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ACP4

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Summary

ACP4 (acid phosphatase 4, HGNC:14376) is a protein-coding gene on chromosome 19q13.33, encoding Testicular acid phosphatase (Q9BZG2). May dephosphorylate receptor tyrosine-protein kinase ERBB4 and inhibits its ligand-induced proteolytic cleavage.

Acid phosphatases are enzymes capable of hydrolyzing orthophosphoric acid esters in an acid medium. This gene is up-regulated by androgens and is down-regulated by estrogens in the prostate cancer cell line. This gene exhibits a lower level of expression in testicular cancer tissues than in normal tissues. The protein encoded by this gene has structural similarity to prostatic and lysosomal acid phosphatases. Alternatively spliced transcript variants have been described, but their biological validity has not been determined.

Source: NCBI Gene 93650 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): amelogenesis imperfecta, type 1J (Strong, GenCC) — +1 more curated relationship
  • GWAS associations: 6
  • Clinical variants (ClinVar): 139 total — 9 pathogenic, 6 likely-pathogenic
  • MANE Select transcript: NM_033068

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:14376
Approved symbolACP4
Nameacid phosphatase 4
Location19q13.33
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000142513
Ensembl biotypeprotein_coding
OMIM606362
Entrez93650

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000270593

RefSeq mRNA: 1 — MANE Select: NM_033068 NM_033068

CCDS: CCDS12802

Canonical transcript exons

ENST00000270593 — 11 exons

ExonStartEnd
ENSE000009546495079059450790698
ENSE000009546525079207350792171
ENSE000009546545079368450793816
ENSE000009546565079445750794581
ENSE000009546575079478650794964
ENSE000011241465079504350795219
ENSE000013765065079165650791802
ENSE000013824235079224250792337
ENSE000013853165079388850793970
ENSE000013901325079077450790860
ENSE000016655395079041550790525

Expression profiles

Bgee: expression breadth broad, 99 present calls, max score 91.45.

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
tendon of biceps brachiiUBERON:000818891.45gold quality
buccal mucosa cellCL:000233690.58gold quality
tibialis anteriorUBERON:000138579.51silver quality
upper arm skinUBERON:000426377.31gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450276.09silver quality
epithelial cell of pancreasCL:000008375.72gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047372.83gold quality
biceps brachiiUBERON:000150772.69silver quality
nasal cavity epitheliumUBERON:000538471.75gold quality
trabecular bone tissueUBERON:000248371.55silver quality
secondary oocyteCL:000065571.13silver quality
cardia of stomachUBERON:000116270.11gold quality
jejunal mucosaUBERON:000039970.07gold quality
jejunumUBERON:000211569.87gold quality
ileal mucosaUBERON:000033169.78silver quality
spermCL:000001969.68gold quality
cardiac muscle of right atriumUBERON:000337969.59gold quality
left ventricle myocardiumUBERON:000656669.42gold quality
pancreatic ductal cellCL:000207969.36silver quality
amniotic fluidUBERON:000017369.18silver quality
vena cavaUBERON:000408768.76gold quality
esophagus squamous epitheliumUBERON:000692068.29silver quality
kidney epitheliumUBERON:000481967.76gold quality
medial globus pallidusUBERON:000247767.63gold quality
mucosa of sigmoid colonUBERON:000499367.53silver quality
cartilage tissueUBERON:000241867.48gold quality
upper leg skinUBERON:000426266.71gold quality
tibiaUBERON:000097966.70silver quality
globus pallidusUBERON:000187566.68gold quality
layer of synovial tissueUBERON:000761666.63gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

ExperimentMarker?Max mean expression
E-ANND-3no1.29

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 4)

  • ACPT biallelic mutations caused non-syndromic, generalized hypoplastic autosomal-recessive amelogenesis imperfecta in individuals from six unrelated Turkish families. Analysis of the ACPT crystal structure suggests that these mutations damaged the activity of ACPT by altering the sizes and charges of key amino acid side chains, limiting accessibility of the catalytic core, and interfering with homodimerization. (PMID:27843125)
  • ACPT missense mutation segregates with hypoplastic amelogenesis imperfecta in two unrelated families. (PMID:28513613)
  • Recessive Mutations in ACP4 Cause Amelogenesis Imperfecta. (PMID:34036831)
  • Enamel defects in Acp4(R110C/R110C) mice and human ACP4 mutations. (PMID:36183038)

