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 (Definitive), mode of inheritance: AR
• abetalipoproteinemia (Strong), mode of inheritance: AR
• abetalipoproteinemia (Supportive), 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 (944 variants)
• Abetalipoproteinaemia (267 variants)
• Inborn_genetic_diseases (90 variants)
• MTTP-related_disorder (22 variants)
• not_specified (21 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	11	339	1	352
missense	2	7	334	16	1	360
nonsense	24	30	2			56
start loss						0
frameshift	41	37				78
splice donor/acceptor (+/-2bp)	10	24				34
Total	77	99	347	355	2

Highest pathogenic variant AF is 0.00008844189

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
		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

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

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