Alternative titles; symbols
HGNC Approved Gene Symbol: ACP2
Cytogenetic location: 11p11.2 Genomic coordinates (GRCh38): 11:47,239,302-47,248,814 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 11p11.2 | ?Lysosomal acid phosphatase deficiency | 200950 | Autosomal recessive | 1 |
The ACP2 gene encodes lysosomal acid phosphatase-2 (EC 3.1.3.2), an enzyme with an acidic pH optimum that is expressed in the lysosomal compartment. Lysosomal acid phosphatase, which is found in all tissues, played a pivotal role in the discovery of lysosomes and is widely used as a biochemical marker for lysosomes (Mannan et al., 2004).
Pohlmann et al. (1988) isolated a cDNA clone corresponding to the human lysosomal acid phosphatase gene from a human placenta cDNA library. The cDNA hybridized with a 2.3-kb mRNA transcript from human liver and HL-60 promyelocytes. The deduced amino acid sequence contains a 30-residue putative signal sequence followed by a 393-amino acid protein with 8 potential glycosylation sites and a hydrophobic region. Sequence homology to prostate-specific acid phosphatase (ACPP; 171790) suggested a common evolutionary link between the 2 enzymes.
The ACP2 locus is syntenic with the LDHA locus (150000) and therefore can be assigned to chromosome 11. Shows et al. (1976) concluded the order of loci on chromosome 11 to be LDHA--ESA4--ACP2. Jones and Kao (1978) assigned the ACP2 gene to chromosome 11p12-p11.
Pohlmann et al. (1988) assigned the gene to human chromosome 11 by study of DNA from a panel of human-mouse cell hybrids.
Lundin and Allison (1966) suggested that lysosomal acid phosphatase is chemically and genetically distinct from red cell acid phosphatase (ACP1; 171500).
Beckman et al. (1970) studied variants of acid phosphatase isolated from human leukocytes and placenta.
Saftig et al. (1997) generated mice deficient in Acp2 by targeted disruption. Acp2 -/- mice were fertile and developed normally. Microscopic examination of various peripheral organs revealed lysosomal storage in podocytes and tubular epithelial cells of the kidney, with a regionally different ultrastructural appearance of the stored material. Within the central nervous system, lysosomal storage was detected to a regionally different extent in microglia, ependymal cells, and astroglia, concomitant with the development of a progressive astrogliosis and microglial activation. Whereas behavioral and neuromotor analyses were unable to distinguish between control and deficient mice, approximately 7% of the deficient animals developed generalized seizures. From the age of 6 months onward, conspicuous alterations of bone structure became apparent, resulting in a kyphoscoliotic malformation of the lower thoracic vertebral column. Saftig et al. (1997) concluded that lysosomal acid phosphatase has a unique function in only a subset of cells, where its deficiency causes the storage of heterogeneous-appearing material in lysosomes.
Mannan et al. (2004) reported a spontaneous autosomal recessive mouse mutant, 'nax' (for naked and ataxia), caused by a point mutation in the Acp2 gene. Affected mice showed severe growth retardation during development and delayed appearance of body hair, with the posterior part of the mice remaining naked throughout adult development. Adult nax mice were more than 50% smaller than wildtype mice. Nax mice also showed tremor and an ataxia-like phenotype. Postmortem examination showed that the cerebellum of nax mice was significantly smaller than wildtype and displayed disrupted cytoarchitecture, with absence of the inner granule cell layer and ectopically placed Purkinje cells with dendrites that extend in an uncoordinated fashion and appear short and disoriented. Electron microscopy showed large lysosomal inclusions within cells of the nax cerebellar cortex. Examination of hair follicles from the nax mice revealed short and thin hair shafts with eosinophilic inclusion bodies. Linkage analysis mapped the nax locus to a 0.8-Mb region on mouse chromosome 2 that shows syntenic homology with human 11p13-p11. Sequence analysis identified a homozygous 740A-G transition in exon 7 of the Acp2 gene, resulting in a gly244-to-glu (G244E) substitution in a conserved residue of the protein. Functional analysis showed that the G244E mutant enzyme was inactive. Mannan et al. (2004) noted that the nax mouse phenotype differed from the Acp2-null mouse phenotype described by Saftig et al. (1997).
Beckman, G., Beckman, L., Tarnvik, A. A rare subunit variant shared by five acid phosphatase isozymes from human leukocytes and placentae. Hum. Hered. 20: 81-85, 1970. [PubMed: 5444878] [Full Text: https://doi.org/10.1159/000152297]
Bruns, G. A. P., Gerald, P. S. Human acid phosphatase in somatic cell hybrids. Science 184: 480-482, 1974. [PubMed: 4856491] [Full Text: https://doi.org/10.1126/science.184.4135.480]
Harris, H., Hopkinson, D. A., Robson, E. B. The incidence of rare alleles determining electrophoretic variants: data on 43 enzyme loci in man. Ann. Hum. Genet. 37: 237-253, 1974. [PubMed: 4812947] [Full Text: https://doi.org/10.1111/j.1469-1809.1974.tb01832.x]
Jones, C., Kao, F.-T. Regional mapping of the gene for human lysosomal acid phosphatase (ACP-2) using a hybrid clone panel containing segments of human chromosome 11. Hum. Genet. 45: 1-10, 1978. [PubMed: 730175] [Full Text: https://doi.org/10.1007/BF00277567]
Lundin, L. G., Allison, A. C. Acid phosphatases from different organs and animal forms compared by starch-gel electrophoresis. Acta Chem. Scand. 20: 2572-2579, 1966.
Mannan, A. U., Roussa, E., Kraus, C., Rickmann, M., Maenner, J., Nayernia, K., Krieglstein, K., Reis, A., Engel, W. Mutation in the gene encoding lysosomal acid phosphatase (Acp2) causes cerebellum and skin malformation in mouse. Neurogenetics 5: 229-238, 2004. [PubMed: 15503243] [Full Text: https://doi.org/10.1007/s10048-004-0197-9]
Pohlmann, R., Krentler, C., Schmidt, B., Schroder, W., Lorkowski, G., Culley, J., Mersmann, G., Geier, C., Waheed, A., Gottschalk, S., Grzeschik, K.-H., Hasilik, A., von Figura, K. Human lysosomal acid phosphatase: cloning, expression and chromosomal assignment. EMBO J. 7: 2343-2350, 1988. [PubMed: 3191910] [Full Text: https://doi.org/10.1002/j.1460-2075.1988.tb03078.x]
Saftig, P., Hartmann, D., Lullmann-Rauch, R., Wolff, J., Evers, M., Koster, A., Hetman, M., von Figura, K., Peters, C. Mice deficient in lysosomal acid phosphatase develop lysosomal storage in the kidney and central nervous system. J. Biol. Chem. 272: 18628-18635, 1997. [PubMed: 9228031] [Full Text: https://doi.org/10.1074/jbc.272.30.18628]
Shows, T. B., Brown, J. A., Lalley, P. A. Assignment and linear order of human acid phosphatase-2, esterase-A4, and lactate dehydrogenase-A genes on chromosome 11. Cytogenet. Cell Genet. 16: 231-234, 1976. [PubMed: 975882] [Full Text: https://doi.org/10.1159/000130598]