Cross-species orthologs

18 orthologs

OrganismSymbolGene ID
mus_musculusAcp4ENSMUSG00000012777
rattus_norvegicusAcp4ENSRNOG00000021659
drosophila_melanogasterAcph-1FBGN0000032
drosophila_melanogasterCG9449FBGN0036875
drosophila_melanogasterCG9451FBGN0036876
drosophila_melanogasterCG9452FBGN0036877
caenorhabditis_elegansWBGENE00007328
caenorhabditis_elegansWBGENE00007331
caenorhabditis_elegansWBGENE00008801
caenorhabditis_elegansWBGENE00008802
caenorhabditis_elegansWBGENE00008804
caenorhabditis_elegansWBGENE00009146
caenorhabditis_elegansWBGENE00011879
caenorhabditis_elegansWBGENE00015161
caenorhabditis_elegansWBGENE00016152
caenorhabditis_elegansWBGENE00022181
caenorhabditis_elegansWBGENE00022770
caenorhabditis_elegansWBGENE00206373

Paralogs (5): ACP3 (ENSG00000014257), ACP2 (ENSG00000134575), FRA10AC1 (ENSG00000148690), PXYLP1 (ENSG00000155893), ACP6 (ENSG00000162836)

Protein

Protein identifiers

Testicular acid phosphatase — Q9BZG2 (reviewed: Q9BZG2)

Alternative names: Acid phosphatase 4

All UniProt accessions (1): Q9BZG2

UniProt curated annotations — full annotation on UniProt →

Function. May dephosphorylate receptor tyrosine-protein kinase ERBB4 and inhibits its ligand-induced proteolytic cleavage. May play a role in odontogenesis.

Subunit / interactions. Homodimer.

Subcellular location. Membrane.

Tissue specificity. Expressed mainly in the testis. Also expressed in the brain where they are enriched at the postsynaptic sites. Expressed at lower levels in the trachea, prostate, bone marrow, spinal cord, colon, fetal brain, heart, thymus, fetal liver, spleen, leukocytes, ovary, small intestine, pancreas and skeletal muscle. Expression is significantly lower in testicular cancer tissues than in normal testicular tissues. Isoform 3 is expressed in the testis, trachea, prostate and bone marrow.

Post-translational modifications. Glycosylated.

Disease relevance. Amelogenesis imperfecta 1J (AI1J) [MIM:617297] A form of amelogenesis imperfecta, a disorder characterized by defective enamel formation. The enamel may be hypoplastic, hypomineralized or both, and affected teeth may be discoloured, sensitive or prone to disintegration. AI1J is an autosomal recessive form characterized by hypoplastic enamel, enamel discolorization ranging from yellow to black, and normal dentin. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated by mibolerone (a synthetic androgen) and dihydrotestosterone (DHT) and is down-regulated by estrogen and progestin.

Similarity. Belongs to the histidine acid phosphatase family.

Isoforms (3)

UniProt IDNamesCanonical?
Q9BZG2-11yes
Q9BZG2-22, Variant 3
Q9BZG2-33, Truncated variant 1, Truncated variant 2

RefSeq proteins (1): NP_149059* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000560His_Pase_clade-2Family
IPR029033His_PPase_superfamHomologous_superfamily
IPR033379Acid_Pase_ASActive_site
IPR050645Histidine_acid_phosphataseFamily

Pfam: PF00328

Catalyzed reactions (Rhea), 1 shown:

  • a phosphate monoester + H2O = an alcohol + phosphate (RHEA:15017)

UniProt features (22 total): sequence variant 5, glycosylation site 4, disulfide bond 3, splice variant 3, topological domain 2, active site 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9BZG2-F188.300.76

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 (2): 41 (nucleophile); 289 (proton donor)

Disulfide bonds (3): 159–378, 214–312, 353–357

Glycosylation sites (4): 339, 191, 269, 330

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 97 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, GOBP_NEGATIVE_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_NEUROGENESIS, GOBP_CELL_CELL_SIGNALING, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_PROTEIN_MATURATION, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_REGULATION_OF_SYNAPTIC_PLASTICITY

GO Biological Process (6): negative regulation of protein processing (GO:0010955), negative regulation of neuron projection development (GO:0010977), odontogenesis (GO:0042476), regulation of neuronal synaptic plasticity (GO:0048168), negative regulation of ERBB4 signaling pathway (GO:0120154), peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity (GO:1990264)

GO Molecular Function (4): acid phosphatase activity (GO:0003993), protein tyrosine phosphatase activity (GO:0004725), receptor tyrosine kinase binding (GO:0030971), hydrolase activity (GO:0016787)

GO Cellular Component (5): lysosome (GO:0005764), postsynaptic membrane (GO:0045211), glutamatergic synapse (GO:0098978), membrane (GO:0016020), synaptic membrane (GO:0097060)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
synapse2
protein processing1
negative regulation of proteolysis1
regulation of protein processing1
negative regulation of protein maturation1
regulation of neuron projection development1
neuron projection development1
negative regulation of cell projection organization1
animal organ morphogenesis1
regulation of synaptic plasticity1
ERBB4 signaling pathway1
negative regulation of ERBB signaling pathway1
negative regulation of protein kinase activity1
peptidyl-tyrosine dephosphorylation1
phosphatase activity1
phosphoprotein phosphatase activity1
signaling receptor binding1
protein tyrosine kinase binding1
catalytic activity1
lytic vacuole1
synaptic membrane1
postsynapse1
cellular anatomical structure1
plasma membrane region1

Protein interactions and networks

STRING

648 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
ACP4ENAMQ9NRM1717
ACP4AMTNQ6UX39687
ACP4AMBNQ9NP70672
ACP4KLK4Q9Y5K2652
ACP4ODAPHQ17RF5620
ACP4FAM20AQ96MK3588
ACP4AMELXQ99217542
ACP4WDR72Q3MJ13539
ACP4ODAMA1E959535
ACP4KLK1P06870514
ACP4MMP20O60882513
ACP4ACP7Q6ZNF0500
ACP4ACP5P13686473
ACP4TGM5O43548462
ACP4DSG4Q86SJ6460

IntAct

0 interactions, top by confidence:

BioGRID (1): ACPT (Affinity Capture-RNA)

ESM2 similar proteins: A0JND9, D3YTS9, O19058, O35795, O55026, O75173, P08648, P11117, P17405, P20611, P21217, P24638, P29376, P56433, Q04519, Q0P5F0, Q0V8G3, Q0VD19, Q11128, Q11131, Q32M88, Q4R5N9, Q4R942, Q5MY95, Q5NVF6, Q5RFQ8, Q62994, Q63148, Q6IY74, Q8BH73, Q8HYJ3, Q8HYJ4, Q8HYJ5, Q8HYJ7, Q8HZR3, Q8K1S1, Q8N135, Q923W9, Q9BZG2, Q9H3T2

Diamond homologs: A6H730, B1H1P9, D3YTS9, P11117, P15309, P20611, P20646, P24638, Q0P5F0, Q10944, Q19076, Q3KQG9, Q4R5N9, Q5BLY5, Q5NVF6, Q5R8C0, Q8CE08, Q9BZG2, Q09451, A6H757, Q09448, Q09549, Q8BP40, Q9NPH0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic9
Likely pathogenic6
Uncertain significance94
Likely benign17
Benign8

Top pathogenic / likely-pathogenic (15)

Variant IDHGVSClassification
374864NM_033068.3(ACP4):c.226C>T (p.Arg76Cys)Pathogenic
374865NM_033068.3(ACP4):c.382G>C (p.Ala128Pro)Pathogenic
374866NM_033068.3(ACP4):c.397G>A (p.Glu133Lys)Pathogenic
375694NM_033068.3(ACP4):c.746C>T (p.Pro249Leu)Pathogenic
375700NM_033068.3(ACP4):c.428C>T (p.Thr143Met)Pathogenic
4687880NM_033068.3(ACP4):c.254T>C (p.Leu85Pro)Pathogenic
4687881NM_033068.3(ACP4):c.435del (p.Val146fs)Pathogenic
4687882NM_033068.3(ACP4):c.845T>C (p.Met282Thr)Pathogenic
980768GRCh37/hg19 19q13.33-13.43(chr19:48463931-57095254)x3Pathogenic
1526670GRCh37/hg19 19q13.33-13.41(chr19:49911081-53127438)Likely pathogenic
1723827NM_033068.3(ACP4):c.227_244delinsA (p.Arg76fs)Likely pathogenic
2445430NM_033068.3(ACP4):c.645+1G>ALikely pathogenic
2445431NM_033068.3(ACP4):c.736G>A (p.Val246Met)Likely pathogenic
3062398GRCh37/hg19 19q13.33-13.41(chr19:48905537-51614930)x3Likely pathogenic
4849306NM_033068.3(ACP4):c.984_986+1delLikely pathogenic

SpliceAI

1619 predictions. Top by Δscore:

VariantEffectΔscore
19:50790858:G:GTdonor_gain1.0000
19:50791797:GA:Gdonor_gain1.0000
19:50791798:A:Gdonor_gain1.0000
19:50792151:G:GTdonor_gain1.0000
19:50793797:G:GTdonor_gain1.0000
19:50793807:C:Gdonor_gain1.0000
19:50793813:GGGG:Gdonor_gain1.0000
19:50793814:G:GTdonor_gain1.0000
19:50793883:CTCA:Cacceptor_loss1.0000
19:50793884:TCAG:Tacceptor_loss1.0000
19:50793886:A:AGacceptor_gain1.0000
19:50793886:AG:Aacceptor_gain1.0000
19:50793886:AGG:Aacceptor_gain1.0000
19:50793887:G:GAacceptor_loss1.0000
19:50793887:G:GGacceptor_gain1.0000
19:50793887:GG:Gacceptor_gain1.0000
19:50793887:GGG:Gacceptor_gain1.0000
19:50793968:GCT:Gdonor_gain1.0000
19:50793971:G:GGdonor_gain1.0000
19:50793983:G:Tdonor_gain1.0000
19:50794577:GGAGG:Gdonor_gain1.0000
19:50794578:GAGGG:Gdonor_gain1.0000
19:50794580:GG:Gdonor_gain1.0000
19:50794581:GG:Gdonor_gain1.0000
19:50790651:G:GTdonor_gain0.9900
19:50790698:GGTG:Gdonor_loss0.9900
19:50790699:G:GGdonor_gain0.9900
19:50790700:T:Adonor_loss0.9900
19:50790701:GA:Gdonor_loss0.9900
19:50790857:GGAG:Gdonor_gain0.9900

AlphaMissense

2665 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
19:50791668:A:CS106R0.997
19:50791670:C:AS106R0.997
19:50791670:C:GS106R0.997
19:50791695:A:CS115R0.997
19:50791697:T:AS115R0.997
19:50791697:T:GS115R0.997
19:50790777:G:TG74W0.995
19:50791669:G:TS106I0.995
19:50790607:G:TG42V0.994
19:50794461:A:TD289V0.994
19:50791797:G:CD149H0.993
19:50790607:G:AG42D0.992
19:50793713:G:CW225C0.992
19:50793713:G:TW225C0.992
19:50790777:G:AG74R0.991
19:50790777:G:CG74R0.991
19:50791699:C:AA116D0.991
19:50791696:G:TS115I0.989
19:50791698:G:CA116P0.989
19:50791704:G:CA118P0.989
19:50790605:T:AH41Q0.988
19:50790605:T:GH41Q0.988
19:50790613:G:CR44P0.988
19:50793711:T:AW225R0.988
19:50793711:T:CW225R0.988
19:50794460:G:CD289H0.988
19:50790671:G:CW63C0.987
19:50790671:G:TW63C0.987
19:50790600:C:AR40S0.986
19:50790802:G:AG82D0.986

dbSNP variants (sampled 300 via entrez): RS1000273753 (19:50792195 C>T), RS1000563269 (19:50793108 T>A,C), RS1000636970 (19:50792851 TA>T,TAA), RS1001552935 (19:50788946 T>C), RS1001558230 (19:50794119 C>T), RS1001712214 (19:50792950 C>G,T), RS1002614393 (19:50789241 T>C), RS1002645388 (19:50789007 G>C,T), RS1003618283 (19:50790284 G>C), RS1003728827 (19:50794845 G>A), RS1004165030 (19:50794714 A>C), RS1004485094 (19:50792518 A>C,G), RS1004815586 (19:50792780 A>G), RS1005176163 (19:50790601 G>A,C,T), RS1006270471 (19:50795693 A>G,T)

Disease associations

OMIM: gene MIM:606362 | disease phenotypes: MIM:104500, MIM:617297

GenCC curated gene-disease

DiseaseClassificationInheritance
amelogenesis imperfecta, type 1JStrongAutosomal recessive
amelogenesis imperfecta type 1SupportiveAutosomal dominant

Mondo (3): amelogenesis imperfecta (MONDO:0019507), amelogenesis imperfecta, type 1J (MONDO:0015008), amelogenesis imperfecta type 1 (MONDO:0015047)

Orphanet (2): Amelogenesis imperfecta (Orphanet:88661), Hypoplastic amelogenesis imperfecta (Orphanet:100031)

HPO phenotypes

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

GWAS associations

6 associations (top):

StudyTraitp-value
GCST006479_101Diverticular disease9.000000e-06
GCST009268_6Dental caries (decayed, missing and filled tooth surfaces)3.000000e-06
GCST010536_5Carotid plaque maximum area5.000000e-06
GCST010538_6Sum of carotid plaque area2.000000e-07
GCST010539_7Sum of stenosis3.000000e-06
GCST012489_102Heel bone mineral density x serum urate levels interaction1.000000e-08

EFO canonical traits (4, from GWAS)

EFO IDTrait name
EFO:0009959diverticular disease
EFO:0006501carotid plaque build
EFO:0004531urate measurement
EFO:0009270heel bone mineral density

MeSH disease descriptors (1)

DescriptorNameTree numbers
D000567Amelogenesis ImperfectaC07.650.800.295.250; C07.793.700.295.250; C16.131.850.800.295.250

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

ChemicalActions (top 5)PubMed papers
bisphenol Adecreases expression, affects cotreatment, decreases methylation2
CGP 52608affects binding, increases reaction1
Fulvestrantaffects cotreatment, decreases methylation1
Benzo(a)pyrenedecreases methylation1
Dexamethasoneaffects cotreatment, decreases expression1
Indomethacinaffects cotreatment, decreases expression1
Valproic Acidincreases methylation1
1-Methyl-3-isobutylxanthineaffects cotreatment, decreases expression1
Antirheumatic Agentsincreases expression1

Clinical trials (associated diseases)

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

TrialPhaseStatusTitle
NCT01746121Not specifiedTERMINATEDAmelogenesis Imperfecta
NCT02994862Not specifiedUNKNOWNE. Max Laminate Veneers With and Without Using Galla Chinnesis as Natural Cross Linking and Remineralizing Agent
NCT03810859Not specifiedUNKNOWNNon-syndromic Inherited Anomalies of Mineralized Tooth Tissues: a Whole Exome Study to Identify New Pathogenic Variants
NCT04704089Not specifiedRECRUITINGColorimetric, Ultra-structural and Elemental Comparison of Dental Enamel Defects
NCT04897724Not specifiedUNKNOWNClinical Performance of Composites in Patients With Amelogenesis Imperfecta
NCT04927962Not specifiedCOMPLETEDPsycho-social Impact of Amelogenesis and Dentinogenesis Imperfecta
NCT05343247Not specifiedCOMPLETEDDental Age Estimation by Different Methods in Patients With Amelogenesis Imperfecta
NCT07250906Not specifiedRECRUITINGOral Health Related Quality of Life of Children With Amelogenesis Imperfecta

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 74

This page pulls from 74 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot