateral globus pallidus	UBERON:0002476	96.58	gold quality
colonic epithelium	UBERON:0000397	96.50	gold quality
lower lobe of lung	UBERON:0008949	96.36	gold quality
spinal cord	UBERON:0002240	95.98	gold quality
lung	UBERON:0002048	95.33	gold quality

Single-cell (SCXA)

Detected in 32 experiment(s), a significant marker in 31.

Experiment	Marker?	Max mean expression
E-MTAB-10553	yes	23874.21
E-HCAD-9	yes	20940.66
E-MTAB-6308	yes	14066.30
E-MTAB-6653	yes	11240.15
E-GEOD-130148	yes	10868.49
E-MTAB-9435	yes	10351.69
E-HCAD-15	yes	9083.94
E-MTAB-6701	yes	7922.56
E-CURD-126	yes	7841.99
E-HCAD-1	yes	7595.04
E-MTAB-10287	yes	7068.17
E-CURD-98	yes	6522.98
E-CURD-122	yes	5587.39
E-MTAB-8060	yes	2935.27
E-MTAB-8271	yes	2371.21

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PLCG2, TREM2

miRNA regulators (miRDB)

6 targeting APOC1, 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-10401-5P	99.99	65.79	948
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-3137	97.26	66.78	761
HSA-MIR-6762-5P	96.55	64.62	972
HSA-MIR-6845-5P	96.55	64.65	969

Literature-anchored findings (GeneRIF, showing 40)

