APOB

Summary

APOB (apolipoprotein B, HGNC:603) is a protein-coding gene on chromosome 2p24.1, encoding Apolipoprotein B-100 (P04114). Apolipoprotein B is a major protein constituent of chylomicrons (apo B-48), LDL (apo B-100) and VLDL (apo B-100). It is haploinsufficient (ClinGen: sufficient evidence).

This gene product is the main apolipoprotein of chylomicrons and low density lipoproteins (LDL), and is the ligand for the LDL receptor. It occurs in plasma as two main isoforms, apoB-48 and apoB-100: the former is synthesized exclusively in the gut and the latter in the liver. The intestinal and the hepatic forms of apoB are encoded by a single gene from a single, very long mRNA. The two isoforms share a common N-terminal sequence. The shorter apoB-48 protein is produced after RNA editing of the apoB-100 transcript at residue 2180 (CAA->UAA), resulting in the creation of a stop codon, and early translation termination. Mutations in this gene or its regulatory region cause hypobetalipoproteinemia, normotriglyceridemic hypobetalipoproteinemia, and hypercholesterolemia due to ligand-defective apoB, diseases affecting plasma cholesterol and apoB levels.

Source: NCBI Gene 338 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypercholesterolemia, autosomal dominant, type B (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 163 (top 1% of genes corpus-wide)
• Clinical variants (ClinVar): 5,263 total — 166 pathogenic, 75 likely-pathogenic (top 1% of genes corpus-wide)
• GTEx eGene: eQTL in 19 tissues, sQTL in 2 (q < 0.05)
• Phenotypes (HPO): 52
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.54 (moderately constrained)
• MANE Select transcript: NM_000384
• Interaction hub: 4,004 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:603
Approved symbol	APOB
Name	apolipoprotein B
Location	2p24.1
Locus type	gene with protein product
Status	Approved
Aliases	ApoB-100
Ensembl gene	ENSG00000084674
Ensembl biotype	protein_coding
OMIM	107730
Entrez	338

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 4 nonsense_mediated_decay

MANE Select: ENST00000233242

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2

ENST00000233242, ENST00000399256, ENST00000673739, ENST00000673882, ENST00000975037, ENST00000975038, ENST00000975040, ENST00001105507, ENST00001143783

RefSeq mRNA: 1 — MANE Select: NM_000384 NM_000384

CCDS: CCDS1703

Canonical transcript exons

ENST00000233242 — 29 exons

Exon	Start	End
ENSE00000542194	21022831	21023042
ENSE00000542197	21016439	21016649
ENSE00000542198	21015370	21015545
ENSE00000542200	21014448	21014593
ENSE00000542203	21004561	21004675
ENSE00000716597	21004269	21004452
ENSE00000717143	21013160	21013533
ENSE00000717361	21015073	21015260
ENSE00000717995	21018992	21019113
ENSE00000718108	21019723	21019905
ENSE00000718481	21023525	21023692
ENSE00000718984	21027828	21028065
ENSE00000719046	21028327	21028538
ENSE00000808795	21001429	21003334
ENSE00000932261	21043513	21043551
ENSE00000932262	21042361	21042476
ENSE00000932263	21040938	21041083
ENSE00000932264	21037958	21038111
ENSE00000932265	21037100	21037255
ENSE00000932266	21035584	21035708
ENSE00000932267	21034816	21034901
ENSE00000932268	21033299	21033518
ENSE00000932269	21032354	21032581
ENSE00000932270	21029898	21030015
ENSE00000932271	21029639	21029785
ENSE00000932272	21026788	21026964
ENSE00000932273	21024933	21025124
ENSE00000999274	21043864	21044073
ENSE00001183453	21005080	21012651

Expression profiles

Bgee: expression breadth ubiquitous, 116 present calls, max score 99.95.

FANTOM5 (CAGE): breadth broad, TPM avg 30.3554 / max 5798.7888, expressed in 199 samples.

Highest expression (Bgee): jejunal mucosa, liver, ileal mucosa, ileum, lobe of liver.

Genetic regulation across tissues (GTEx eQTL / sQTL)

APOB is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 19 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 21 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	eqtl	2.9e-68	-0.86	2:21037729:G:A
Skin Not Sun Exposed Suprapubic	eqtl	1.3e-41	-0.82	2:21037729:G:A
Heart Left Ventricle	eqtl	9.9e-30	-0.34	2:21042269:C:A
Adipose Subcutaneous	eqtl	4.3e-23	+0.36	2:21097378:T:C
Nerve Tibial	eqtl	2.5e-12	+0.27	2:21087355:AATG:A
Heart Atrial Appendage	eqtl	8.6e-11	-0.22	2:21042269:C:A
Artery Tibial	eqtl	2.9e-08	-0.18	2:21044589:G:A
Colon Sigmoid	eqtl	2.6e-07	-0.28	2:21044589:G:A
Esophagus Muscularis	eqtl	4.3e-07	-0.21	2:21041028:G:A
Esophagus Gastroesophageal Junction	eqtl	2.5e-06	-0.25	2:21044589:G:A
Adipose Visceral Omentum	eqtl	1.4e-05	+0.27	2:21192001:C:T
Brain Spinal cord cervical c-1	eqtl	5.0e-04	-0.50	2:21082323:A:G
Brain Substantia nigra	eqtl	9.5e-04	-0.47	2:21041028:G:A
Brain Hypothalamus	eqtl	9.6e-04	-0.42	2:21044589:G:A
Muscle Skeletal	eqtl	7.9e-03	+0.17	2:21071042:A:C
Artery Aorta	eqtl	1.2e-02	+0.13	2:21046369:T:A
Lung	eqtl	1.9e-02	+0.21	2:20952398:C:G
Small Intestine Terminal Ileum	sqtl	2.1e-02	-2.41	2:20428205:A:G
Spleen	eqtl	3.6e-02	-1.57	2:20657676:T:C
Liver	eqtl	4.3e-02	+0.21	2:20885650:T:C

FANTOM5 promoters

showing 10 of 86 alternative TSS:

Promoter ID	TPM avg	Samples expressed
27277	26.2482	163
27275	0.1881	41
27207	0.1784	40
27161	0.1720	34
27173	0.1507	34
27205	0.1497	37
27163	0.1256	29
27208	0.1179	29
27203	0.1175	27
27274	0.1001	25

Top tissues by expression

showing 100 of 261 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.95	gold quality
liver	UBERON:0002107	99.54	gold quality
ileal mucosa	UBERON:0000331	99.16	gold quality
ileum	UBERON:0002116	99.13	silver quality
right lobe of liver	UBERON:0001114	99.07	gold quality
duodenum	UBERON:0002114	95.65	gold quality
small intestine	UBERON:0002108	86.15	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.38	gold quality
jejunum	UBERON:0002115	82.47	gold quality
heart right ventricle	UBERON:0002080	77.40	gold quality
right atrium auricular region	UBERON:0006631	74.18	gold quality
cardiac atrium	UBERON:0002081	74.10	gold quality
myocardium	UBERON:0002349	73.03	silver quality
cardiac ventricle	UBERON:0002082	72.19	gold quality
heart left ventricle	UBERON:0002084	72.19	gold quality
cardiac muscle of right atrium	UBERON:0003379	70.77	silver quality
adrenal tissue	UBERON:0018303	70.74	gold quality
heart	UBERON:0000948	70.59	gold quality
left ventricle myocardium	UBERON:0006566	68.16	silver quality
descending thoracic aorta	UBERON:0002345	66.51	gold quality
blood vessel layer	UBERON:0004797	65.71	gold quality
thoracic aorta	UBERON:0001515	65.59	gold quality
ascending aorta	UBERON:0001496	65.28	gold quality
aorta	UBERON:0000947	64.58	gold quality
colonic epithelium	UBERON:0000397	64.04	silver quality
popliteal artery	UBERON:0002250	63.73	gold quality
tibial artery	UBERON:0007610	63.62	gold quality
apex of heart	UBERON:0002098	62.86	gold quality
buccal mucosa cell	CL:0002336	62.30	silver quality
synovial joint	UBERON:0002217	62.08	silver quality
calcaneal tendon	UBERON:0003701	61.32	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	59.50	gold quality
right coronary artery	UBERON:0001625	59.28	gold quality
adipose tissue	UBERON:0001013	58.58	gold quality
tibialis anterior	UBERON:0001385	58.24	silver quality
connective tissue	UBERON:0002384	57.99	gold quality
quadriceps femoris	UBERON:0001377	57.25	gold quality
vastus lateralis	UBERON:0001379	57.15	gold quality
muscle tissue	UBERON:0002385	56.67	gold quality
layer of synovial tissue	UBERON:0007616	56.10	silver quality
left coronary artery	UBERON:0001626	55.94	gold quality
gall bladder	UBERON:0002110	55.76	gold quality
intestine	UBERON:0000160	55.66	gold quality
coronary artery	UBERON:0001621	55.34	gold quality
hindlimb stylopod muscle	UBERON:0004252	55.28	gold quality
embryo	UBERON:0000922	55.01	gold quality
subcutaneous adipose tissue	UBERON:0002190	54.01	gold quality
tendon	UBERON:0000043	53.81	gold quality
adipose tissue of abdominal region	UBERON:0007808	53.38	gold quality
bone marrow cell	CL:0002092	52.35	gold quality
omental fat pad	UBERON:0010414	51.96	gold quality
pancreatic ductal cell	CL:0002079	51.94	silver quality
peritoneum	UBERON:0002358	51.93	gold quality
thoracic mammary gland	UBERON:0005200	51.71	gold quality
lower esophagus muscularis layer	UBERON:0035833	51.68	gold quality
lower esophagus	UBERON:0013473	51.66	gold quality
mammary gland	UBERON:0001911	51.52	gold quality
epithelial cell of pancreas	CL:0000083	51.33	gold quality
cranial nerve II	UBERON:0000941	51.32	silver quality
esophagogastric junction muscularis propria	UBERON:0035841	51.01	gold quality
upper arm skin	UBERON:0004263	50.47	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
nasal cavity epithelium	UBERON:0005384	50.34	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
muscle organ	UBERON:0001630	50.17	gold quality
skeletal muscle organ	UBERON:0014892	50.16	gold quality
substantia nigra pars reticulata	UBERON:0001966	49.66	silver quality
kidney	UBERON:0002113	49.38	gold quality
thymus	UBERON:0002370	49.31	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
fundus of stomach	UBERON:0001160	49.04	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
oviduct epithelium	UBERON:0004804	48.73	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
vermiform appendix	UBERON:0001154	48.46	gold quality
biceps brachii	UBERON:0001507	48.22	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
amniotic fluid	UBERON:0000173	48.11	silver quality
cervix epithelium	UBERON:0004801	48.04	gold quality
kidney epithelium	UBERON:0004819	47.99	gold quality
muscle of leg	UBERON:0001383	47.97	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
urinary bladder	UBERON:0001255	47.89	gold quality
adult mammalian kidney	UBERON:0000082	47.82	silver quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
metanephric glomerulus	UBERON:0004736	47.74	gold quality
lymph node	UBERON:0000029	47.64	gold quality
endometrium	UBERON:0001295	47.64	silver quality
renal glomerulus	UBERON:0000074	47.60	gold quality
caecum	UBERON:0001153	47.57	gold quality
mammalian vulva	UBERON:0000997	47.52	gold quality
periodontal ligament	UBERON:0008266	47.14	gold quality
uterine cervix	UBERON:0000002	47.09	silver quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	5335.23
E-CURD-98	yes	5242.96
E-MTAB-9543	yes	4346.42
E-GEOD-125970	yes	1351.65
E-MTAB-10553	yes	1256.47
E-HCAD-9	yes	64.55
E-MTAB-9388	yes	10.59
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Group enriched

