MTTP microsomal triglyceride transfer protein [Homo sapiens (human)] - Gene

Summary

Official Symbol: MTTPprovided by HGNC
Official Full Name: microsomal triglyceride transfer proteinprovided by HGNC
Primary source: HGNC:HGNC:7467
See related: Ensembl:ENSG00000138823 MIM:157147
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ABL; MTP
Summary: 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. [provided by RefSeq, Jul 2008]
Expression: Biased expression in small intestine (RPKM 140.0), duodenum (RPKM 122.9) and 1 other tissue See more
Orthologs: mouse all

Genomic context

Location:: 4q23

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	4	NC_000004.12 (99564078..99623997)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (100485240..100545154)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Targeted next generation DNA sequencing revealed several rare heterozygous missense variants in both MTTP and APOB genes known or predicted to be deleterious, in addition to a novel heterozygous missense variant in SAR1B, which encodes the gene causing chylomicron retention disease
Title: Complex genetic architecture in severe hypobetalipoproteinemia.
Deleterious and protective mutations in MTTP, PNPLA3, and TM6SF2 have been found in Japanese males at risk for non-alcoholic fatty liver disease.
Title: Identification of deleterious rare variants in MTTP, PNPLA3, and TM6SF2 in Japanese males and association studies with NAFLD.
The authors conclude that alternate splicing plays a key role in regulating cellular MTP levels by introducing distinct promoter regions and unique 5'-UTRs, which contain elements that alter translation efficiency, enabling the cell to optimize MTP activity.
Title: Discovery of Novel Splice Variants and Regulatory Mechanisms for Microsomal Triglyceride Transfer Protein in Human Tissues.
these data reveal clear cellular defects in induced pluripotent stem cells-derived hepatocytes and cardiomyocytes lacking MTTP activity, including a cardiomyocyte-specific regulated stress response to elevated lipids.
Title: Lack of MTTP Activity in Pluripotent Stem Cell-Derived Hepatocytes and Cardiomyocytes Abolishes apoB Secretion and Increases Cell Stress.
two new hypolipidemic patients with very low plasma triglyceride and apolipoprotein B (apoB) levels with plasma lipid profiles similar to abetalipoproteinemia (ABL) patients, are reported.
Title: Structure-function analyses of microsomal triglyceride transfer protein missense mutations in abetalipoproteinemia and hypobetalipoproteinemia subjects.
results of this study, examining a cohort of obese children, suggest that the genetic variation at MTTP rs2306986 was associated with higher susceptibility to NAFLD
Title: Association of MTTP gene variants with pediatric NAFLD: A candidate-gene-based analysis of single nucleotide variations in obese children.
Data suggest that amphipathic beta-strands in 200 N-terminal residues of beta1 domain of APOB are required for secretion of lipid-rich or lipid-poor particles; residues 300-700 or 1050-1500 of beta1 domain appear to be required for secretion of lipid-rich particles; MTTP is required for secretion of intact APOB but not of truncated APOB. (APOB = apolipoprotein B; MTTP = microsomal triglyceride transfer protein)
Title: Relationship between Amphipathic β Structures in the β<sub>1</sub> Domain of Apolipoprotein B and the Properties of the Secreted Lipoprotein Particles in McA-RH7777 Cells.
In chronic hepatitis C patients infected with HCV genotype 3 and with the TT/GT genotype of the MTTP -493G/T SNP, a significant increase in hepatic steatosis was observed, which may indicate that this SNP has a significant influence on the accumulation of triglycerides in hepatocytes.
Title: Genetic variation in the microsomal triglyceride transfer protein (-493G/T) is associated with hepatic steatosis in patients infected with hepatitis C virus.
High expression of MTTP is associated with high carotid intima-media thickness.
Title: Vascular Disease Is Associated With the Expression of Genes for Intestinal Cholesterol Transport and Metabolism.
Its gene mutations are associated with abetalipoproteinemia, developmental delay and hepatic steatosis.
Title: Microsomal triglyceride transfer protein gene mutations in Turkish children: A novel mutation and clinical follow up.

Submit: New GeneRIF Correction See all GeneRIFs (98)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Abetalipoproteinaemia MedGen: C0000744 OMIM: 200100 GeneReviews: Abetalipoproteinemia	Compare labs
Metabolic syndrome X MedGen: C0524620 OMIM: 605552 GeneReviews: Not available	Compare labs

NHGRI GWAS Catalog

Description
A possible mechanism behind autoimmune disorders discovered by genome-wide linkage and association analysis in celiac disease. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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Chylomicron-mediated lipid transport, organism-specific biosystem (from REACTOME)
Chylomicron-mediated lipid transport, organism-specific biosystemChylomicrons transport triacylglycerol, phospholipid, and cholesterol derived from dietary lipid from the small intestine to other tissues of the body. Each chylomicron assembles around a single mole...
Circadian rythm related genes, organism-specific biosystem (from WikiPathways)
Circadian rythm related genes, organism-specific biosystemThis is currently not a pathway but a list of circadian rhythm related genes and proteins. The source for this information is the gene ontology. The genes and proteins were filtered for "circadian rh...
Fat digestion and absorption, organism-specific biosystem (from KEGG)
Fat digestion and absorption, organism-specific biosystemFat is an important energy source from food. More than 95% of dietary fat is long-chain triacylglycerols (TAG), the remaining being phospholipids (4.5%) and sterols. In the small intestine lumen, die...
Fat digestion and absorption, conserved biosystem (from KEGG)
Fat digestion and absorption, conserved biosystemFat is an important energy source from food. More than 95% of dietary fat is long-chain triacylglycerols (TAG), the remaining being phospholipids (4.5%) and sterols. In the small intestine lumen, die...
Lipid digestion, mobilization, and transport, organism-specific biosystem (from REACTOME)
Lipid digestion, mobilization, and transport, organism-specific biosystemProcesses annotated here include the digestion of dietary lipids, sterol uptake, the formation and turnover of lipoproteins (chylomicrons, VLDL, LDL, and HDL), and the mobilization of fatty acids thr...
Lipoprotein metabolism, organism-specific biosystem (from REACTOME)
Lipoprotein metabolism, organism-specific biosystemBecause of their hydrophobicity, lipids are found in the extracellular spaces of the human body primarily in the form of lipoprotein complexes. Chylomicrons form in the small intestine and transport ...
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Metabolism of lipids and lipoproteins, organism-specific biosystem (from REACTOME)
Metabolism of lipids and lipoproteins, organism-specific biosystemLipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphi...
Statin Pathway, organism-specific biosystem (from WikiPathways)
Statin Pathway, organism-specific biosystemStatins inhibit endogenous cholesterol production by competitive inhibition of HMG-CoA reductase (HMGCR), the enzyme that catalyzes conversion of HMG-CoA to mevalonate, an early rate-limiting step in...
VLDL biosynthesis, organism-specific biosystem (from REACTOME)
VLDL biosynthesis, organism-specific biosystemVery low-density lipoprotein (VLDL) is synthesised in the liver in two steps. First, apolipoprotein B-100 (APOB-100) is co- and post-translationally lipidated in the rough ER lumen. After transfer to...
VLDL interactions, organism-specific biosystem (from REACTOME)
VLDL interactions, organism-specific biosystemVery-low-density lipoprotein (VLDL) is a lipoprotein made by the liver (Gibbons et al. 2004) and is one of the five major groups of lipoproteins (chylomicrons, VLDL, LDL, IDL and HDL) that enable fat...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

MTTP (e-PCR)
- UniSTS:519174

SHGC-12008 (e-PCR)
- UniSTS:12049

STS-N41015 (e-PCR)
- UniSTS:54811

SHGC-67823 (e-PCR)
- UniSTS:83499

STS-X59657 (e-PCR)
- UniSTS:10797

D4S979 (e-PCR)
- UniSTS:35972

SHGC-67619 (e-PCR)
- UniSTS:6535

GDB:384603 (e-PCR)
- UniSTS:157084

Homology

Homologs of the MTTP gene: The MTTP gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, and frog.
Orthologs from Annotation Pipeline: 250 organisms have orthologs with human gene MTTP
The Hierarchical Catalog of Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
lipid binding	IEA Inferred from Electronic Annotation more info
lipid transporter activity	IDA Inferred from Direct Assay more info	PubMed
lipid transporter activity	TAS Traceable Author Statement more info
phospholipid transporter activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
phospholipid transporter activity	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein heterodimerization activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
cholesterol homeostasis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
chylomicron assembly	TAS Traceable Author Statement more info
lipid metabolic process	TAS Traceable Author Statement more info	PubMed
lipoprotein metabolic process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
phospholipid transport	IDA Inferred from Direct Assay more info	PubMed
plasma lipoprotein particle assembly	IDA Inferred from Direct Assay more info	PubMed
protein secretion	IMP Inferred from Mutant Phenotype more info	PubMed
triglyceride transport	IDA Inferred from Direct Assay more info	PubMed
triglyceride transport	IMP Inferred from Mutant Phenotype more info	PubMed
very-low-density lipoprotein particle assembly	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
Golgi apparatus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
basolateral plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
endoplasmic reticulum	IBA Inferred from Biological aspect of Ancestor more info	PubMed
endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
endoplasmic reticulum lumen	TAS Traceable Author Statement more info
receptor complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: microsomal triglyceride transfer protein large subunit

Names: microsomal triglyceride transfer protein (large polypeptide, 88kDa)

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011469.1 RefSeqGene

Range

4996..64915

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000253.3 → NP_000244.2 microsomal triglyceride transfer protein large subunit isoform 1 precursor

See identical proteins and their annotated locations for NP_000244.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript but encodes the shorter isoform (1).

Source sequence(s)

AI623321, BC125110, BE047932, CB162574, DB458800, X91148

Consensus CDS

CCDS3651.1

UniProtKB/Swiss-Prot

P55157

Related

ENSP00000400821.1, ENST00000457717.5

Conserved Domains (1) summary

pfam01347
Location:28 → 584

Vitellogenin_N; Lipoprotein amino terminal region
NM_001300785.1 → NP_001287714.1 microsomal triglyceride transfer protein large subunit isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in its 5' UTR and coding region, compared to variant 1. The encoded isoform (2) has a longer and distinct N-terminus, compared to isoform 1.

Source sequence(s)

AI623321, AK302602, BC125110, BE047932, CB162574, DB458800, X91148

Consensus CDS

CCDS75169.1

UniProtKB/Swiss-Prot

P55157

UniProtKB/TrEMBL

B7Z7X3, E9PBP6

Related

ENSP00000427679.1, ENST00000511045.5

Conserved Domains (1) summary

pfam01347
Location:55 → 611

Vitellogenin_N; Lipoprotein amino terminal region