ACP5

Chr 19AR

acid phosphatase 5, tartrate resistant

Also known as: HPAP, TRACP5a, TRACP5b, TRAP, TRAcP, TrATPase

NCBI Gene: 54ENSG00000102575UniProt: P13686

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]

Primary Disease Associations & Inheritance

Spondyloenchondrodysplasia with immune dysregulationMIM #607944
AR
360
ClinVar variants
50
Pathogenic / LP
0.08
pLI score
2
Active trials
Clinical Summary— ACP5
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.
📋
ClinVar Variants
50 Pathogenic / Likely Pathogenic· 164 VUS of 360 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.72LOEUF
pLI 0.079
Z-score 2.25
OE 0.32 (0.15–0.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.40Z-score
OE missense 0.92 (0.81–1.04)
181 obs / 196.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.32 (0.15–0.72)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.81–1.04)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
0≤1.21.6
LoF obs/exp: 4 / 12.6Missense obs/exp: 181 / 196.8Syn Z: 0.56

ClinVar Variant Classifications

360 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic7
VUS164
Likely Benign125
Benign13
Conflicting8
43
Pathogenic
7
Likely Pathogenic
164
VUS
125
Likely Benign
13
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
5
22
0
43
Likely Pathogenic
3
2
2
0
7
VUS
2
146
16
0
164
Likely Benign
0
10
31
84
125
Benign
0
0
7
6
13
Conflicting
—8
Total211637890360

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ACP5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ACP5-related spondyloenchondrodysplasia with immune dysregulation

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spondyloenchondrodysplasia with immune dysregulation

MIM #607944

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
MAPK1/3 kinase-dependent ULK1 degradation attenuates mitophagy and promotes breast cancer bone metastasis.
Deng R et al.·Autophagy
2021
Trio Whole Exome Sequencing in Chinese Childhood-Onset Lupus Reveals Novel Candidate Genes.
Ma J et al.·Arthritis Rheumatol
2025
The regulatory role of ACP5 in the diesel exhaust particle-induced AHR inflammatory signaling pathway in a human bronchial epithelial cell line.
Yu A et al.·Sci Rep
2025
Monogenic lupus: it's all new!
Costa-Reis P et al.·Curr Opin Immunol
2017Review
Arcyriaflavin A Alleviates Osteoporosis by Suppressing RANKL-Induced Osteoclastogenesis.
Zhu M et al.·Int J Mol Sci
2025
Clinical, laboratory, and molecular characteristics of patients with spondyloenchondrodysplasia: a case series study.
Pekpak Şahinoğlu E et al.·Eur J Pediatr
2025Cohort
Cross-talk between oxidative stress and lipid metabolism regulators reveals molecular clusters and immunological characterization in polycystic ovarian syndrome.
Tan C et al.·Lipids Health Dis
2024
A NOTCH2 pathogenic variant and HES1 regulate osteoclastogenesis in induced pluripotent stem cells.
Canalis E et al.·Bone
2025
Inhibition of tartrate-resistant acid phosphatase 5 can prevent cardiac fibrosis after myocardial infarction.
Yang S et al.·Mol Med
2024
Spondyloenchondrodysplasia in five new patients: identification of three novel ACP5 variants with variable neurological presentations.
Elhossini RM et al.·Mol Genet Genomics
2023Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Perimenopausal Bone Loss

Prunes Preventing Bone Loss in Perimenopause

RECRUITING
NCT07120997Phase NAPenn State UniversityStarted 2025-12-11
PrunesCalcium supplementVitamin D Supplement
Osteoporosis, Postmenopausal

Treatment With Zoledronate Subsequent to Denosumab in Osteoporosis 2 (ZOLARMAB2)

ACTIVE NOT RECRUITING
NCT05655013Phase PHASE4Aarhus University HospitalStarted 2023-05-10
ZoledronatePlacebo

External Resources

Links to major genomics databases and tools