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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
TTPA
alpha tocopherol transfer protein
Chromosome 8 Β· 8q12.3
NCBI Gene: 7274Ensembl: ENSG00000137561.6HGNC: HGNC:12404UniProt: P49638
51PubMed Papers
21Diseases
0Drugs
91Pathogenic Variants
FUNCTIONAL ROLE
Transporter
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
lipid transfer activityprotein bindingvitamin E bindingphosphatidylinositol-3,4-bisphosphate bindingAtaxia with vitamin E deficiencyfamilial isolated deficiency of vitamin Ehereditary ataxiaRare hereditary ataxia
✦AI Summary

TTPA encodes alpha-tocopherol transfer protein, which binds alpha-tocopherol and facilitates its transfer between cellular membranes and release from hepatocytes [PubMed:7887897]. The protein exhibits lipid transfer activity and binds phosphatidylinositol bisphosphates, with conformational changes induced by these interactions promoting alpha-tocopherol release. TTPA is essential for systemic vitamin E distribution to peripheral tissues including the brain, heart, muscle, and adipose tissue. Genetic defects in TTPA cause ataxia with vitamin E deficiency (AVED), an autosomal recessive cerebellar ataxia characterized by progressive neurodegeneration 1. The c.744delA frameshift mutation represents the most frequent TTPA pathogenic variant, particularly in Tunisian populations. TTPA knockout mice (Ttpa-/-) demonstrate severe systemic alpha-tocopherol depletion, with undetectable levels in brain, muscle, and serum, while retaining only residual tissue stores 2. Clinically, alpha-tocopherol deficiency manifests as spinocerebellar ataxia, peripheral neuropathy, myopathy, and impaired immune function 2. TTPA-deficient mice exhibit exacerbated inflammatory responses and reduced grip strength following systemic lipopolysaccharide administration, suggesting vitamin E deficiency increases vulnerability to inflammatory stress. TTPA function is therefore critical for maintaining adequate antioxidant capacity and neurological health.

Sources cited
1
TTPA binds alpha-tocopherol and enhances its transfer between membranes and release from liver cells
PMID: 7887897
2
TTPA-deficient mice show tissue-specific alpha-tocopherol depletion; alpha-tocopherol deficiency causes neurologic disorders including spinocerebellar ataxia, peripheral neuropathy, and myopathy; Ttpa-/- mice demonstrate exacerbated grip strength reduction with LPS-induced inflammation
PMID: 38141774
3
TTPA mutations cause ataxia with vitamin E deficiency (AVED); c.744delA is the most frequent pathogenic variant in Tunisia
PMID: 38109176
⚠Limited data available β€” This gene has 3 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜21
Ataxia with vitamin E deficiencyOpen Targets
0.81Strong
familial isolated deficiency of vitamin EOpen Targets
0.75Strong
hereditary ataxiaOpen Targets
0.46Moderate
Rare hereditary ataxiaOpen Targets
0.46Moderate
Retinal dystrophyOpen Targets
0.45Moderate
genetic disorderOpen Targets
0.41Moderate
ovarian dysfunctionOpen Targets
0.31Weak
Abdominal painOpen Targets
0.30Weak
HeadacheOpen Targets
0.29Weak
Limb painOpen Targets
0.29Weak
dementiaOpen Targets
0.27Weak
Abnormal central motor functionOpen Targets
0.27Weak
cervical carcinomaOpen Targets
0.23Weak
optic atrophyOpen Targets
0.11Weak
Female infertility due to fertilization defectOpen Targets
0.07Suggestive
oocyte maturation defect 14Open Targets
0.06Suggestive
oocyte maturation defect 5Open Targets
0.06Suggestive
female infertility due to oocyte meiotic arrestOpen Targets
0.06Suggestive
Hydatidiform MoleOpen Targets
0.05Suggestive
infectionOpen Targets
0.05Suggestive
Ataxia with vitamin E deficiencyUniProt
Pathogenic Variants91
NM_000370.3(TTPA):c.661C>T (p.Arg221Trp)Pathogenic
Familial isolated deficiency of vitamin E|not provided|Gastric cancer|Malignant tumor of esophagus|CHD7-related CHARGE syndrome
β˜…β˜…β˜†β˜†2026β†’ Residue 221
NM_000370.3(TTPA):c.513_514insTT (p.Thr172fs)Pathogenic
ATAXIA, FRIEDREICH-LIKE, WITH ISOLATED VITAMIN E DEFICIENCY|Familial isolated deficiency of vitamin E|not provided|Retinal dystrophy|CHD7-related CHARGE syndrome
β˜…β˜…β˜†β˜†2026β†’ Residue 172
NM_000370.3(TTPA):c.80del (p.Gly27fs)Likely pathogenic
Familial isolated deficiency of vitamin E
β˜…β˜…β˜†β˜†2026β†’ Residue 27
NM_000370.3(TTPA):c.19del (p.Gln7fs)Pathogenic
Familial isolated deficiency of vitamin E|not provided|Inborn genetic diseases
β˜…β˜…β˜†β˜†2026β†’ Residue 7
NM_000370.3(TTPA):c.421G>A (p.Glu141Lys)Pathogenic
Familial isolated deficiency of vitamin E
β˜…β˜…β˜†β˜†2025β†’ Residue 141
NM_000370.3(TTPA):c.744del (p.Glu249fs)Pathogenic
ATAXIA, FRIEDREICH-LIKE, WITH ISOLATED VITAMIN E DEFICIENCY|Familial isolated deficiency of vitamin E|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 249
NM_000370.3(TTPA):c.84_91dup (p.Leu31fs)Pathogenic
not provided|Familial isolated deficiency of vitamin E
β˜…β˜…β˜†β˜†2025β†’ Residue 31
NM_000370.3(TTPA):c.400C>T (p.Arg134Ter)Pathogenic
ATAXIA, FRIEDREICH-LIKE, WITH ISOLATED VITAMIN E DEFICIENCY|Familial isolated deficiency of vitamin E|not provided|Retinal dystrophy|TTPA-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 134
NM_000370.3(TTPA):c.2T>C (p.Met1Thr)Pathogenic
Familial isolated deficiency of vitamin E|not provided|TTPA-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 1
NM_000370.3(TTPA):c.487del (p.Trp163fs)Pathogenic
ATAXIA, FRIEDREICH-LIKE, WITH ISOLATED VITAMIN E DEFICIENCY|Familial isolated deficiency of vitamin E|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 163
NM_000370.3(TTPA):c.218_219dup (p.Tyr74fs)Pathogenic
not provided|Familial isolated deficiency of vitamin E
β˜…β˜…β˜†β˜†2025β†’ Residue 74
NM_000370.3(TTPA):c.358G>A (p.Ala120Thr)Pathogenic
Familial isolated deficiency of vitamin E|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 120
NM_000370.3(TTPA):c.552G>A (p.Thr184=)Pathogenic
Familial isolated deficiency of vitamin E|not provided|ATAXIA, FRIEDREICH-LIKE, WITH ISOLATED VITAMIN E DEFICIENCY
β˜…β˜…β˜†β˜†2024β†’ Residue 184
NM_000370.3(TTPA):c.303T>G (p.His101Gln)Pathogenic
ATAXIA WITH ISOLATED VITAMIN E DEFICIENCY AND RETINITIS PIGMENTOSA|Familial isolated deficiency of vitamin E
β˜…β˜…β˜†β˜†2024β†’ Residue 101
NM_000370.3(TTPA):c.227_229delinsATT (p.Trp76_Arg77delinsTyrTer)Pathogenic
Familial isolated deficiency of vitamin E|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 76
NM_000370.3(TTPA):c.205-2A>GPathogenic
Familial isolated deficiency of vitamin E|not provided
β˜…β˜…β˜†β˜†2024
NM_000370.3(TTPA):c.2T>A (p.Met1Lys)Pathogenic
Familial isolated deficiency of vitamin E|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 1
NM_000370.3(TTPA):c.652dup (p.Ile218fs)Pathogenic
not provided|Familial isolated deficiency of vitamin E
β˜…β˜…β˜†β˜†2024β†’ Residue 218
NM_000370.3(TTPA):c.205-1G>CPathogenic
Familial isolated deficiency of vitamin E|not provided
β˜…β˜…β˜†β˜†2024
NM_000370.3(TTPA):c.173C>A (p.Ala58Asp)Likely pathogenic
not provided|Familial isolated deficiency of vitamin E
β˜…β˜…β˜†β˜†2024β†’ Residue 58
View on ClinVar β†—
Related Genes
ATCAYProtein interaction91%PRUNE2Protein interaction77%SLC6A11Protein interaction76%BNIP2Protein interaction74%FXNProtein interaction74%PLCXD3Shared pathway20%
Tissue Expression6 tissues
Liver
100%
Brain
1%
Lung
0%
Bone Marrow
0%
Ovary
0%
Heart
0%
Gene Interaction Network
Click a node to explore
TTPAATCAYPRUNE2SLC6A11BNIP2FXNPLCXD3
PROTEIN STRUCTURE
Preparing viewer…
PDB1R5L Β· 1.50 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.28LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.88 [0.62–1.28]
RankingsWhere TTPA stands among ~20K protein-coding genes
  • #8,749of 20,598
    Most Researched51
  • #842of 5,498
    Most Pathogenic Variants91 Β· top quartile
  • #13,450of 17,882
    Most Constrained (LOEUF)1.28
Genes detectedTTPA
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Human tissue-type plasminogen activator.
PMID: 24718307
Thromb Haemost Β· 2014
1.00
2
CHI3L1 on fibrinolytic system imbalance in chronic rhinosinusitis with nasal polyp.
PMID: 38975344
Front Immunol Β· 2024
0.90
3
Ξ±-Tocopherol Depletion Exacerbates Lipopolysaccharide-Induced Reduction of Grip Strength.
PMID: 38141774
J Nutr Β· 2024
0.80
4
Genetic heterogeneity within a consanguineous family involving
PMID: 38109176
J Neurogenet Β· 2023
0.70
5
Rapamycin and thrombosis.
PMID: 22593201
Angiology Β· 2012
0.60