• APOC1 might be an additional susceptibility gene for late onset Alzheimer disease. (PMID:11825674)
• regulated expression of gene cluster in macrophages (PMID:12032151)
• Thermal unfolding of discoidal complexes of apolipoprotein (apo) C-1 with dimyristoyl phosphatidylcholine (DMPC) reveals a novel mechanism of lipoprotein stabilization that is based on kinetics rather than thermodynamics. (PMID:12044170)
• Effects of mutations in apolipoprotein C-1 on the reconstitution and kinetic stability of discoidal lipoproteins. (PMID:12705839)
• The effect of APOC1 genes on brain MRI measures were studied in subjects with age-associated memory impairment. The effects of APOC1 on hippocampal volumes appeared to be more robust than those of the APOE polymorphism. (PMID:12736801)
• The endogenous retroviral promoters (LTRs) of the human endothelin B receptor (EDNRB) and apolipoprotein C1 (APOC1) genes have high sequence identity but differ in activity and tissue specificity. (PMID:12805445)
• overexpression of APOC1 prevents rosiglitazone-induced peripheral fatty acid uptake leading to severe hepatic steatosis (PMID:14523051)
• overexpression of apoCI does not represent a suitable method for decreasing total CE transfer activity in CETP/apoCI transgenic mice, owing to an hyperlipidaemia-mediated effect on CETP gene expression (PMID:15339254)
• apoC-I is a potent inhibitor of LPL-mediated triglyceride lipolysis (PMID:15576844)
• role of apolipoprotein C1 in the infection process of hepatitis C virus (PMID:15767578)
• Results suggested that both apoE and apoCI on chromosome 19 were the susceptibility loci for coronary artery disease, their linkage disequilibrium should be responsible for the development of coronary artery disease . (PMID:15793777)
• Increased amounts of apolipoprotein C-I enriched HDL may have physiological significance and identify a novel group of low-birth-weight infants apparently distinct from traditionally classified small-for-gestational-age infants. (PMID:15840864)
• The molecular mechanism of the apoCI-mediated blockade of CETP activity is reported. (PMID:16159884)
• ApoCI polymorphism is related to coronary disease in the Chinese Han population, with smoking and alcohol drinking increasing the genetic predisposition to disease. (PMID:16459141)
• irrespective of receptor-mediated remnant clearance by the liver, liver-specific expression of recombinant human apoCI causes hypertriglyceridemia in the absence of the VLDLr and apoCIII in mice (PMID:16478678)
• APOC1 HpaI polymorphism is associated with gallstone disease and shows gender-specific differences. (PMID:16631424)
• Through avid binding to LPS, apoCI improved the presentation of LPS to macrophages in vitro and in mice, thereby stimulating the inflammatory response to LPS, reducing the number of circulating bacteria, and protecting mice against fatal sepsis. (PMID:16935938)
• Five gender-matched sibling pairs, persons with Mexican ancestry, showed a 1.34-fold higher body mass index for those with S45 ApoC1 (P=0.022). ApoC1 may contribute to the elevated rates of diabetes in relevant ethnic groups. (PMID:17310220)
• positive cooperativity in binding of alpha-helices to phospholipid surface, which may result from direct and/or lipid-mediated protein-protein interactions, may be important for lipoprotein metabolism and for protein-membrane binding. (PMID:17341095)
• ApoC-I losses during hemodialysis might be beneficial by improving the ability of very low-density lipoprotein to be a substrate for lipoprotein lipase thus improving plasma triglyceride metabolism. (PMID:17667986)
• Study demonstrates that apoC-I, an exchangeable apolipoprotein that predominantly resides in HDL, specifically enhances HCV infectivity and increases the fusion rates between viral and target membranes via a direct interaction with the HCV surface. (PMID:17761674)
• The expression of apo C1 and apo E are closely associated with the susceptibility to the pathogenesis of atherosclerosis (PMID:17936795)
• Specific expression of ApoC-1 and its role in preventing spontaneous apoptosis in pancreatic cancer cells suggest that ApoC-1 contributes to the aggressiveness of pancreatic cancer. (PMID:18037960)
• findings in human APOC1(+/+) transgenic mice underscore the role of skin barrier integrity in the pathogenesis of atopic dermatitis (PMID:18049452)
• human apoC-I expression impairs cognitive functions in mice independent of apoE expression, which supports the potential of a modulatory role for apoC-I during the development of Alzheimer’s disease (PMID:18160739)
• ApoC1 associates intracellularly via its C-terminal region with surface components of virions during viral morphogenesis and may play a major role in the replication cycle of HCV (PMID:18667498)
• High concentrations of ApoCI are associated with increased triglycerides and decreased visceral fat mass in men with metabolic syndrome X. (PMID:18835943)
• Data show that the C-terminal alpha-helix of human apoC-I contains major lipid-binding determinants which play a role in stabilizing the structure of apoC-I, mediating phospholipid interactions, and promoting discoidal particle morphology. (PMID:18984910)
• APOC1 and its protein isoform are potential bortezomib response markers in multiple myeloma patients. (PMID:19062221)
• Data show that in African Americans, but not in Caucasians, apoC-I (but not apoE) genotypes were associated with variation in lipoprotein phenotypes, and in particular, the apoC-I H2-allele was associated with an anti-atherogenic pattern. (PMID:19252179)
• ApoC-I may have an important role in glucose and lipid metabolism and may be useful for early demonstration of metabolic abnormality in women with polycystic ovary syndrome. (PMID:19368908)
• Cholesteryl ester transfer protein is the sole major determinant of cholesteryl ester transfer in normolipidemic rabbit plasma as a result of the inability of rabbit apoCI to change HDL electronegativity. (PMID:19417222)
• Apolipoprotein C-I reduces cholesteryl esters selective uptake from LDL and HDL by binding to HepG2 cells and lipoproteins (PMID:19761869)
• Results identified haptoglobin alpha-1, apolipoprotein C-I and apolipoprotein C-III as candidate biomarkers in PTC. (PMID:19785722)
• Single nucleotide polymorphism in apolipoprotein C-I gene was associated with renal cell carcinoma. (PMID:19808960)
• From genetic association studies in Canadian Oji-Cree subjects, APOC1 T45S polymorphism may be linked to obesity, adipocyte regulation, body fat, waist circumference, hyperglycemia, and plasma leptin and apolipoprotein C-I levels. (PMID:19812053)
• ApoE e4 and APOC1 A alleles have a better association with Alzheimer disease than ApoE e4 alone. (PMID:20145290)
• 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)
• data show that apoCI genotype is associated with serum levels of triglycerides and CRP, confirming the role of apoCI in lipid metabolism and suggesting that it also influences inflammation (PMID:20580041)
• New isoforms of apoC-I, were detected in the cohort of individuals with coronary artery disease using mass spectrometry while the expected apoC-I isoforms were absent. (PMID:21187063)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	apoc1	ENSDARG00000092170
mus_musculus	Apoc1	ENSMUSG00000040564
rattus_norvegicus	Apoc1	ENSRNOG00000018426

