Alt. symbols: TPPII

Approved name: tripeptidyl peptidase 2
Alt. names: tripeptidyl peptidase II

Location: 13q33.1: 102596958 - 102679958 (+)
Gene type: protein_coding, 29 transcripts.

Scores: LoFtool: 0.066600 | pLI: 0.99986319 | LOEUF: 0.263

HGNC: 12016

NCBI: 7174, RefSeq: NG_063544.1

Ensembl: ENSG00000134900.13

LRG_1341 | Status: public

OMIM: 190470

Expression | ProteinAtlas

TPP2 encodes a ubiquitously expressed cytosolic protease involved in protein degradation. The enzyme removes tripeptides from the N-terminal end of longer peptides to help in the elimination of proteins downstream of the proteasome-ubiquitin degradation pathway. This also contributes to the maintenance of free amino acid pools for protein synthesis. TPP2 has also been implicated in stimulation of adipogenesis and the generation of thymic self-peptides and degradation of MHC class I epitopes, suggesting a role in immune function. It may be able to complement 26S proteasome function to some extent under conditions in which the latter is inhibited.

Biallelic mutations in TPP2 are associated with Immunodeficiency-78 with autoimmunity and developmental delay (IMD78) [MIM: 619220], an autosomal recessive systemic disorder characterized by immune dysregulation in the form of both immunodeficiency - featuring recurrent sinopulmonary or skin infections and increased susceptibility to bacterial, viral, and fungal infections - and autoimmunity, particularly cytopenias but also autoimmune hepatitis or thyroid disease, and CNS involvement with multi ple sclerosis-like sterile inflammation or vasculitis with stroke (PMID: 25414442, 30533531, 33586135). Laboratory studies show lymphopenia with advanced differentiation and premature senescence of CD8+ T cells and B cells; many patients show autoantibody production and some have hypergammaglobulinemia. Skin, hair and nail findings as well as developmental delays and variable intellectual disability may also be present. Many patients die prematurely, but successful hematopoietic bone marrow transplant may be curative. [Load More]