GeneBe

MTTP

protein-coding

microsomal triglyceride transfer protein

Gene 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]

Previous symbols:
  • MTP

MANE transcript

NM_001386140.1

Inheritance

AR

ClinVar variants

P:260U:349B:365

Top phenotype

Abetalipoproteinemia

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr4:99,564,081-99,623,997

External References & Databases

Ensembl (ENSG00000138823)NCBI Gene (4547)OMIM (157147)HGNC:7467GenCCUniProt (P55157)AlphaFoldClinVar (MTTP)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~59.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

abetalipoproteinemiaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008692

Submitter: Orphanet

abetalipoproteinemiaDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008692

Submitter: Natera

abetalipoproteinemiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008692

Submitter: Labcorp Genetics (formerly Invitae)

abetalipoproteinemiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0008692

Submitter: PanelApp Australia

abetalipoproteinemiaDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008692

Submitter: Ambry Genetics

abetalipoproteinemiaDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008692

Submitter: G2P

Clinical Genomic Database (CGD)

AbetalipoproteinemiaAR

Manifestation: Gastrointestinal; Hematologic; Neurologic; Ophthalmologic

Intervention: Gastrointestinal

Rationale: Dietary measures (eg, with a low fat diet and supplementation of essential fatty acids and fat-soluble vitamins) can be beneficial, and early initiation can prevent/decrease severe sequelae

Refs: 15411425; 14925152; 13745738; 14237436; 4135110; 848999; 716878; 7425890; 6959555; 2339706; 1439810; 8361539; 9686820; 17275380; 18239027; 18611256; 20402070; 21333248; 21394827; 21502686; 23090820; 23556456; 24288038Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MTTP variants in ClinVar

6 Conditions Cataloged
not providedTotal: 957
AbetalipoproteinaemiaTotal: 369
not specifiedTotal: 97
Inborn genetic diseasesTotal: 91
MTTP-related disorderTotal: 40
Metabolic syndrome XTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001386140.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
11
clinvar
343
clinvar
 354
missense
2
clinvar
5
clinvar
336
clinvar
22
clinvar
 365
nonsense
39
clinvar
34
clinvar
2
clinvar
 75
start loss
0
frameshift
93
clinvar
51
clinvar
 144
splice donor/acceptor (+/-2bp)
10
clinvar
26
clinvar
 36
Total1441163493650974

Highest pathogenic variant AF is 0.00008844189

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001386140.1RefSeqNP_001373069.118MANE Select
ENST00000265517.10EnsemblENSP00000265517.518MANE Select
NM_000253.4RefSeqNP_000244.218Standard
NM_001300785.2RefSeqNP_001287714.216Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
mttpDanio rerio

Structure: subintestinal vein

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Fat digestion and absorption - Homo sapiens (human)
  • Statin Pathway, Pharmacodynamics
  • Demo complete
  • Statin Pathway
  • Chylomicron assembly

Biological Process

  • lipid metabolic process
  • protein secretion
  • phospholipid transport
  • triglyceride transport
  • plasma lipoprotein particle assembly

Molecular Function

  • lipid transporter activity
  • protein binding
  • phospholipid transporter activity
  • lipid binding
  • protein heterodimerization activity

Cellular Component

  • endoplasmic reticulum
  • endoplasmic reticulum lumen
  • Golgi apparatus
  • basolateral plasma membrane
  • receptor complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000457717
Coding exons
18
Length
60239
Individuals with no LoFs
125680
Homozygous LoFs
0
Heterozygous LoFs
68
Defined
125748
p
0.000270
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.034024640.8660.00002515851
Missense (PolyPhen)69104.360.661171353
Synonymous0.5381641730.9480.000009991733
Loss of Function3.661641.40.3860.00000204546

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000250.00025rare
Latino/Admixed American0.0000580.000058rare
Ashkenazi Jewish0.00270.0027notable
East Asian0.000270.00027rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.000220.00022rare
South Asian0.0000980.000098rare
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Catalyzes the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces (PubMed:23475612, PubMed:8939939, PubMed:26224785, PubMed:25108285, PubMed:22236406). Required for the secretion of plasma lipoproteins that contain apolipoprotein B (PubMed:23475612, PubMed:8939939, PubMed:26224785). {ECO:0000269|PubMed:22236406, ECO:0000269|PubMed:23475612, ECO:0000269|PubMed:25108285, ECO:0000269|PubMed:26224785, ECO:0000269|PubMed:8939939}.;
Disease
DISEASE: 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. {ECO:0000269|PubMed:10679949, ECO:0000269|PubMed:10946006, ECO:0000269|PubMed:22236406, ECO:0000269|PubMed:23475612, ECO:0000269|PubMed:25108285, ECO:0000269|PubMed:26224785, ECO:0000269|PubMed:8939939}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.450

Intolerance Scores

LoFtool
0.582
RVIS EVS
1.43
RVIS percentile EVS
94.99

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.691

Gene Damage Prediction

AllRecessiveDominant
MendelianHighMediumHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh
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