MTTP

microsomal triglyceride transfer protein

Basic information

Region (hg38): 4:99564081-99623997

Previous symbols: [ "MTP" ]

Links

ENSG00000138823

∙ NCBI:4547 ∙ OMIM:157147 ∙ HGNC:7467 ∙ Uniprot:P55157 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

abetalipoproteinemia (Strong), mode of inheritance: AR
abetalipoproteinemia (Strong), mode of inheritance: AR
abetalipoproteinemia (Supportive), mode of inheritance: AR
abetalipoproteinemia (Definitive), mode of inheritance: AR
abetalipoproteinemia (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Abetalipoproteinemia	AR	Gastrointestinal	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	Gastrointestinal; Hematologic; Neurologic; Ophthalmologic	15411425; 14925152; 13745738; 14237436; 4135110; 848999; 716878; 7425890; 6959555; 2339706; 1439810; 8361539; 9686820; 17275380; 18239027; 18611256; 20402070; 21333248; 21394827; 21502686; 23090820; 23556456; 24288038

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MTTP gene.

not_provided (925 variants)
Abetalipoproteinaemia (266 variants)
Inborn_genetic_diseases (82 variants)
MTTP-related_disorder (22 variants)
not_specified (19 variants)
Metabolic_syndrome_X (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MTTP gene is commonly pathogenic or not. These statistics are base on transcript: NM_001386140.1. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar	10 clinvar	334 clinvar	1 clinvar	346
missense	3 clinvar	6 clinvar	322 clinvar	15 clinvar	1 clinvar	347
nonsense	23 clinvar	30 clinvar	1 clinvar			54
start loss						0
frameshift	41 clinvar	37 clinvar				78
splice donor/acceptor (+/-2bp)	10 clinvar	23 clinvar				33
Total	77	97	333	349	2

Highest pathogenic variant AF is 0.00008844189

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MTTP	protein_coding	protein_coding	ENST00000457717	18	60239

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000104	1.00	125680	0	68	125748	0.000270

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.03	402	464	0.866	0.0000251	5851
Missense in Polyphen		69	104.36	0.66117		1353
Synonymous	0.538	164	173	0.948	0.00000999	1733
Loss of Function	3.66	16	41.4	0.386	0.00000204	546

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000305	0.000304
Ashkenazi Jewish	0.00268	0.00268
East Asian	0.000272	0.000272
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000220	0.000220
Middle Eastern	0.000272	0.000272
South Asian	0.0000980	0.0000980
Other	0.000163	0.000163

dbNSFP

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.;
Pathway: Fat digestion and absorption - Homo sapiens (human);Statin Pathway, Pharmacodynamics;Demo complete;Statin Pathway;Chylomicron assembly;VLDL assembly;Plasma lipoprotein assembly;Transport of small molecules;Glycerophospholipid metabolism;Plasma lipoprotein assembly, remodeling, and clearance (Consensus)

Recessive Scores

pRec: 0.450

Intolerance Scores

loftool: 0.582
rvis_EVS: 1.43
rvis_percentile_EVS: 94.99

Haploinsufficiency Scores

pHI: 0.364
hipred: Y
hipred_score: 0.589
ghis

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.691

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	Medium	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

Gene name: Mttp
Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; embryo phenotype; liver/biliary system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);

Zebrafish Information Network

Gene name: mttp
Affected structure: subintestinal vein
Phenotype tag: abnormal
Phenotype quality: morphology

Gene ontology

Biological process: lipid metabolic process;protein secretion;phospholipid transport;triglyceride transport;plasma lipoprotein particle assembly;chylomicron assembly;very-low-density lipoprotein particle assembly;lipoprotein metabolic process;cholesterol homeostasis
Cellular component: endoplasmic reticulum;endoplasmic reticulum lumen;Golgi apparatus;basolateral plasma membrane;receptor complex
Molecular function: lipid transporter activity;protein binding;phospholipid transporter activity;lipid binding;protein heterodimerization activity