TPK1

Chr 7

thiamin pyrophosphokinase 1

Also known as: HTPK1, PP20, THMD5

NCBI Gene: 27010ENSG00000196511UniProt: Q9H3S4

The protein encoded by this gene functions as a homodimer and catalyzes the conversion of thiamine to thiamine pyrophosphate, a cofactor for some enzymes of the glycolytic and energy production pathways. Defects in this gene are a cause of thiamine metabolism dysfunction syndrome-5. [provided by RefSeq, Apr 2017]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtThiamine metabolism dysfunction syndrome 5, episodic encephalopathy type

Clinical highlights

Gene-disease validity (ClinGen)
Leigh syndrome · ARModerateconsider for supplementary testing
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
0
Active trials
23
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.70
LOEUF
DN
Mechanism· predicted
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GeneReview available — TPK1
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.70LOEUF
pLI 0.091
Z-score 2.33
OE 0.31 (0.15–0.70)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.34Z-score
OE missense 0.92 (0.79–1.07)
121 obs / 132.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.31 (0.15–0.70)
0≤0.351.4
Missense OE?0.92 (0.79–1.07)
0≤0.61.4
Synonymous OE?0.94
0≤1.21.6
LoF obs/exp: 4 / 13.1Missense obs/exp: 121 / 132.1Syn Z: 0.34

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients