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): 1,272 total — 80 pathogenic, 94 likely-pathogenic (top 2% of genes corpus-wide)
• GTEx eGene: eQTL in 10 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 69
• Drug target: yes — 3 via a complex or family; 3 molecules with ChEMBL bioactivity
• Approved drugs acting on a complex or family including it: 1 — Lomitapide Mesylate (Microsomal triglyceride transfer protein)
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.67 (unconstrained)
• 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: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000265517

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 4: 3, TSL 5: 1

ENST00000265517, ENST00000422897, ENST00000457717, ENST00000504724, ENST00000505094, ENST00000511045, ENST00000511610, ENST00001107115

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
ENSE00002440082	99612913	99613140
ENSE00002465266	99611143	99611240
ENSE00002475893	99618974	99619098
ENSE00002515066	99611332	99611453
ENSE00002520237	99621061	99621231
ENSE00002526062	99608766	99608977
ENSE00003651555	99581905	99582092
ENSE00004791264	99622677	99623997

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.

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

Genetic regulation across tissues (GTEx eQTL / sQTL)

MTTP is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 10 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

10 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	6.4e-49	+0.61	4:99529970:G:A
Artery Aorta	eqtl	1.0e-22	+0.72	4:99586989:A:AC
Artery Tibial	eqtl	2.6e-11	+0.35	4:99586989:A:AC
Cells EBV-transformed lymphocytes	eqtl	7.0e-11	-0.30	4:99529555:C:T
Heart Left Ventricle	eqtl	3.2e-04	-0.18	4:99562490:C:G
Ovary	eqtl	5.5e-03	-0.50	4:99720956:A:G
Skin Sun Exposed Lower leg	eqtl	1.3e-02	-0.26	4:99617922:A:ATTGC
Nerve Tibial	eqtl	2.2e-02	+0.63	4:100083641:A:G
Colon Transverse	eqtl	3.0e-02	-0.23	4:99528208:TAAAAG:T
Colon Sigmoid	eqtl	3.4e-02	-0.17	4:99323064:A:G

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

showing 100 of 281 tissues 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
cardiac ventricle	UBERON:0002082	60.36	gold quality
metanephros	UBERON:0000081	59.24	gold quality
muscle layer of sigmoid colon	UBERON:0035805	58.94	gold quality
intestine	UBERON:0000160	58.80	gold quality
sperm	CL:0000019	58.66	silver quality
right ovary	UBERON:0002118	58.37	gold quality
prefrontal cortex	UBERON:0000451	58.33	gold quality
male germ cell	CL:0000015	58.18	silver quality
oocyte	CL:0000023	57.49	gold quality
heart	UBERON:0000948	57.12	gold quality
right atrium auricular region	UBERON:0006631	55.75	gold quality
sigmoid colon	UBERON:0001159	55.50	gold quality
cardiac atrium	UBERON:0002081	55.25	gold quality
hindlimb stylopod muscle	UBERON:0004252	54.80	gold quality
cortical plate	UBERON:0005343	54.73	silver quality
adrenal tissue	UBERON:0018303	54.50	gold quality
ascending aorta	UBERON:0001496	54.47	gold quality
thoracic aorta	UBERON:0001515	54.16	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	53.56	gold quality
metanephros cortex	UBERON:0010533	53.06	gold quality
descending thoracic aorta	UBERON:0002345	52.99	gold quality
spinal cord	UBERON:0002240	52.42	gold quality
adult organism	UBERON:0007023	52.30	silver quality
aorta	UBERON:0000947	52.29	gold quality
cranial nerve II	UBERON:0000941	52.21	silver quality
Brodmann (1909) area 9	UBERON:0013540	52.18	gold quality
hypothalamus	UBERON:0001898	52.14	gold quality
corpus callosum	UBERON:0002336	52.06	gold quality
cerebellar vermis	UBERON:0004720	51.73	gold quality
frontal cortex	UBERON:0001870	51.55	gold quality
neocortex	UBERON:0001950	51.55	gold quality
urinary bladder	UBERON:0001255	51.35	gold quality
muscle of leg	UBERON:0001383	51.27	gold quality
deltoid	UBERON:0001476	51.21	gold quality
muscle tissue	UBERON:0002385	51.19	gold quality
muscle organ	UBERON:0001630	51.04	gold quality
skeletal muscle organ	UBERON:0014892	51.04	gold quality
caudate nucleus	UBERON:0001873	50.96	gold quality
cingulate cortex	UBERON:0003027	50.88	gold quality
popliteal artery	UBERON:0002250	50.85	gold quality
substantia nigra	UBERON:0002038	50.82	gold quality
tibial artery	UBERON:0007610	50.78	gold quality
renal medulla	UBERON:0000362	50.77	gold quality
vermiform appendix	UBERON:0001154	50.77	gold quality
lymph node	UBERON:0000029	50.66	gold quality
fundus of stomach	UBERON:0001160	50.56	gold quality
quadriceps femoris	UBERON:0001377	50.51	gold quality
anterior cingulate cortex	UBERON:0009835	50.51	gold quality
lower esophagus muscularis layer	UBERON:0035833	50.51	gold quality
lower esophagus	UBERON:0013473	50.48	gold quality
right uterine tube	UBERON:0001302	50.43	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
islet of Langerhans	UBERON:0000006	50.40	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
apex of heart	UBERON:0002098	50.23	gold quality
artery	UBERON:0001637	50.20	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
amygdala	UBERON:0001876	50.10	gold quality
gastrocnemius	UBERON:0001388	50.01	gold quality
smooth muscle tissue	UBERON:0001135	49.91	gold quality
oviduct epithelium	UBERON:0004804	49.90	gold quality
nucleus accumbens	UBERON:0001882	49.89	gold quality
epithelium of bronchus	UBERON:0002031	49.86	silver quality
midbrain	UBERON:0001891	49.67	gold quality
vastus lateralis	UBERON:0001379	49.63	gold quality
thymus	UBERON:0002370	49.60	gold quality
colon	UBERON:0001155	49.57	gold quality
bronchus	UBERON:0002185	49.50	silver quality
caecum	UBERON:0001153	49.47	gold 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

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 69 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Small intestine	tissue	259.2	high
Liver	tissue	249.2	medium
Duodenum	tissue	228.9	high
Kidney	tissue	12.1	not detected
Testis	tissue	9.0	not detected
Caudate putamen	tissue	6.3
Frontal cortex	tissue	5.5
Retina	tissue	5.1
Ovary	tissue	3.1	not detected
Nucleus accumbens	tissue	1.4
Gallbladder	tissue	1.2	not detected
Locus coeruleus	tissue	1.2
Hippocampus	tissue	1.1	not detected
Epididymis	tissue	1.0	not detected
Postcentral gyrus	tissue	1.0
Urinary bladder	tissue	0.8	not detected
Spinal cord	tissue	0.8
Stomach 1	tissue	0.7	not detected
Pituitary gland	tissue	0.6
Heart muscle	tissue	0.6	not detected
Fallopian tube	tissue	0.6	not detected
Smooth muscle	tissue	0.5	not detected
Medulla oblongata	tissue	0.4
Prostate	tissue	0.4	not detected
Lymph node	tissue	0.3	not detected
Pons	tissue	0.3
Rectum	tissue	0.3	not detected
Skeletal muscle	tissue	0.3	not detected
Tongue	tissue	0.3
Choroid plexus	tissue	0.3
Midbrain	tissue	0.3
Breast	tissue	0.2	not detected
Prefrontal cortex	tissue	0.2
Cerebral cortex	tissue	0.2	not detected
Seminal vesicle	tissue	0.2	not detected
Adipose tissue	tissue	0.2	not detected
Motor cortex	tissue	0.2
Basal ganglia	tissue	0.2	not detected
Putamen	tissue	0.2
Thalamus	tissue	0.2
Hypothalamus	tissue	0.2
Superior colliculi	tissue	0.2
Substantia nigra	tissue	0.2
Lung	tissue	0.2	not detected
Corpus callosum	tissue	0.2
Thymus	tissue	0.2
Hippocampal formation	tissue	0.2
Ventral forebrain	tissue	0.2
Periaqueductal gray	tissue	0.2
Septum	tissue	0.2
Retrosplenial cortex	tissue	0.2
Appendix	tissue	0.2	not detected
Cervix	tissue	0.1	not detected
Skin 1	tissue	0.1	not detected
Esophagus	tissue	0.1	not detected
Salivary gland	tissue	0.1	not detected
Colon	tissue	0.1	not detected
Endometrium 1	tissue	0.1	not detected
Amygdala	tissue	0.1
Thyroid gland	tissue	0.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Corpus callosum, genu (white matter) (3.4), Periaquaductal grey, lateral (3.0), Supraoptic nucleus (2.7), Corpus callosum, splenium (white matter) (2.6), Dorsal funiculus (white matter) (2.4).

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)

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

showing 30 of 87 miRNAs:

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

gnomAD constraint: pLI 6.72e-07, LOEUF 0.672, missense Z 1.95 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000265517 — one region, missense o/e 0.89. 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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:106926) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 27 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased circulating LDL cholesterol level	3
decreased circulating VLDL cholesterol level	3
abnormal circulating cholesterol level	2
decreased circulating HDL cholesterol level	2
decreased circulating cholesterol level	2
increased liver triglyceride level	2
increased liver cholesterol level	2
abnormal triglyceride level	1
abnormal liver physiology	1
exencephaly	1
incomplete rostral neuropore closure	1
abnormal lipid level	1
pale yolk sac	1
hemorrhage	1
abnormal lipid homeostasis	1
hepatic steatosis	1
decreased circulating triglyceride level	1
decreased erythrocyte cell number	1
increased liver weight	1
abnormal circulating lipid level	1
decreased circulating VLDL triglyceride level	1
embryonic growth retardation	1
abnormal circulating protein level	1
embryonic lethality during organogenesis, incomplete penetrance	1
abnormal visceral yolk sac blood island morphology	1

+2 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
Mesocricetus auratus	P55158	94.1%	Diamond
Bos taurus	P55156	90.6%	Diamond
Sus scrofa	Q865F1	90.6%	Diamond
Megalobrama amblycephala	A0A0N6WHT4	89.1%	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
ADH7	protein-coding	131
DAPP1	protein-coding	27071
C4orf54	protein-coding	285556
C4orf17	protein-coding	84103
TRMT10A	protein-coding	93587
DNAJB14	protein-coding	79982
LAMTOR3	protein-coding	8649

Protein

Protein identifiers

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

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

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_M	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)

• 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 33, helix 27, 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 by resolution:

PDB	Title	Method	Resolution (Å)
6I7S	Microsomal triglyceride transfer protein	X-RAY DIFFRACTION	2.5
8EOJ	Microsomal triglyceride transfer protein	ELECTRON MICROSCOPY	3.07

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of lipid/glycolipid metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; endoplasmic reticulum

Antibody reliability (HPA): IH uncertain · IF approved

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)

Type	Positions
Disulfide bond	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 partially reduce …
187	no loss on localization to the endoplasmic reticulum and does not reduce interaction with apob, but inhibits interaction with p4hb/pdi …
187	no loss on localization to the endoplasmic reticulum, does not reduce interaction with apob or p4hb/pdi, partially inhibits triglyceride …
189	no loss on localization to the endoplasmic reticulum and does not reduce interaction with apob, but inhibits interaction with p4hb/pdi …
189	no loss on localization to the endoplasmic reticulum, does not reduce interaction with apob or p4hb/pdi, partially inhibits triglyceride …
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

3 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

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

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 (15): lipid metabolic process (GO:0006629), circadian rhythm (GO:0007623), protein secretion (GO:0009306), phospholipid transport (GO:0015914), triglyceride transport (GO:0034197), 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), response to calcium ion (GO:0051592), lipid transport (GO:0006869), sterol transport (GO:0015918), intermembrane lipid transfer (GO:0120009), ceramide 1-phosphate transport (GO:1902389)

GO Molecular Function (12): lipid carrier activity (GO:0005319), 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 (8): endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), Golgi apparatus (GO:0005794), 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

4 top-level categories:

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

47 GO namespaces:

Category	Terms
lipid transport	3
binding	3
phospholipid transfer activity	3
plasma lipoprotein particle assembly	2
phospholipid transport	2
lipid transfer activity	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
cell projection membrane	2
primary metabolic process	1
rhythmic process	1
protein transport	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
protein-lipid complex assembly	1
plasma lipoprotein particle organization	1
regulation of plasma lipoprotein particle levels	1
protein metabolic process	1
sterol homeostasis	1
response to metal ion	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
sterol transfer activity	1
ceramide transfer activity	1
ceramide 1-phosphate transport	1
endoplasmic reticulum	1
intracellular organelle lumen	1
basal plasma membrane	1
plasma membrane region	1
brush border	1
apical plasma membrane	1
microvillus	1
membrane-bounded organelle	1
protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 14 of 36 annotations. The rest are phylogenetic / computational / electronic (IEA).

14 experimentally-supported GO terms:

GO term	NS	Evidence
phospholipid transport	BP	direct assay
plasma lipoprotein particle assembly	BP	direct assay
protein secretion	BP	direct assay
triglyceride transport	BP	direct assay
Golgi apparatus	CC	direct assay
endoplasmic reticulum	CC	direct assay
signaling receptor complex	CC	direct assay
ceramide 1-phosphate transfer activity	MF	direct assay
cholesterol transfer activity	MF	direct assay
phosphatidylcholine transfer activity	MF	direct assay
phosphatidylethanolamine transfer activity	MF	direct assay
phospholipid transfer activity	MF	direct assay
protein heterodimerization activity	MF	direct assay
triglyceride transfer activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,234 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTTP	APOB	P04114	975
MTTP	APOO	Q9BUR5	855
MTTP	HMGCR	P04035	772
MTTP	APOA1	P02647	743
MTTP	SREBF1	P36956	733
MTTP	LPA	P08519	729
MTTP	APOE	P02649	717
MTTP	GPT	P24298	712
MTTP	APOA4	P06727	700
MTTP	SAR1B	Q9Y6B6	676
MTTP	NPC1L1	Q9UHC9	665
MTTP	DGAT1	O75907	662
MTTP	PCSK9	Q8NBP7	661
MTTP	LDLR	P01130	661
MTTP	PPARA	Q07869	660

IntAct

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

3 partners by confidence:

Partner	Interaction type	MIscore	Records
PDIA3	physical association	0.740	5
APOB	physical association	0.700	4
SNW1	physical association	0.400	1

BioGRID (17 interactions; top human partners by supporting records): APOB (Two-hybrid; 2 records), C9orf72 (Affinity Capture-MS), CUL3 (Affinity Capture-MS), FIS1 (Affinity Capture-MS), LRRC31 (Affinity Capture-MS), NF2 (Affinity Capture-MS), NUP43 (Proximity Label-MS), P4HB (Affinity Capture-Western), PDIA2 (Affinity Capture-Western), PRKDC (Cross-Linking-MS (XL-MS)), SNW1 (Cross-Linking-MS (XL-MS)), SPPL3 (Positive Genetic), TMPO (Affinity Capture-MS), TRIM67 (Affinity Capture-MS)

SIGNOR signaling

2 signaling interactions:

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

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
★ MTTP-P4HB complex	2	MTTP, P4HB

Disease & clinical

Genetic variants

Variant evidence for MTTP: 1,272 ClinVar records (174 pathogenic / likely pathogenic); 2 PharmGKB clinical annotations; 8 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

1,272 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	80
Likely pathogenic	94
Uncertain significance	394
Likely benign	560
Benign	58

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 174 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
14243	NM_001386140.1(MTTP):c.2593G>T (p.Gly865Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	9
14235	NM_001386140.1(MTTP):c.1783C>T (p.Arg595Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
638950	NM_001386140.1(MTTP):c.1867+1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	7
1072850	NM_001386140.1(MTTP):c.419dup (p.Asn140fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
435905	NM_001386140.1(MTTP):c.708_709del (p.His236fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1452643	NM_001386140.1(MTTP):c.1026_1030dup (p.Ile344fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1687508	NM_001386140.1(MTTP):c.640del (p.Ala214fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2445867	NM_001386140.1(MTTP):c.2342+1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	2
646677	NM_001386140.1(MTTP):c.1868-2A>G	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
1066159	NM_001386140.1(MTTP):c.1067+1G>C	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
1486711	NM_001386140.1(MTTP):c.619-1G>C	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
983772	NM_001386140.1(MTTP):c.1705C>T (p.Gln569Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1028159	NM_001386140.1(MTTP):c.502-2A>G	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1520206	NM_001386140.1(MTTP):c.502-1G>C	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2203554	NM_001386140.1(MTTP):c.62-2A>G	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2

Per-variant reference — Sugi Variant

Explore MTTP’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; 37 predictions of 1,492):

Position(s)	Effect	Δscore	Sites
4:99583372–99583373	acceptor_loss	1.0000	6
4:99583514	donor_gain	1.0000
4:99583518–99583519	donor_loss	1.0000	6
4:99591352–99591353	donor_loss	1.0000	5
4:99591791–99591792	donor_loss	1.0000	5
4:99591796	donor_gain	1.0000
4:99597217	donor_gain	1.0000
4:99600562	acceptor_gain	1.0000
4:99600563–99600564	acceptor_loss	1.0000	6
4:99600734–99600735	donor_loss	1.0000	5

AlphaMissense

1,374 missense substitutions predicted likely pathogenic (of 5,872 scored), across 449 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
F707	8	0.967	0.993
F819	8	0.955	0.994
D169	8	0.943	0.981
D361	8	0.931	0.982
S768	8	0.930	0.997
N874	8	0.927	0.994
F813	8	0.871	0.982
F824	8	0.857	0.959
F156	8	0.827	0.973
C827	7	0.996	0.998
C878	7	0.992	0.997
C174	7	0.985	0.994
W770	7	0.971	0.998
C194	7	0.968	0.983
W69	7	0.933	0.982
F393	7	0.928	0.976
C440	7	0.906	0.938
E672	7	0.895	0.984
E167	7	0.894	0.928
E570	7	0.881	0.944

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Liver Hepatocellular Carcinoma)

Disease associations

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

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
abetalipoproteinemia	Definitive	Autosomal recessive	6

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (15 panels, 15 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

15 panels:

Panel	Rating
Adult-onset neurological disorders	green
Ataxia and cerebellar anomalies - childhood onset	green
Hereditary ataxia	green
Hereditary ataxia and cerebellar anomalies, childhood onset	green
Hereditary ataxia, adult onset	green
Hereditary neuropathy	green
Hereditary neuropathy or pain disorder	green
Hypotonic infant	green
Intestinal failure or congenital diarrhoea	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Paediatric disorders	green
Retinal disorders	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (2): abetalipoproteinemia (MONDO:0008692), metabolic syndrome X (MONDO:0011565)

Orphanet (1): Abetalipoproteinemia (Orphanet:14)

HPO phenotypes

showing 60 of 69 phenotypes (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
HP:0001927	Acanthocytosis
HP:0002013	Vomiting
HP:0002028	Chronic diarrhea
HP:0002066	Gait ataxia
HP:0002136	Broad-based gait
HP:0002240	Hepatomegaly
HP:0002403	Positive Romberg sign
HP:0002493	Upper motor neuron dysfunction
HP:0002495	Impaired vibratory sensation
HP:0002570	Steatorrhea
HP:0002630	Fat malabsorption
HP:0002751	Kyphoscoliosis
HP:0002878	Respiratory failure
HP:0002904	Hyperbilirubinemia
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003073	Hypoalbuminemia
HP:0003146	Hypocholesterolemia
HP:0003198	Myopathy
HP:0003233	Decreased circulating HDL-C concentration
HP:0003326	Myalgia
HP:0003376	Steppage gait
HP:0003487	Babinski sign
HP:0003563	Decreased circulating LDL-C concentration
HP:0004905	Reduced circulating vitamin A concentration
HP:0006858	Impaired distal proprioception
HP:0007305	CNS demyelination
HP:0007703	Abnormal retinal pigmentation
HP:0007894	Fundus hypopigmentation
HP:0008151	Prolonged prothrombin time
HP:0008181	Abetalipoproteinemia

GWAS associations

8 associations:

Study	Trait	p-value
GCST006921_6	Regular attendance at a pub or social club	4e-25
GCST010244_368	Triglyceride levels	6e-15
GCST006611_3	HDL cholesterol	8e-13
GCST90013405_3	Liver enzyme levels (alanine transaminase)	1e-12
GCST90013663_45	Alanine aminotransferase levels	1e-10
GCST90013664_13	Aspartate aminotransferase levels	3e-10
GCST90016673_1	Percent liver fat	2e-9
GCST002112_3	Celiac disease	5e-6

EFO canonical traits (from GWAS)

5 canonical traits:

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

2 disease descriptors:

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

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

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes MTTP — the drug acts on the assembly or class, not necessarily on this subunit alone.

3 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
LOMITAPIDE MESYLATE	Microsomal triglyceride transfer protein	2	4
IMPLITAPIDE	Microsomal triglyceride transfer protein	2	2
SLX-4090	Microsomal triglyceride transfer protein	2	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,390 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

3 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL354541	LOMITAPIDE	4	1,219
CHEMBL2105662	LOMITAPIDE MESYLATE	4	99
CHEMBL410414	DIRLOTAPIDE	2	1,072

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

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

Variant	Association	Level	Drugs	Phenotypes
rs1800591	Efficacy	3	pravastatin	Coronary Artery Disease
rs1800591	Efficacy	3	atorvastatin	Hyperlipoproteinemia Type II

PharmGKB variants

1 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1800591	MTTP	3	0.00	2	pravastatin;atorvastatin

PharmGKB variant annotations

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

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs1800591	atorvastatin	Efficacy	Genotype TT is associated with increased response to atorvastatin in men with Hyperlipoproteinemia Type II.	PMID:15864113

Binding affinities (BindingDB)

