ACP3

Summary

ACP3 (acid phosphatase 3, HGNC:125) is a protein-coding gene on chromosome 3q22.1, encoding Prostatic acid phosphatase (P15309). A non-specific tyrosine phosphatase that dephosphorylates a diverse number of substrates under acidic conditions (pH 4-6) including alkyl, aryl, and acyl orthophosphate monoesters and phosphorylated proteins.

This gene encodes an enzyme that catalyzes the conversion of orthophosphoric monoester to alcohol and orthophosphate. It is synthesized under androgen regulation and is secreted by the epithelial cells of the prostate gland. An alternatively spliced transcript variant encoding a longer isoform has been found for this gene. This isoform contains a transmembrane domain and is localized in the plasma membrane-endosomal-lysosomal pathway.

Source: NCBI Gene 55 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 67 total
• Druggable target: yes
• MANE Select transcript: NM_001099

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:125
Approved symbol	ACP3
Name	acid phosphatase 3
Location	3q22.1
Locus type	gene with protein product
Status	Approved
Aliases	ACP-3, PAP, TM-PAP
Ensembl gene	ENSG00000014257
Ensembl biotype	protein_coding
OMIM	171790
Entrez	55

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000336375, ENST00000351273, ENST00000475741, ENST00000483689, ENST00000489084, ENST00000493235, ENST00000495911, ENST00000507647, ENST00000512463

RefSeq mRNA: 3 — MANE Select: NM_001099 NM_001099, NM_001134194, NM_001292037

CCDS: CCDS3073, CCDS46916, CCDS77818

Canonical transcript exons

ENST00000336375 — 10 exons

Exon	Start	End
ENSE00000778270	132337456	132337554
ENSE00000778274	132352720	132352823
ENSE00001341899	132356686	132358841
ENSE00001922674	132317407	132317576
ENSE00003459977	132344927	132345059
ENSE00003504116	132332192	132332344
ENSE00003512281	132342552	132342644
ENSE00003553491	132331647	132331733
ENSE00003627877	132328267	132328362
ENSE00003686715	132349920	132350002

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 97.16.

FANTOM5 (CAGE): breadth broad, TPM avg 8.6219 / max 1462.7660, expressed in 883 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38622	4.5481	694
38623	3.0663	543
38621	0.2807	156
38620	0.2540	92
38626	0.2050	107
38625	0.1853	93
38624	0.0826	46

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
prostate gland	UBERON:0002367	97.16	gold quality
tongue squamous epithelium	UBERON:0006919	96.22	gold quality
esophagus squamous epithelium	UBERON:0006920	93.54	gold quality
sperm	CL:0000019	92.51	gold quality
epithelium of esophagus	UBERON:0001976	92.49	gold quality
penis	UBERON:0000989	91.95	gold quality
urethra	UBERON:0000057	91.80	gold quality
esophagus mucosa	UBERON:0002469	91.73	gold quality
monocyte	CL:0000576	91.46	gold quality
mononuclear cell	CL:0000842	90.82	gold quality
leukocyte	CL:0000738	90.20	gold quality
squamous epithelium	UBERON:0006914	90.10	gold quality
oral cavity	UBERON:0000167	89.83	gold quality
upper leg skin	UBERON:0004262	88.86	gold quality
male germ cell	CL:0000015	88.85	gold quality
germinal epithelium of ovary	UBERON:0001304	88.40	gold quality
mammalian vulva	UBERON:0000997	88.35	gold quality
gingival epithelium	UBERON:0001949	87.64	gold quality
gingiva	UBERON:0001828	87.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.27	gold quality
lower esophagus mucosa	UBERON:0035834	85.50	gold quality
cervix epithelium	UBERON:0004801	85.10	gold quality
nephron tubule	UBERON:0001231	83.63	gold quality
amniotic fluid	UBERON:0000173	83.40	gold quality
skin of abdomen	UBERON:0001416	83.24	gold quality
zone of skin	UBERON:0000014	82.69	gold quality
skin of leg	UBERON:0001511	82.32	gold quality
tonsil	UBERON:0002372	81.54	gold quality
blood	UBERON:0000178	81.37	gold quality
cervix squamous epithelium	UBERON:0006922	80.66	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	5706.74
E-CURD-119	yes	43.01
E-HCAD-10	yes	12.98
E-ANND-3	yes	6.73

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, ESR1, ESR2, MYC, PARP1, PGR, PRRX1

miRNA regulators (miRDB)

70 targeting ACP3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-6803-5P	99.19	63.90	1026

Literature-anchored findings (GeneRIF, showing 40)

• sliding model in which the position-specific tethering of NURF forces a translocating ISWI ATPase to pump a DNA distortion over the histone octamer, thereby changing the translational position of the nucleosome. (PMID:15262970)
• Data show that removal of p55 deregulated the expression of E2F targets that are normally repressed by dE2F2/RBF-1 and -2 complexes in a cell cycle-independent manner but had no effect on the expression of targets normally coupled with cell proliferation. (PMID:15456884)
• The nucleosome-binding subunits Su(z)12 and Nurf55 anchor the E(z) enzyme on chromatin substrates, an essential process in maintaining HOX gene silencing during development. (PMID:15776017)
• A Pcl-PSC2 complex is the histone methyltransferase that generates the high levels of histone3-lysine27 trimethylation in Polycomb target genes that are needed to maintain a Polycomb-repressed chromatin state. (PMID:17762866)
• Results establish that dCAF-1-p180 is an essential gene for Drosophila development and further underscore the importance of dCAF-1 in regulating gene expression and DNA repair in vivo. (PMID:17916346)
• Structural basis of histone H4 recognition by p55. (PMID:18443147)
• larval endocycling cells lacking CAF-1 large subunit exhibit normal dynamics of progression through endocycles, although accumulating defects, such as perturbation of nucleosomal organisation, reduction of DNA replication and accumulation of DNA damage (PMID:19066929)
• results suggest that the ISWI-containing NURF complex functions as a co-activator of Armadillo to promote Wg-mediated transcription. (PMID:19713963)
• spreading of heterochromatin is compromised in flies that have reduced CAF-1 p180. Furthermore, reduced CAF-1 p180 causes a defect in the dynamics of heterochromatic markers in early Drosophila embryos. (PMID:20663913)
• analysis of Caf1 mutant tissue suggests that Caf1 plays important roles in cell survival and segment identity, and loss of Caf1 is associated with a reduction in the Polycomb Repressive Complex 2 (PRC2)-specific histone methylation mark H3K27me3 (PMID:21490066)
• Chromatin-modifying complex component Nurf55/p55 associates with histones H3 and H4 and polycomb repressive complex 2 subunit Su(z)12 through partially overlapping binding sites. (PMID:21550984)
• these studies suggest that p55 is not crucial for PRC2-mediated gene silencing in vivo, and the vital function of p55 is probably not dependent on its interaction with histone H4. (PMID:22241697)
• CAF1-p180 and CAF1-p75 subunits mediate assembly of two different forms of chromatin. (PMID:23810557)
• CAF-1 promotes Notch signaling through epigenetic control of target gene expression during Drosophila development. (PMID:23942516)
• CCR4 and CAF1, the two deadenylases in the CCR4-NOT complex, can remove 3’ terminal non-A residues in an exonucleolytic manner. (PMID:27484313)
• Results of genetic interaction analyses revealed that Mi-2 and Caf1/p55, components of the Nucleosome Remodeling and Deacetylase (NuRD) complex, genetically antagonize the role of DREF in germline stem cell maintenance. Taken together, these data suggest that DREF contributes to intrinsic components of the germline stem cell regulatory network that maintains competence to self-renew. (PMID:31226128)
• Effect of tartaric acid on conformation and stability of human prostatic phosphatase: an infrared spectroscopic and calorimetric study. (PMID:11833784)
• Identification and characterization of regulatory elements of the human prostatic acid phosphatase promoter. (PMID:12032838)
• analysis of mRNA levels in hyperplastic prostate stimulated with steroid hormones and growth factors (PMID:12362977)
• equilibrium unfolding of dimeric human prostatic acid phosphatase involves an inactive monomeric intermediate (PMID:12719131)
• In dilute solutions, several active prostatic acid phosphatase species exist, which are involved in concentration-dependent dissociation/association equilibria (PMID:12962324)
• Human prostatic acid phosphatase’s regulatory regions were analyzed in transgenic mice and cell line transfections, in order to clarify the mechanisms of tissue-specific gene expression (PMID:14623260)
• protein binding with Con A in seminal plasma (PMID:14690244)
• Transcriptional activation of the prostatic acid phosphatase gene by NF-kappaB in human prostate cancer cells. (PMID:15240830)
• Prostatic acid phosphatase inactivates lysophosphatidic acid in seminal plasma. (PMID:15280042)
• analysis of prostatic acid phosphatase binding (PMID:15578709)
• the GAAAATATGATA-like elements are involved in the transcriptional regulation of hPAP promoter constructs in prostatic cells. (PMID:15985366)
• JFC1 differentially regulates the secretion of PSAP and PSA, and Rab27a and PI3K play a central role in the exocytosis of prostate-specific markers. (PMID:16004602)
• 1,25D-mediated decreases in prostate cancer cells and C81 LN cell growth are in part due to decreases in tyrosine kinase signaling that result from up-regulation of cellular prostatic acid phosphatase. (PMID:16076555)
• PAP (133-152) and PAP (173-192) were immunogenic and processed from whole PAP in HLA-DRB1*1501 tg mice. These peptides were capable of stimulating CD4 T lymphocytes from HLA-DRB1*1501-positive patients with granulomatous prostatitis and normal donors. (PMID:17455230)
• Prostatic acid phosphatase is not a prostate specific target (PMID:17638863)
• Suppresses pain by functioning as an ecto-5’-nucleotidase, activating A1-adenosine receptors in the dorsal spinal cord. (PMID:18940592)
• presence of Prostatic Acid Phosphatase in breast cyst fluid may suggest its possible role in the development of breast cancer from cystic breast diseases (PMID:19108401)
• PSAP might be predictive of tumor stage in incidental prostate cancer and represent a valuable adjunct for clinical decisions in terms of individual therapeutic management. (PMID:19301031)
• Prostatic acid phosphatase boosts the infectivity of xenotropic murine leukemia virus-related virus. (PMID:19403677)
• Report safety and immunological efficacy of a DNA vaccine encoding prostatic acid phosphatase in patients with stage D0 prostate cancer. (PMID:19636017)
• The obtained N-terminal amino-acid sequence of boar PTAP showed 92% identity with the N-terminal amino-acid sequence of human PAP. The determined sequence of a 354 bp nucleotide fragment showed 90% identity with the corresponding sequence of human PAP. (PMID:19759923)
• molecular details of PAPf39 peptide fibril formation may aid in elucidating the mechanism of how PAPf39 fibrils are involved in HIV etiology (PMID:19902966)
• Data show that prostatic acid phosphatase(PAP) as a sensitive tumor marker for prostate cancer. (PMID:20392611)
• prostatic acid phosphatase, an authentic tyrosine phosphatase, dephosphorylates ErbB-2 and regulates prostate cancer cell growth (PMID:20498373)

Cross-species orthologs

18 orthologs

Organism	Symbol	Gene ID
mus_musculus	Acp3	ENSMUSG00000032561
rattus_norvegicus	Acp3	ENSRNOG00000011820
drosophila_melanogaster	Acph-1	FBGN0000032
drosophila_melanogaster	CG9449	FBGN0036875
drosophila_melanogaster	CG9451	FBGN0036876
drosophila_melanogaster	CG9452	FBGN0036877
caenorhabditis_elegans		WBGENE00007328
caenorhabditis_elegans		WBGENE00007331
caenorhabditis_elegans		WBGENE00008801
caenorhabditis_elegans		WBGENE00008802
caenorhabditis_elegans		WBGENE00008804
caenorhabditis_elegans		WBGENE00009146
caenorhabditis_elegans		WBGENE00011879
caenorhabditis_elegans		WBGENE00015161
caenorhabditis_elegans		WBGENE00016152
caenorhabditis_elegans		WBGENE00022181
caenorhabditis_elegans		WBGENE00022770
caenorhabditis_elegans		WBGENE00206373

Paralogs (5): ACP2 (ENSG00000134575), ACP4 (ENSG00000142513), FRA10AC1 (ENSG00000148690), PXYLP1 (ENSG00000155893), ACP6 (ENSG00000162836)

Protein

Protein identifiers

Prostatic acid phosphatase — P15309 (reviewed: P15309)

Alternative names: 5’-nucleotidase, Acid phosphatase 3, Ecto-5’-nucleotidase, Protein tyrosine phosphatase ACP3, Thiamine monophosphatase

All UniProt accessions (3): P15309, E9PFE6, H0Y8T3

UniProt curated annotations — full annotation on UniProt →

Function. A non-specific tyrosine phosphatase that dephosphorylates a diverse number of substrates under acidic conditions (pH 4-6) including alkyl, aryl, and acyl orthophosphate monoesters and phosphorylated proteins. Has lipid phosphatase activity and inactivates lysophosphatidic acid in seminal plasma. Tyrosine phosphatase that acts as a tumor suppressor of prostate cancer through dephosphorylation of ERBB2 and deactivation of MAPK-mediated signaling. In addition to its tyrosine phosphatase activity has ecto-5’-nucleotidase activity in dorsal root ganglion (DRG) neurons. Generates adenosine from AMP which acts as a pain suppressor. (Microbial infection) Forms amyloid beta-sheet fibrils in semen. These fibrils, termed SEVI (semen-derived enhancer of viral infection) capture HIV virions, attach them to target cells and enhance infection. SEVI amyloid fibrils are degraded by polyphenol epigallocatechin-3-gallate (EGCG), a constituent of green tea. Target cell attachment and enhancement of HIV infection is inhibited by surfen. Also similarly boosts XMRV (xenotropic murine leukemia virus-related virus) infection.

Subunit / interactions. Homodimer; dimer formation is required for phosphatase activity.

Subcellular location. Secreted Cell membrane. Lysosome membrane. Nucleus. Cytoplasm. Cytosol.

Tissue specificity. Highly expressed in the prostate, restricted to glandular and ductal epithelial cells. Also expressed in bladder, kidney, pancreas, lung, cervix, testis and ovary. Weak expression in a subset of pancreatic islet cells, squamous epithelia, the pilosebaceous unit, colonic neuroendocrine cells and skin adnexal structures. Low expression in prostate carcinoma cells and tissues. Widely expressed. Expressed in the sarcolemma of skeletal muscle.

Post-translational modifications. N-glycosylated. High mannose content, partially sialylated and fucosylated biantennary complex. Also fucosylated with partially sialylated triantennary complex oligosaccharides. Proteolytically cleaved in seminal fluid to produce several peptides. Peptide PAPf39, the most prominent, forms amyloid beta-sheet fibrils, SEVI (semen-derived enhancer of viral infection).

Activity regulation. Phosphatase activity inhibited by L(+)-tartrate, and by its derivative, alpha-benzylaminobenzylphosphonic acid.

Miscellaneous. Has been used as a diagnostic tool for staging metastatic prostatic cancer.

Similarity. Belongs to the histidine acid phosphatase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P15309-1	1, Secreted PAP, sPAP	yes
P15309-2	2, TMPase, TM-PAP, cellular PAP, cPAP, cPAcP
P15309-3	3

RefSeq proteins (3): NP_001090, NP_001127666, NP_001278966 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000560	His_Pase_clade-2	Family
IPR029033	His_PPase_superfam	Homologous_superfamily
IPR033379	Acid_Pase_AS	Active_site
IPR050645	Histidine_acid_phosphatase	Family

Pfam: PF00328

Enzyme classification (BRENDA):

• EC 3.1.3.2 — acid phosphatase (BRENDA: 170 organisms, 858 substrates, 644 inhibitors, 497 Km, 138 kcat entries)

Substrate kinetics (BRENDA)

124 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
P-NITROPHENYL PHOSPHATE	0.0002–25	98
4-NITROPHENYL PHOSPHATE	—	84
ATP	0.066–30	22
PHENYL PHOSPHATE	0.16–17	15
PHOSPHOENOLPYRUVATE	0.05–2.1	12
ADP	0.1–8.7	11
1-NAPHTHYL PHOSPHATE	0.079–6.4	8
DIPHOSPHATE	0.08–4.6	8
4-METHYLUMBELLIFERYL PHOSPHATE	0.02–3.8	7
GTP	0.16–8.6	7
PHOSPHOTYROSINE	0.18–4.1	7
2-GLYCEROPHOSPHATE	0.4–66.7	6
3’-AMP	0.091–3.3	6
2-NAPHTHYL PHOSPHATE	0.13–4.5	5
5’-AMP	0.08–3.9	5

Catalyzed reactions (Rhea), 4 shown:

• O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)
• a ribonucleoside 5’-phosphate + H2O = a ribonucleoside + phosphate (RHEA:12484)
• a phosphate monoester + H2O = an alcohol + phosphate (RHEA:15017)
• 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H2O = 1-(9Z-octadecenoyl)-sn-glycerol + phosphate (RHEA:39835)

UniProt features (74 total): helix 16, sequence conflict 14, strand 14, sequence variant 5, site 4, binding site 4, glycosylation site 3, disulfide bond 3, splice variant 2, mutagenesis site 2, active site 2, turn 2, signal peptide 1, chain 1, peptide 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
3PPD	X-RAY DIFFRACTION	1.5
9NMV	X-RAY DIFFRACTION	1.97
9NMY	X-RAY DIFFRACTION	2.01
9NMU	X-RAY DIFFRACTION	2.1
9NMW	X-RAY DIFFRACTION	2.11
9NMX	X-RAY DIFFRACTION	2.19
1ND6	X-RAY DIFFRACTION	2.4
9YTD	ELECTRON MICROSCOPY	2.5
1ND5	X-RAY DIFFRACTION	2.9
2HPA	X-RAY DIFFRACTION	2.9
8XJ4	ELECTRON MICROSCOPY	3.19
1CVI	X-RAY DIFFRACTION	3.2
2L3H	SOLUTION NMR
2L77	SOLUTION NMR
2L79	SOLUTION NMR
2MG0	SOLUTION NMR
7ZZV	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15309-F1	92.51	0.87

