TTPA

alpha tocopherol transfer protein

Basic information

Region (hg38): 8:63048553-63086053

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 (346 variants)
Familial_isolated_deficiency_of_vitamin_E (122 variants)
Inborn_genetic_diseases (43 variants)
not_specified (15 variants)
TTPA-related_disorder (8 variants)
ATAXIA,_FRIEDREICH-LIKE,_WITH_ISOLATED_VITAMIN_E_DEFICIENCY (6 variants)
Retinal_dystrophy (4 variants)
Abnormal_central_motor_function (1 variants)
ATAXIA_WITH_ISOLATED_VITAMIN_E_DEFICIENCY_AND_RETINITIS_PIGMENTOSA (1 variants)
Optic_atrophy (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. These statistics are base on transcript: NM_000000370.3. 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	6 clinvar	142 clinvar	3 clinvar	152
missense		14 clinvar	127 clinvar	2 clinvar		143
nonsense	11 clinvar	6 clinvar	1 clinvar			18
start loss	1	2				3
frameshift	21 clinvar	22 clinvar				43
splice donor/acceptor (+/-2bp)	3 clinvar	12 clinvar	1 clinvar			16
Total	36	57	135	144	3

Highest pathogenic variant AF is 0.000178444

Loading clinvar variants...

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