TPMT (Thiopurine S-methyltransferase) variants and mutations

TPMT (also known as Thiopurine S-methyltransferase) is a human protein-coding gene encoding a thiopurine S-methyltransferase protein. It methylates and inactivates thiopurine metabolites, strongly influencing how much cytotoxic thioguanine nucleotide accumulates during therapy. Reduced-function alleles can cause profound myelosuppression at standard thiopurine doses, making genotype or enzyme activity clinically actionable. This analysis covers 388 TPMT variants and mutations. Of these, 96% have computational variant effect predictions. Disease context includes thiopurine S-methyltransferase deficiency, aging, and neurodegenerative disease. Example TPMT variants include G3D, G3S, and T4S.

Variant analysis overview

Gene: TPMT
Protein: Thiopurine S-methyltransferase
UniProt accession: P51580
Organism: Homo sapiens
Variants analyzed: 388
Variant scope: all variants
Completed: 2026-08-10

Variant and mutation evidence

Variant composition: 256 unspecified-consequence records; 1 stop retained variant; 14 frameshift variants; 37 synonymous variants; 73 missense variants; 1 stop-gained variants; 1 in-frame deletions; 3 splice-region variants; 2 in-frame insertions
Prediction scores: 373 variants have prediction scores (96% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: thiopurine S-methyltransferase deficiency, aging, neurodegenerative disease, inborn errors of metabolism, cancer, autoimmune disorder of central nervous system, atrial fibrillation, Decreased total leukocyte count, acute lymphoblastic leukemia, atrial flutter, malignant colon neoplasm, colonic neoplasm.

Protein structure and variant hotspots

Protein features: 6 binding sites; 2 post-translational modification sites.
PTM context: 2 variants overlap post-translational modification sites.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.

Notable TPMT variants

Examples include G3D, G3S, T4S, R5S, D9N, I10M, I10S, I10V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

TPMT analysis run — TPMT (388 variants) — completed 2026-08-10