TTPA

alpha tocopherol transfer protein

Basic information

Region (hg38): 8:63048552-63086053

Previous symbols: [ "AVED" ]

Links

ENSG00000137561 ∙ NCBI:7274 ∙ OMIM:600415 ∙ HGNC:12404 ∙ Uniprot:P49638 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial isolated deficiency of vitamin E (Definitive), mode of inheritance: AR
• familial isolated deficiency of vitamin E (Strong), mode of inheritance: AR
• familial isolated deficiency of vitamin E (Supportive), mode of inheritance: AR
• familial isolated deficiency of vitamin E (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ataxia with vitamin E deficiency	AR	Gastrointestinal	Preventive treatment with vitamin E administration can ameliorate signs and symptoms of disease; Untreated, individuals typically present with neurological manifestations, including progressive ataxia, and knowledge can allow early treatment (which involves chronic supplementation with high-dose oral vitamin E, with the goal of maintaining plasma vitamin E concentrations in the high-normal range)	Gastrointestinal; Neurologic	4000224; 3361234; 7887897; 7719340; 8602747; 8972536; 463307; 10552255; 11554913; 12039660; 15300460; 20301419; 34663645

ClinVar

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

• not provided (293 variants)
• Familial isolated deficiency of vitamin E (129 variants)
• Inborn genetic diseases (20 variants)
• not specified (15 variants)
• Ataxia, Friedreich-like, with isolated vitamin E deficiency (6 variants)
• TTPA-related condition (2 variants)
• Abnormal central motor function (1 variants)
• Ataxia and retinitis pigmentosa with isolated vitamin E deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TTPA 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			3	99	3	105
missense	1	2	92			95
nonsense	9	7	1			17
start loss		3				3
frameshift	14	20				34
inframe indel			1			1
splice donor/acceptor (+/-2bp)	4	6				10
splice region		1	3	6	3	13
non coding			36	32	15	83
Total	28	38	133	131	18

Highest pathogenic variant AF is 0.0000920

Variants in TTPA

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

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

Position	Type	Phenotype	Significance	ClinVar
8-63059536-A-G		Familial isolated deficiency of vitamin E	Uncertain significance (Jan 12, 2018)
8-63059654-G-A		Familial isolated deficiency of vitamin E	Uncertain significance (Jan 12, 2018)
8-63059765-C-T		Familial isolated deficiency of vitamin E	Benign (Jan 13, 2018)
8-63059766-G-A		Familial isolated deficiency of vitamin E	Uncertain significance (Jan 13, 2018)
8-63059767-GTTAT-G		Familial isolated deficiency of vitamin E	Uncertain significance (Jun 14, 2016)
8-63059811-G-C		Familial isolated deficiency of vitamin E	Uncertain significance (Jan 13, 2018)
8-63059828-G-A		Familial isolated deficiency of vitamin E	Uncertain significance (Jan 13, 2018)
8-63059830-A-C		Familial isolated deficiency of vitamin E	Uncertain significance (Jan 13, 2018)
8-63059845-C-T		Familial isolated deficiency of vitamin E	Uncertain significance (Jan 12, 2018)
8-63059848-C-T		Familial isolated deficiency of vitamin E	Benign (Jan 13, 2018)
8-63059858-T-C		Familial isolated deficiency of vitamin E	Uncertain significance (Jan 12, 2018)
8-63059884-G-C		Familial isolated deficiency of vitamin E	Uncertain significance (Jan 12, 2018)
8-63059887-T-G		Familial isolated deficiency of vitamin E	Uncertain significance (Jan 13, 2018)
8-63060005-T-C		Familial isolated deficiency of vitamin E	Uncertain significance (Jan 13, 2018)
8-63060070-ATAT-A		Familial isolated deficiency of vitamin E	Uncertain significance (Jun 14, 2016)
8-63060088-T-A		Familial isolated deficiency of vitamin E	Uncertain significance (Jan 13, 2018)
8-63060117-A-G		Familial isolated deficiency of vitamin E	Uncertain significance (Jan 12, 2018)
8-63060159-C-T		Familial isolated deficiency of vitamin E	Benign (Jan 12, 2018)
8-63060318-G-A		Familial isolated deficiency of vitamin E	Uncertain significance (Jan 13, 2018)
8-63060320-C-T		Familial isolated deficiency of vitamin E	Likely benign (Jan 13, 2018)
8-63060435-C-T		Familial isolated deficiency of vitamin E	Uncertain significance (Jan 13, 2018)
8-63060446-G-A		Familial isolated deficiency of vitamin E	Uncertain significance (Jan 13, 2018)
8-63060470-G-A		Familial isolated deficiency of vitamin E	Benign (Jan 13, 2018)
8-63060476-G-A		Familial isolated deficiency of vitamin E	Uncertain significance (Jan 13, 2018)
8-63060483-C-T		Familial isolated deficiency of vitamin E	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TTPA	protein_coding	protein_coding	ENST00000260116	5	37501

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00144	0.882	125662	0	78	125740	0.000310

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.303	135	145	0.929	0.00000730	1800
Missense in Polyphen		49	52.808	0.92789		660
Synonymous	-0.142	56	54.7	1.02	0.00000267	547
Loss of Function	1.36	6	10.8	0.553	5.25e-7	127

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000410	0.000410
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000510	0.000510
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds alpha-tocopherol, enhances its transfer between separate membranes, and stimulates its release from liver cells (PubMed:7887897). Binds both phosphatidylinol 3,4-bisphosphate and phosphatidylinol 4,5-bisphosphate; the resulting conformation change is important for the release of the bound alpha-tocopherol (By similarity). {ECO:0000250, ECO:0000269|PubMed:7887897}.
• Disease: DISEASE: Ataxia with isolated vitamin E deficiency (AVED) [MIM:277460]: An autosomal recessive disease characterized by undetectable or markedly reduced plasma levels of vitamin E, spinocerebellar degeneration, ataxia, areflexia and proprioception loss. {ECO:0000269|PubMed:15065857, ECO:0000269|PubMed:15300460, ECO:0000269|PubMed:7566022, ECO:0000269|PubMed:8602747, ECO:0000269|PubMed:9463307}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Metabolism of fat-soluble vitamins;Metabolism;Metabolism of vitamins and cofactors;Vitamin E (Consensus)

Recessive Scores

• pRec: 0.589

Intolerance Scores

• loftool: 0.478
• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.25

Haploinsufficiency Scores

• pHI: 0.179
• hipred: N
• hipred_score: 0.444
• ghis: 0.505

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.711

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ttpa
• Phenotype: 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); vision/eye 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); reproductive system phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: ttpa
• Affected structure: immature eye
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: embryonic placenta development;lipid metabolic process;response to nutrient;response to pH;response to toxic substance;vitamin E metabolic process;vitamin transport;intracellular pH reduction;negative regulation of cell death;negative regulation of establishment of blood-brain barrier;intermembrane lipid transfer
• Cellular component: late endosome;cytosol
• Molecular function: protein binding;phosphatidylinositol-4,5-bisphosphate binding;vitamin E binding;phosphatidylinositol-3,4-bisphosphate binding;intermembrane lipid transfer activity