160 measured of 179 human assays (180 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL2147281	IC50	0.001 nM
CHEMBL2147286	IC50	0.001 nM
CHEMBL2147290	IC50	0.002 nM
CHEMBL2147283	IC50	0.01 nM
9-(4-{5-Methyl-4-[(4’-trifluoromethyl-biphenyl-2-carbonyl)-amino]-benzoimidazol-1-yl}-butyl)-9H-fluorene-9-carboxylic acid (2,2,2-trifluoro-ethyl)-amide	IC50	0.02 nM
CHEMBL2147296	IC50	0.021 nM
CHEMBL2147292	IC50	0.025 nM
9-(4-{2,5-Dimethyl-4-[(4’-trifluoromethyl-biphenyl-2-carbonyl)-amino]-benzoimidazol-1-yl}-butyl)-9H-fluorene-9-carboxylic acid (2,2,2-trifluoro-ethyl)-amide	IC50	0.03 nM
CHEMBL2147294	IC50	0.058 nM
9-(4-{2-Isopropyl-4-[(4’-trifluoromethyl-biphenyl-2-carbonyl)-amino]-benzoimidazol-1-yl}-butyl)-9H-fluorene-9-carboxylic acid (2,2,2-trifluoro-ethyl)-amide	IC50	0.06 nM
CHEMBL2147293	IC50	0.066 nM
CHEMBL2147301	IC50	0.101 nM
CHEMBL2147298	IC50	0.105 nM
CHEMBL2147299	IC50	0.122 nM
9-(4-{2-Methyl-4-[(4’-trifluoromethyl-biphenyl-2-carbonyl)-amino]-benzoimidazol-1-yl}-butyl)-9H-fluorene-9-carboxylic acid (2,2,2-trifluoro-ethyl)-amide	IC50	0.15 nM
9-(4-{4-[(4’-Trifluoromethyl-biphenyl-2-carbonyl)-amino]-benzoimidazol-1-yl}-butyl)-9H-fluorene-9-carboxylic acid (2,2,2-trifluoro-ethyl)-amide	IC50	0.24 nM
CHEMBL2147295	IC50	0.253 nM
CHEMBL2147280	IC50	0.345 nM
CHEMBL2147279	IC50	0.378 nM
CHEMBL2147285	IC50	0.44 nM
CHEMBL2147300	IC50	0.484 nM
9-(4-{4-[(4’’-Trifluoromethyl-biphenyl-2-carbonyl)-amino]-piperidin-1-yl}-butyl)-9H-fluorene-9-carboxylic acid (2,2,2-trifluoro-ethyl)-amide	IC50	0.5 nM
CHEMBL2147284	IC50	0.55 nM
(R)-6-methyl-N-(2-(thiazol-2-ylmethylamino)-2,3-dihydro-1H-inden-5-yl)-4’-(trifluoromethyl)biphenyl-2-carboxamide	IC50	0.6 nM
{5-[(6-Methyl-4’-trifluoromethyl-biphenyl-2-carbonyl)-amino]-indan-2-yl}-carbamic acid methyl ester	IC50	0.7 nM
CHEMBL2147291	IC50	0.83 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
4’-trifluoromethyl-biphenyl-2-carboxylic acid (4-{[(S)-(cyclopropylmethyl-carbamoyl)-phenyl-methyl]-carbamoyl}-3-ethoxy-phenyl)-amide	IC50	1.01 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
CHEMBL2146489	IC50	1.2 nM
CHEMBL2147297	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
4’-trifluoromethyl-biphenyl-2-carboxylic acid {2-methyl-4-[((S)-phenyl-propylcarbamoyl-methyl)-carbamoyl]-phenyl}-amide	IC50	1.64 nM
4’-trifluoromethyl-biphenyl-2-carboxylic acid (4-{[(S)-(cyclopropylmethyl-carbamoyl)-phenyl-methyl]-carbamoyl}-2-methoxy-phenyl)-amide	IC50	1.68 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’-trifluoromethyl-biphenyl-2-carboxylic acid [2-methoxy-4-((S)-2-oxo-1-phenyl-2-pyrrolidin-1-yl-ethylcarbamoyl)-phenyl]-amide	IC50	1.75 nM
4’-trifluoromethyl-biphenyl-2-carboxylic acid (4-{[(S)-(cyclopropylmethyl-carbamoyl)-phenyl-methyl]-carbamoyl}-2-ethyl-phenyl)-amide	IC50	1.78 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
9-(4-{2-Propyl-4-[(4’-trifluoromethyl-biphenyl-2-carbonyl)-amino]-benzoimidazol-1-yl}-butyl)-9H-fluorene-9-carboxylic acid (2,2,2-trifluoro-ethyl)-amide	IC50	2 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

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	increases expression, affects cotreatment, affects expression, decreases expression	7
Aflatoxin B1	affects expression, decreases expression, decreases methylation	6
Valproic Acid	affects expression, decreases expression	5
Oleic Acid	increases expression, affects cotreatment, decreases expression, decreases reaction	5
sodium arsenite	affects methylation, decreases expression, increases expression	4
Acetaminophen	decreases expression, affects cotreatment	4
Palmitic Acid	decreases expression, decreases reaction, increases expression, affects cotreatment	4
bisphenol A	affects expression, affects cotreatment, affects methylation, increases expression	3
Benzo(a)pyrene	decreases expression, increases methylation	3
Deoxycholic Acid	affects cotreatment, decreases expression	3
Chenodeoxycholic Acid	affects cotreatment, decreases expression	2
Glycochenodeoxycholic Acid	decreases expression, affects cotreatment	2
Glycocholic Acid	decreases expression, affects cotreatment	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)

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

showing 60 of 197 trials:

NCT	Phase	Status	Title
NCT00205504	Phase 4	COMPLETED	Oral Contraceptives in the Metabolic Syndrome
NCT00224822	Phase 4	COMPLETED	The Effects of Aripiprazole on Patients With Metabolic Syndrome
NCT00225355	Phase 4	TERMINATED	Rosiglitazone Versus Placebo in Chronic Stable Angina
NCT00242814	Phase 4	COMPLETED	Phase IV, 9 Weeks Comparison Between MICARDIS 80 mg and Amlodipine 10 mg on Biological PPAR Gamma Activities
NCT00272311	Phase 4	COMPLETED	Aspirin Dose and Atherosclerosis in Patients With Metabolic Syndrome
NCT00296803	Phase 4	COMPLETED	PROCLAIM: Study Examining Effects of Clopidogrel Compared to Placebo on Inflammation in Subjects With Metabolic Syndrome
NCT00304993	Phase 4	COMPLETED	Study of Niacin and Rosiglitazone in Dysmetabolic Dyslipidemia
NCT00325936	Phase 4	COMPLETED	The Effects of Cilnidipine on Metabolic Syndrome Improvement
NCT00338949	Phase 4	COMPLETED	Ziprasidone for Improving Insulin Sensitivity in People With Schizophrenia Who Are at Risk for Diabetes
NCT00395486	Phase 4	COMPLETED	ROMEO (Rosuvastatin in Metabolic syndrOme)
NCT00515021	Phase 4	COMPLETED	Diurnal Variation of Plasminogen Activator Inhibitor-1
NCT00573950	Phase 4	UNKNOWN	Effects of Cilostazol on Plasma Adipocytokine and Arterial Stiffness
NCT00608465	Phase 4	TERMINATED	Defining Strategies for Improving Endothelial and Fibrinolytic Dysfunction in Obesity
NCT01887119	Phase 4	TERMINATED	Aldosterone Antagonism and Microvascular Function
NCT02283242	Phase 4	COMPLETED	Galantamine Effects in Patients With Metabolic Syndrome
NCT00147264	Phase 3	COMPLETED	Telmisartan-Induced Reduction in Intra-Myocellular Lipids Trial
NCT00228176	Phase 3	TERMINATED	Atherosclerosis Underlying Development Assessed by Intima-Media Thickness in Patients on Rimonabant
NCT00243984	Phase 3	SUSPENDED	Efficacy of Topiramate for Weight Loss in Subjects With Metabolic Syndrome
NCT00663104	Phase 3	TERMINATED	Effect of Exercise and Phytoestrogen on Bone, Metabolic Syndrome Criteria and Complaints of the Early Menopause
NCT01465620	Phase 3	COMPLETED	Dietetic and Hygiene Measures in Metabolic Neuropathies: the Neurodiet Study
NCT01794429	Phase 3	COMPLETED	Treatment of Antipsychotic-associated Obesity With a GLP-1 Analogue
NCT01849068	Phase 3	COMPLETED	Effects of Selective Inhibition of Cholesterol Absorption With Ezetimibe on Intestinal Cholesterol Homeostasis in Dyslipidemic Men With Insulin-resistance - a Pilot Study
NCT01872182	Phase 3	TERMINATED	Efficacy and Safety Study of ALS-L1023 in Patients With Abdominal Obesity of Metabolic Syndrome
NCT02672592	Phase 3	COMPLETED	Effects of Interleukin-1 Beta on Low Testosterone Levels in Men With Obesity and Metabolic Syndrome