Protein

Protein identifiers

Apolipoprotein C-I — P02654 (reviewed: P02654)

Alternative names: Apolipoprotein C1

All UniProt accessions (8): P02654, K7EJI9, K7EKP1, K7ELM9, K7ELU7, K7EPF9, K7EPR9, K7ERI9

UniProt curated annotations — full annotation on UniProt →

Function. Inhibitor of lipoprotein binding to the low density lipoprotein (LDL) receptor, LDL receptor-related protein, and very low density lipoprotein (VLDL) receptor. Associates with high density lipoproteins (HDL) and the triacylglycerol-rich lipoproteins in the plasma and makes up about 10% of the protein of the VLDL and 2% of that of HDL. Appears to interfere directly with fatty acid uptake and is also the major plasma inhibitor of cholesteryl ester transfer protein (CETP). Binds free fatty acids and reduces their intracellular esterification. Modulates the interaction of APOE with beta-migrating VLDL and inhibits binding of beta-VLDL to the LDL receptor-related protein.

Subcellular location. Secreted.

Tissue specificity. Synthesized mainly in liver and to a minor degree in intestine. Also found in the lung and spleen.

Miscellaneous. Apolipoprotein C-I is present in acidic (APOC1A) and basic (APOC1B) forms in P.paniscus, P.abelii and P.troglodytes and perhaps also in baboons and macaques. The two genes for ApoC-I arose through a duplication process that occurred after the divergence of New World monkeys from the human lineage. In human, the acidic form has become a pseudogene sometime between the divergence of bonobos and chimpanzees from the human lineage and the appearance of the Denisovans. Pseudogenization resulted when the codon for the penultimate amino acid in the signal sequence was changed to a stop codon.

Similarity. Belongs to the apolipoprotein C1 family.

RefSeq proteins (4): NP_001307994, NP_001307995, NP_001366616, NP_001636* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006781	ApoC-I	Family
IPR043081	ApoC-1_sf	Homologous_superfamily

Pfam: PF04691

UniProt features (7 total): chain 2, sequence variant 2, signal peptide 1, helix 1, strand 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
6DVU	X-RAY DIFFRACTION	1.8
6DXR	X-RAY DIFFRACTION	2
6NF3	X-RAY DIFFRACTION	2.33
6DZ6	X-RAY DIFFRACTION	3
1ALE	SOLUTION NMR
1ALF	SOLUTION NMR
1IOJ	SOLUTION NMR
1OPP	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02654-F1	71.63	0.00

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: 328 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, MODULE_172, GOBP_ACYLGLYCEROL_HOMEOSTASIS, MODULE_52, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, MCLACHLAN_DENTAL_CARIES_UP, GOBP_REGULATION_OF_TRIGLYCERIDE_METABOLIC_PROCESS, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GNF2_GSTM1, LI_WILMS_TUMOR, STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN, GNF2_HPN, ROVERSI_GLIOMA_COPY_NUMBER_UP