26 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	1114.1	not detected
Small intestine	tissue	286.7	not detected
Duodenum	tissue	170.7	not detected
Heart muscle	tissue	2.7	not detected
Adipose tissue	tissue	2.5	not detected
Choroid plexus	tissue	0.9
Cervix	tissue	0.7	not detected
Locus coeruleus	tissue	0.5
Hippocampus	tissue	0.5	not detected
Nucleus accumbens	tissue	0.4
Gallbladder	tissue	0.4	not detected
Postcentral gyrus	tissue	0.4
Stomach 1	tissue	0.3	not detected
Kidney	tissue	0.3	not detected
Lymph node	tissue	0.2	not detected
Testis	tissue	0.2	not detected
Smooth muscle	tissue	0.2	not detected
Endometrium 1	tissue	0.2	not detected
Prostate	tissue	0.2	not detected
Appendix	tissue	0.2	not detected
Breast	tissue	0.1	not detected
Ovary	tissue	0.1	not detected
Seminal vesicle	tissue	0.1	not detected
Esophagus	tissue	0.1	not detected
Tongue	tissue	0.1
Spleen	tissue	0.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 183; highest nTPM — Blood vessel (1.6), Medial olivary nucleus (1.1), Lateral funiculus (white matter) (1.0), Occipital cortex (white matter) (1.0), Supraoptic nucleus (1.0).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ATF3, CEBPA, CEBPB, CEBPG, ESR1, FOXA1, FOXA2, FOXM1, HNF1A, HNF4A, NR0B2, NR2F1, NR2F2, NR2F6, PITX2, PPARA, PPARD, PPARG, RAD21, RERE, SP1, TP53

miRNA regulators (miRDB)

Targeting APOB by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

27 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-4699-5P	98.99	67.50	1210
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-6529-3P	98.68	66.76	1020
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-4766-3P	98.48	67.94	1347
HSA-MIR-4432	97.80	67.87	705
HSA-MIR-615-3P	90.62	68.07	69

Functional genomics

gnomAD constraint: pLI 1.35e-11, LOEUF 0.537, missense Z 0.964 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000233242 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
2:21,001,733–21,011,362	3281 / 3171.0	1.03	no
2:21,011,363–21,011,635	64 / 99.9	0.64	no
2:21,011,636–21,043,945	2085 / 2079.7	1.00	no
ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• C–>U editing of neurofibromatosis 1 mRNA occurs in tumors that express both the type II transcript and apobec-1, the catalytic subunit of the apolipoprotein B mRNA-editing enzyme (PMID:11727199)
• defective gene causes hypercholesterolemia ) (PMID:11833852)
• Polymorphisms do not contribute substantially to the risk of holoprosencephaly (PMID:11857554)
• The T-allele of apolipoprotein b codon 2488 polymorphism influenced parameters related to the insulin resistance syndrome (PMID:11869298)
• Inhibition of cholesterol esterification with ACAT inhibitor significantly attenuated apoB48 secretion under basal and stimulatory conditions by a mechanism which enhanced apoB48 degradation. (PMID:11882317)
• There is a higher prevalence of an XbaI polymorphism in patients with severe aortic valve stenosis (PMID:11903341)
• hypobetalipoproteinemia due to a mutation affecting the splicing of the APOB gene encoding apolipoprotein B (PMID:11940084)
• The effect of six polymorphisms in the Apolipoprotein B gene on parameters of lipid metabolism (PMID:11940087)
• Mutations in apoB on LDL give rise to a phenotype of elevated LDL cholesterol. Disturbances in IDL metabolism provide the basis for understanding why FDB is less severe than FH. The apoB-LDL receptor interaction is important in the IDL to LDL conversion. (PMID:11947895)
• APOA1 to APOB ratio is related to myocardial infarction and stroke (PMID:12011770)
• Influence of an asparagine to lysine mutation at amino acid 3516 of apolipoprotein B on low-density lipoprotein receptor binding. (PMID:12031600)
• A p38-MAPK-activating property of LDL resides in the B-site of apoB100 which binds to a platlet receptor, causing platelet activation. (PMID:12038793)
• Identification of the proteoglycan binding site (PMID:12070165)
• Novel mutations of APOB cause ApoB truncations shorter than apoB-30 and are not detectable in plasma from familial hypobetalipoproteinemia patients. (PMID:12124991)
• ApoB expression is regulated by TGF-beta and other cytokines (PMID:12177061)
• The flavonoid quercetin bound to LDL lipoproteins can efficiently repair oxidative damage to amino acid constituents of apoB-100 in LDL. (PMID:12206678)
• R3500Q mutation of the apolipoprotein B gene, a common cause of FH in central Europe, is infrequent in the general Spanish population, but it is common in Galicia (PMID:12208478)
• Adenoviral vector-mediated SR-BI overexpression in livers of human apoB transgenic mice reduced plasma HDL-cholesterol and apolipoprotein A-I (but not apoB) concentrations to nearly undetectable levels 3 days after adenovirus infusion (PMID:12235173)
• correct folding of apoB is dependent on the assistance of molecular chaperones (PMID:12397072)
• APOB genotype was evaluated for an association between infant genetic variation and the risk for spina bifida cystica (PMID:12397634)
• the conformation of apoB on the LDL surface depends strongly on the physical state of the lipoprotein core, and less on the lipid composition of the core per se (PMID:12505152)
• in overweight/obese men, the quantity of adipose tissue mass determines the kinetics of very-low-density-lipoprotein-apolipoprotein B-100 (PMID:12529498)
• This protein is found in cholesterol-containing drusen and basal deposits of human eyes with age-related maculopathy. (PMID:12547700)
• A novel nontruncating gene mutation, R463W, causes familial hypobetalipoproteinemia. (PMID:12551903)
• Data show that purified pH6 antigen selectively binds to apolipoprotein B (apoB)-containing lipoproteins in human plasma, mainly LDL. (PMID:12576514)
• apoB48 can assemble lipoproteins even without being palmitoylated (PMID:12582154)
• demonstrate that GP78 is a bona fide E3 ligase in the apoB ER-associated degradation pathway (PMID:12670940)
• SP-24/24 genotype of Apo B signal peptide is a linkage marker for a gene conferring increased risk of type II diabetes. (PMID:12736910)
• SREBP1a and APOB have roles in total and low-density lipoprotein cholesterol levels in patients with coronary artery disease (PMID:12752570)
• APO B gene polymorphism is strongly related to the incidence of coronary artery diseases and myocardial infarction. (PMID:12818419)
• Four novel APOB mutations associated with familial hypobetalipoproteinemia. (PMID:12872264)
• data suggest that the relationship between apoB levels, hypercholesterolemia and ischemic heart disease risk cannot have a simple molecular basis in the apoB gene (PMID:12942366)
• Double transgenic mice expressing both apoB-100K4–>S4 and apo[a] contained significant amounts of free apo[a] in the plasma, indicating a less-efficient assembly of Lipoprotein[a] in vivo (PMID:13130121)
• Data support the hypothesis of increased biliary catabolism of cholesterol in subjects with gallbladder disease characterized by lower Apo B and higher Apo A-I serum concentrations. (PMID:14567398)
• There seems to be an association between APOB Xbai polymorphism and gallbladder cancer. (PMID:14618390)
• Site A in apoB100 becomes functional in sPLA2-modified LDL and acts cooperatively with site B resulting in increased proteoglycan-binding activity. The increased binding for proteoglycans of cholesterol-enriched LDL is solely dependent on site B. (PMID:14726411)
• elevation of plasma LDL-cholesterol found in familial hypercholesterolemia is attributable to both decreased clearance of LDL and increased hepatic production of apoB-100-containing lipoproteins (PMID:14967814)
• because apoB-defective familial hypobetalipoproteinemia imparts heightened susceptibility to liver triglyceride accumulation, increasing intraperitoneal adipose tissue and insulin resistance exert greater liver fat-increasing effects in FHBL. (PMID:14967820)
• Allele-specific association between the 3’APOB-VNTR variability and lipid blood levels. (PMID:15028112)
• apoE deficiency results in: impaired catabolism of VLDL/chylomicron and their remnants; 2) an increased rate of catabolism of LDL apoB-100; 3) reduced VLDL apoB production; and 4) a delayed catabolism of Lp(a) (PMID:15102883)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	apobb.1	ENSDARG00000022767
danio_rerio	apoba	ENSDARG00000042780
danio_rerio	apobb.2	ENSDARG00000075016
mus_musculus	Apob	ENSMUSG00000020609
rattus_norvegicus	Apob	ENSRNOG00000005542

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:88052) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 28 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased circulating LDL cholesterol level	5
exencephaly	5
decreased circulating cholesterol level	5
decreased circulating HDL cholesterol level	4
decreased circulating triglyceride level	4
decreased circulating VLDL cholesterol level	4
hydrocephaly	3
hepatic steatosis	2
abnormal circulating apolipoprotein level	2
prenatal lethality, complete penetrance	2
prenatal lethality, incomplete penetrance	2
abnormal circulating cholesterol level	1
increased circulating LDL cholesterol level	1
abnormal circulating HDL cholesterol level	1
abnormal triglyceride level	1
increased circulating triglyceride level	1
abnormal embryo development	1
decreased embryo size	1
hemorrhage	1
reduced male fertility	1
postnatal lethality	1
asthenozoospermia	1
oligozoospermia	1
abnormal cholesterol homeostasis	1
herniated liver	1

+3 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Xenopus laevis	P19009	93.0%	Diamond
Oryctolagus cuniculus	P17165	84.7%	Diamond
Gallus gallus	P11682	30.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
GDF7	protein-coding	151449
LDAH	protein-coding	60526
TDRD15	protein-coding	100129278
LINC02850	ncRNA	101928271

Protein

Protein identifiers

Apolipoprotein B-100 — P04114 (reviewed: P04114)

All UniProt accessions (3): A0A669KB70, A8MUN2, P04114

UniProt curated annotations — full annotation on UniProt →

Function. Apolipoprotein B is a major protein constituent of chylomicrons (apo B-48), LDL (apo B-100) and VLDL (apo B-100). Apo B-100 functions as a recognition signal for the cellular binding and internalization of LDL particles by the apoB/E receptor.

Subunit / interactions. Interacts with PCSK9. Interacts with MTTP. Interacts with AUP1. Interacts with CIDEB.

Subcellular location. Cytoplasm. Secreted. Lipid droplet.

Post-translational modifications. Palmitoylated; structural requirement for proper assembly of the hydrophobic core of the lipoprotein particle.

Disease relevance. Hypobetalipoproteinemia, familial, 1 (FHBL1) [MIM:615558] A disorder of lipid metabolism characterized by less than 5th percentile age- and sex-specific levels of low density lipoproteins, and dietary fat malabsorption. Clinical presentation may vary from no symptoms to severe gastrointestinal and neurological dysfunction similar to abetalipoproteinemia. The disease is caused by variants affecting the gene represented in this entry. Most cases of FHBL1 result from nonsense mutations in the APOB gene that lead to a premature stop codon, which generate prematurely truncated apo B protein products. Hypercholesterolemia, familial, 2 (FHCL2) [MIM:144010] A form of hypercholesterolemia, a disorder of lipoprotein metabolism characterized by elevated serum low-density lipoprotein (LDL) cholesterol levels, which result in excess deposition of cholesterol in tissues and leads to xanthelasma, xanthomas, accelerated atherosclerosis and increased risk of premature coronary heart disease. FHCL2 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry. Defects in APOB associated with defects in other genes (polygenic) can contribute to hypocholesterolemia.

Induction. Up-regulated in response to enterovirus 71 (EV71) infection (at protein level).

Polymorphism. Genetic variations in APOB define the low density lipoprotein cholesterol level quantitative trait locus 4 (LDLCQ4) [MIM:615558].

RefSeq proteins (1): NP_000375* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001747	Vitellogenin_M	Domain
IPR009454	Lipid_transpt_open_b-sht	Domain
IPR011030	Lipovitellin_superhlx_dom	Homologous_superfamily
IPR015255	Vitellinogen_open_b-sht	Domain
IPR015816	Vitellinogen_b-sht_N	Homologous_superfamily
IPR015817	Vitellinogen_open_b-sht_sub1	Homologous_superfamily
IPR015819	Lipid_transp_b-sht_shell	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR022176	ApoB100_C	Domain
IPR052418	Apolipoprotein_B	Family

Pfam: PF01347, PF06448, PF09172, PF12491

UniProt features (160 total): sequence variant 65, sequence conflict 46, glycosylation site 19, region of interest 9, disulfide bond 8, mutagenesis site 4, modified residue 4, chain 2, signal peptide 1, lipid moiety-binding region 1, domain 1

Structure

Experimental structures (PDB)

8 structures by resolution:

PDB	Title	Method	Resolution (Å)
9COO	Nanobody 4 bound to Apolipoprotein B 100	ELECTRON MICROSCOPY	3.73
9BDE	Middle Region of Apolipoprotein B 100 bound to Low Density Lipoprotein Receptor	ELECTRON MICROSCOPY	4.18
9BD8	ApoB 100 beta barrel bound to LDLR beta propeller	ELECTRON MICROSCOPY	4.8
9BD1	beta/alpha1 region of ApoB 100	ELECTRON MICROSCOPY	5.4
9BDT	Apolipoprotein B 100 bound to LDL receptor and legobody	ELECTRON MICROSCOPY	5.4
9E9R	The Structure of ApoB100 from Human Low-Density Lipoprotein	ELECTRON MICROSCOPY	9
9EA7	The Structure of ApoB100 from Human Low-Density Lipoprotein	ELECTRON MICROSCOPY	9
9EAG	The Structure of ApoB100 from Human Low-Density Lipoprotein	ELECTRON MICROSCOPY	9

Predicted structure (AlphaFold)

No AlphaFold model available for P04114 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Human Protein Atlas

Protein class: Metabolic proteins, Predicted secreted proteins, Plasma proteins, Candidate cardiovascular disease genes, Disease related genes, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of lipid/glycolipid metabolism, Other congenital disorders of metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; vesicles

Antibody reliability (HPA): IH supported · IF supported

Functional residue map

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

Post-translational modifications (5)

Type	Positions
N6-acetyllysine	2004
Phosphoserine	3279, 4048
Phosphothreonine	4052
S-palmitoyl cysteine	1112

Disulfide bonds (8)

Type	Positions
Disulfide bond	39–88, 78–97, 186–212, 245–261, 385–390, 478–513, 966–976, 3194–3324

Glycosylation sites (19)

Type	Positions
N-linked (glcnac…) asparagine	34, 185, 983, 1368, 1377, 1523, 2239, 2560, 2779, 2982, 3101, 3224, 3336, 3358, 3411, 3465, 3895, 4237, 4431

Mutagenesis-validated functional residues (4)

Position	Phenotype
483	impairs protein secretion.
483	does not affect protein secretion.
490	impairs protein secretion.
490	does not affect protein secretion.

Function

Pathways and Gene Ontology

Reactome pathways

13 curated (TAS) of 42; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

42 pathways:

ID	Pathway	Evidence
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis	curated
R-HSA-202733	Cell surface interactions at the vascular wall	curated
R-HSA-8963888	Chylomicron assembly	curated
R-HSA-8963901	Chylomicron remodeling	curated
R-HSA-8856828	Clathrin-mediated endocytosis	curated
R-HSA-9707616	Heme signaling	curated
R-HSA-8964041	LDL remodeling	curated
R-HSA-432142	Platelet sensitization by LDL	curated
R-HSA-8957275	Post-translational protein phosphorylation	curated
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	curated
R-HSA-5686938	Regulation of TLR by endogenous ligand	curated
R-HSA-3000497	Scavenging by Class H Receptors	curated
R-HSA-8866423	VLDL assembly	curated
R-HSA-2173782	Binding and Uptake of Ligands by Scavenger Receptors	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—
R-HSA-8964026	Chylomicron clearance	electronic
R-HSA-109582	Hemostasis	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-8964038	LDL clearance	electronic
R-HSA-199991	Membrane Trafficking	—
R-HSA-1430728	Metabolism	—
R-HSA-6806667	Metabolism of fat-soluble vitamins	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-196854	Metabolism of vitamins and cofactors	—
R-HSA-8963898	Plasma lipoprotein assembly	—
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance	—
R-HSA-8964043	Plasma lipoprotein clearance	—
R-HSA-8963899	Plasma lipoprotein remodeling	—
R-HSA-418346	Platelet homeostasis	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-975634	Retinoid metabolism and transport	electronic
R-HSA-3000480	Scavenging by Class A Receptors	electronic
R-HSA-3000471	Scavenging by Class B Receptors	electronic
R-HSA-3000484	Scavenging by Class F Receptors	electronic
R-HSA-9709957	Sensory Perception	—
R-HSA-168898	Toll-like Receptor Cascades	—
R-HSA-382551	Transport of small molecules	—
R-HSA-8964046	VLDL clearance	electronic
R-HSA-5653656	Vesicle-mediated transport	—
R-HSA-2187338	Visual phototransduction	—

MSigDB gene sets: 402 (showing top): GOBP_CELLULAR_RESPONSE_TO_LIPOPROTEIN_PARTICLE_STIMULUS, MODULE_52, GOBP_REGULATION_OF_LIPID_STORAGE, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, REACTOME_INNATE_IMMUNE_SYSTEM, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_STEROL_HOMEOSTASIS, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, MODULE_64, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_ARTERY_DEVELOPMENT, GOBP_PROTEIN_LIPID_COMPLEX_ASSEMBLY, GOBP_MALE_GAMETE_GENERATION, REACTOME_MEMBRANE_TRAFFICKING, GOBP_POSITIVE_REGULATION_OF_MACROPHAGE_DERIVED_FOAM_CELL_DIFFERENTIATION

GO Biological Process (17): triglyceride mobilization (GO:0006642), cholesterol metabolic process (GO:0008203), response to virus (GO:0009615), positive regulation of macrophage derived foam cell differentiation (GO:0010744), positive regulation of lipid storage (GO:0010884), positive regulation of cholesterol storage (GO:0010886), cholesterol transport (GO:0030301), low-density lipoprotein particle remodeling (GO:0034374), very-low-density lipoprotein particle assembly (GO:0034379), low-density lipoprotein particle clearance (GO:0034383), cholesterol homeostasis (GO:0042632), lipoprotein transport (GO:0042953), cellular response to lipoprotein particle stimulus (GO:0071402), lipid metabolic process (GO:0006629), lipid transport (GO:0006869), signal transduction (GO:0007165), steroid metabolic process (GO:0008202)

GO Molecular Function (8): phospholipid binding (GO:0005543), heparin binding (GO:0008201), lipase binding (GO:0035473), receptor ligand activity (GO:0048018), low-density lipoprotein particle receptor binding (GO:0050750), cholesterol transfer activity (GO:0120020), lipid carrier activity (GO:0005319), protein binding (GO:0005515)

GO Cellular Component (25): extracellular region (GO:0005576), cytoplasm (GO:0005737), early endosome (GO:0005769), endoplasmic reticulum lumen (GO:0005788), endoplasmic reticulum membrane (GO:0005789), smooth endoplasmic reticulum (GO:0005790), lipid droplet (GO:0005811), cytosol (GO:0005829), plasma membrane (GO:0005886), endosome membrane (GO:0010008), clathrin-coated endocytic vesicle membrane (GO:0030669), endosome lumen (GO:0031904), mature chylomicron (GO:0034359), chylomicron remnant (GO:0034360), very-low-density lipoprotein particle (GO:0034361), low-density lipoprotein particle (GO:0034362), intermediate-density lipoprotein particle (GO:0034363), chylomicron (GO:0042627), neuronal cell body (GO:0043025), lysosomal lumen (GO:0043202), intracellular membrane-bounded organelle (GO:0043231), extracellular exosome (GO:0070062), endoplasmic reticulum exit site (GO:0070971), endocytic vesicle lumen (GO:0071682), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

14 top-level categories:

Category	Pathways
Binding and Uptake of Ligands by Scavenger Receptors	4
Plasma lipoprotein clearance	3
Plasma lipoprotein assembly	2
Plasma lipoprotein remodeling	2
Hemostasis	1
Metabolism of proteins	1
Platelet homeostasis	1
Toll-like Receptor Cascades	1
Clathrin-mediated endocytosis	1
Membrane Trafficking	1
Post-translational protein modification	1
Cellular responses to stress	1
Visual phototransduction	1
Metabolism of fat-soluble vitamins	1

GO top-level categories

showing 60 of 67 GO namespaces:

Category	Terms
cellular anatomical structure	3
endosome	3
cellular response to stimulus	2
endoplasmic reticulum	2
intracellular organelle lumen	2
chylomicron	2
triglyceride-rich plasma lipoprotein particle	2
plasma lipoprotein particle	2
triglyceride metabolic process	1
sterol metabolic process	1
secondary alcohol metabolic process	1
response to other organism	1
macrophage derived foam cell differentiation	1
regulation of macrophage derived foam cell differentiation	1
positive regulation of cell differentiation	1
regulation of lipid storage	1
lipid storage	1
positive regulation of cellular process	1
positive regulation of lipid localization	1
cholesterol storage	1
positive regulation of lipid storage	1
regulation of cholesterol storage	1
sterol transport	1
plasma lipoprotein particle remodeling	1
plasma lipoprotein particle assembly	1
plasma lipoprotein particle clearance	1
low-density lipoprotein particle disassembly	1
sterol homeostasis	1
protein transport	1
lipoprotein localization	1
primary metabolic process	1
transport	1
lipid localization	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
lipid metabolic process	1
lipid binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
enzyme binding	1
signaling receptor binding	1
signal transduction	1
signaling receptor activator activity	1
lipoprotein particle receptor binding	1
cholesterol binding	1
sterol transfer activity	1
molecular carrier activity	1
binding	1
intracellular anatomical structure	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
intracellular membraneless organelle	1
cytoplasm	1
membrane	1
cell periphery	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 27 of 51 annotations. The rest are phylogenetic / computational / electronic (IEA).

27 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to lipoprotein particle stimulus	BP	direct assay
cholesterol homeostasis	BP	mutant phenotype
cholesterol metabolic process	BP	mutant phenotype
cholesterol transport	BP	mutant phenotype
low-density lipoprotein particle clearance	BP	mutant phenotype
low-density lipoprotein particle remodeling	BP	mutant phenotype
positive regulation of cholesterol storage	BP	direct assay
positive regulation of lipid storage	BP	direct assay
positive regulation of macrophage derived foam cell differentiation	BP	direct assay
response to virus	BP	expression pattern
chylomicron	CC	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
endoplasmic reticulum exit site	CC	direct assay
extracellular exosome	CC	high-throughput assay
extracellular region	CC	high-throughput assay
intermediate-density lipoprotein particle	CC	direct assay
low-density lipoprotein particle	CC	direct assay
mature chylomicron	CC	direct assay
neuronal cell body	CC	direct assay
very-low-density lipoprotein particle	CC	direct assay
cholesterol transfer activity	MF	mutant phenotype
heparin binding	MF	direct assay
lipase binding	MF	physical interaction
low-density lipoprotein particle receptor binding	MF	mutant phenotype
phospholipid binding	MF	direct assay
receptor ligand activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 4,004 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APOB	APOA1	P02647	977
APOB	MTTP	P55157	975
APOB	APOBEC1	P41238	973
APOB	LPA	P08519	966
APOB	PCSK9	Q8NBP7	963
APOB	LDLR	P01130	959
APOB	APOE	P02649	953
APOB	CETP	P11597	944
APOB	APOA2	P02652	944
APOB	APOC3	P02656	937
APOB	APOBEC2	Q9Y235	913
APOB	APOBEC3B	Q9UH17	903
APOB	APOA4	P06727	897
APOB	NPC1L1	Q9UHC9	893
APOB	SCARB1	Q8WTV0	892

IntAct

Human interaction partners of APOB in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

25 partners by confidence:

Partner	Interaction type	MIscore	Records
MTTP	physical association	0.700	4
AUP1	colocalization	0.610	5
LDLR	direct interaction	0.560	4
SLC10A7	association	0.530	2
VCP	association	0.530	1
ZDHHC11	association	0.530	1
FADS2	physical association	0.400	1
SPTAN1	physical association	0.400	1
TMEM41B	physical association	0.400	1
AKT2	physical association	0.370	1
ARFGAP1	physical association	0.370	1
BNLF1	physical association	0.370	1
BNRF1	physical association	0.370	1
PRDX4	physical association	0.370	1
SMAD3	physical association	0.370	1
APOA1	association	0.350	1
CERS4	association	0.350	1
CKLF	association	0.350	1
CYB5R3	association	0.350	1
ELOVL3	association	0.350	1
GOLT1A	association	0.350	1
IFITM5	association	0.350	1
SLC19A1	association	0.350	1
SLC2A2	association	0.350	1
SLC37A3	association	0.350	1

BioGRID (224 interactions; top human partners by supporting records): APOA1 (Affinity Capture-Western; 5 records), AUP1 (Affinity Capture-MS; 5 records), HSP90B1 (Affinity Capture-Western; 3 records), PDIA4 (Affinity Capture-Western; 3 records), TMEM41B (Affinity Capture-MS; 3 records), VCP (Affinity Capture-Western; 3 records), ACTN1 (Cross-Linking-MS (XL-MS); 2 records), CALCR (Affinity Capture-Western; 2 records), CALR (Affinity Capture-RNA; 2 records), CANX (Affinity Capture-Western; 2 records), CTAGE5 (Affinity Capture-Western; 2 records), DERL1 (Affinity Capture-Western; 2 records), EGFR (Affinity Capture-MS; 2 records), FAF2 (Affinity Capture-MS; 2 records), LITAF (Affinity Capture-MS; 2 records)

SIGNOR signaling

10 signaling interactions:

A	Effect	B	Mechanism
HBB	“up-regulates quantity by stabilization”	APOB
HBA1	“up-regulates quantity by stabilization”	APOB
INS	“down-regulates quantity by destabilization”	APOB
APOB	up-regulates	VLDL_assembly
APOB	up-regulates	LDL_assembly
mTORC1	“down-regulates quantity by repression”	APOB	“translation regulation”
MTTP	“up-regulates activity”	APOB	lipidation
RAD21	“down-regulates quantity”	APOB	“transcriptional regulation”
AMFR	“down-regulates quantity by destabilization”	APOB	ubiquitination
APOB	up-regulates	LDLR	binding

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ APOB-BCHE complex	2	APOB, BCHE

Ligand–receptor pairs (CellPhoneDB) (2)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

2 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
TREM2;TYROBP	ligand	Signaling by Apolipoprotein
APOBR	ligand	Signaling by Apolipoprotein

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 25 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Vesicle-mediated transport	5	9.7×	6e-03

Disease & clinical

Genetic variants

Variant evidence for APOB: 5,263 ClinVar records (241 pathogenic / likely pathogenic); 5 PharmGKB clinical annotations; 163 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

5,263 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	166
Likely pathogenic	75
Uncertain significance	2093
Likely benign	1895
Benign	51

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 241 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
895430	NM_000384.3(APOB):c.7600C>T (p.Arg2534Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
1323322	NM_000384.3(APOB):c.1315C>T (p.Arg439Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
17883	NM_000384.3(APOB):c.3997C>T (p.Arg1333Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
17892	NM_000384.3(APOB):c.9200del (p.Lys3067fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
431499	NM_000384.3(APOB):c.4651C>T (p.Gln1551Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
17881	NM_000384.3(APOB):c.5263_5266del (p.Asn1755fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
69511	NM_000384.3(APOB):c.7537C>T (p.Arg2513Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
1704963	NM_000384.3(APOB):c.11330C>A (p.Ser3777Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
477783	NM_000384.3(APOB):c.1830-1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	2
843259	NM_000384.3(APOB):c.8392G>T (p.Glu2798Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
855100	NM_000384.3(APOB):c.4006C>T (p.Gln1336Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
925921	NM_000384.3(APOB):c.11124del (p.Phe3708fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
927955	NM_000384.3(APOB):c.6034C>T (p.Arg2012Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1070406	NM_000384.3(APOB):c.7699C>T (p.Gln2567Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1323319	NM_000384.3(APOB):c.3511G>T (p.Glu1171Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2

Per-variant reference — Sugi Variant

Explore APOB’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 1,782):

Position(s)	Effect	Δscore	Sites
2:21003335–21003336	acceptor_loss	1.0000	6
2:21003341	acceptor_gain	1.0000
2:21004267–21004268	donor_loss	1.0000	4
2:21013158–21013159	donor_loss	1.0000	5
2:21014446–21014447	donor_loss	1.0000	5
2:21014594–21014595	acceptor_loss	1.0000	4
2:21014601	acceptor_gain	1.0000
2:21016437–21016438	donor_loss	1.0000	4
2:21016662	acceptor_gain	1.0000
2:21018991	donor_loss	1.0000

