GeneBe

ACP5

protein-coding

acid phosphatase 5, tartrate resistant, the group of Acid phosphatases

Gene summary

This gene encodes an iron containing glycoprotein which catalyzes the conversion of orthophosphoric monoester to alcohol and orthophosphate. It is the most basic of the acid phosphatases and is the only form not inhibited by L(+)-tartrate. [provided by RefSeq, Aug 2008]

MANE transcript

NM_001611.5

Inheritance

AR

ClinVar variants

P:43U:158B:104

Top phenotype

Spondyloenchondrodysplasia with immune dysregulation

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr19:11,574,653-11,579,993

External References & Databases

Ensembl (ENSG00000102575)NCBI Gene (54)OMIM (171640)HGNC:124GenCCUniProt (P13686)AlphaFoldClinVar (ACP5)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~5.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Spondyloenchondrodysplasia with immune dysregulationDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011939

Submitter: G2P

Spondyloenchondrodysplasia with immune dysregulationSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011939

Submitter: Labcorp Genetics (formerly Invitae)

Spondyloenchondrodysplasia with immune dysregulationSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011939

Submitter: Orphanet

Spondyloenchondrodysplasia with immune dysregulationSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011939

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Spondyloenchondrodysplasia with immune dysregulationAR

Manifestation: Allergy/Immunology/Infectious; Endocrine; Musculoskeletal; Neurologic

Intervention: Allergy/Immunology/Infectious

Rationale: Individuals may have immune deficiency, and a variety of infections have been reported, including pneunomia, upper respiratory infections, and severe varicella infections, and thus antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; Individuals may also have a variety of autoimmune manifestations, including hypothyroidism, and treatment may be beneficial

Comments: Clinically recognizable non-immune features may not be recognized early; The condition can affect multiple organ systems for which early knowledge of disease could be beneficial, including infectious and autoimmune sequelae

Refs: 12786759; 17497723; 17163538; 18924170; 21217755; 21217752; 26854080; 26951490Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ACP5 variants in ClinVar

6 Conditions Cataloged
Spondyloenchondrodysplasia with immune dysregulationTotal: 308
not providedTotal: 50
Inborn genetic diseasesTotal: 50
not specifiedTotal: 29
ACP5-related disorderTotal: 18
See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001611.5. 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.

EffectPLPVUSLBBSum
synonymous
89
clinvar
2
clinvar
 91
missense
4
clinvar
6
clinvar
152
clinvar
12
clinvar
1
clinvar
 175
nonsense
6
clinvar
4
clinvar
3
clinvar
 13
start loss
1
clinvar
 1
frameshift
17
clinvar
5
clinvar
1
clinvar
 23
splice donor/acceptor (+/-2bp)
1
clinvar
1
clinvar
 2
Total28151581013305

Highest pathogenic variant AF is 0.000042745367

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 64 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001611.5RefSeqNP_001602.14MANE Select
ENST00000648477.1EnsemblENSP00000496973.14MANE Select
NM_001111034.3RefSeqNP_001104504.14Standard
NM_001111035.3RefSeqNP_001104505.14Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Lysosome - Homo sapiens (human)
  • Riboflavin metabolism - Homo sapiens (human)
  • Rheumatoid arthritis - Homo sapiens (human)
  • Osteoclast differentiation - Homo sapiens (human)
  • Osteoclast Signaling

Biological Process

  • ossification
  • riboflavin metabolic process
  • dephosphorylation
  • response to lipopolysaccharide
  • negative regulation of interleukin-1 beta production

Molecular Function

  • acid phosphatase activity
  • ferrous iron binding
  • ferric iron binding

Cellular Component

  • lysosome
  • cytosol
  • integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000592828
Coding exons
4
Length
4349
Individuals with no LoFs
125733
Homozygous LoFs
0
Heterozygous LoFs
15
Defined
125748
p
0.0000596
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.4001811970.9200.00001282096
Missense (PolyPhen)5078.8180.63437894
Synonymous0.5608086.60.9240.00000580687
Loss of Function2.25412.60.3176.33e-7121

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.000170.00017rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000620.000062rare
South Asian0.0000330.000033rare
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Involved in osteopontin/bone sialoprotein dephosphorylation. Its expression seems to increase in certain pathological states such as Gaucher and Hodgkin diseases, the hairy cell, the B-cell, and the T-cell leukemias.;
Disease
DISEASE: Spondyloenchondrodysplasia with immune dysregulation (SPENCDI) [MIM:607944]: A disease characterized by vertebral and metaphyseal dysplasia, spasticity with cerebral calcifications, and strong predisposition to autoimmune diseases. The skeletal dysplasia is characterized by radiolucent and irregular spondylar and metaphyseal lesions that represent islands of chondroid tissue within bone. {ECO:0000269|PubMed:21217752, ECO:0000269|PubMed:21217755}. Note=The disease is caused by mutations affecting the gene represented in this entry. ACP5 inactivating mutations result in a functional excess of phosphorylated osteopontin causing deregulation of osteopontin signaling and consequential autoimmune disease.;

Recessive Scores

pRec
0.254

Intolerance Scores

LoFtool
0.138
RVIS EVS
0.35
RVIS percentile EVS
74.58

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.995

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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