GO Biological Process (22): lipid metabolic process (GO:0006629), triglyceride metabolic process (GO:0006641), cholesterol metabolic process (GO:0008203), negative regulation of triglyceride catabolic process (GO:0010897), negative regulation of phosphatidylcholine catabolic process (GO:0010900), negative regulation of very-low-density lipoprotein particle clearance (GO:0010916), regulation of cholesterol transport (GO:0032374), negative regulation of cholesterol transport (GO:0032375), cholesterol efflux (GO:0033344), phospholipid efflux (GO:0033700), plasma lipoprotein particle remodeling (GO:0034369), high-density lipoprotein particle remodeling (GO:0034375), very-low-density lipoprotein particle assembly (GO:0034379), chylomicron remnant clearance (GO:0034382), very-low-density lipoprotein particle clearance (GO:0034447), lipoprotein metabolic process (GO:0042157), negative regulation of fatty acid biosynthetic process (GO:0045717), negative regulation of lipid metabolic process (GO:0045833), negative regulation of receptor-mediated endocytosis (GO:0048261), negative regulation of lipid catabolic process (GO:0050995), triglyceride homeostasis (GO:0070328), lipid transport (GO:0006869)

GO Molecular Function (6): phospholipase inhibitor activity (GO:0004859), fatty acid binding (GO:0005504), phosphatidylcholine binding (GO:0031210), lipase inhibitor activity (GO:0055102), phosphatidylcholine-sterol O-acyltransferase activator activity (GO:0060228), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), endoplasmic reticulum (GO:0005783), very-low-density lipoprotein particle (GO:0034361), high-density lipoprotein particle (GO:0034364), chylomicron (GO:0042627)

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
cholesterol transport	3
negative regulation of lipid catabolic process	2
plasma lipoprotein particle	2
primary metabolic process	1
acylglycerol metabolic process	1
sterol metabolic process	1
secondary alcohol metabolic process	1
regulation of triglyceride catabolic process	1
triglyceride catabolic process	1
negative regulation of triglyceride metabolic process	1
regulation of phosphatidylcholine catabolic process	1
phosphatidylcholine catabolic process	1
negative regulation of phospholipid metabolic 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
regulation of sterol transport	1
negative regulation of sterol transport	1
regulation of cholesterol transport	1
phospholipid transport	1
protein-lipid complex remodeling	1
plasma lipoprotein particle organization	1
regulation of plasma lipoprotein particle levels	1
plasma lipoprotein particle remodeling	1
plasma lipoprotein particle assembly	1
triglyceride-rich lipoprotein particle clearance	1
plasma lipoprotein particle clearance	1
protein metabolic process	1
fatty acid biosynthetic process	1
regulation of fatty acid biosynthetic process	1
negative regulation of fatty acid metabolic process	1
negative regulation of lipid biosynthetic process	1
lipid metabolic 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
negative regulation of catabolic process	1
lipid catabolic process	1

Protein interactions and networks

STRING

1304 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOC1	APOC2	P02655	999
APOC1	APOE	P02649	996
APOC1	APOC3	P02656	992
APOC1	APOA1	P02647	992
APOC1	APOB	P04114	986
APOC1	APOA2	P02652	960
APOC1	APOC4	P55056	940
APOC1	CLU	P10909	896
APOC1	APOA4	P06727	891
APOC1	CETP	P11597	855
APOC1	APOD	P05090	843
APOC1	PEPD	P12955	779
APOC1	APOA5	Q6Q788	778
APOC1	APOM	O95445	776
APOC1	TOMM40	O96008	755

IntAct

92 interactions, top by confidence:

A	B	Type	Score
MICOS13	APOC1	psi-mi:“MI:0915”(physical association)	0.560
GSDMA	APOC1	psi-mi:“MI:0915”(physical association)	0.560
APOC1	TEX44	psi-mi:“MI:0915”(physical association)	0.560
APOC1	SYT16	psi-mi:“MI:0915”(physical association)	0.560
APOC1	ACSF2	psi-mi:“MI:0915”(physical association)	0.560
APOC1	SPG21	psi-mi:“MI:0915”(physical association)	0.560
APOC1	LETMD1	psi-mi:“MI:0915”(physical association)	0.560
APOC1	TPRG1	psi-mi:“MI:0915”(physical association)	0.560
APOC1	RADIL	psi-mi:“MI:0915”(physical association)	0.560
APOC1	MAIP1	psi-mi:“MI:0915”(physical association)	0.560
APOC1	FOXD4L3	psi-mi:“MI:0915”(physical association)	0.560
APOC1	MICOS13	psi-mi:“MI:0915”(physical association)	0.560
APOC1	CIDEB	psi-mi:“MI:0915”(physical association)	0.560
MPC2	APOC1	psi-mi:“MI:0915”(physical association)	0.560
APOC1	NFU1	psi-mi:“MI:0915”(physical association)	0.560
APOC1	BCL2L2	psi-mi:“MI:0915”(physical association)	0.560
	APOC1	psi-mi:“MI:0915”(physical association)	0.560
APOC1	RTP5	psi-mi:“MI:0915”(physical association)	0.560
APOC1	GSDMA	psi-mi:“MI:0915”(physical association)	0.560
APOC1	MTERF3	psi-mi:“MI:0915”(physical association)	0.560
APOC1	MP68	psi-mi:“MI:0915”(physical association)	0.560
APOC1	ACACA	psi-mi:“MI:0915”(physical association)	0.560
APOC1	DHRSX	psi-mi:“MI:0915”(physical association)	0.560
APOC1	MTCH2	psi-mi:“MI:0915”(physical association)	0.560
APOC1	RSAD2	psi-mi:“MI:0915”(physical association)	0.560
APOC1	H4C7	psi-mi:“MI:0915”(physical association)	0.560
HIGD1C	APOC1	psi-mi:“MI:0915”(physical association)	0.560
SIRPB1	APOC1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (41): APOC1 (Synthetic Lethality), APOC1 (Two-hybrid), APOC1 (Two-hybrid), APOC1 (Two-hybrid), APOC1 (Two-hybrid), APOC1 (Two-hybrid), APOC1 (Two-hybrid), RSAD2 (Two-hybrid), CIDEB (Two-hybrid), SYT16 (Two-hybrid), MPC2 (Two-hybrid), C14orf2 (Two-hybrid), MTERF3 (Two-hybrid), RADIL (Two-hybrid), C2orf47 (Two-hybrid)

ESM2 similar proteins: A0A096P2H7, A0A1A6FVC0, A0A1U7QUM6, H9FNA4, P02654, P0CE37, P0CE38, P0CE39, P0CF78, P0DKU8, P0DKV2, P0DKV3, P0DKV4, P0DKV5, P0DM83, P0DMP0, P0DMT8, P0DOA2, P0DOA4, P0DPG1, P0DPG8, P0DPG9, P0DPH0, P0DPH2, P0DPH3, P0DPH4, P0DPH6, P0DTG2, P0DTG3, P0DTG4, P0DTG5, P0DTG6, P0DTG7, P0DTG8, P0DTQ7, P0DTQ8, P0DTR7, P0DTT3, P0DTT4, P0DTT5

Diamond homologs: A0A096P2H7, A0A1A6FVC0, A0A1U7QUM6, G8F204, H9FNA4, P02654, P0CE37, P0CE38, P0CE39, P0CE40, P0CF78, P0DKU7, P0DKU8, P0DKV2, P0DKV3, P0DKV4, P0DKV5, P0DM82, P0DM83, P0DM84, P0DMA7, P0DMP0, P0DMT8, P0DOA2, P0DOA4, P0DP51, P0DPG0, P0DPG1, P0DPG8, P0DPG9, P0DPH0, P0DPH1, P0DPH2, P0DPH3, P0DPH4, P0DPH5, P0DPH6, P0DTG2, P0DTG3, P0DTG4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	10
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
253540	GRCh37/hg19 19q13.2-13.32(chr19:43013365-47241534)x1	Pathogenic

SpliceAI

621 predictions. Top by Δscore:

Variant	Effect	Δscore
19:44916302:GA:G	donor_gain	1.0000
19:44916321:A:G	donor_gain	1.0000
19:44916326:G:GG	donor_gain	1.0000
19:44914670:A:AG	acceptor_gain	0.9900
19:44914671:G:GG	acceptor_gain	0.9900
19:44914792:G:GT	donor_gain	0.9900
19:44914871:G:C	acceptor_gain	0.9900
19:44914871:GA:G	acceptor_gain	0.9900
19:44916304:G:GG	donor_gain	0.9900
19:44916323:GCG:G	donor_gain	0.9900
19:44916326:GTT:G	donor_loss	0.9900
19:44919171:AG:A	acceptor_gain	0.9900
19:44919172:GG:G	acceptor_gain	0.9900
19:44919172:GGGA:G	acceptor_gain	0.9900
19:44914478:G:GT	donor_gain	0.9800
19:44914487:GAGGT:G	donor_loss	0.9800
19:44914488:AGGT:A	donor_loss	0.9800
19:44914489:GGT:G	donor_loss	0.9800
19:44914490:GTGA:G	donor_loss	0.9800
19:44914491:T:G	donor_loss	0.9800
19:44914866:CTCCA:C	acceptor_loss	0.9800
19:44914867:TCCA:T	acceptor_loss	0.9800
19:44914868:CCAGA:C	acceptor_loss	0.9800
19:44914869:CA:C	acceptor_loss	0.9800
19:44914870:A:AG	acceptor_gain	0.9800
19:44914871:G:GA	acceptor_loss	0.9800
19:44914871:G:GG	acceptor_gain	0.9800
19:44914871:GAGT:G	acceptor_gain	0.9800
19:44914946:GAAGG:G	donor_loss	0.9800
19:44914947:A:T	donor_gain	0.9800

AlphaMissense

485 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:44914917:T:A	V9D	0.851
19:44914926:T:A	V12E	0.795
19:44914929:T:A	V13D	0.793
19:44914923:T:A	V11E	0.788
19:44914911:T:A	L7H	0.785
19:44914932:T:G	L14R	0.756
19:44914914:C:G	P8R	0.755
19:44914920:T:G	L10R	0.751
19:44916283:T:C	L51P	0.746
19:44914911:T:G	L7R	0.745
19:44914920:T:A	L10Q	0.690
19:44914949:G:C	G20R	0.690
19:44914932:T:A	L14Q	0.685
19:44916298:A:T	K56I	0.685
19:44916274:C:A	A48D	0.684
19:44916277:G:C	R49P	0.679
19:44916241:T:C	L37P	0.677
19:44916273:G:C	A48P	0.660
19:44916295:T:C	I55T	0.651
19:44916271:A:T	K47M	0.643
19:44914941:T:A	V17D	0.641
19:44914949:G:T	G20C	0.634
19:44919179:G:C	W67C	0.632
19:44919179:G:T	W67C	0.632
19:44919206:G:C	K76N	0.631
19:44919206:G:T	K76N	0.631
19:44916253:G:T	G41V	0.624
19:44914914:C:A	P8Q	0.623
19:44916241:T:G	L37R	0.619
19:44916295:T:G	I55S	0.618

dbSNP variants (sampled 300 via entrez): RS1000036279 (19:44916708 T>C), RS1000660483 (19:44916406 T>A,C), RS1000756644 (19:44916148 A>C), RS1000797915 (19:44915286 A>C), RS1000840065 (19:44912557 C>T), RS1001446687 (19:44918059 G>A), RS1002382009 (19:44917483 C>T), RS1003069196 (19:44914669 C>T), RS1003191155 (19:44912399 AT>A,ATT), RS1003347137 (19:44917488 G>A,C), RS1004034343 (19:44915107 G>A,T), RS1004223192 (19:44917056 C>T), RS1004743721 (19:44917407 C>T), RS1004976353 (19:44916477 A>G), RS1005025704 (19:44916251 T>C)

Disease associations

OMIM: gene MIM:107710 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

242 associations (top):

Study	Trait	p-value
GCST000124_1	Alzheimer’s disease	2.000000e-44
GCST000132_2	LDL cholesterol	3.000000e-43
GCST000134_3	LDL cholesterol	1.000000e-60
GCST000151_2	LDL cholesterol	1.000000e-20
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
GCST000430_5	C-reactive protein	5.000000e-27
GCST000533_27	Lipid metabolism phenotypes	1.000000e-27
GCST000533_72	Lipid metabolism phenotypes	3.000000e-51
GCST000533_73	Lipid metabolism phenotypes	1.000000e-37
GCST000671_4	Lipoprotein-associated phospholipase A2 activity and mass	6.000000e-24
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
GCST000965_17	C-reactive protein levels	9.000000e-139
GCST001131_1	Longevity	2.000000e-16
GCST001231_3	Carotid intima media thickness	4.000000e-06
GCST001231_6	Carotid intima media thickness	2.000000e-08
GCST001273_4	Lipoprotein-associated phospholipase A2 activity and mass	5.000000e-30
GCST001280_7	Alzheimer’s disease (age of onset)	1.000000e-12
GCST001392_14	Lipid metabolism phenotypes	3.000000e-58
GCST001529_1	Alzheimer’s disease	8.000000e-149
GCST001703_3	Apolipoprotein Levels	2.000000e-14
GCST001727_7	Lipoprotein-associated phospholipase A2 activity and mass	1.000000e-56
GCST001868_1	Alzheimer’s disease biomarkers	4.000000e-12

EFO canonical traits (45, 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:0004529	lipid measurement
EFO:0004746	lipoprotein-associated phospholipase A(2) measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004847	age at onset
EFO:0004732	lipoprotein measurement
EFO:0005194	amyloid-beta measurement
EFO:0004874	memory performance
EFO:0006806	paragraph delayed recall measurement
EFO:0006805	word list delayed recall measurement
EFO:0007707	cerebral amyloid deposition measurement
EFO:0007653	clinical ideal cardiovascular health
EFO:0007800	body fat percentage
EFO:0007804	LDL cholesterol change measurement
EFO:0007930	LDL cholesterol:HDL cholesterol ratio
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0004763	p-tau measurement
EFO:0004760	t-tau measurement
EFO:0007708	t-tau:beta-amyloid 1-42 ratio measurement
EFO:0007985	platelet crit
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0007998	cognitive impairment measurement
EFO:0007709	p-tau:beta-amyloid 1-42 ratio measurement
EFO:0007796	parental longevity
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7412	APOC1, APOE	2B	12.50	7	Antivirals for treatment of HIV infections;combinations;ritonavir;fluvastatin;atorvastatin;pravastatin;fenofibrate;warfarin
rs429358	APOC1, APOE, TOMM40	3	3.00	5	acenocoumarol;warfarin;simvastatin;Antivirals for treatment of HIV infections;combinations;ritonavir;warfarin;HMG-CoA reductase inhibitors
rs445925	APOC1, APOE	3	1.25	1	HMG-CoA reductase inhibitors
rs4420638	APOC1		0.00	0

CTD chemical–gene interactions

51 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	5
Benzo(a)pyrene	increases expression, increases methylation, decreases expression, decreases methylation	4
Tetrachlorodibenzodioxin	increases expression	4
bisphenol A	affects expression, increases expression	2
Cisplatin	increases expression, affects expression, affects cotreatment	2
Aflatoxin B1	affects expression, decreases expression	2
bisphenol F	increases expression	1
methylmercuric chloride	decreases expression	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
9,10-dihydro-9,10-dihydroxybenzo(a)pyrene	increases expression	1
tanshinone	increases expression	1
perfluorooctanoic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
belinostat	decreases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
jinfukang	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Resveratrol	increases expression	1
Pioglitazone	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1
Allergens	decreases expression	1
Caffeine	affects cotreatment, increases expression	1
Capsaicin	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_HD68	HCT 116 APOC1(-/-)	Cancer cell line	Male

Clinical trials (associated diseases)

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