ACP2

protein-coding

acid phosphatase 2, lysosomal, the group of Acid phosphatases

Gene summary

The protein encoded by this gene belongs to the histidine acid phosphatase family, which hydrolyze orthophosphoric monoesters to alcohol and phosphate. This protein is localized to the lysosomal membrane, and is chemically and genetically distinct from the red cell acid phosphatase. Mice lacking this gene showed multiple defects, including bone structure alterations, lysosomal storage defects, and an increased tendency towards seizures. An enzymatically-inactive allele of this gene in mice showed severe growth retardation, hair-follicle abnormalities, and an ataxia-like phenotype. Alternatively spliced transcript variants have been found for this gene. A C-terminally extended isoform is also predicted to be produced by the use of an alternative in-frame translation termination codon via a stop codon readthrough mechanism. [provided by RefSeq, Oct 2017]

MANE transcript

NM_001610.4

Inheritance

ClinVar variants

U:63B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.45

Max pathogenic AF

—

Genomic locus

chr11:47,239,302-47,248,906

External References & Databases

Ensembl (ENSG00000134575)

Transcript & Mutation Effects

hg38 • Region Span ~9.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

lysosomal acid phosphatase deficiencyNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0008705

Submitter: Labcorp Genetics (formerly Invitae)

lysosomal acid phosphatase deficiencyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0008705

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ACP2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 62

not providedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001610.4. 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					2 clinvar	2
missense			59 clinvar	4 clinvar		63
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	63	4	2	69

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001610.4	RefSeq	NP_001601.1	11	MANE Select
ENST00000672073.1	Ensembl	ENSP00000500291.1	11	MANE Select
NM_001302489.2	RefSeq	NP_001289418.1	11	Standard
NM_001302490.2	RefSeq	NP_001289419.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Lysosome - Homo sapiens (human)
Riboflavin metabolism - Homo sapiens (human)
miR-targeted genes in epithelium - TarBase
miR-targeted genes in leukocytes - TarBase
miR-targeted genes in lymphocytes - TarBase

Biological Process

skeletal system development
lysosome organization
dephosphorylation

Molecular Function

acid phosphatase activity

Cellular Component

lysosome
lysosomal membrane
membrane
integral component of membrane
lysosomal lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000256997
Coding exons: 11
Length: 9605
Individuals with no LoFs: 125649
Homozygous LoFs: 0
Heterozygous LoFs: 98
Defined: 125747
p: 0.000390

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.826	234	272	0.859	0.0000173	2722
Missense (PolyPhen)		83	101.52	0.81756		1115
Synonymous	0.644	100	109	0.921	0.00000668	856
Loss of Function	2.48	11	24.2	0.455	0.00000112	254

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00074	0.00068	rare
Latino/Admixed American	0.0015	0.0013	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00093	0.00092	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.00027	0.00026	rare
Other	0.0015	0.00081	notable

dbNSFP Gene Annotations

Source: dbNSFP

Disease: DISEASE: Note=Lysosomal acid phosphatase has been shown to be deficient in cultured fibroblasts from patients manifesting intermittent vomiting, hypotonia, lethargy, opisthotonos, terminal bleeding and death in early infancy. {ECO:0000269|PubMed:5410815}.;

Recessive Scores

pRec: 0.465

Intolerance Scores

LoFtool: 0.734
RVIS EVS: 0.09
RVIS percentile EVS: 60.47

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.994

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium