TPP2
Chr 13ARtripeptidyl peptidase 2
Also known as: IMD78, TPP-2, TPP-II, TPPII
This cytosolic tripeptidyl-peptidase removes N-terminal tripeptides from polypeptides as part of the proteolytic cascade downstream of the 26S proteasome and plays an important role in MHC class I antigen presentation and intracellular amino acid homeostasis. Biallelic mutations cause autosomal recessive immunodeficiency 78 with autoimmunity and developmental delay. The gene is highly constrained against loss-of-function variants (pLI 0.999, LOEUF 0.263), indicating intolerance to protein-truncating mutations.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
TPP2 · 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