MTTP

Summary

MTTP (microsomal triglyceride transfer protein, HGNC:7467) is a protein-coding gene on chromosome 4q23, encoding Microsomal triglyceride transfer protein large subunit (P55157). Catalyzes the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces.

MTP encodes the large subunit of the heterodimeric microsomal triglyceride transfer protein. Protein disulfide isomerase (PDI) completes the heterodimeric microsomal triglyceride transfer protein, which has been shown to play a central role in lipoprotein assembly. Mutations in MTP can cause abetalipoproteinemia.

Source: NCBI Gene 4547 — RefSeq curated summary.

At a glance

• Gene–disease (curated): abetalipoproteinemia (Definitive, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 1,250 total — 79 pathogenic, 91 likely-pathogenic
• Phenotypes (HPO): 69
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001386140

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7467
Approved symbol	MTTP
Name	microsomal triglyceride transfer protein
Location	4q23
Locus type	gene with protein product
Status	Approved
Aliases	ABL
Ensembl gene	ENSG00000138823
Ensembl biotype	protein_coding
OMIM	157147
Entrez	4547

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000265517, ENST00000422897, ENST00000457717, ENST00000504724, ENST00000505094, ENST00000511045, ENST00000511610

RefSeq mRNA: 3 — MANE Select: NM_001386140 NM_000253, NM_001300785, NM_001386140

CCDS: CCDS3651, CCDS75169

Canonical transcript exons

ENST00000265517 — 18 exons

Exon	Start	End
ENSE00000801353	99597067	99597224
ENSE00000801354	99600565	99600733
ENSE00000801355	99601607	99601714
ENSE00000969952	99583374	99583517
ENSE00000969953	99589643	99589750
ENSE00000969954	99591235	99591351
ENSE00000969955	99591651	99591790
ENSE00000969956	99594733	99594883
ENSE00000998549	99606748	99606960
ENSE00001657517	99574824	99574970
ENSE00001751263	99622677	99623997
ENSE00002440082	99612913	99613140
ENSE00002465266	99611143	99611240
ENSE00002475893	99618974	99619098
ENSE00002515066	99611332	99611453
ENSE00002520237	99621061	99621231
ENSE00002526062	99608766	99608977
ENSE00003651555	99581905	99582092

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 99.78.

FANTOM5 (CAGE): breadth broad, TPM avg 4.2102 / max 1407.2767, expressed in 198 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49015	2.3814	130
49016	1.5580	148
203295	0.1320	47
49014	0.0790	6
49011	0.0335	2
49013	0.0133	1
49010	0.0113	1
49012	0.0017	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.78	gold quality
ileal mucosa	UBERON:0000331	96.84	gold quality
ileum	UBERON:0002116	96.76	silver quality
liver	UBERON:0002107	95.59	gold quality
duodenum	UBERON:0002114	95.52	gold quality
right lobe of liver	UBERON:0001114	93.95	gold quality
small intestine	UBERON:0002108	84.82	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.18	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.19	gold quality
jejunum	UBERON:0002115	79.97	gold quality
ventricular zone	UBERON:0003053	77.49	gold quality
nephron tubule	UBERON:0001231	74.44	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.71	gold quality
adult mammalian kidney	UBERON:0000082	68.55	gold quality
kidney epithelium	UBERON:0004819	67.98	gold quality
testis	UBERON:0000473	67.63	gold quality
left testis	UBERON:0004533	67.32	gold quality
right testis	UBERON:0004534	66.97	gold quality
kidney	UBERON:0002113	66.87	gold quality
ganglionic eminence	UBERON:0004023	66.78	gold quality
buccal mucosa cell	CL:0002336	66.49	silver quality
metanephric glomerulus	UBERON:0004736	64.49	gold quality
renal glomerulus	UBERON:0000074	64.46	gold quality
gall bladder	UBERON:0002110	63.42	gold quality
embryo	UBERON:0000922	63.16	gold quality
left ovary	UBERON:0002119	62.82	gold quality
cortex of kidney	UBERON:0001225	62.62	gold quality
ovary	UBERON:0000992	61.47	gold quality
heart left ventricle	UBERON:0002084	61.05	gold quality
tibia	UBERON:0000979	60.62	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	486.65
E-MTAB-7316	yes	27.10
E-ANND-3	yes	6.25

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CLOCK, CNBP, HNF1A, HNF4A, NR1H4, NR2F1, NR2F2, PITX2, PPARA, PPARG, PPARGC1B, RXRA, SP1, SREBF1, SREBF2, TCF3

miRNA regulators (miRDB)

87 targeting MTTP, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• MTP can function in both rough and smooth regions of endoplasmic reticulum in human hepatoma cells. (PMID:12020640)
• Increased MTP gene expression and apoB mRNA levels are found in ventricular myocytes of patients undergoing coronary artery bypass surgery. (PMID:12231571)
• insulin inhibits MTP gene transcription through MAPK(erk) cascade but not through the PI 3-kinase pathway (PMID:12716735)
• MTP genotye -493G/T polymorphism only has a minor effect on LDL cholesterol subfraction pattern in chinese patient. (PMID:12818411)
• genetic association study identified a haplotype marker within microsomal transfer protein as a modifier of human lifespan (PMID:14615589)
• Microsomal triglyceride transfer protein (MTP) has been associated with ABL. (PMID:14741197)
• functional polymorphisms in MTP and MnSOD may be involved in determining susceptibility of non-alcoholic steatohepatitis (PMID:15094225)
• The MTP-493T variant confers an increased risk of CHD unrelated to plasma lipids & lipoproteins, but eliminated by pravastatin treatment. A direct effect of the MTP polymorphism on myocardial lipid metabolism & vulnerability cannot be excluded. (PMID:15136504)
• The -493T MTP promoter polymorphism is associated with a less atherogenic lipoprotein profile and lower carotid tunica intima/media thickness in obese patients. MTP may play a role in the development of obesity-induced dyslipidemia and atherosclerosis. (PMID:15297289)
• HNF-4 and FXR, are closely involved in MTP gene expression, and the results provide evidence for a novel interaction between bile acids and lipoprotein metabolism. (PMID:15337761)
• human placenta expresses both apoB and MTP (PMID:15504742)
• human microsomal triglyceride transfer protein is transcriptionally regulated by hepatocyte nuclear factor-4alpha (PMID:15547294)
• MTP gene polymorphisms were associated with plasma lipoprotein/lipid levels in men with visceral obesity. (PMID:15635487)
• MTP is expressed in retinal pigment epithelium, the ARPE-19 cell line (PMID:15654125)
• Results demonstrate that the biogenesis of vitellogenins A1 is microsomal triglyceride transfer protein (MTP)-dependent and that MTP is the likely ancestral member of the LLTP gene family. (PMID:15701598)
• Bitter lemon juice reduced the secretion of new triglycerides and decreased microsomal triglyceride transfer protein. (PMID:15795421)
• the MTP -493 GT polymorphism modulates pre- and post-treatment plasma triglyceride values of familial hypercholesterolaemia in Spanish subjects in a gender-specific way (PMID:15864113)
• Results suggest that MTP -493G –> T polymorphism was associated with bone mineral density (BMD) in premenopausal women, with the TT genotype being related to increased BMD. (PMID:15953542)
• Our longitudinal study of survival in the 10th decade of life and an association study in a genetically homogeneous population provided no support for an association between the Microsomal Transfer Protein gene and extreme longevity. (PMID:16015282)
• MTP plays a central role in regulating the cholesterol content of the chylomicron particle (PMID:16183064)
• A polymorphism in the MTTP gene affects the spectrum of endogenous apolipoprotein B-containing lipoprotein particles produced in humans. (PMID:16291571)
• Intestinal gene expression is increassed in type 2 diabetees. (PMID:16518588)
• the Ile128Thr polymorphism confers reduced structural stability, leading to decreased binding of MTTP to LDL particles (PMID:16617174)
• the rare allele of the MTP I128T polymorphism may be protective against impaired glucose tolerance, type 2 diabetes and other parameters of the metabolic syndrome (PMID:16721486)
• In Ashkenazi Jewish patients there is a conserved haplotype and a common MTP mutation, p.G865X, with a carrier frequency of 1:131 in this population. (PMID:17275380)
• MTP -493 G/T polymorphism may impact nonalcoholic steatohepatitis by modulating postprandial lipemia and lipoprotein metabolism (PMID:17464986)
• Results describe the effects of polymorphisms in the genes encoding microsome triglycerides transfer protein (MTP) and beta3-adrenergic receptor (beta3-AR) on lipid and glucose metabolism. (PMID:17476189)
• PMA increased ApoB secretion and transcriptional level of microsomal triglyceride transfer protein (MTP). (PMID:17647275)
• the initial addition of phospholipids to apoB:1000 and initiation of apoB-containing lipoprotein assembly occur independently of MTP lipid transfer activity. (PMID:17690102)
• Study supports the notion that the rare MTP-493T/T genotype is associated both with higher levels of inflammatory parameters and with low levels of LDL-cholesterol. (PMID:17825806)
• the functional impact of common MTTP promoter polymorphisms rs1800804:T>C (-164T>C), rs1800803:A>T (-400A>T), and rs1800591:G>T (-493G>T) using gene-reporter assays in intestinal Caco-2 and liver Huh-7 cells (PMID:17854051)
• MTP triglyceride transfer activity first appeared in fish and speculate that the acquisition of triglyceride transfer activity by MTP provided for a significant advantage in the evolution of larger and more complex organisms (PMID:17924655)
• analysis of an APOB gene mutation causing familial hypobetalipoproteinaemia and of a microsomal triglyceride transfer protein (MTP) gene mutation causing abetalipoproteinaemia (PMID:18027103)
• For the MTTP -493G/T polymorphism, although all TT subjects presented high apolipoprotein B-48, a genotype x sex interaction was present for palmitic acid, linolenic acid, eicosatrienoic acid, and insulin. (PMID:18065580)
• investigation of the effect of the MTP -493G/T polymorphism on clinical and biochemical parameters in relation to the presence of metabolic syndrome (PMID:18280132)
• The (-)493TT single nucleotide polymorphism in the microsomal triglyceride transfer protein (MTP) promoter region is associated with altered lipoprotein levels and with presence of peripheral arterial disease (PAD). (PMID:18325332)
• In conclusion the presence of T allele of MTP-493G/T gene polymorphism predisposes patients infected with hepatitis C virus genotype 3 to develop higher degree of fatty liver accumulation. (PMID:18482281)
• MTP is a target of the transcription factor FoxO1 and excessive VLDL production associated with insulin resistance is caused by the inability of insulin to regulate FoxO1 transcriptional activation of MTP [commentary] (PMID:18497882)
• FoxO1 mediates insulin regulation of MTP production and augmented MTP levels may be a causative factor for VLDL overproduction and hypertriglyceridemia in diabetes (PMID:18497885)
• Microsomal triglyceride transfer protein regulates endogenous and exogenous antigen presentation by group 1 CD1 molecules. (PMID:18624350)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mttp	ENSDARG00000008637
mus_musculus	Mttp	ENSMUSG00000028158
rattus_norvegicus	Mttp	ENSRNOG00000010655
drosophila_melanogaster	Mtp	FBGN0266369
caenorhabditis_elegans		WBGENE00001099

Protein

Protein identifiers

Microsomal triglyceride transfer protein large subunit — P55157 (reviewed: P55157)

All UniProt accessions (4): P55157, D6R915, D6RAB8, E9PBP6

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces. Required for the assembly and secretion of plasma lipoproteins that contain apolipoprotein B. May be involved in regulating cholesteryl ester biosynthesis in cells that produce lipoproteins.

Subunit / interactions. Heterodimer; heterodimerizes with the protein disulfide isomerase (P4HB/PDI). Interacts with APOB. Interacts with PRAP1.

Subcellular location. Endoplasmic reticulum. Golgi apparatus.

Tissue specificity. Liver and small intestine. Also found in ovary, testis and kidney.

Disease relevance. Abetalipoproteinemia (ABL) [MIM:200100] An autosomal recessive disorder of lipoprotein metabolism. Affected individuals produce virtually no circulating apolipoprotein B-containing lipoproteins (chylomicrons, VLDL, LDL, lipoprotein(A)). Malabsorption of the antioxidant vitamin E occurs, leading to spinocerebellar and retinal degeneration. The disease is caused by variants affecting the gene represented in this entry.

Induction. Positively regulated by cholesterol and negatively regulated by insulin.

Isoforms (2)

UniProt ID	Names	Canonical?
P55157-1	1	yes
P55157-2	2

RefSeq proteins (3): NP_000244, NP_001287714, NP_001373069* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001747	Vitellogenin_N	Domain
IPR011030	Lipovitellin_superhlx_dom	Homologous_superfamily
IPR015816	Vitellinogen_b-sht_N	Homologous_superfamily
IPR015819	Lipid_transp_b-sht_shell	Homologous_superfamily
IPR039988	MTTP	Family
IPR045811	MTP_lip-bd	Domain

Pfam: PF01347, PF19444

Catalyzed reactions (Rhea), 4 shown:

• a 1,2-diacyl-sn-glycero-3-phosphocholine(in) = a 1,2-diacyl-sn-glycero-3-phosphocholine(out) (RHEA:38571)
• a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) = a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(out) (RHEA:38895)
• a cholesterol ester(in) = a cholesterol ester(out) (RHEA:39007)
• a triacyl-sn-glycerol(in) = a triacyl-sn-glycerol(out) (RHEA:39011)

UniProt features (102 total): strand 34, helix 26, sequence variant 18, mutagenesis site 12, turn 5, splice variant 2, signal peptide 1, chain 1, domain 1, disulfide bond 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6I7S	X-RAY DIFFRACTION	2.5
8EOJ	ELECTRON MICROSCOPY	3.07

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55157-F1	86.73	0.56

Functional residue map

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

Disulfide bonds (1): 174–194

Mutagenesis-validated functional residues (12):

Position	Phenotype
169	no loss on localization to the endoplasmic reticulum and does not reduce interaction with apob or p4hb/pdi, does partial
187	no loss on localization to the endoplasmic reticulum and does not reduce interaction with apob, but inhibits interaction
187	no loss on localization to the endoplasmic reticulum, does not reduce interaction with apob or p4hb/pdi, partially inhib
189	no loss on localization to the endoplasmic reticulum and does not reduce interaction with apob, but inhibits interaction
189	no loss on localization to the endoplasmic reticulum, does not reduce interaction with apob or p4hb/pdi, partially inhib
435	no loss on localization to the endoplasmic reticulum. inhibits triglyceride transfer activity.
435	no loss on localization to the endoplasmic reticulum. does not inhibit triglyceride transfer activity.
528	does not inhibit triglyceride transfer activity.
528	inhibits triglyceride transfer activity.
540	strongly reduces triglyceride transfer activity.
540	does not inhibit triglyceride transfer activity and apolipoprotein b secretion.
878	inhibits triglyceride transfer activity.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-8866423	VLDL assembly
R-HSA-8963888	Chylomicron assembly
R-HSA-8964041	LDL remodeling
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-382551	Transport of small molecules
R-HSA-8963898	Plasma lipoprotein assembly
R-HSA-8963899	Plasma lipoprotein remodeling

MSigDB gene sets: 395 (showing top): GOBP_CIRCADIAN_RHYTHM, RNGTGGGC_UNKNOWN, FREAC2_01, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_STEROL_HOMEOSTASIS, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, GOBP_GLUTAMINE_FAMILY_AMINO_ACID_METABOLIC_PROCESS, HNF1_Q6, GOBP_PROTEIN_LIPID_COMPLEX_ASSEMBLY, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS

GO Biological Process (19): lipid metabolic process (GO:0006629), triglyceride metabolic process (GO:0006641), circadian rhythm (GO:0007623), protein secretion (GO:0009306), phospholipid transport (GO:0015914), triglyceride transport (GO:0034197), low-density lipoprotein particle remodeling (GO:0034374), plasma lipoprotein particle assembly (GO:0034377), chylomicron assembly (GO:0034378), very-low-density lipoprotein particle assembly (GO:0034379), lipoprotein metabolic process (GO:0042157), cholesterol homeostasis (GO:0042632), lipoprotein transport (GO:0042953), response to calcium ion (GO:0051592), establishment of localization in cell (GO:0051649), lipid transport (GO:0006869), sterol transport (GO:0015918), intermembrane lipid transfer (GO:0120009), ceramide 1-phosphate transport (GO:1902389)

GO Molecular Function (13): lipid carrier activity (GO:0005319), obsolete phospholipid transporter activity (GO:0005548), lipid binding (GO:0008289), apolipoprotein binding (GO:0034185), protein-containing complex binding (GO:0044877), protein heterodimerization activity (GO:0046982), phospholipid transfer activity (GO:0120014), phosphatidylcholine transfer activity (GO:0120019), cholesterol transfer activity (GO:0120020), triglyceride transfer activity (GO:0140344), ceramide 1-phosphate transfer activity (GO:1902388), phosphatidylethanolamine transfer activity (GO:1904121), protein binding (GO:0005515)

GO Cellular Component (9): endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), Golgi apparatus (GO:0005794), cytosol (GO:0005829), basolateral plasma membrane (GO:0016323), brush border membrane (GO:0031526), microvillus membrane (GO:0031528), vesicle (GO:0031982), signaling receptor complex (GO:0043235)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Plasma lipoprotein assembly	2
Plasma lipoprotein assembly, remodeling, and clearance	2
Plasma lipoprotein remodeling	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid transport	3
binding	3
phospholipid transfer activity	3
cytoplasm	3
protein transport	2
plasma lipoprotein particle assembly	2
phospholipid transport	2
lipid transfer activity	2
endomembrane system	2
intracellular membrane-bounded organelle	2
cell projection membrane	2
primary metabolic process	1
acylglycerol metabolic process	1
rhythmic process	1
secretion by cell	1
establishment of protein localization to extracellular region	1
protein localization to extracellular region	1
organophosphate ester transport	1
acylglycerol transport	1
plasma lipoprotein particle remodeling	1
protein-lipid complex assembly	1
plasma lipoprotein particle organization	1
regulation of plasma lipoprotein particle levels	1
protein metabolic process	1
sterol homeostasis	1
lipoprotein localization	1
response to metal ion	1
establishment of localization	1
cellular localization	1
transport	1
lipid localization	1
organic hydroxy compound transport	1
membrane organization	1
ceramide transport	1
molecular carrier activity	1
protein binding	1
protein dimerization activity	1
phospholipid binding	1
phosphatidylcholine binding	1
cholesterol binding	1

Protein interactions and networks

STRING

1408 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTTP	APOB	P04114	999
MTTP	APOO	Q9BUR5	837
MTTP	HMGCR	P04035	776
MTTP	APOA1	P02647	753
MTTP	SREBF1	P36956	749
MTTP	DGAT1	O75907	746
MTTP	HNF4A	P41235	739
MTTP	LPA	P08519	727
MTTP	APOE	P02649	726
MTTP	GPT	P24298	723
MTTP	SAR1B	Q9Y6B6	699
MTTP	APOA4	P06727	694
MTTP	PPARA	Q07869	679
MTTP	PNPLA2	Q96AD5	677
MTTP	FASN	P49327	674

IntAct

14 interactions, top by confidence:

A	B	Type	Score
MTTP	PDIA3	psi-mi:“MI:0915”(physical association)	0.740
MTTP	PDIA3	psi-mi:“MI:0403”(colocalization)	0.740
MTTP	APOB	psi-mi:“MI:0915”(physical association)	0.700
MTTP	SNW1	psi-mi:“MI:0915”(physical association)	0.400
		psi-mi:“MI:0914”(association)	0.350
UGT2B7	ACTN4	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): MTTP (Two-hybrid), MTTP (Affinity Capture-Western), MTTP (Affinity Capture-Western), MTTP (Affinity Capture-Western), MTTP (Affinity Capture-MS), MTTP (Affinity Capture-MS), SNW1 (Proximity Label-MS), MTTP (Affinity Capture-MS), MTTP (Proximity Label-MS), MTTP (Affinity Capture-MS), MTTP (Positive Genetic), PRKDC (Cross-Linking-MS (XL-MS)), MTTP (Affinity Capture-MS), MTTP (Affinity Capture-MS), MTTP (Proximity Label-MS)

ESM2 similar proteins: A0A0N6WHT4, A0A0R4IVV0, A4IH88, D4A1W8, E9Q414, F1PCT7, O08601, O75787, P02845, P04114, P05690, P06125, P18709, P18947, P18948, P25235, P55155, P55156, P55157, P55158, P81134, P87498, Q05808, Q25490, Q27309, Q2VQM5, Q2VQM6, Q3SZI6, Q3UUQ7, Q5R563, Q6AXS4, Q6DDG2, Q6RG02, Q765A7, Q7TMA5, Q7Z1M0, Q865F1, Q868N5, Q90243, Q90508

Diamond homologs: A0A0N6WHT4, A0A0R4IVV0, D4A1W8, O08601, P55156, P55157, P55158, Q865F1

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SREBF1	“up-regulates quantity by expression”	MTTP	“transcriptional regulation”
MTTP	“up-regulates activity”	APOB	lipidation

Disease & clinical

Clinical variants and AI predictions

ClinVar

1250 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	79
Likely pathogenic	91
Uncertain significance	391
Likely benign	554
Benign	62

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1028157	NM_001386140.1(MTTP):c.2578G>T (p.Glu860Ter)	Pathogenic
1069670	NC_000004.11:g.(?_100522557)_100534157del	Pathogenic
1070986	NM_001386140.1(MTTP):c.290del (p.Gly97fs)	Pathogenic
1072850	NM_001386140.1(MTTP):c.419dup (p.Asn140fs)	Pathogenic
1072851	NM_001386140.1(MTTP):c.2218-2A>G	Pathogenic
1323301	NM_001386140.1(MTTP):c.501+1G>A	Pathogenic
1355057	NM_001386140.1(MTTP):c.1708G>T (p.Glu570Ter)	Pathogenic
1356942	NM_001386140.1(MTTP):c.598G>T (p.Gly200Ter)	Pathogenic
1373188	NM_001386140.1(MTTP):c.2126dup (p.Tyr710fs)	Pathogenic
1401466	NC_000004.11:g.(?100495488)(100510917_?)del	Pathogenic
1407188	NM_001386140.1(MTTP):c.2256_2257insCCAATATA (p.Val753delinsProIleTer)	Pathogenic
1407271	NM_001386140.1(MTTP):c.924G>A (p.Trp308Ter)	Pathogenic
1411259	NM_001386140.1(MTTP):c.83T>G (p.Leu28Ter)	Pathogenic
1421683	NM_001386140.1(MTTP):c.1815T>A (p.Tyr605Ter)	Pathogenic
14234	NM_001386140.1(MTTP):c.215del (p.Pro72fs)	Pathogenic
14235	NM_001386140.1(MTTP):c.1783C>T (p.Arg595Ter)	Pathogenic
14237	NM_001386140.1(MTTP):c.1237-1G>A	Pathogenic
14239	NM_001386140.1(MTTP):c.1237_1344del (p.Ser413_Lys448del)	Pathogenic
14240	NM_001386140.1(MTTP):c.2338A>T (p.Asn780Tyr)	Pathogenic
14241	NM_001386140.1(MTTP):c.1769G>T (p.Ser590Ile)	Pathogenic
14243	NM_001386140.1(MTTP):c.2593G>T (p.Gly865Ter)	Pathogenic
1437947	NM_001386140.1(MTTP):c.1616_1617del (p.Val539fs)	Pathogenic
1450470	NM_001386140.1(MTTP):c.988del (p.Leu330fs)	Pathogenic
1452643	NM_001386140.1(MTTP):c.1026_1030dup (p.Ile344fs)	Pathogenic
1454038	NM_001386140.1(MTTP):c.2349dup (p.Val784fs)	Pathogenic
1455229	NM_001386140.1(MTTP):c.534C>A (p.Tyr178Ter)	Pathogenic
1455866	NM_001386140.1(MTTP):c.2335A>T (p.Lys779Ter)	Pathogenic
1455885	NM_001386140.1(MTTP):c.1686_1689del (p.Ser563fs)	Pathogenic
1458029	NM_001386140.1(MTTP):c.1401dup (p.Glu468fs)	Pathogenic
1687508	NM_001386140.1(MTTP):c.640del (p.Ala214fs)	Pathogenic

SpliceAI

2658 predictions. Top by Δscore:

Variant	Effect	Δscore
4:99583370:CCA:C	acceptor_loss	1.0000
4:99583370:CCAGA:C	acceptor_gain	1.0000
4:99583372:A:AG	acceptor_gain	1.0000
4:99583372:A:T	acceptor_loss	1.0000
4:99583372:AGAT:A	acceptor_gain	1.0000
4:99583373:G:GA	acceptor_gain	1.0000
4:99583373:GA:G	acceptor_gain	1.0000
4:99583373:GAT:G	acceptor_gain	1.0000
4:99583373:GATG:G	acceptor_gain	1.0000
4:99583373:GATGA:G	acceptor_gain	1.0000
4:99583514:A:T	donor_gain	1.0000
4:99583514:AAAGG:A	donor_loss	1.0000
4:99583515:AAGG:A	donor_loss	1.0000
4:99583516:AGG:A	donor_loss	1.0000
4:99583517:GGTAA:G	donor_loss	1.0000
4:99583518:G:A	donor_loss	1.0000
4:99583519:T:A	donor_loss	1.0000
4:99591348:TCAG:T	donor_loss	1.0000
4:99591349:CAGGT:C	donor_loss	1.0000
4:99591350:AGG:A	donor_loss	1.0000
4:99591351:GGTA:G	donor_loss	1.0000
4:99591352:G:GA	donor_loss	1.0000
4:99591353:T:A	donor_loss	1.0000
4:99591647:TTAG:T	acceptor_loss	1.0000
4:99591784:TATCG:T	donor_gain	1.0000
4:99591785:ATCGA:A	donor_gain	1.0000
4:99591788:G:GT	donor_gain	1.0000
4:99591788:GAA:G	donor_gain	1.0000
4:99591790:AG:A	donor_loss	1.0000
4:99591791:G:A	donor_loss	1.0000

AlphaMissense

5872 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:99619066:G:C	W770C	0.998
4:99619066:G:T	W770C	0.998
4:99621197:T:A	C827S	0.998
4:99621197:T:C	C827R	0.998
4:99621198:G:A	C827Y	0.998
4:99621198:G:C	C827S	0.998
4:99621199:C:G	C827W	0.998
4:99611400:A:C	S646R	0.997
4:99611402:T:A	S646R	0.997
4:99611402:T:G	S646R	0.997
4:99619058:A:C	S768R	0.997
4:99619060:C:A	S768R	0.997
4:99619060:C:G	S768R	0.997
4:99619064:T:A	W770R	0.997
4:99619064:T:C	W770R	0.997
4:99619076:T:C	S774P	0.997
4:99622795:T:A	C878S	0.997
4:99622796:G:C	C878S	0.997
4:99613061:T:C	L713S	0.996
4:99619062:T:C	L769S	0.996
4:99622796:G:A	C878Y	0.996
4:99622797:C:G	C878W	0.996
4:99621198:G:T	C827F	0.995
4:99622795:T:C	C878R	0.995
4:99622796:G:T	C878F	0.995
4:99591253:T:A	C174S	0.994
4:99591254:G:C	C174S	0.994
4:99611362:T:C	L633P	0.994
4:99621174:T:C	F819S	0.994
4:99621174:T:G	F819C	0.994

dbSNP variants (sampled 300 via entrez): RS1000012827 (4:99610854 T>C), RS1000063307 (4:99571895 T>A), RS1000078429 (4:99595366 C>T), RS1000094006 (4:99562471 T>C,G), RS1000116645 (4:99572167 A>C), RS1000232054 (4:99579025 A>G,T), RS1000276994 (4:99589490 T>C), RS1000398830 (4:99623589 C>G), RS1000417569 (4:99600414 GAA>G), RS1000495944 (4:99568765 G>A), RS1000524433 (4:99617716 GAA>G,GA,GAAA), RS1000543879 (4:99604959 A>C), RS1000595179 (4:99565806 TGAA>T), RS1000611842 (4:99612506 G>A), RS1000640400 (4:99604614 C>G,T)

Disease associations

OMIM: gene MIM:157147 | disease phenotypes: MIM:200100, MIM:605552

GenCC curated gene-disease

Disease	Classification	Inheritance
abetalipoproteinemia	Definitive	Autosomal recessive

Mondo (3): abetalipoproteinemia (MONDO:0008692), metabolic syndrome X (MONDO:0011565), retinal disorder (MONDO:0005283)

Orphanet (1): Abetalipoproteinemia (Orphanet:14)

HPO phenotypes

69 total (30 of 69 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000488	Retinopathy
HP:0000508	Ptosis
HP:0000510	Rod-cone dystrophy
HP:0000529	Progressive visual loss
HP:0000546	Retinal degeneration
HP:0000551	Color vision defect
HP:0000575	Scotoma
HP:0000602	Ophthalmoplegia
HP:0000618	Blindness
HP:0000662	Nyctalopia
HP:0000707	Abnormality of the nervous system
HP:0000821	Hypothyroidism
HP:0000938	Osteopenia
HP:0001097	Keratoconjunctivitis sicca
HP:0001251	Ataxia
HP:0001260	Dysarthria
HP:0001284	Areflexia
HP:0001310	Dysmetria
HP:0001394	Cirrhosis
HP:0001395	Hepatic fibrosis
HP:0001397	Hepatic steatosis
HP:0001508	Failure to thrive
HP:0001635	Congestive heart failure
HP:0001640	Cardiomegaly
HP:0001761	Pes cavus
HP:0001762	Talipes equinovarus
HP:0001892	Abnormal bleeding
HP:0001903	Anemia
HP:0001923	Reticulocytosis

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002112_3	Celiac disease	5.000000e-06
GCST006611_3	HDL cholesterol	8.000000e-13
GCST006921_3	Regular attendance at a pub or social club	4.000000e-25
GCST010244_318	Triglyceride levels	6.000000e-15
GCST90013405_28	Liver enzyme levels (alanine transaminase)	1.000000e-12
GCST90013663_36	Alanine aminotransferase levels	1.000000e-10
GCST90013664_13	Aspartate aminotransferase levels	3.000000e-10
GCST90016673_1	Percent liver fat	2.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009592	social interaction measurement
EFO:0004530	triglyceride measurement
EFO:0004736	aspartate aminotransferase measurement
EFO:0010821	liver fat measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D000012	Abetalipoproteinemia	C16.320.565.398.500.440.500; C18.452.584.500.875.440.500; C18.452.584.563.500.440.500; C18.452.648.398.500.440.500
D024821	Metabolic Syndrome	C18.452.394.968.500.570; C18.452.625
D012164	Retinal Diseases	C11.768

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2364681 (PROTEIN COMPLEX), CHEMBL2569 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,322 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL2105662	LOMITAPIDE MESYLATE	4	96
CHEMBL354541	LOMITAPIDE	4	1,163
CHEMBL410414	DIRLOTAPIDE	2	1,063

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

ChEMBL bioactivities

189 potent at pChembl≥5 of 189 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.95	IC50	0.0113	nM	DIRLOTAPIDE
10.70	IC50	0.02	nM	CHEMBL355892
10.68	IC50	0.021	nM	CHEMBL2147296
10.60	IC50	0.025	nM	CHEMBL2147292
10.52	IC50	0.03	nM	CHEMBL355007
10.24	IC50	0.058	nM	CHEMBL2147294
10.22	IC50	0.06	nM	CHEMBL168680
10.18	IC50	0.066	nM	CHEMBL2147293
10.00	IC50	0.101	nM	CHEMBL2147301
9.98	IC50	0.105	nM	CHEMBL2147298
9.91	IC50	0.122	nM	CHEMBL2147299
9.82	IC50	0.15	nM	CHEMBL168216
9.62	IC50	0.24	nM	CHEMBL353385
9.60	IC50	0.253	nM	CHEMBL2147295
9.46	IC50	0.345	nM	CHEMBL2147280
9.42	IC50	0.378	nM	CHEMBL2147279
9.36	IC50	0.44	nM	CHEMBL2147285
9.31	IC50	0.484	nM	CHEMBL2147300
9.26	IC50	0.55	nM	CHEMBL2147284
9.25	IC50	0.56	nM	CHEMBL2147296
9.22	IC50	0.6	nM	CHEMBL2147286
9.22	IC50	0.6	nM	CHEMBL474892
9.20	IC50	0.63	nM	CHEMBL2147301
9.13	IC50	0.74	nM	CHEMBL2147281
9.11	IC50	0.77	nM	CHEMBL2147290
9.10	IC50	0.8	nM	LOMITAPIDE
9.08	IC50	0.83	nM	CHEMBL2147291
9.05	IC50	0.9	nM	CHEMBL423915
9.00	IC50	1	nM	CHEMBL355007
9.00	IC50	1	nM	CHEMBL168216
9.00	IC50	1	nM	CHEMBL355892
9.00	IC50	1.01	nM	CHEMBL126377
8.96	IC50	1.1	nM	CHEMBL2147292
8.92	IC50	1.2	nM	CHEMBL2147287
8.92	IC50	1.21	nM	CHEMBL2146489
8.92	IC50	1.2	nM	CHEMBL2147297
8.82	IC50	1.5	nM	CHEMBL2147280
8.79	IC50	1.64	nM	CHEMBL382891
8.78	IC50	1.68	nM	CHEMBL207354
8.76	IC50	1.75	nM	CHEMBL210652
8.75	IC50	1.78	nM	CHEMBL378844
8.74	IC50	1.8	nM	CHEMBL2147279
8.70	IC50	2	nM	CHEMBL353483
8.70	IC50	2	nM	CHEMBL377951
8.66	IC50	2.2	nM	CHEMBL2147283
8.63	IC50	2.34	nM	CHEMBL380472
8.60	IC50	2.53	nM	CHEMBL207443
8.57	IC50	2.7	nM	DIRLOTAPIDE
8.55	IC50	2.8	nM	CHEMBL2147282
8.55	IC50	2.8	nM	CHEMBL2147289

PubChem BioAssay actives

197 with measured affinity, of 243 total; 50 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
9-[4-[5-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]benzimidazol-1-yl]butyl]-N-(2,2,2-trifluoroethyl)fluorene-9-carboxamide	105915: In vitro inhibition of human microsomal triglyceride transfer protein in HepG2 cells using apoB secretion assay	ic50	<0.0001	uM
2-[[2-(4-tert-butylphenyl)benzoyl]amino]-N-[(1S)-2-[(4-fluorophenyl)methyl-methylamino]-2-oxo-1-phenylethyl]quinoline-6-carboxamide	688268: Inhibition of MTP in human HepG2 cells assessed as unbound drug level causing inhibition of apoB secretion after 40 hrs by ELISA	ic50	<0.0001	uM
2-[[2-(4-tert-butylphenyl)benzoyl]amino]-N-[(1S)-2-[(4-fluorophenyl)methylamino]-2-oxo-1-phenylethyl]quinoline-6-carboxamide	688268: Inhibition of MTP in human HepG2 cells assessed as unbound drug level causing inhibition of apoB secretion after 40 hrs by ELISA	ic50	<0.0001	uM
N-[(1S)-2-[(4-fluorophenyl)methyl-methylamino]-2-oxo-1-phenylethyl]-2-[[2-(4-propan-2-yloxyphenyl)benzoyl]amino]quinoline-6-carboxamide	688268: Inhibition of MTP in human HepG2 cells assessed as unbound drug level causing inhibition of apoB secretion after 40 hrs by ELISA	ic50	<0.0001	uM
N-[(1S)-2-[(4-fluorophenyl)methyl-methylamino]-2-oxo-1-phenylethyl]-2-[[2-(4-methylphenyl)benzoyl]amino]quinoline-6-carboxamide	688268: Inhibition of MTP in human HepG2 cells assessed as unbound drug level causing inhibition of apoB secretion after 40 hrs by ELISA	ic50	<0.0001	uM
2-[[2-(4-tert-butylphenyl)benzoyl]amino]-N-[(1S)-2-(methylamino)-2-oxo-1-phenylethyl]quinoline-6-carboxamide	688268: Inhibition of MTP in human HepG2 cells assessed as unbound drug level causing inhibition of apoB secretion after 40 hrs by ELISA	ic50	<0.0001	uM
N-[(1S)-2-[(4-fluorophenyl)methyl-methylamino]-2-oxo-1-phenylethyl]-2-[[2-(4-propan-2-ylphenyl)benzoyl]amino]quinoline-6-carboxamide	688268: Inhibition of MTP in human HepG2 cells assessed as unbound drug level causing inhibition of apoB secretion after 40 hrs by ELISA	ic50	<0.0001	uM
N-[(1S)-2-[(4-fluorophenyl)methyl-methylamino]-2-oxo-1-phenylethyl]-2-[[2-[4-(1-hydroxy-2-methylpropan-2-yl)phenyl]benzoyl]amino]quinoline-6-carboxamide	688268: Inhibition of MTP in human HepG2 cells assessed as unbound drug level causing inhibition of apoB secretion after 40 hrs by ELISA	ic50	<0.0001	uM
N-[(1S)-2-[(4-fluorophenyl)methyl-methylamino]-2-oxo-1-phenylethyl]-2-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]quinoline-6-carboxamide	688268: Inhibition of MTP in human HepG2 cells assessed as unbound drug level causing inhibition of apoB secretion after 40 hrs by ELISA	ic50	<0.0001	uM
N-[(1S)-2-[(4-fluorophenyl)methylamino]-2-oxo-1-phenylethyl]-2-[[2-(4-propan-2-yloxyphenyl)benzoyl]amino]quinoline-6-carboxamide	688268: Inhibition of MTP in human HepG2 cells assessed as unbound drug level causing inhibition of apoB secretion after 40 hrs by ELISA	ic50	<0.0001	uM
9-[4-[2,5-dimethyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]benzimidazol-1-yl]butyl]-N-(2,2,2-trifluoroethyl)fluorene-9-carboxamide	105915: In vitro inhibition of human microsomal triglyceride transfer protein in HepG2 cells using apoB secretion assay	ic50	<0.0001	uM
N-[(1S)-2-[benzyl(methyl)amino]-2-oxo-1-phenylethyl]-1-methyl-5-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]indole-2-carboxamide	688268: Inhibition of MTP in human HepG2 cells assessed as unbound drug level causing inhibition of apoB secretion after 40 hrs by ELISA	ic50	<0.0001	uM
9-[4-[2-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]benzimidazol-1-yl]butyl]-N-(2,2,2-trifluoroethyl)fluorene-9-carboxamide	105915: In vitro inhibition of human microsomal triglyceride transfer protein in HepG2 cells using apoB secretion assay	ic50	0.0001	uM
9-[4-[2-propan-2-yl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]benzimidazol-1-yl]butyl]-N-(2,2,2-trifluoroethyl)fluorene-9-carboxamide	105915: In vitro inhibition of human microsomal triglyceride transfer protein in HepG2 cells using apoB secretion assay	ic50	0.0001	uM
N-[(1S)-2-[(4-fluorophenyl)methylamino]-2-oxo-1-phenylethyl]-2-[[2-[4-(1-hydroxy-2-methylpropan-2-yl)phenyl]benzoyl]amino]quinoline-6-carboxamide	688268: Inhibition of MTP in human HepG2 cells assessed as unbound drug level causing inhibition of apoB secretion after 40 hrs by ELISA	ic50	0.0001	uM
N-[(1S)-2-[(4-fluorophenyl)methyl-methylamino]-2-oxo-1-phenylethyl]-2-[[2-[4-(1-hydroxypropan-2-yloxy)phenyl]benzoyl]amino]quinoline-6-carboxamide	688268: Inhibition of MTP in human HepG2 cells assessed as unbound drug level causing inhibition of apoB secretion after 40 hrs by ELISA	ic50	0.0001	uM
2-[4-[2-[[6-[[(1S)-2-[(4-fluorophenyl)methyl-methylamino]-2-oxo-1-phenylethyl]carbamoyl]quinolin-2-yl]carbamoyl]phenyl]phenyl]-2-methylpropanoic acid	688268: Inhibition of MTP in human HepG2 cells assessed as unbound drug level causing inhibition of apoB secretion after 40 hrs by ELISA	ic50	0.0001	uM
N-[(1S)-2-(methylamino)-2-oxo-1-phenylethyl]-2-[[2-(4-propan-2-yloxyphenyl)benzoyl]amino]quinoline-6-carboxamide	688268: Inhibition of MTP in human HepG2 cells assessed as unbound drug level causing inhibition of apoB secretion after 40 hrs by ELISA	ic50	0.0001	uM
N-[(1S)-2-[(4-fluorophenyl)methyl-methylamino]-2-oxo-1-phenylethyl]-2-[[2-(4-hydroxyphenyl)benzoyl]amino]quinoline-6-carboxamide	688268: Inhibition of MTP in human HepG2 cells assessed as unbound drug level causing inhibition of apoB secretion after 40 hrs by ELISA	ic50	0.0001	uM
N-(2,2,2-trifluoroethyl)-9-[4-[4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]benzimidazol-1-yl]butyl]fluorene-9-carboxamide	105915: In vitro inhibition of human microsomal triglyceride transfer protein in HepG2 cells using apoB secretion assay	ic50	0.0002	uM
N-[(1S)-2-amino-2-oxo-1-phenylethyl]-1-methyl-5-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]indole-2-carboxamide	688268: Inhibition of MTP in human HepG2 cells assessed as unbound drug level causing inhibition of apoB secretion after 40 hrs by ELISA	ic50	0.0003	uM
2-[4-[2-[[6-[[(1S)-2-[(4-fluorophenyl)methylamino]-2-oxo-1-phenylethyl]carbamoyl]quinolin-2-yl]carbamoyl]phenyl]phenyl]-2-methylpropanoic acid	688268: Inhibition of MTP in human HepG2 cells assessed as unbound drug level causing inhibition of apoB secretion after 40 hrs by ELISA	ic50	0.0003	uM
1-methyl-N-[(1S)-2-(methylamino)-2-oxo-1-phenylethyl]-5-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]indole-2-carboxamide	688268: Inhibition of MTP in human HepG2 cells assessed as unbound drug level causing inhibition of apoB secretion after 40 hrs by ELISA	ic50	0.0004	uM
N-[(1S)-2-[(4-fluorophenyl)methyl-methylamino]-2-oxo-1-phenylethyl]-2-[[2-(4-propylphenyl)benzoyl]amino]quinoline-6-carboxamide	688269: Inhibition of MTP in human HepG2 cells assessed as inhibition of apoB secretion after 40 hrs by ELISA	ic50	0.0004	uM
2-[4-[2-[[6-[[(1S)-2-[(4-fluorophenyl)methyl-methylamino]-2-oxo-1-phenylethyl]carbamoyl]quinolin-2-yl]carbamoyl]phenyl]phenoxy]propanoic acid	688268: Inhibition of MTP in human HepG2 cells assessed as unbound drug level causing inhibition of apoB secretion after 40 hrs by ELISA	ic50	0.0005	uM
3-methyl-N-[(2R)-2-(1,3-thiazol-2-ylmethylamino)-2,3-dihydro-1H-inden-5-yl]-2-[4-(trifluoromethyl)phenyl]benzamide	392426: Inhibition of MTP in human HepG2 cells assessed as apolipoprotein B production by ELISA	ic50	0.0006	uM
2-[[2-(4-ethylphenyl)benzoyl]amino]-N-[(1S)-2-[(4-fluorophenyl)methyl-methylamino]-2-oxo-1-phenylethyl]quinoline-6-carboxamide	688269: Inhibition of MTP in human HepG2 cells assessed as inhibition of apoB secretion after 40 hrs by ELISA	ic50	0.0006	uM
N-[(1S)-2-[(4-fluorophenyl)methyl-methylamino]-2-oxo-1-phenylethyl]-2-[[2-[4-[(2-methylpropan-2-yl)oxy]phenyl]benzoyl]amino]quinoline-6-carboxamide	688269: Inhibition of MTP in human HepG2 cells assessed as inhibition of apoB secretion after 40 hrs by ELISA	ic50	0.0008	uM
Lomitapide	105916: In vitro inhibition of human microsomal triglyceride transfer protein in HepG2 cells using apoB secretion assay	ic50	0.0008	uM
methyl N-[(2R)-5-[[3-methyl-2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-2,3-dihydro-1H-inden-2-yl]carbamate	392426: Inhibition of MTP in human HepG2 cells assessed as apolipoprotein B production by ELISA	ic50	0.0009	uM
N-[(1S)-2-(cyclopropylmethylamino)-2-oxo-1-phenylethyl]-2-methoxy-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]benzamide	266349: Inhibition of MTP in canine liver microsomes	ic50	0.0010	uM
3-methyl-N-[(1S)-2-oxo-1-phenyl-2-(propylamino)ethyl]-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]benzamide	266349: Inhibition of MTP in canine liver microsomes	ic50	0.0016	uM
N-[(1S)-2-(cyclopropylmethylamino)-2-oxo-1-phenylethyl]-3-methoxy-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]benzamide	266349: Inhibition of MTP in canine liver microsomes	ic50	0.0017	uM
3-methoxy-N-[(1S)-2-oxo-1-phenyl-2-pyrrolidin-1-ylethyl]-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]benzamide	266349: Inhibition of MTP in canine liver microsomes	ic50	0.0018	uM
N-[(1S)-2-(cyclopropylmethylamino)-2-oxo-1-phenylethyl]-3-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]benzamide	266349: Inhibition of MTP in canine liver microsomes	ic50	0.0018	uM
9-[4-[2-propyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]benzimidazol-1-yl]butyl]-N-(2,2,2-trifluoroethyl)fluorene-9-carboxamide	105914: In vitro inhibition of human Microsomal Triglyceride Transfer Protein, (triglyceride transfer assay)	ic50	0.0020	uM
3-methoxy-N-[(1S)-2-oxo-1-phenyl-2-(propylamino)ethyl]-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]benzamide	266349: Inhibition of MTP in canine liver microsomes	ic50	0.0020	uM
N-[(1S)-2-[ethyl(propyl)amino]-2-oxo-1-phenylethyl]-3-methoxy-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]benzamide	266349: Inhibition of MTP in canine liver microsomes	ic50	0.0023	uM
N-[(1S)-2-oxo-1-phenyl-2-(propylamino)ethyl]-6-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]pyridine-3-carboxamide	266349: Inhibition of MTP in canine liver microsomes	ic50	0.0025	uM
2-[[2-(4-ethoxyphenyl)benzoyl]amino]-N-[(1S)-2-[(4-fluorophenyl)methyl-methylamino]-2-oxo-1-phenylethyl]quinoline-6-carboxamide	688269: Inhibition of MTP in human HepG2 cells assessed as inhibition of apoB secretion after 40 hrs by ELISA	ic50	0.0028	uM
N-[(1S)-2-[(4-fluorophenyl)methyl-methylamino]-2-oxo-1-phenylethyl]-2-[(2-phenylbenzoyl)amino]quinoline-6-carboxamide	688269: Inhibition of MTP in human HepG2 cells assessed as inhibition of apoB secretion after 40 hrs by ELISA	ic50	0.0028	uM
N-[(1S)-2-[(4-fluorophenyl)methyl-methylamino]-2-oxo-1-phenylethyl]-2-[[2-(4-methoxyphenyl)benzoyl]amino]quinoline-6-carboxamide	688269: Inhibition of MTP in human HepG2 cells assessed as inhibition of apoB secretion after 40 hrs by ELISA	ic50	0.0030	uM
9-[4-[5-[[2-(1,3-benzoxazol-2-yl)benzoyl]amino]-2-oxo-1,3,2lambda5-dioxaphosphinan-2-yl]butyl]-N-(2,2,2-trifluoroethyl)fluorene-9-carboxamide	248670: In vitro inhibitory concentration against human Microsomal triglyceride transfer protein	ic50	0.0030	uM
N-[[4-[[(1S)-2-(benzylamino)-2-oxo-1-phenylethyl]carbamoyl]phenyl]methyl]-2-[4-(trifluoromethyl)phenyl]benzamide	266349: Inhibition of MTP in canine liver microsomes	ic50	0.0030	uM
3-methyl-N-[(1S)-2-oxo-1-phenyl-2-pyrrolidin-1-ylethyl]-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]benzamide	266349: Inhibition of MTP in canine liver microsomes	ic50	0.0034	uM
N-[(1S)-2-(benzylamino)-2-oxo-1-phenylethyl]-3-methyl-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]benzamide	266349: Inhibition of MTP in canine liver microsomes	ic50	0.0035	uM
3-methyl-N-[(2R)-2-(pyridin-2-ylmethylamino)-2,3-dihydro-1H-inden-5-yl]-2-[4-(trifluoromethyl)phenyl]benzamide	392426: Inhibition of MTP in human HepG2 cells assessed as apolipoprotein B production by ELISA	ic50	0.0035	uM
N-[(1S)-2-(benzylamino)-2-oxo-1-phenylethyl]-3-methoxy-4-[[2-[4-(trifluoromethyl)phenyl]benzoyl]amino]benzamide	266349: Inhibition of MTP in canine liver microsomes	ic50	0.0039	uM
N-[[4-[[(1S)-2-[benzyl(methyl)amino]-2-oxo-1-phenylethyl]carbamoyl]phenyl]methyl]-2-[4-(trifluoromethyl)phenyl]benzamide	266349: Inhibition of MTP in canine liver microsomes	ic50	0.0041	uM
methyl N-[(2S)-5-[[3-methyl-2-[4-(trifluoromethyl)phenyl]benzoyl]amino]-2,3-dihydro-1H-inden-2-yl]carbamate	392426: Inhibition of MTP in human HepG2 cells assessed as apolipoprotein B production by ELISA	ic50	0.0043	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	affects expression, decreases expression, increases expression, affects cotreatment	7
Aflatoxin B1	decreases expression, decreases methylation, affects expression	6
Valproic Acid	affects expression, decreases expression	5
Oleic Acid	affects cotreatment, decreases expression, decreases reaction, increases expression	5
sodium arsenite	affects methylation, decreases expression, increases expression	4
Acetaminophen	decreases expression, affects cotreatment	4
Palmitic Acid	affects cotreatment, decreases expression, decreases reaction, increases expression	4
bisphenol A	affects expression, affects cotreatment, affects methylation, increases expression	3
Benzo(a)pyrene	decreases expression, increases methylation	3
Deoxycholic Acid	decreases expression, affects cotreatment	3
Chenodeoxycholic Acid	affects cotreatment, decreases expression	2
Glycochenodeoxycholic Acid	affects cotreatment, decreases expression	2
Glycocholic Acid	affects cotreatment, decreases expression	2
Glycodeoxycholic Acid	affects cotreatment, decreases expression	2
Quercetin	decreases expression	2
Tartrazine	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases expression, decreases expression, increases stability	2
Thapsigargin	decreases expression, increases expression	2
CDN1163	decreases reaction, increases abundance, increases expression	1
fluorotelomer sulfonic acids	increases expression	1
dicrotophos	decreases expression	1
taxifolin	decreases activity	1
lasiocarpine	decreases expression	1
methyleugenol	decreases expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, decreases expression	1
chlortoluron	decreases expression	1
deoxynivalenol	decreases expression	1
trichostatin A	affects expression, decreases reaction	1
enilconazole	decreases expression	1

ChEMBL screening assays

19 unique, capped per target: 15 binding, 4 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1015043	Binding	Inhibition of microsomal triglyceride transfer protein by cell based assay	Design, synthesis, and biological evaluation of (2R,alphaS)-3,4-dihydro-2-[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-5-[3-(trifluoromethoxy)-phenyl]-alpha-(trifluoromethyl)-1(2H)-quinolineethanol as potent and orally active cholesteryl ester transfer protein inhibitor. — J Med Chem
CHEMBL712304	Functional	In vitro inhibition of human microsomal triglyceride transfer protein in HepG2 cells using apoB secretion assay	A novel series of highly potent benzimidazole-based microsomal triglyceride transfer protein inhibitors. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_EL44	PENN144i-M7-16	Induced pluripotent stem cell	Male
CVCL_EL50	PENN150i-M7-9	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00205504	PHASE4	COMPLETED	Oral Contraceptives in the Metabolic Syndrome
NCT00224822	PHASE4	COMPLETED	The Effects of Aripiprazole on Patients With Metabolic Syndrome
NCT00225355	PHASE4	TERMINATED	Rosiglitazone Versus Placebo in Chronic Stable Angina
NCT00242814	PHASE4	COMPLETED	Phase IV, 9 Weeks Comparison Between MICARDIS 80 mg and Amlodipine 10 mg on Biological PPAR Gamma Activities
NCT00272311	PHASE4	COMPLETED	Aspirin Dose and Atherosclerosis in Patients With Metabolic Syndrome
NCT00296803	PHASE4	COMPLETED	PROCLAIM: Study Examining Effects of Clopidogrel Compared to Placebo on Inflammation in Subjects With Metabolic Syndrome
NCT00304993	PHASE4	COMPLETED	Study of Niacin and Rosiglitazone in Dysmetabolic Dyslipidemia
NCT00325936	PHASE4	COMPLETED	The Effects of Cilnidipine on Metabolic Syndrome Improvement
NCT00338949	PHASE4	COMPLETED	Ziprasidone for Improving Insulin Sensitivity in People With Schizophrenia Who Are at Risk for Diabetes
NCT00395486	PHASE4	COMPLETED	ROMEO (Rosuvastatin in Metabolic syndrOme)
NCT00515021	PHASE4	COMPLETED	Diurnal Variation of Plasminogen Activator Inhibitor-1
NCT00573950	PHASE4	UNKNOWN	Effects of Cilostazol on Plasma Adipocytokine and Arterial Stiffness
NCT00608465	PHASE4	TERMINATED	Defining Strategies for Improving Endothelial and Fibrinolytic Dysfunction in Obesity
NCT01887119	PHASE4	TERMINATED	Aldosterone Antagonism and Microvascular Function
NCT02283242	PHASE4	COMPLETED	Galantamine Effects in Patients With Metabolic Syndrome
NCT00147264	PHASE3	COMPLETED	Telmisartan-Induced Reduction in Intra-Myocellular Lipids Trial
NCT00228176	PHASE3	TERMINATED	Atherosclerosis Underlying Development Assessed by Intima-Media Thickness in Patients on Rimonabant
NCT00243984	PHASE3	SUSPENDED	Efficacy of Topiramate for Weight Loss in Subjects With Metabolic Syndrome
NCT00663104	PHASE3	TERMINATED	Effect of Exercise and Phytoestrogen on Bone, Metabolic Syndrome Criteria and Complaints of the Early Menopause
NCT01465620	PHASE3	COMPLETED	Dietetic and Hygiene Measures in Metabolic Neuropathies: the Neurodiet Study
NCT01794429	PHASE3	COMPLETED	Treatment of Antipsychotic-associated Obesity With a GLP-1 Analogue
NCT01849068	PHASE3	COMPLETED	Effects of Selective Inhibition of Cholesterol Absorption With Ezetimibe on Intestinal Cholesterol Homeostasis in Dyslipidemic Men With Insulin-resistance - a Pilot Study
NCT01872182	PHASE3	TERMINATED	Efficacy and Safety Study of ALS-L1023 in Patients With Abdominal Obesity of Metabolic Syndrome
NCT02672592	PHASE3	COMPLETED	Effects of Interleukin-1 Beta on Low Testosterone Levels in Men With Obesity and Metabolic Syndrome
NCT00166036	PHASE2	COMPLETED	Effect of Statins on Oxidative Stress and Endothelial Progenitor Cells
NCT00200993	PHASE2	COMPLETED	Peripheral Effects of Exercise on Cardiovascular Health (STRRIDE I)
NCT00264667	PHASE2	COMPLETED	Study In Patients With Dyslipidaemia
NCT00275145	PHASE2	COMPLETED	Effects of Resistance and Aerobic Exercise on Cardiovascular Health
NCT00327002	PHASE2	COMPLETED	A Mechanistic Study of the Effects of LY518674 on High-Density Lipoprotein Cholesterol (HDL-C) Metabolism
NCT00400231	PHASE2	COMPLETED	The Fenofibrate and Metformin for Atherogenic Dyslipidemia (FAMA) Study
NCT00455325	PHASE2	COMPLETED	Chloroquine to Treat People With Metabolic Syndrome Aim2 (ARCH-MS)
NCT00671515	PHASE2	COMPLETED	Pioglitazone for the Treatment of Major Depressive Disorder Comorbid With Metabolic Syndrome
NCT00675857	PHASE2	COMPLETED	A Phase IIa Proof-of-concept Study of NC-503 in Patients With Type II Diabetes
NCT01145066	PHASE2	COMPLETED	Botanical Oil Supplementation in Diabetic and Metabolic Syndrome Subjects
NCT01351753	PHASE2	TERMINATED	Drug Therapy Induced Weight Loss to Improve Blood Vessel Function in Subjects With Obesity
NCT02017561	PHASE2	COMPLETED	Metformin in the Diastolic Dysfunction of Metabolic Syndrome
NCT02114892	PHASE2	COMPLETED	Effect of Resveratrol Administration on Metabolic Syndrome, Insulin Sensitivity and Insulin Secretion
NCT02288572	PHASE2	COMPLETED	Probiotic Bacteria in Prevention of the Metabolic Syndrome
NCT02337933	PHASE2	COMPLETED	Effect of Ursolic Acid Administration on Insulin Sensitivity and Metabolic Syndrome
NCT02767869	PHASE2	COMPLETED	Effect of Banaba (Lagerstroemia Speciosa) on Metabolic Syndrome, Insulin Secretion and Insulin Sensitivity