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ACP5
acid phosphatase 5, tartrate resistant
The ACP5 gene provides instructions for tartrate-resistant acid phosphatase type 5 (TRAP), an enzyme crucial for bone remodelling and immune system regulation. ACP5 encodes an enzyme called tartrate-resistant acid phosphatase type 5 (TRAP), which plays a significant role in both bone metabolism and immune function.
ACP5 is located on the short (p) arm of chromosome 19, at band 19p13.2. Arm ratio per GRCh38 - banding schematic.
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Overview
The ACP5 gene is responsible for producing tartrate-resistant acid phosphatase type 5, commonly known as TRAP. This enzyme is vital for several physiological processes, primarily involving bone metabolism and the immune system. TRAP's function is closely linked to the regulation of osteopontin, a protein active in both bone and immune cells, which affects processes like bone tissue breakdown and immune responses.
Genetic variations within the ACP5 gene can impact its normal function, leading to conditions such as spondyloenchondrodysplasia with immune dysregulation (SPENCDI), characterised by skeletal abnormalities and immune system dysfunction.
What the gene does
The ACP5 gene produces the enzyme tartrate-resistant acid phosphatase type 5 (TRAP), which primarily regulates the activity of osteopontin. Osteopontin is a protein found in bone cells (osteoclasts) and immune cells, performing various functions in these contexts. TRAP exists in two main isoforms: TRAP5a, predominantly found in immune cells, and TRAP5b, mainly in osteoclasts.
In bone remodelling, osteoclasts break down old bone tissue. Osteopontin is activated, allowing osteoclasts to attach to bones. TRAP5b then inactivates osteopontin once bone breakdown is complete, prompting osteoclasts to detach. Similarly, in the immune system, TRAP5a inactivates osteopontin in macrophages and dendritic cells when its action is no longer required. Osteopontin assists in fighting infection by promoting inflammation, regulating immune cell activity, and activating various immune cells necessary for combating pathogens.
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Chromosome location
The ACP5 gene is situated on chromosome 19, specifically at band 19p13.2. This genomic location indicates its position on the short arm of chromosome 19. The gene provides instructions for a protein that is 325 amino acids in length.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variations in the ACP5 gene can alter the function of the TRAP enzyme, potentially affecting its ability to regulate osteopontin. These changes can lead to a range of clinical manifestations, particularly those involving bone development and immune system regulation. Genetic variants typically involve single amino acid changes or result in a truncated, non-functional protein.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.325G>A | p.Gly109Arg | Pathogenic/Likely pathogenic | ★★☆☆ | ACP5-related disorder |
c.369C>A | p.Tyr123Ter | Pathogenic | ★★☆☆ | Spondyloenchondrodysplasia with immune dysregulation |
c.526C>T | p.Arg176Ter | Pathogenic | ★★☆☆ | Inborn genetic diseases |
c.643G>A | p.Gly215Arg | Pathogenic/Likely pathogenic | ★★☆☆ | Spondyloenchondrodysplasia with immune dysregulation |
c.738C>A | p.Tyr246Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Spondyloenchondrodysplasia with immune dysregulation |
c.772_790del | p.Ser258fs | Pathogenic/Likely pathogenic | ★★☆☆ | Spondyloenchondrodysplasia with immune dysregulation |
c.799del | p.Ser267fs | Pathogenic | ★★☆☆ | Spondyloenchondrodysplasia with immune dysregulation |
c.136del | p.Arg46fs | Pathogenic | ★☆☆☆ | Spondyloenchondrodysplasia with immune dysregulation |
c.222C>A | p.Tyr74Ter | Pathogenic | ★☆☆☆ | Spondyloenchondrodysplasia with immune dysregulation |
c.250_251del | p.Lys84fs | Pathogenic | ★☆☆☆ | Spondyloenchondrodysplasia with immune dysregulation |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Mutations within the ACP5 gene are associated with spondyloenchondrodysplasia with immune dysregulation (SPENCDI). This condition is characterised by a combination of abnormal bone growth, affecting skeletal development, and dysregulation of the immune system. Research has identified various genetic alterations in ACP5 that contribute to the development of SPENCDI.
No disease links recorded for this gene in our reference set.
UK clinical status
The ACP5 gene is recognised within several NHS Genomic Medicine Service clinical panels, highlighting its clinical relevance in the UK. It is included in panels for COVID-19 research, DDG2P (developmental disorders), foetal anomalies (R21), intracerebral calcification disorders, primary immunodeficiency or monogenic inflammatory bowel disease (R15), skeletal dysplasia (R104), and white matter disorders and cerebral calcification of childhood onset.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the ACP5 gene do?
The ACP5 gene provides instructions for making an enzyme called tartrate-resistant acid phosphatase type 5 (TRAP). This enzyme is crucial for regulating the activity of osteopontin, a protein involved in bone remodelling and immune system function.
What conditions are associated with ACP5 gene mutations?
Mutations in the ACP5 gene are primarily associated with spondyloenchondrodysplasia with immune dysregulation (SPENCDI). This condition affects both bone growth and the normal functioning of the immune system.
What is osteopontin and how does TRAP interact with it?
Osteopontin is a protein found in bone cells and immune cells, where it plays various roles. TRAP, produced by the ACP5 gene, regulates osteopontin by activating and inactivating it as needed, helping to control processes like bone breakdown and immune responses.
References
- Lausch E, Janecke A, Bros M. Genetic deficiency of tartrate-resistant acid phosphatase associated with skeletal dysplasia, cerebral calcifications and autoimmunity. Nature genetics. 2011. PMID: 21217752
- Briggs TA, Rice GI, Daly S. Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature. Nature genetics. 2011. PMID: 21217755
- Behrens TW, Graham RR. TRAPing a new gene for autoimmunity. Nature genetics. 2011. PMID: 21270835
- Hayman AR. Tartrate-resistant acid phosphatase (TRAP) and the osteoclast/immune cell dichotomy. Autoimmunity. 2008. PMID: 18365835