AlphaMissense

2,952 missense substitutions predicted likely pathogenic (of 30,213 scored), across 1,290 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F705	8	0.763	0.910
C186	7	0.958	0.979
C245	7	0.956	0.975
C261	7	0.954	0.975
C212	7	0.948	0.980
C97	7	0.925	0.981
F46	7	0.917	0.961
C976	7	0.914	0.960
C78	7	0.906	0.984
C385	7	0.906	0.950
N155	7	0.904	0.980
C390	7	0.885	0.947
F592	7	0.879	0.964
C88	7	0.878	0.935
C966	7	0.875	0.934
C513	7	0.874	0.945
C478	7	0.859	0.924
E263	7	0.855	0.937
W3153	7	0.842	0.960
F348	7	0.836	0.945

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Liver Hepatocellular Carcinoma)

Disease associations

OMIM: gene MIM:107730 | disease phenotypes: MIM:144010, MIM:615558, MIM:143890

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
hypercholesterolemia, autosomal dominant, type B	Definitive	Autosomal dominant	5
familial hypobetalipoproteinemia 1	Strong	Autosomal recessive	3
homozygous familial hypercholesterolemia	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

2 validity classifications:

Disease	Classification	Inheritance
hypercholesterolemia, autosomal dominant, type B	Definitive	AD
familial hypobetalipoproteinemia 1	Definitive	SD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (12 panels, 12 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

12 panels:

Panel	Rating
Additional findings health related	green
Additional findings health related - adults	green
Additional findings health related - children	green
Familial hypercholesterolaemia	green
Familial hypercholesterolaemia (GMS)	green
Hypotonic infant	green
Intestinal failure or congenital diarrhoea	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Paediatric disorders	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (7): hypercholesterolemia, autosomal dominant, type B (MONDO:0007751), familial hypobetalipoproteinemia 1 (MONDO:0014252), hypobetalipoproteinemia (MONDO:0017774), familial hypercholesterolemia (MONDO:0005439), hypercholesterolemia, familial, 1 (MONDO:0007750), homozygous familial hypercholesterolemia (MONDO:0018328), inborn errors of metabolism (MONDO:0019052)

Orphanet (3): Hypobetalipoproteinemia (Orphanet:31154), Homozygous familial hypercholesterolemia (Orphanet:391665), Rare inborn errors of metabolism (Orphanet:68367)

HPO phenotypes

52 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000510	Rod-cone dystrophy
HP:0000546	Retinal degeneration
HP:0000799	Renal steatosis
HP:0000822	Hypertension
HP:0000991	Xanthomatosis
HP:0001084	Corneal arcus
HP:0001114	Xanthelasma
HP:0001138	Optic neuropathy
HP:0001251	Ataxia
HP:0001315	Diminished deep tendon reflex
HP:0001397	Hepatic steatosis
HP:0001645	Sudden cardiac death
HP:0001653	Mitral regurgitation
HP:0001658	Myocardial infarction
HP:0001677	Coronary artery atherosclerosis
HP:0001681	Angina pectoris
HP:0001920	Renal artery stenosis
HP:0001927	Acanthocytosis
HP:0002094	Dyspnea
HP:0002155	Hypertriglyceridemia
HP:0002570	Steatorrhea
HP:0002829	Arthralgia
HP:0003077	Hyperlipidemia
HP:0003124	Hypercholesterolemia
HP:0003141	Elevated circulating LDL-C concentration
HP:0003146	Hypocholesterolemia
HP:0003233	Decreased circulating HDL-C concentration
HP:0003563	Decreased circulating LDL-C concentration
HP:0003593	Infantile onset
HP:0004381	Supravalvular aortic stenosis
HP:0004416	Precocious atherosclerosis
HP:0004905	Reduced circulating vitamin A concentration
HP:0004950	Peripheral arterial stenosis
HP:0004963	Calcification of the aorta
HP:0005162	Abnormal left ventricular function
HP:0005177	Premature arteriosclerosis
HP:0005181	Premature coronary artery atherosclerosis
HP:0006693	Myocardial steatosis
HP:0007201	Cerebral artery atherosclerosis
HP:0010874	Tendon xanthomatosis
HP:0012373	Abnormal eye physiology
HP:0012397	Aortic atherosclerotic lesion
HP:0012638	Abnormal nervous system physiology
HP:0030148	Heart murmur
HP:0030882	Coronary artery aneurysm
HP:0031956	Elevated circulating aspartate aminotransferase concentration
HP:0031964	Elevated circulating alanine aminotransferase concentration
HP:0100261	Abnormal tendon morphology
HP:0100513	Decreased circulating vitamin E concentration
HP:3000062	Abnormal internal carotid artery morphology

GWAS associations

showing 30 of 163 associations:

Study	Trait	p-value
GCST010243_188	Apolipoprotein B levels	0.000000e+00
GCST010245_136	LDL cholesterol levels	9e-312
GCST008079_68	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2e-249
GCST008078_104	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	5e-226
GCST008079_5	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	5e-213
GCST010244_330	Triglyceride levels	6e-197
GCST008078_143	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2e-193
GCST002222_24	LDL cholesterol	1e-182
GCST004233_35	LDL cholesterol levels	2e-179
GCST010242_60	HDL cholesterol levels	4e-140
GCST002221_27	Cholesterol, total	3e-139
GCST004235_9	Total cholesterol levels	3e-136
GCST010241_221	Apolipoprotein A1 levels	9e-136
GCST008086_67	LDL cholesterol levels in current drinkers	2e-127
GCST010173_181	Triglyceride levels	1e-117
GCST000759_5	LDL cholesterol	4e-114
GCST010243_196	Apolipoprotein B levels	9e-112
GCST008086_54	LDL cholesterol levels in current drinkers	2e-101
GCST000760_48	Cholesterol, total	4e-96
GCST009366_18	LDL cholesterol levels x long total sleep time interaction (2df test)	5e-90
GCST009365_66	LDL cholesterol levels x short total sleep time interaction (2df test)	1e-80
GCST008077_87	LDL cholesterol levels	1e-78
GCST009366_17	LDL cholesterol levels x long total sleep time interaction (2df test)	3e-78
GCST009365_68	LDL cholesterol levels x short total sleep time interaction (2df test)	5e-74
GCST007931_84	Medication use (HMG CoA reductase inhibitors)	9e-72
GCST000533_70	Lipid metabolism phenotypes	4e-64
GCST002898_28	LDL cholesterol	2e-63
GCST006611_143	HDL cholesterol	5e-63
GCST011347_52	Low density lipoprotein cholesterol levels	2e-60
GCST008077_3	LDL cholesterol levels	9e-57

EFO canonical traits (from GWAS)

21 canonical traits:

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004574	total cholesterol measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004529	lipid measurement
EFO:0000195	metabolic syndrome
EFO:0004723	coronary artery calcification
EFO:0004746	lipoprotein-associated phospholipase A(2) measurement
EFO:0005763	pulse pressure measurement
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0004329	alcohol drinking
EFO:0005105	lipid or lipoprotein measurement
EFO:0007804	LDL cholesterol change measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004615	apolipoprotein B measurement
EFO:0005689	non-high density lipoprotein cholesterol measurement
EFO:0006925	lipoprotein A measurement
EFO:0007985	platelet crit
EFO:0004309	platelet count
EFO:0009188	Red cell distribution width
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors

4 disease descriptors:

Descriptor	Name	Tree numbers
D000090542	Homozygous Familial Hypercholesterolemia	C16.320.565.398.481.500; C18.452.584.500.500.644.475.500; C18.452.584.563.481.500; C18.452.648.398.481.500
D006995	Hypobetalipoproteinemias	C16.320.565.398.500.440; C18.452.584.500.875.440; C18.452.584.563.500.440; C18.452.648.398.500.440
D008661	Metabolism, Inborn Errors	C16.320.565; C18.452.648
C566267	Hypobetalipoproteinemia, Familial, 1 *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4549 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

5 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs1367117	Efficacy	3	irbesartan	Hypertension
rs1367117	Toxicity	3	warfarin	Heart valve replacement;Hemorrhage
rs1801701	Efficacy	3	irbesartan	Hypertrophy;Left Ventricular
rs676210	Efficacy	3	fenofibrate	Hypertriglyceridemia
rs679899	Toxicity	3	warfarin	Heart valve replacement;Hemorrhage

PharmGKB variants

4 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs676210	APOB	3	2.50	1	fenofibrate
rs1367117	APOB	3	4.00	2	irbesartan;warfarin
rs1801701	APOB	3	1.50	1	irbesartan
rs679899	APOB	3	3.00	1	warfarin

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

7 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs679899	warfarin	Toxicity	Allele G is associated with increased risk of Hemorrhage when treated with warfarin in people with heart valve replacement as compared to allele A.	PMID:31186542
rs1367117	warfarin	Toxicity	Allele G is associated with increased risk of Hemorrhage when treated with warfarin in people with heart valve replacement as compared to allele A.	PMID:31186542
rs13306198	apixaban, dabigatran, edoxaban, rivaroxaban	Toxicity	Genotypes AA + AG is associated with increased likelihood of Hemorrhage when treated with apixaban, dabigatran, edoxaban or rivaroxaban as compared to genotype GG.	PMID:36145636
rs1367117	irbesartan	Efficacy, Metabolism/PK	Genotype AG is associated with response to irbesartan in people with Hypertension.	PMID:15453913
rs1367117	irbesartan	Efficacy	Genotype GG is associated with response to irbesartan in people with Hypertension.	PMID:15453913
rs676210	fenofibrate	Efficacy	Genotype AA is associated with increased response to fenofibrate in people with Hypertriglyceridemia as compared to genotypes AG + GG.	PMID:20724655
rs1801701	irbesartan	Efficacy	Genotype CC is associated with increased response to irbesartan in people with Hypertrophy, Left Ventricular as compared to genotypes CT + TT.	PMID:15614026

Binding affinities (BindingDB)

49 measured of 49 human assays (49 total across all organisms); most potent 49 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
{5-[(6-Methyl-4’-trifluoromethyl-biphenyl-2-carbonyl)-amino]-indan-2-yl}-carbamic acid methyl ester	IC50	0.7 nM
6-Methyl-4’-trifluoromethyl-biphenyl-2-carboxylic acid [2-(thiophene-2-sulfonylamino)-indan-5-yl]-amide	IC50	0.9 nM
4,6-Dimethyl-4’-trifluoromethyl-biphenyl-2-carboxylic acid [2-(thiophene-2-sulfonylamino)-indan-5-yl]-amide	IC50	1 nM
{5-[(4,6-Dimethyl-4’-trifluoromethyl-biphenyl-2-carbonyl)-amino]-indan-2-yl}-carbamic acid methyl ester	IC50	1.1 nM
4’-Fluoro-6-methyl-biphenyl-2-carboxylic acid (2-benzenesulfonylamino-indan-5-yl)-amide	IC50	1.2 nM
4’-Trifluoromethyl-biphenyl-2-carboxylic acid (2-benzenesulfonylamino-indan-5-yl)-amide	IC50	1.3 nM
4’-Fluoro-6-methyl-biphenyl-2-carboxylic acid [2-(thiophene-2-sulfonylamino)-indan-5-yl]-amide	IC50	1.4 nM
6-Methyl-4’-trifluoromethyl-biphenyl-2-carboxylic acid [7-(thiophene-2-sulfonylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-amide	IC50	1.6 nM
{2-[(6-Methyl-4’-trifluoromethyl-biphenyl-2-carbonyl)-amino]-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-yl}-carbamic acid methyl ester	IC50	1.6 nM
(S)-6-methyl-N-(2-(pyridin-2-ylmethylamino)-2,3-dihydro-1H-inden-5-yl)-4’-(trifluoromethyl)biphenyl-2-carboxamide	IC50	1.7 nM
4-{5-[(6-Methyl-4’-trifluoromethyl-biphenyl-2-carbonyl)-amino]-indan-2-yl}-piperazine-1-carboxylic acid methyl ester	IC50	1.8 nM
6-Methyl-4’-trifluoromethyl-biphenyl-2-carboxylic acid (2-methanesulfonylamino-indan-5-yl)-amide	IC50	1.8 nM
{5-[(6,4’-Bis-trifluoromethyl-biphenyl-2-carbonyl)-amino]-indan-2-yl}-carbamic acid methyl ester	IC50	1.8 nM
{5-[(4’-Trifluoromethyl-biphenyl-2-carbonyl)-amino]-indan-2-yl}-carbamic acid methyl ester	IC50	1.9 nM
6-Methyl-4’-trifluoromethyl-biphenyl-2-carboxylic acid {2-[(thiophene-2-sulfonylamino)-methyl]-indan-5-yl}-amide	IC50	1.9 nM
{2-[(4’-Chloro-6-methyl-biphenyl-2-carbonyl)-amino]-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-yl}-carbamic acid methyl ester	IC50	2 nM
4’-Chloro-6-methoxy-biphenyl-2-carboxylic acid (2-benzenesulfonylamino-indan-5-yl)-amide	IC50	2 nM
{5-[(4-Methyl-4’-trifluoromethyl-biphenyl-2-carbonyl)-amino]-indan-2-yl}-carbamic acid methyl ester	IC50	2.2 nM
{5-[(4,6-Dimethyl-4’-trifluoromethyl-biphenyl-2-carbonyl)-amino]-indan-2-ylmethyl}-carbamic acid methyl ester	IC50	2.2 nM
6-Methyl-4’-trifluoromethyl-biphenyl-2-carboxylic acid (7-methanesulfonylamino-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-amide	IC50	2.3 nM
{2-[(4,6-Dimethyl-4’-trifluoromethyl-biphenyl-2-carbonyl)-amino]-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-yl}-carbamic acid methyl ester	IC50	2.4 nM
4’-Chloro-6-methyl-biphenyl-2-carboxylic acid (2-benzenesulfonylamino-indan-5-yl)-amide	IC50	2.4 nM
6,4’-Dimethyl-biphenyl-2-carboxylic acid (2-benzenesulfonylamino-indan-5-yl)-amide	IC50	2.5 nM
{5-[(4,6-Dimethyl-4’-trifluoromethyl-biphenyl-2-carbonyl)-amino]-indan-2-yl}-carbamic acid methyl ester	IC50	2.5 nM
4,6-Dimethyl-4’-trifluoromethyl-biphenyl-2-carboxylic acid [2-(thiophene-2-sulfonylamino)-indan-5-yl]-amide	IC50	2.6 nM
4’-Chloro-6-methyl-biphenyl-2-carboxylic acid [2-(thiophene-2-sulfonylamino)-indan-5-yl]-amide	IC50	3 nM
{5-[(4’-Chloro-4,6-dimethyl-biphenyl-2-carbonyl)-amino]-indan-2-yl}-carbamic acid methyl ester	IC50	3.4 nM
{5-[(6-Methyl-4’-trifluoromethyl-biphenyl-2-carbonyl)-amino]-indan-2-ylmethyl}-carbamic acid methyl ester	IC50	4.1 nM
4’-Chloro-6-methyl-biphenyl-2-carboxylic acid (7-methanesulfonylamino-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-amide	IC50	5 nM
{5-[(4’-Trifluoromethyl-biphenyl-2-carbonyl)-amino]-indan-2-yl}-carbamic acid methyl ester	IC50	5.2 nM
4’-Cyano-6-methyl-biphenyl-2-carboxylic acid (2-benzenesulfonylamino-indan-5-yl)-amide	IC50	5.5 nM
(R)-methyl 5-(6-methyl-4’-(trifluoromethyl)biphenyl-2-ylcarboxamido)-2,3-dihydro-1H-inden-2-ylcarbamate	IC50	6.4 nM
6-Methyl-4’-trifluoromethyl-biphenyl-2-carboxylic acid [2-(methanesulfonylamino-methyl)-indan-5-yl]-amide	IC50	6.5 nM
4’-Chloro-6-methyl-biphenyl-2-carboxylic acid (2-methanesulfonylamino-indan-5-yl)-amide	IC50	6.6 nM
{5-[(4,4’-Bis-trifluoromethyl-biphenyl-2-carbonyl)-amino]-indan-2-yl}-carbamic acid methyl ester	IC50	7.5 nM
4’-Fluoro-6-methyl-biphenyl-2-carboxylic acid (2-methanesulfonylamino-indan-5-yl)-amide	IC50	8.3 nM
{5-[(4’-Chloro-6-methyl-biphenyl-2-carbonyl)-amino]-indan-2-ylmethyl}-carbamic acid methyl ester	IC50	8.7 nM
6-Methyl-4’-trifluoromethyl-biphenyl-2-carboxylic acid (2-methanesulfonylamino-indan-5-yl)-amide	IC50	8.8 nM
(2-{5-[(6-Methyl-4’-trifluoromethyl-biphenyl-2-carbonyl)-amino]-indan-2-yl}-ethyl)-carbamic acid methyl ester	IC50	10 nM
Biphenyl-2-carboxylic acid (2-benzenesulfonylamino-indan-5-yl)-amide	IC50	12 nM
4’-Chloro-6-methoxy-biphenyl-2-carboxylic acid (2-methanesulfonylamino-indan-5-yl)-amide	IC50	15 nM
4’-Chloro-6-methyl-biphenyl-2-carboxylic acid [2-(methanesulfonylamino-methyl)-indan-5-yl]-amide	IC50	16 nM
4’-Trifluoromethyl-biphenyl-2-carboxylic acid (2-benzenesulfonylamino-indan-5-yl)-amide	IC50	42 nM
4-{5-[(6-Methyl-4’-trifluoromethyl-biphenyl-2-carbonyl)-amino]-indan-2-yl}-piperazine-1-carboxylic acid methyl ester	IC50	43 nM
4’-Trifluoromethyl-biphenyl-2-carboxylic acid (2-methanesulfonylamino-indan-5-yl)-amide	IC50	60 nM
4’-Trifluoromethyl-biphenyl-2-carboxylic acid [2-(3,3-dimethyl-ureido)-indan-5-yl]-amide	IC50	120 nM
4’-Trifluoromethyl-biphenyl-2-carboxylic acid (2-acetylamino-indan-5-yl)-amide	IC50	120 nM
4’-Trifluoromethyl-biphenyl-2-carboxylic acid (2-benzoylamino-indan-5-yl)-amide	IC50	270 nM
4’-Trifluoromethyl-biphenyl-2-carboxylic acid (2-benzylamino-indan-5-yl)-amide	IC50	340 nM

ChEMBL bioactivities

49 potent at pChembl≥5 of 49 total, top 49 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.15	IC50	0.7	nM	CHEMBL142450
9.05	IC50	0.9	nM	CHEMBL336873
9.00	IC50	1	nM	CHEMBL139834
8.96	IC50	1.1	nM	CHEMBL143284
8.92	IC50	1.2	nM	CHEMBL344814
8.89	IC50	1.3	nM	CHEMBL357886
8.85	IC50	1.4	nM	CHEMBL356091
8.80	IC50	1.6	nM	CHEMBL142272
8.80	IC50	1.6	nM	CHEMBL142975
8.77	IC50	1.7	nM	CHEMBL142972
8.74	IC50	1.8	nM	CHEMBL359428
8.74	IC50	1.8	nM	CHEMBL422295
8.74	IC50	1.8	nM	CHEMBL142928
8.72	IC50	1.9	nM	CHEMBL139992
8.72	IC50	1.9	nM	CHEMBL143626
8.70	IC50	2	nM	CHEMBL356126
8.70	IC50	2	nM	CHEMBL343406
8.66	IC50	2.2	nM	CHEMBL143514
8.66	IC50	2.2	nM	CHEMBL142733
8.64	IC50	2.3	nM	CHEMBL343874
8.62	IC50	2.4	nM	CHEMBL140754
8.62	IC50	2.4	nM	CHEMBL341974
8.60	IC50	2.5	nM	CHEMBL358141
8.60	IC50	2.5	nM	CHEMBL344439
8.59	IC50	2.6	nM	CHEMBL344849
8.52	IC50	3	nM	CHEMBL423194
8.47	IC50	3.4	nM	CHEMBL343837
8.39	IC50	4.1	nM	CHEMBL142332
8.30	IC50	5	nM	CHEMBL141014
8.28	IC50	5.2	nM	CHEMBL142731
8.26	IC50	5.5	nM	CHEMBL141036
8.19	IC50	6.4	nM	CHEMBL423915
8.19	IC50	6.5	nM	CHEMBL359248
8.18	IC50	6.6	nM	CHEMBL412375
8.12	IC50	7.5	nM	CHEMBL356937
8.08	IC50	8.3	nM	CHEMBL143821
8.06	IC50	8.8	nM	CHEMBL142763
8.06	IC50	8.7	nM	CHEMBL358538
8.00	IC50	10	nM	CHEMBL344801
7.92	IC50	12	nM	CHEMBL143535
7.82	IC50	15	nM	CHEMBL141881
7.80	IC50	16	nM	CHEMBL142616
7.38	IC50	42	nM	CHEMBL434703
7.37	IC50	43	nM	CHEMBL358768
7.22	IC50	60	nM	CHEMBL140786
6.92	IC50	120	nM	CHEMBL143610
6.92	IC50	120	nM	CHEMBL143647
6.57	IC50	270	nM	CHEMBL143684
6.47	IC50	340	nM	CHEMBL142519

