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 (63 variants)
• Abetalipoproteinaemia (14 variants)
• MTTP-related disorder (2 variants)
• Inborn genetic diseases (1 variants)
• Metabolic syndrome X;Abetalipoproteinaemia (1 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	309	6	316
missense	1	2	255	22	1	281
nonsense	22	29	1			52
start loss						0
frameshift	39	29				68
inframe indel			2	1		3
splice donor/acceptor (+/-2bp)	7	17				24
splice region		1	13	55	4	73
non coding			28	149	47	224
Total	69	77	287	481	54

Highest pathogenic variant AF is 0.0000394

Variants in MTTP

This is a list of pathogenic ClinVar variants found in the MTTP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-99564087-G-C		Abetalipoproteinaemia • not specified	Benign (Jun 14, 2016)
4-99564098-G-A		Abetalipoproteinaemia	Benign (Jun 14, 2016)
4-99564125-G-A		Abetalipoproteinaemia • not specified • MTTP-related disorder	Conflicting classifications of pathogenicity (Mar 01, 2023)
4-99564134-G-A		Abetalipoproteinaemia	Uncertain significance (Jan 13, 2018)
4-99564183-TC-T			Uncertain significance (Jun 02, 2021)
4-99564186-C-G		Abetalipoproteinaemia	Uncertain significance (Jan 12, 2018)
4-99564190-C-A		Abetalipoproteinaemia	Uncertain significance (Jan 13, 2018)
4-99564240-G-A		MTTP-related disorder	Likely benign (Sep 13, 2019)
4-99574331-G-T			Benign (Jan 22, 2024)
4-99574660-T-C			Benign (Jan 22, 2024)
4-99574826-T-C		Abetalipoproteinaemia	Uncertain significance (Jan 13, 2018)
4-99574828-C-T		Abetalipoproteinaemia	Uncertain significance (Jan 13, 2018)
4-99574856-C-T		Abetalipoproteinaemia	Uncertain significance (Jan 13, 2018)
4-99574882-T-C		Abetalipoproteinaemia	Uncertain significance (Jan 13, 2018)
4-99574882-TGGATGCAGTTGAGGATTGCTGGTCAATATGATTCTTCTTGCTGTGC-T			Uncertain significance (Dec 10, 2021)
4-99574890-G-A		Abetalipoproteinaemia	Uncertain significance (Jan 12, 2018)
4-99574904-G-A		Abetalipoproteinaemia	Likely benign (Jul 11, 2024)
4-99574916-CT-C			Pathogenic (Jun 25, 2023)
4-99574921-T-TG			Likely pathogenic (Aug 01, 2022)
4-99574922-G-C		Inborn genetic diseases	Uncertain significance (Jun 02, 2024)
4-99574925-G-T		Inborn genetic diseases	Uncertain significance (Jan 26, 2022)
4-99574927-G-T			Likely benign (Feb 01, 2024)
4-99574929-T-G			Uncertain significance (Jul 22, 2022)
4-99574931-T-TCTGAA		Abetalipoproteinaemia	Likely pathogenic (Feb 28, 2022)
4-99574933-T-C			Likely benign (Sep 24, 2022)

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

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