Antibody-complex structures (SAbDab): 1 — 9YTD

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (6): 138 (required for homodimerization); 144 (required for homodimerization); 206 (required for structural stability); 44 (nucleophile); 290 (proton donor); 49 (important for substrate specificity)

Ligand- & substrate-binding residues (4): 43; 47; 111; 289

Disulfide bonds (3): 161–372, 215–313, 347–351

Glycosylation sites (3): 94, 220, 333

Mutagenesis-validated functional residues (2):

Position	Phenotype
206	greatly reduced enzyme activity, marked decrease in structural stability, and increased binding of the inhibitor, l(+)-t
206	reduced enzyme activity, marked decrease in structural stability, and increased binding of the inhibitor, l(+)-tartrate.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 258 (showing top): GOBP_G_PROTEIN_COUPLED_PURINERGIC_RECEPTOR_SIGNALING_PATHWAY, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_SENSORY_PERCEPTION_OF_PAIN, GOBP_NUCLEOBASE_METABOLIC_PROCESS, BACH2_01, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_REGULATION_OF_SENSORY_PERCEPTION, TGANTCA_AP1_C, GOBP_REGULATION_OF_NERVOUS_SYSTEM_PROCESS

GO Biological Process (7): purine nucleobase metabolic process (GO:0006144), lipid metabolic process (GO:0006629), thiamine metabolic process (GO:0006772), nucleotide metabolic process (GO:0009117), adenosine metabolic process (GO:0046085), regulation of sensory perception of pain (GO:0051930), positive regulation of adenosine receptor signaling pathway (GO:0060168)

GO Molecular Function (12): acid phosphatase activity (GO:0003993), protein tyrosine phosphatase activity (GO:0004725), 5’-nucleotidase activity (GO:0008253), phosphatase activity (GO:0016791), choline binding (GO:0033265), thiamine phosphate phosphatase activity (GO:0042131), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), lysophosphatidic acid phosphatase activity (GO:0052642), molecular adaptor activity (GO:0060090), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (17): obsolete extracellular space (GO:0005615), nucleus (GO:0005634), lysosomal membrane (GO:0005765), multivesicular body (GO:0005771), cytosol (GO:0005829), plasma membrane (GO:0005886), vesicle membrane (GO:0012506), filopodium (GO:0030175), Golgi cisterna (GO:0031985), azurophil granule membrane (GO:0035577), apical part of cell (GO:0045177), extracellular exosome (GO:0070062), extracellular region (GO:0005576), cytoplasm (GO:0005737), lysosome (GO:0005764), membrane (GO:0016020), secretory granule (GO:0030141)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
phosphatase activity	3
binding	2
nucleobase metabolic process	1
purine-containing compound metabolic process	1
primary metabolic process	1
primary alcohol metabolic process	1
thiamine-containing compound metabolic process	1
nucleoside phosphate metabolic process	1
purine ribonucleoside metabolic process	1
sensory perception of pain	1
regulation of sensory perception	1
G protein-coupled adenosine receptor signaling pathway	1
positive regulation of G protein-coupled receptor signaling pathway	1
regulation of adenosine receptor signaling pathway	1
phosphoprotein phosphatase activity	1
nucleotidase activity	1
phosphoric ester hydrolase activity	1
cation binding	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
molecular_function	1
catalytic activity	1
intracellular membrane-bounded organelle	1
lysosome	1
lytic vacuole membrane	1
late endosome	1
cytoplasm	1
membrane	1
cell periphery	1
organelle membrane	1
vesicle	1
actin-based cell projection	1
Golgi stack	1
Golgi apparatus subcompartment	1
lysosomal membrane	1
secretory granule membrane	1
azurophil granule	1
extracellular vesicle	1

Protein interactions and networks

STRING

984 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACP3	KLK2	P20151	948
ACP3	KLK3	P07288	937
ACP3	KLKB1	P03952	934
ACP3	SLC45A3	Q96JT2	915
ACP3	TGM4	P49221	882
ACP3	MSMB	P08118	880
ACP3	ANO7	Q6IWH7	772
ACP3	GBA1	P04062	766
ACP3	STEAP2	Q8NFT2	727
ACP3	SNAPIN	O95295	688
ACP3	STEAP4	Q687X5	638
ACP3	AZGP1	P25311	619
ACP3	SYT7	O43581	584
ACP3	RDH11	Q8TC12	549
ACP3	AASDHPPT	Q9NRN7	518