PubChem BioAssay actives

49 with measured affinity, of 50 total; 49 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
methyl N-[(2S)-5-[[3-methyl-2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-2,3-dihydro-1H-inden-2-yl]carbamate	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0007	uM
3-methyl-N-[(2R)-2-(thiophen-2-ylsulfonylamino)-2,3-dihydro-1H-inden-5-yl]-2-[4-(trifluoromethyl)phenyl]benzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0009	uM
3,5-dimethyl-N-[(2R)-2-(thiophen-2-ylsulfonylamino)-2,3-dihydro-1H-inden-5-yl]-2-[4-(trifluoromethyl)phenyl]benzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0010	uM
methyl N-[(2S)-5-[[3,5-dimethyl-2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-2,3-dihydro-1H-inden-2-yl]carbamate	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0011	uM
N-[2-(benzenesulfonamido)-2,3-dihydro-1H-inden-5-yl]-2-(4-fluorophenyl)-3-methylbenzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0012	uM
N-[2-(benzenesulfonamido)-2,3-dihydro-1H-inden-5-yl]-2-[4-(trifluoromethyl)phenyl]benzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0013	uM
2-(4-fluorophenyl)-3-methyl-N-[2-(thiophen-2-ylsulfonylamino)-2,3-dihydro-1H-inden-5-yl]benzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0014	uM
methyl N-[3-[[3-methyl-2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl]carbamate	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0016	uM
3-methyl-N-[7-(thiophen-2-ylsulfonylamino)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-3-yl]-2-[4-(trifluoromethyl)phenyl]benzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0016	uM
3-methyl-N-[(2S)-2-(pyridin-2-ylmethylamino)-2,3-dihydro-1H-inden-5-yl]-2-[4-(trifluoromethyl)phenyl]benzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0017	uM
N-[(2R)-2-(methanesulfonamido)-2,3-dihydro-1H-inden-5-yl]-3-methyl-2-[4-(trifluoromethyl)phenyl]benzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0018	uM
methyl 4-[(2S)-5-[[3-methyl-2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-2,3-dihydro-1H-inden-2-yl]piperazine-1-carboxylate	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0018	uM
methyl N-[(2S)-5-[[3-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-2,3-dihydro-1H-inden-2-yl]carbamate	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0018	uM
methyl N-[(2S)-5-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-2,3-dihydro-1H-inden-2-yl]carbamate	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0019	uM
3-methyl-N-[2-[(thiophen-2-ylsulfonylamino)methyl]-2,3-dihydro-1H-inden-5-yl]-2-[4-(trifluoromethyl)phenyl]benzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0019	uM
N-[2-(benzenesulfonamido)-2,3-dihydro-1H-inden-5-yl]-2-(4-chlorophenyl)-3-methoxybenzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0020	uM
methyl N-[3-[[2-(4-chlorophenyl)-3-methylbenzoyl]amino]-6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl]carbamate	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0020	uM
methyl N-[[5-[[3,5-dimethyl-2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-2,3-dihydro-1H-inden-2-yl]methyl]carbamate	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0022	uM
methyl N-[(2S)-5-[[5-methyl-2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-2,3-dihydro-1H-inden-2-yl]carbamate	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0022	uM
N-[7-(methanesulfonamido)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-3-yl]-3-methyl-2-[4-(trifluoromethyl)phenyl]benzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0023	uM
methyl N-[3-[[3,5-dimethyl-2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl]carbamate	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0024	uM
N-[2-(benzenesulfonamido)-2,3-dihydro-1H-inden-5-yl]-2-(4-chlorophenyl)-3-methylbenzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0024	uM
methyl N-[(2R)-5-[[3,5-dimethyl-2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-2,3-dihydro-1H-inden-2-yl]carbamate	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0025	uM
N-[2-(benzenesulfonamido)-2,3-dihydro-1H-inden-5-yl]-3-methyl-2-(4-methylphenyl)benzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0025	uM
3,5-dimethyl-N-[(2S)-2-(thiophen-2-ylsulfonylamino)-2,3-dihydro-1H-inden-5-yl]-2-[4-(trifluoromethyl)phenyl]benzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0026	uM
2-(4-chlorophenyl)-3-methyl-N-[2-(thiophen-2-ylsulfonylamino)-2,3-dihydro-1H-inden-5-yl]benzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0030	uM
methyl N-[5-[[2-(4-chlorophenyl)-3,5-dimethylbenzoyl]amino]-2,3-dihydro-1H-inden-2-yl]carbamate	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0034	uM
methyl N-[[5-[[3-methyl-2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-2,3-dihydro-1H-inden-2-yl]methyl]carbamate	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0041	uM
2-(4-chlorophenyl)-N-[7-(methanesulfonamido)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-3-yl]-3-methylbenzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0050	uM
methyl N-[(2R)-5-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-2,3-dihydro-1H-inden-2-yl]carbamate	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0052	uM
N-[2-(benzenesulfonamido)-2,3-dihydro-1H-inden-5-yl]-2-(4-cyanophenyl)-3-methylbenzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0055	uM
methyl N-[(2R)-5-[[3-methyl-2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-2,3-dihydro-1H-inden-2-yl]carbamate	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0064	uM
N-[2-(methanesulfonamidomethyl)-2,3-dihydro-1H-inden-5-yl]-3-methyl-2-[4-(trifluoromethyl)phenyl]benzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0065	uM
2-(4-chlorophenyl)-N-[2-(methanesulfonamido)-2,3-dihydro-1H-inden-5-yl]-3-methylbenzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0066	uM
methyl N-[(2S)-5-[[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-2,3-dihydro-1H-inden-2-yl]carbamate	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0075	uM
2-(4-fluorophenyl)-N-[2-(methanesulfonamido)-2,3-dihydro-1H-inden-5-yl]-3-methylbenzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0083	uM
methyl N-[[5-[[2-(4-chlorophenyl)-3-methylbenzoyl]amino]-2,3-dihydro-1H-inden-2-yl]methyl]carbamate	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0087	uM
N-[(2S)-2-(methanesulfonamido)-2,3-dihydro-1H-inden-5-yl]-3-methyl-2-[4-(trifluoromethyl)phenyl]benzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0088	uM
methyl N-[2-[5-[[3-methyl-2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-2,3-dihydro-1H-inden-2-yl]ethyl]carbamate	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0100	uM
N-[2-(benzenesulfonamido)-2,3-dihydro-1H-inden-5-yl]-2-phenylbenzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0120	uM
2-(4-chlorophenyl)-N-[2-(methanesulfonamido)-2,3-dihydro-1H-inden-5-yl]-3-methoxybenzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0150	uM
2-(4-chlorophenyl)-N-[2-(methanesulfonamidomethyl)-2,3-dihydro-1H-inden-5-yl]-3-methylbenzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0160	uM
N-[(2S)-2-(benzenesulfonamido)-2,3-dihydro-1H-inden-5-yl]-2-[4-(trifluoromethyl)phenyl]benzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0420	uM
methyl 4-[(2R)-5-[[3-methyl-2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-2,3-dihydro-1H-inden-2-yl]piperazine-1-carboxylate	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0430	uM
N-[2-(methanesulfonamido)-2,3-dihydro-1H-inden-5-yl]-2-[4-(trifluoromethyl)phenyl]benzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.0600	uM
N-(2-acetamido-2,3-dihydro-1H-inden-5-yl)-2-[4-(trifluoromethyl)phenyl]benzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.1200	uM
N-[2-(dimethylcarbamoylamino)-2,3-dihydro-1H-inden-5-yl]-2-[4-(trifluoromethyl)phenyl]benzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.1200	uM
N-(2-benzamido-2,3-dihydro-1H-inden-5-yl)-2-[4-(trifluoromethyl)phenyl]benzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.2700	uM
N-[2-(benzylamino)-2,3-dihydro-1H-inden-5-yl]-2-[4-(trifluoromethyl)phenyl]benzamide	220646: Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	ic50	0.3400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Simvastatin	affects response to substance, affects expression, increases reaction, affects cotreatment, decreases expression (+1 more)	10
Bezafibrate	decreases reaction, increases expression, decreases expression, decreases secretion	8
Atorvastatin	decreases expression, decreases secretion	7
Benzo(a)pyrene	decreases expression, increases methylation	6
Valproic Acid	decreases expression, decreases methylation, increases expression	6
Oleic Acid	decreases reaction, increases expression, decreases secretion, increases secretion, affects cotreatment (+1 more)	6
Quercetin	affects cotreatment, decreases expression, increases expression, decreases secretion, decreases reaction (+2 more)	5
Niacin	affects cotreatment, decreases expression	4
bisphenol A	affects expression, decreases expression, increases expression	3
Acetaminophen	decreases expression	3
Copper	increases reduction, affects binding, decreases reaction, increases oxidation, increases reaction	3
Aflatoxin B1	affects expression, affects cotreatment, decreases expression, decreases methylation	3
taxifolin	decreases expression, decreases secretion	2
perfluorooctanoic acid	decreases expression	2
acetylleucyl-leucyl-norleucinal	decreases reaction, decreases secretion, decreases expression, increases expression, increases secretion	2
lactacystin	increases reaction, increases secretion, increases degradation, decreases expression, decreases reaction (+2 more)	2
Rosuvastatin Calcium	decreases expression	2
Fluvastatin	decreases expression, increases reaction, affects cotreatment, affects response to substance	2
Irbesartan	affects response to substance	2
Amiodarone	decreases expression	2
Ascorbic Acid	decreases reaction, increases oxidation, increases reaction, affects cotreatment, decreases expression	2
Atenolol	increases expression	2
Cadmium	affects binding, decreases expression, increases abundance	2
Caffeine	increases phosphorylation, affects cotreatment, decreases expression	2
Folic Acid	affects cotreatment, decreases expression, increases expression	2
Glucosamine	decreases localization, increases ubiquitination, decreases expression, decreases reaction, decreases secretion	2
Lovastatin	decreases expression, decreases secretion, affects cotreatment	2
Vitamin E	increases oxidation, increases reaction, affects cotreatment, decreases expression, decreases reaction	2
Zinc	affects binding, decreases expression, decreases reaction	2
Cyclosporine	decreases expression	2

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL824105	Binding	Inhibition of apolipoprotein B (apoB) secreted by human hepatoma cells (Hep G2) at 100 nM	Diaminoindanes as microsomal triglyceride transfer protein inhibitors. — *J Med Chem*

Cellosaurus cell lines

3 cell lines: 3 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A1WB	GZHMCi002-A	Induced pluripotent stem cell	Female
CVCL_A7JG	CIBi009-A	Induced pluripotent stem cell	Male
CVCL_D3AI	GM29104	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 164 trials:

NCT	Phase	Status	Title
NCT00655265	Phase 4	COMPLETED	A Study of the Safety and Efficacy of Patients With Familial Hypercholesterolaemia Taking Colesevelam as add-on Therapy to Their Existing Medication
NCT00916643	Phase 4	COMPLETED	Low-Density Lipoprotein (LDL) Apheresis Using H.E.L.P. Therapy
NCT03331666	Phase 4	TERMINATED	Impact of LDL-cholesterol Lowering on Platelet Activation
NCT05465278	Phase 4	COMPLETED	Alirocumab and Plaque Burden In Familial Hypercholesterolaemia
NCT01457690	Phase 3	COMPLETED	Study of the Absorption of Vitamin E Water-soluble Form (Pegylated) in the Familial Hypocholesterolemia With Chylomicron Retention
NCT00730236	Phase 3	COMPLETED	A Safety and Efficacy Study of AEGR-733 to Treat Homozygous Familial Hypercholesterolemia (FH)
NCT01841684	Phase 3	TERMINATED	Efficacy and Tolerability of Anacetrapib Added to Ongoing Lipid-Lowering Therapy in Adult Participants With Homozygous Familial Hypercholesterolemia (HoFH) (MK-0859-042)
NCT02226198	Phase 3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia
NCT02434497	Phase 3	COMPLETED	A Study to Evaluate the Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia
NCT02765841	Phase 3	WITHDRAWN	Evaluate the Efficacy and Safety of Lomitapide in Pediatric Patients With Homozygous Familial Hypercholesterolemia on Stable Lipid-lowering Therapy
NCT03156621	Phase 3	COMPLETED	Study in Participants With Homozygous Familial Hypercholesterolemia (HoFH)
NCT03399786	Phase 3	COMPLETED	Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia
NCT03409744	Phase 3	COMPLETED	Evaluate the Long-Term Safety and Efficacy of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia
NCT03814187	Phase 3	COMPLETED	Trial to Assess the Effect of Long Term Dosing of Inclisiran in Subjects With High CV Risk and Elevated LDL-C
NCT03851705	Phase 3	COMPLETED	A Study of Inclisiran in Participants With Homozygous Familial Hypercholesterolemia (HoFH)
NCT04034485	Phase 3	COMPLETED	Phase 3 Study to Evaluate the Efficacy and Safety of LIB003 With Evolocumab in HoFH
NCT04233918	Phase 3	COMPLETED	Evaluate the Efficacy and Safety of Evinacumab in Pediatric Patients With Homozygous Familial Hypercholesterolemia
NCT05611528	Phase 3	COMPLETED	Safety and Effectiveness of Evinacumab for the Treatment of Homozygous Familial Hypercholesterolemia
NCT05682378	Phase 3	RECRUITING	Long-term Safety and Tolerability of Inclisiran in Participants With HeFH or HoFH Who Have Completed the Pediatric ORION-16, ORION-13, ORION-20, or ORION-19 Studies
NCT06712771	Phase 3	ACTIVE_NOT_RECRUITING	A Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of VSA003 in Chinese HoFH Patients
NCT06723652	Phase 3	COMPLETED	A Multicenter, Randomized, Double-blind, Placebo-controlled Phase III Clinical Study Evaluating the Efficacy and Safety of SHR-1918 in Patients With Homozygous Familial Hypercholesterolemia
NCT07037771	Phase 3	ACTIVE_NOT_RECRUITING	A Phase 3 Study of Zodasiran in Adolescent and Adult Subjects With Homozygous Familial Hypercholesterolemia (YOSEMITE)
NCT07473843	Phase 3	NOT_YET_RECRUITING	Study of Zodasiran in Adolescent Participants With Homozygous Familial Hypercholesterolemia
NCT00355615	Phase 3	COMPLETED	PLUTO: Pediatric Lipid-redUction Trial of rOsuvastatin
NCT00552097	Phase 3	COMPLETED	Effect of Ezetimibe Plus Simvastatin Versus Simvastatin Alone on Atherosclerosis in the Carotid Artery (ENHANCE)(P02578)
NCT00607373	Phase 3	COMPLETED	Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) in Homozygous Familial Hypercholesterolemia
NCT00694109	Phase 3	COMPLETED	An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 (Mipomersen) in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia
NCT00827606	Phase 3	COMPLETED	Atorvastatin Three Year Pediatric Study
NCT00943306	Phase 3	COMPLETED	Long Term, Follow-on Study of Lomitapide in Patients With Homozygous Familial Hypercholesterolemia
NCT01524289	Phase 3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT01813006	Phase 3	COMPLETED	Effect of Omega-3 Fatty Acid on Endothelial Function
NCT02624869	Phase 3	COMPLETED	Safety, Tolerability and Efficacy of Evolocumab (AMG 145) in Children With Inherited Elevated Low-density Lipoprotein Cholesterol (Familial Hypercholesterolemia)
NCT02748057	Phase 3	COMPLETED	A Clinical Trial to Assess the Long Term Safety and Tolerability of MK-0653H in Japanese Participants With Hypercholesterolemia (MK-0653H-833)
NCT03884452	Phase 3	COMPLETED	Ezetimibe (SCH 58235) Taken With Either Atorvastatin or Simvastatin in Participants With Familial Hypercholesterolemia (MK-0653-018)
NCT04798430	Phase 3	ENROLLING_BY_INVITATION	Long-term Efficacy and Safety of OLE LIB003 in HoFH, HeFH, and High-risk CVD Patients Requiring Further LDL-C Reduction
NCT05142722	Phase 3	COMPLETED	Randomized Study to Evaluate the Effect of Obicetrapib on Top of Maximum Tolerated Lipid-Modifying Therapies
NCT05238519	Phase 3	COMPLETED	Improved Diagnosis of Familial Hypercholesterolemia Across the Northland (ID-FH)
NCT05425745	Phase 3	COMPLETED	Evaluate the Effect of Obicetrapib in Patients With HeFH on Top of Maximum Tolerated Lipid-Modifying Therapies.
NCT05952856	Phase 3	COMPLETED	A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-013) CORALreef Lipids
NCT05952869	Phase 3	COMPLETED	A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Heterozygous Familial Hypercholesterolemia (MK-0616-017/CORALreef HeFH)
NCT06005597	Phase 3	COMPLETED	Study of Obicetrapib & Ezetimibe Fixed Dose Combination on Top of Maximum Tolerated Lipid-Modifying Therapies
NCT00362180	Phase 2	COMPLETED	Measure Liver Fat Content After ISIS 301012 (Mipomersen) Administration
NCT01412034	Phase 2	COMPLETED	Effect of CER-001 on Plaque Volume in Homozygous Familial Hypercholesterolemia (HoFH) Subjects
NCT01556906	Phase 2	COMPLETED	Safety, Tolerability and Efficacy of Microsomal Triglyceride Protein (MTP) Inhibitor
NCT02265952	Phase 2	COMPLETED	Study of REGN1500 in Participants With Homozygous Familial Hypercholesterolemia (HoFH)
NCT02472535	Phase 2	COMPLETED	Study to Evaluate the Effects of MBX-8025 in Patients With HoFH
NCT02963311	Phase 2	COMPLETED	A Study of ALN-PCSSC in Participants With Homozygous Familial Hypercholesterolemia (HoFH)
NCT03455777	Phase 2	WITHDRAWN	Study of AKCEA-ANGPTL3-LRX (ISIS 703802) in Patients With Homozygous Familial Hypercholesterolemia (HoFH)
NCT03933293	Phase 2	COMPLETED	A Study to Evaluate the Safety and Efficacy of the PCSK9 Inhibitor AK102 in Patients With HoFH
NCT05217667	Phase 2	TERMINATED	Study of ARO-ANG3 in Participants With Homozygous Familial Hypercholesterolemia (HOFH)
NCT06009393	Phase 2	COMPLETED	Evaluate the Efficacy and Safety of SHR-1918 in Patients With Homozygous Familial Hypercholesterolemia
NCT07133815	Phase 2	NOT_YET_RECRUITING	Evaluate the Long-term Efficacy and Safety of SHR-1918 in Patients With Homozygous Familial Hypercholesterolemia
NCT07489209	Phase 2	RECRUITING	A Dose-exploration Study of EDP167 in HoFH
NCT00079846	Phase 2	TERMINATED	Implitapide in Patients With Homozygous Familial Hypercholesterolemia (HoFH) on Maximal Concurrent Lipid-Lowering Therapy
NCT00079859	Phase 2	TERMINATED	Implitapide in Patients With Heterozygous Familial Hypercholesterolemia (HeFH) on Maximal Concurrent Lipid-Lowering Therapy
NCT00477594	Phase 2	COMPLETED	Open Label Extension of ISIS 301012 (Mipomersen) to Treat Familial Hypercholesterolemia
NCT00751608	Phase 2	WITHDRAWN	Effect of APL180 on Endothelial Function in Familial Hypercholesterolemia Patients
NCT02597127	Phase 2	COMPLETED	Trial to Evaluate the Effect of ALN-PCSSC Treatment on Low Density Lipoprotein Cholesterol (LDL-C)
NCT03060577	Phase 2	COMPLETED	An Extension Trial of Inclisiran in Participants With Cardiovascular Disease and High Cholesterol
NCT04455581	Phase 2	UNKNOWN	A Study to Determine the Safety, Tolerability, and Efficacy of SHR-1209 in Patients With Familial Hypercholesterolemia

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for APOB across ~30M SureChEMBL compounds — explore on Sugi Predict.