TPK1
Chr 7ARthiamin pyrophosphokinase 1
Also known as: HTPK1, PP20, THMD5
The protein catalyzes the phosphorylation of thiamine to thiamine pyrophosphate (TPP), a critical cofactor for mitochondrial pyruvate dehydrogenase and enzymes involved in glycolysis and energy production. Mutations cause thiamine metabolism dysfunction syndrome 5, characterized by episodic encephalopathy, and follow autosomal recessive inheritance. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.7), reflecting its essential role in cellular energy metabolism.
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
TPK1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools