ACP4

protein-coding

acid phosphatase 4, the group of Acid phosphatases

Gene summary

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. [provided by RefSeq, Jul 2008]

Previous symbols:

ACPT

MANE transcript

NM_033068.3

Inheritance

AD, AR

ClinVar variants

P:14U:96B:17

Top phenotype

Amelogenesis imperfecta, type IJ

gnomAD constraint

pLI —, LoF o/e 1.05

Max pathogenic AF

—

Genomic locus

chr19:50,790,415-50,795,219

External References & Databases

Ensembl (ENSG00000142513)

Transcript & Mutation Effects

hg38 • Region Span ~4.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

amelogenesis imperfecta type 1SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015047

Submitter: Orphanet

amelogenesis imperfecta, type 1JSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0015008

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Amelogenesis imperfecta, type IJAR

Manifestation: Dental

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 27843125

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ACP4 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 98

Amelogenesis imperfecta, type 1JTotal: 15

ACP4-related disorderTotal: 13

not providedTotal: 11

Amelogenesis imperfectaTotal: 4

Amelogenesis imperfecta type 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033068.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				8 clinvar	1 clinvar	9
missense	7 clinvar	3 clinvar	94 clinvar	6 clinvar	1 clinvar	111
nonsense			1 clinvar			1
start loss						0
frameshift	1 clinvar	2 clinvar				3
splice donor/acceptor (+/-2bp)		1 clinvar	1 clinvar	1 clinvar		3
Total	8	6	96	15	2	127

Highest pathogenic variant AF is 0.00008120335

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033068.3	RefSeq	NP_149059.1	11	MANE Select
ENST00000270593.2	Ensembl	ENSP00000270593.1	11	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of protein processing
negative regulation of neuron projection development
odontogenesis
regulation of neuronal synaptic plasticity
negative regulation of ERBB4 signaling pathway

Molecular Function

acid phosphatase activity
protein tyrosine phosphatase activity
receptor tyrosine kinase binding

Cellular Component

integral component of membrane
postsynaptic membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000270593
Coding exons: 11
Length: 4810
Individuals with no LoFs: 125645
Homozygous LoFs: 0
Heterozygous LoFs: 102
Defined: 125747
p: 0.000406

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.131	265	271	0.978	0.0000171	2626
Missense (PolyPhen)		104	125.05	0.83164		1225
Synonymous	-0.980	135	121	1.11	0.00000737	970
Loss of Function	-0.216	21	20.0	1.05	9.40e-7	215

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00044	0.00043	rare
Latino/Admixed American	0.00038	0.00035	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00061	0.00060	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00035	0.00034	rare
South Asian	0.0010	0.0010	notable
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May dephosphorylate receptor tyrosine-protein kinase ERBB4 and inhibits its ligand-induced proteolytic cleavage (PubMed:15219672). May play a role in odontogenesis (PubMed:27843125). {ECO:0000269|PubMed:15219672, ECO:0000269|PubMed:27843125}.;
Disease: DISEASE: 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. {ECO:0000269|PubMed:27843125}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.277

Intolerance Scores

RVIS EVS: -0.22
RVIS percentile EVS: 37.54

Essentials

Essential (gene trap): N