IntAct

84 interactions, top by confidence:

A	B	Type	Score
KIF3A	KIF3C	psi-mi:“MI:0914”(association)	0.730
ACP3	ACP3	psi-mi:“MI:0915”(physical association)	0.700
ACP3	ACP3	psi-mi:“MI:0407”(direct interaction)	0.700
ANXA9	PPL	psi-mi:“MI:0914”(association)	0.660
CCNC	MED19	psi-mi:“MI:0914”(association)	0.640
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.640
NPPA	A2ML1	psi-mi:“MI:0914”(association)	0.530
FTH1	A2ML1	psi-mi:“MI:0914”(association)	0.530
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
DNAAF19	KLK10	psi-mi:“MI:0914”(association)	0.530
MMRN1	CTSV	psi-mi:“MI:0914”(association)	0.530
ZIC1	CTSV	psi-mi:“MI:0914”(association)	0.530
AIRE	ALOX12B	psi-mi:“MI:0914”(association)	0.530
CPLX3	CIAO1	psi-mi:“MI:0914”(association)	0.530
FBXL4	DUSP14	psi-mi:“MI:0914”(association)	0.530
GAR1	PRMT5	psi-mi:“MI:0914”(association)	0.530
ACP3	ERBB2	psi-mi:“MI:0914”(association)	0.470
ACP3	ERBB2	psi-mi:“MI:0203”(dephosphorylation reaction)	0.470
DUSP21	ACP3	psi-mi:“MI:0915”(physical association)	0.400
IGHM	APOL1	psi-mi:“MI:0914”(association)	0.350
HAT1	CSTA	psi-mi:“MI:0914”(association)	0.350
TEX101	GGT3P	psi-mi:“MI:0914”(association)	0.350
KLHL11	PIPSL	psi-mi:“MI:0914”(association)	0.350
PLAC8L1	A2ML1	psi-mi:“MI:0914”(association)	0.350
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
ST6GALNAC6	A2ML1	psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
GOT1	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (156): ACPP (Affinity Capture-MS), ACPP (Affinity Capture-MS), ACPP (Affinity Capture-MS), ACPP (Affinity Capture-MS), ACPP (Affinity Capture-MS), ACPP (Affinity Capture-MS), ACPP (Affinity Capture-MS), ACPP (Affinity Capture-MS), ACPP (Affinity Capture-MS), ACPP (Affinity Capture-MS), ACPP (Affinity Capture-MS), ACPP (Affinity Capture-MS), ACPP (Affinity Capture-MS), ACPP (Affinity Capture-MS), ACPP (Affinity Capture-MS)

ESM2 similar proteins: A0A2D0TC04, A6H730, A6H757, B1H1P9, B6EWW8, D2GZV9, E1BPW0, E1C1L6, F8S0Z7, J3SBP3, J3SEZ3, O14638, O35409, O75356, P06802, P07686, P0DQQ4, P11117, P15309, P15396, P20060, P20611, P20646, P22413, P24638, P24822, P49614, P58242, P70627, P97675, Q0P5F0, Q29548, Q3KQG9, Q3MI05, Q3U4B4, Q4R5N9, Q5NVF6, Q5R5M5, Q5R8C0, Q5VXJ0

Diamond homologs: A6H730, B1H1P9, D3YTS9, P11117, P15309, P20611, P20646, P24638, Q0P5F0, Q10944, Q19076, Q3KQG9, Q4R5N9, Q5BLY5, Q5NVF6, Q5R8C0, Q8CE08, Q9BZG2, Q09451, Q09448, Q09549, Q54P71, Q54P72, Q54PR9, Q66H78, Q8TE99, Q8BP40

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ACP3	“up-regulates quantity”	adenosine	“chemical modification”
ACP3	“down-regulates quantity”	AMP	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

67 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1585 predictions. Top by Δscore:

Variant	Effect	Δscore
3:132317572:CTTTG:C	donor_gain	1.0000
3:132317573:TTTG:T	donor_gain	1.0000
3:132317573:TTTGG:T	donor_loss	1.0000
3:132317574:TTGG:T	donor_loss	1.0000
3:132317576:GGT:G	donor_loss	1.0000
3:132317577:G:GG	donor_gain	1.0000
3:132317577:GT:G	donor_loss	1.0000
3:132345058:GG:G	donor_gain	1.0000
3:132345059:GG:G	donor_gain	1.0000
3:132349915:TTAAG:T	acceptor_loss	1.0000
3:132349916:TAA:T	acceptor_loss	1.0000
3:132349918:AGG:A	acceptor_loss	1.0000
3:132349919:G:GC	acceptor_loss	1.0000
3:132350000:GCG:G	donor_gain	1.0000
3:132350000:GCGGT:G	donor_loss	1.0000
3:132350001:CGGTA:C	donor_loss	1.0000
3:132350003:G:GA	donor_loss	1.0000
3:132350003:G:GG	donor_gain	1.0000
3:132350004:TAAG:T	donor_loss	1.0000
3:132317574:TTG:T	donor_gain	0.9900
3:132317575:TG:T	donor_gain	0.9900
3:132317576:GG:G	donor_gain	0.9900
3:132317578:T:A	donor_loss	0.9900
3:132328261:TTTCA:T	acceptor_loss	0.9900
3:132328262:TTCAG:T	acceptor_loss	0.9900
3:132328263:TCAGG:T	acceptor_loss	0.9900
3:132328264:CAGGT:C	acceptor_loss	0.9900
3:132328265:A:G	acceptor_loss	0.9900
3:132331644:T:G	acceptor_gain	0.9900
3:132331645:A:AG	acceptor_gain	0.9900

AlphaMissense

2540 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:132332204:A:C	S106R	0.997
3:132332206:C:A	S106R	0.997
3:132332206:C:G	S106R	0.997
3:132332231:A:C	S115R	0.997
3:132332233:T:A	S115R	0.997
3:132332233:T:G	S115R	0.997
3:132328286:G:C	R47P	0.996
3:132328288:A:C	S48R	0.994
3:132328290:T:A	S48R	0.994
3:132328290:T:G	S48R	0.994
3:132352724:A:T	D290V	0.994
3:132328274:G:C	R43P	0.993
3:132344954:T:A	W226R	0.993
3:132344954:T:C	W226R	0.993
3:132344956:G:C	W226C	0.992
3:132344956:G:T	W226C	0.992
3:132352723:G:C	D290H	0.992
3:132356712:G:C	R332P	0.992
3:132328335:G:C	W63C	0.990
3:132328335:G:T	W63C	0.990
3:132332247:T:C	L120P	0.990
3:132328280:G:T	G45V	0.989
3:132328333:T:A	W63R	0.989
3:132328333:T:C	W63R	0.989
3:132332300:T:A	W138R	0.989
3:132332300:T:C	W138R	0.989
3:132328278:T:A	H44Q	0.988
3:132328278:T:G	H44Q	0.988
3:132328280:G:A	G45E	0.988
3:132328355:T:A	L70H	0.988

dbSNP variants (sampled 300 via entrez): RS1000006397 (3:132348241 G>A,T), RS1000084793 (3:132347190 C>T), RS1000124506 (3:132361432 G>A), RS1000144114 (3:132357053 C>T), RS1000197372 (3:132355605 C>T), RS1000243674 (3:132343703 G>A,C), RS1000355677 (3:132319473 A>C,G), RS1000400128 (3:132363143 C>A), RS1000460868 (3:132363660 C>G), RS1000482181 (3:132354499 T>C), RS1000503960 (3:132331115 A>C), RS1000534322 (3:132354761 G>C,T), RS1000657589 (3:132350870 G>A,T), RS1000690487 (3:132348546 G>A), RS1000858037 (3:132331582 T>A,G)

Disease associations

OMIM: gene MIM:171790 | disease phenotypes:

GenCC curated gene-disease

Mondo (3): acute megakaryoblastic leukemia (MONDO:0018872), mediastinal germ cell tumor (MONDO:0021067), intellectual disability (MONDO:0001071)

Orphanet (2): Acute megakaryoblastic leukemia (Orphanet:518), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004571_4	Iron status biomarkers (total iron binding capacity)	3.000000e-07
GCST004572_14	Iron status biomarkers (transferrin saturation)	3.000000e-07
GCST005951_142	Body mass index	1.000000e-09
GCST009391_1068	Metabolite levels	6.000000e-06
GCST90000047_59	Age at first sexual intercourse	9.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006334	total iron binding capacity
EFO:0004340	body mass index
EFO:0010364	lysophosphatidylcholine 20:5 measurement
EFO:0009749	age at first sexual intercourse measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D007947	Leukemia, Megakaryoblastic, Acute	C04.557.337.539.275.450; C15.378.508.539.275.450

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2633 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

19 potent at pChembl≥5 of 44 total, top 19 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.40	IC50	4	nM	CHEMBL498632
8.30	IC50	5	nM	CHEMBL454997
8.30	IC50	5.012	nM	CHEMBL454997
8.07	IC50	8.6	nM	CHEMBL68858
7.75	IC50	18	nM	CHEMBL507996
7.74	IC50	18.2	nM	CHEMBL507996
7.59	IC50	25.7	nM	CHEMBL501717
7.58	IC50	26	nM	CHEMBL501717
6.70	IC50	198	nM	CHEMBL453954
6.70	IC50	199.5	nM	CHEMBL453954
5.97	IC50	1070	nM	CHEMBL524506
5.97	IC50	1072	nM	CHEMBL524506
5.92	IC50	1210	nM	CHEMBL501710
5.92	IC50	1202	nM	CHEMBL501710
5.85	IC50	1400	nM	CHEMBL300202
5.22	IC50	6000	nM	CHEMBL424224
5.20	IC50	6300	nM	CHEMBL416128
5.05	IC50	9000	nM	CHEMBL106132
5.03	IC50	9300	nM	CHEMBL416111

PubChem BioAssay actives

13 with measured affinity, of 15 total; 7 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[(benzylamino)-phenylmethyl]phosphonic acid	362077: Inhibition of human prostatic acid phosphatase	ic50	0.0040	uM
[(R)-(benzylamino)-phenylmethyl]phosphonic acid;hydrochloride	362077: Inhibition of human prostatic acid phosphatase	ic50	0.0050	uM
[(S)-(4-methoxyphenyl)-[[(1R)-1-phenylethyl]amino]methyl]phosphonic acid;hydrochloride	362077: Inhibition of human prostatic acid phosphatase	ic50	0.0180	uM
[(S)-phenyl-[[(1R)-1-phenylethyl]amino]methyl]phosphonic acid;hydrochloride	362077: Inhibition of human prostatic acid phosphatase	ic50	0.0257	uM
[(S)-(benzylamino)-phenylmethyl]phosphonic acid;hydrochloride	362077: Inhibition of human prostatic acid phosphatase	ic50	0.1980	uM
[(R)-(4-methoxyphenyl)-[[(1S)-1-phenylethyl]amino]methyl]phosphonic acid;hydrochloride	362077: Inhibition of human prostatic acid phosphatase	ic50	1.0700	uM
[(R)-phenyl-[[(1S)-1-phenylethyl]amino]methyl]phosphonic acid;hydrochloride	362077: Inhibition of human prostatic acid phosphatase	ic50	1.2023	uM

CTD chemical–gene interactions

51 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, increases expression, decreases expression, decreases reaction	7
Valproic Acid	affects cotreatment, increases expression, affects expression	5
Panobinostat	affects cotreatment, increases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Progesterone	affects cotreatment, decreases expression, decreases reaction, increases expression	2
Tretinoin	affects expression, increases expression	2
Cyclosporine	increases methylation, decreases expression	2
Particulate Matter	increases expression, affects cotreatment, increases abundance	2
methylselenic acid	affects expression	1
sodium arsenate	decreases expression, increases abundance	1
ethyl-p-hydroxybenzoate	increases expression	1
trichostatin A	increases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
triadimefon	increases expression	1
vanadyl sulfate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
mercuric bromide	affects cotreatment, increases expression	1
bicalutamide	decreases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Zoledronic Acid	decreases expression	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Gemcitabine	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4731874	Binding	Potency index, ratio of sulfamic acid IC50 to compound IC50 for human ecto-5’ nucleotidase expressed in COS7 cell membranes assessed as inorganic phosphate release using AMP as substrate preincubated for 10 mins followed by substrate additi	Synthesis, Characterization, and In Silico Studies of Novel Spirooxindole Derivatives as Ecto-5’-Nucleotidase Inhibitors. — ACS Med Chem Lett

Clinical trials (associated diseases)

201 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT04083170	PHASE2	TERMINATED	Cord Blood Transplant With Dilanubicel for the Treatment of HIV Positive Hematologic Cancers
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT00392353	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Vorinostat and Azacitidine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia
NCT01823198	PHASE1/PHASE2	COMPLETED	Donor Natural Killer Cells and Donor Stem Cell Transplant in Treating Patients With High Risk Myeloid Malignancies
NCT02530619	Not specified	UNKNOWN	Alisertib in Treating Patients With Myelofibrosis or Relapsed or Refractory Acute Megakaryoblastic Leukemia
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders