Alt. symbols: TRAP | HPAP

Approved name: acid phosphatase 5, tartrate resistant
Alt. names: tartrate-resistant acid phosphatase, human purple acid phosphatase

Location: 19p13.2: 11574653 - 11579993 (-)
Gene type: protein_coding, 27 transcripts.

Scores: LoFtool: 0.138000 | pLI: 0.12356835 | LOEUF: 0.724

HGNC: 124

NCBI: 54, RefSeq: NG_028127.1

Ensembl: ENSG00000102575.14

LRG_1218 | Status: public

OMIM: 171640

Expression | ProteinAtlas

ACP5 encodes tartrate-resistant acid phosphatase (TRAP), a metalloenzyme involved in osteopontin/bone sialoprotein dephosphorylation whose expression is restricted to mononuclear phagocytes (PMID: 32214327, 2338077). TRAP exists as two isoforms with different optimal pH and specific activities, derived from differential post-translational processing of a central regulatory loop peptide (PMID: 15929988). Isoform a is a monomeric protein with intact loop peptide, while isoforms 5a and 5b result from proteolytic cleavage into 23 kDa and 16 kDa disulfide-linked heterodimers that are differentially compartmentalized. In macrophages and dendritic cells, only isoform 5a is secreted from cells, making this a good marker for systemic macrophage functions and chronic inflammatory activity (PMID: 17369130). In osteoclasts, on the other hand, isoform 5b is released into circulation with other matrix products during bone resorption, making this a good marker for osteoclast activity (PMID: 15312243).

Biallelic mutations in ACP5 lead to Spondyloenchondrodysplasia with immune dysregulation (SPENCDI) [OMIM: 607944], an immuno-osseous dysplasia combining the typical metaphyseal and vertebral bone lesions of spondyloenchondrodysplasia (SPENCD) with immune dysfunction and neurologic involvement. The skeletal dysplasia is characterized by radiolucent and irregular spondylar and metaphyseal lesions that represent islands of chondroid tissue within bone. Vertebral bodies show dorsally accentuated pla tyspondyly with disturbance of ossification. Variable clinical findings include short stature, rhizomelic micromelia, increased lumbar lordosis, barrel chest, facial anomalies, and clumsy movements. CNS involvement includes spasticity, intellectual disability, and cerebral calcifications. Patients may show some combination of immunodeficiency, auto-inflammation and/or auto-immunity, but the clinical spectrum can vary significantly even within families. Patients show absent serum expression of TRAP, increased levels of serum IFN-alpha and upregulated interferon gene signatures (PMID: 26951490). [Load More]