TPP2

Chr 13

tripeptidyl peptidase 2

Also known as: IMD78, TPP-2, TPP-II, TPPII

NCBI Gene: 7174 ENSG00000134900 UniProt: P29144

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.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a mammalian peptidase that, at neutral pH, removes tripeptides from the N terminus of longer peptides. The protein has a specialized function that is essential for some MHC class I antigen presentation. The protein is a high molecular mass serine exopeptidase; the amino acid sequence surrounding the serine residue at the active site is similar to the peptidases of the subtilisin class rather than the trypsin class. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtImmunodeficiency 78 with autoimmunity and developmental delay

Clinical highlights

Gene-disease validity (ClinGen)

immunodeficiency 78 with autoimmunity and developmental delay · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.26

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

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