NCT00166036	Phase 2	COMPLETED	Effect of Statins on Oxidative Stress and Endothelial Progenitor Cells
NCT00200993	Phase 2	COMPLETED	Peripheral Effects of Exercise on Cardiovascular Health (STRRIDE I)
NCT00264667	Phase 2	COMPLETED	Study In Patients With Dyslipidaemia
NCT00275145	Phase 2	COMPLETED	Effects of Resistance and Aerobic Exercise on Cardiovascular Health
NCT00327002	Phase 2	COMPLETED	A Mechanistic Study of the Effects of LY518674 on High-Density Lipoprotein Cholesterol (HDL-C) Metabolism
NCT00400231	Phase 2	COMPLETED	The Fenofibrate and Metformin for Atherogenic Dyslipidemia (FAMA) Study
NCT00455325	Phase 2	COMPLETED	Chloroquine to Treat People With Metabolic Syndrome Aim2 (ARCH-MS)
NCT00671515	Phase 2	COMPLETED	Pioglitazone for the Treatment of Major Depressive Disorder Comorbid With Metabolic Syndrome
NCT00675857	Phase 2	COMPLETED	A Phase IIa Proof-of-concept Study of NC-503 in Patients With Type II Diabetes
NCT01145066	Phase 2	COMPLETED	Botanical Oil Supplementation in Diabetic and Metabolic Syndrome Subjects
NCT01351753	Phase 2	TERMINATED	Drug Therapy Induced Weight Loss to Improve Blood Vessel Function in Subjects With Obesity
NCT02017561	Phase 2	COMPLETED	Metformin in the Diastolic Dysfunction of Metabolic Syndrome
NCT02114892	Phase 2	COMPLETED	Effect of Resveratrol Administration on Metabolic Syndrome, Insulin Sensitivity and Insulin Secretion
NCT02288572	Phase 2	COMPLETED	Probiotic Bacteria in Prevention of the Metabolic Syndrome
NCT02337933	Phase 2	COMPLETED	Effect of Ursolic Acid Administration on Insulin Sensitivity and Metabolic Syndrome
NCT02767869	Phase 2	COMPLETED	Effect of Banaba (Lagerstroemia Speciosa) on Metabolic Syndrome, Insulin Secretion and Insulin Sensitivity
NCT00315770	Phase 1	UNKNOWN	Health of Young European Families and Fish Consumption
NCT02936687	Phase 1	COMPLETED	Mechanisms of Cerebrovascular Control
NCT00004574	Not specified	COMPLETED	Vitamin Replacement in Abetalipoproteinemia
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT05208879	Not specified	COMPLETED	CArotenoid in hypoChOlesterolemia
NCT00111956	Phase 2/3	COMPLETED	Effects of Tumor Necrosis Factor (TNF)-Alpha Antagonism in Patients With Metabolic Syndrome
NCT00399997	Phase 2/3	UNKNOWN	Evaluation of Effect of Exercise on Prescription
NCT00545805	Phase 2/3	COMPLETED	Surgical Removal of Visceral Fat Tissue (Omentectomy) Associated to Bariatric Surgery: Effects on Insulin Sensitivity
NCT00733772	Phase 2/3	COMPLETED	Flaxseed Intervention on Metabolic Syndrome
NCT00742742	Phase 2/3	COMPLETED	Walnut Intervention on Metabolic Syndrome (WIMS)
NCT01022411	Phase 2/3	COMPLETED	Brown Rice Intervention on Metabolic Syndrome (BRIMS)
NCT01044680	Phase 2/3	COMPLETED	Effects of NUTRIOSE®FB Dietary Fiber Supplementation on Satiety, Body Fat, and Metabolic Syndrome in Overweight Adult Men
NCT02113241	Phase 2/3	COMPLETED	Effect of Dapagliflozin Administration on Metabolic Syndrome, Insulin Sensitivity, and Insulin Secretion
NCT02407522	Phase 2/3	COMPLETED	The Improvements of Dietary Supplement of Black Rice on Metabolic Syndrome
NCT02983188	Phase 2/3	COMPLETED	Berberine as Adjuvant Treatment for Schizophrenia Patients
NCT00130286	Phase 1/2	COMPLETED	Growth Hormone and/or Rosiglitazone for HIV-Associated Increased Abdominal Fat and Insulin Resistance
NCT00194428	Phase 1/2	COMPLETED	Weight and Metabolic Effects of an Almond Enriched Hypocaloric, Low Fat Diet on Overweight and Obese Persons
NCT00327054	Phase 1/2	COMPLETED	Effectiveness of Nigella Sativa (Kalonji) Seed in Dyslipidemia
NCT01004120	Phase 1/2	COMPLETED	Efficacy of a Prebiotic Galactooligosaccharide to Reduce Metabolic Syndrome Risk Factors in Overweight Adults
NCT00350194	Early Phase 1	UNKNOWN	The Effects of Omega-3 Fatty Acids on Metabolic Syndrome

Predicted chemistry — Sugi Predict

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