ACP5

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

Basic information

Region (hg38): 19:11574652-11579993

Links

ENSG00000102575 ∙ NCBI:54 ∙ OMIM:171640 ∙ HGNC:124 ∙ Uniprot:P13686 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Spondyloenchondrodysplasia with immune dysregulation (Definitive), mode of inheritance: AR
• Spondyloenchondrodysplasia with immune dysregulation (Strong), mode of inheritance: AR
• Spondyloenchondrodysplasia with immune dysregulation (Strong), mode of inheritance: AR
• Spondyloenchondrodysplasia with immune dysregulation (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spondyloenchondrodysplasia with immune dysregulation	AR	Allergy/Immunology/Infectious	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	Allergy/Immunology/Infectious; Endocrine; Musculoskeletal; Neurologic	12786759; 17497723; 17163538; 18924170; 21217755; 21217752; 26854080; 26951490
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

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACP5 gene.

• Spondyloenchondrodysplasia with immune dysregulation (260 variants)
• not provided (27 variants)
• Inborn genetic diseases (18 variants)
• not specified (7 variants)
• ACP5-related condition (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACP5 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				61	6	67
missense	2	3	132	3	3	143
nonsense	6	1	2			9
start loss			1			1
frameshift	13	1				14
inframe indel	1		1			2
splice donor/acceptor (+/-2bp)	1		1			2
splice region			3	4		7
non coding			2	15	7	24
Total	23	5	139	79	16

Highest pathogenic variant AF is 0.0000197

Variants in ACP5

This is a list of pathogenic ClinVar variants found in the ACP5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-11575012-A-G		Spondyloenchondrodysplasia with immune dysregulation	Uncertain significance (Aug 22, 2022)
19-11575015-G-A		Spondyloenchondrodysplasia with immune dysregulation	Uncertain significance (Aug 30, 2021)
19-11575017-C-A		Spondyloenchondrodysplasia with immune dysregulation	Uncertain significance (Nov 16, 2020)
19-11575017-C-T		Spondyloenchondrodysplasia with immune dysregulation	Uncertain significance (Aug 22, 2022)
19-11575018-T-C		Spondyloenchondrodysplasia with immune dysregulation	Uncertain significance (Aug 02, 2022)
19-11575023-C-T		Spondyloenchondrodysplasia with immune dysregulation	Uncertain significance (Sep 10, 2021)
19-11575024-G-A		Spondyloenchondrodysplasia with immune dysregulation	Uncertain significance (May 12, 2022)
19-11575024-G-C		Spondyloenchondrodysplasia with immune dysregulation	Uncertain significance (Jul 05, 2022)
19-11575025-C-T		Spondyloenchondrodysplasia with immune dysregulation	Likely benign (Sep 27, 2022)
19-11575028-C-T		Spondyloenchondrodysplasia with immune dysregulation	Likely benign (Jul 31, 2023)
19-11575029-G-A		Spondyloenchondrodysplasia with immune dysregulation	Uncertain significance (Aug 22, 2022)
19-11575033-G-A		Spondyloenchondrodysplasia with immune dysregulation • ACP5-related disorder	Benign/Likely benign (Jan 31, 2024)
19-11575034-C-T		Spondyloenchondrodysplasia with immune dysregulation	Likely benign (Dec 11, 2023)
19-11575038-G-C		Spondyloenchondrodysplasia with immune dysregulation	Uncertain significance (Oct 17, 2022)
19-11575039-T-C		Spondyloenchondrodysplasia with immune dysregulation	Uncertain significance (Jun 03, 2022)
19-11575058-C-T		Spondyloenchondrodysplasia with immune dysregulation	Likely benign (Sep 25, 2022)
19-11575066-C-T		Spondyloenchondrodysplasia with immune dysregulation	Uncertain significance (Jun 27, 2022)
19-11575067-G-C		Spondyloenchondrodysplasia with immune dysregulation	Uncertain significance (Oct 05, 2022)
19-11575068-A-T		Spondyloenchondrodysplasia with immune dysregulation	Uncertain significance (Aug 05, 2022)
19-11575069-T-A		Spondyloenchondrodysplasia with immune dysregulation	Uncertain significance (Feb 11, 2020)
19-11575074-G-A		Spondyloenchondrodysplasia with immune dysregulation	Uncertain significance (Mar 07, 2020)
19-11575079-A-G		Spondyloenchondrodysplasia with immune dysregulation	Likely benign (Jan 15, 2022)
19-11575086-T-C		Spondyloenchondrodysplasia with immune dysregulation	Uncertain significance (Jul 19, 2022)
19-11575105-C-T		Inborn genetic diseases	Uncertain significance (Apr 25, 2022)
19-11575116-C-T		Spondyloenchondrodysplasia with immune dysregulation	Uncertain significance (Aug 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACP5	protein_coding	protein_coding	ENST00000592828	4	4349

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0787	0.912	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.400	181	197	0.920	0.0000128	2096
Missense in Polyphen		50	78.818	0.63437		894
Synonymous	0.560	80	86.6	0.924	0.00000580	687
Loss of Function	2.25	4	12.6	0.317	6.33e-7	121

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000174	0.000174
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000617	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

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.
• Pathway: Lysosome - Homo sapiens (human);Riboflavin metabolism - Homo sapiens (human);Rheumatoid arthritis - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Osteoclast Signaling;RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;Metabolism;Vitamin B2 (riboflavin) metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors (Consensus)

Recessive Scores

• pRec: 0.254

Intolerance Scores

• loftool: 0.138
• rvis_EVS: 0.35
• rvis_percentile_EVS: 74.58

Haploinsufficiency Scores

• pHI: 0.161
• hipred: N
• hipred_score: 0.429
• ghis: 0.394

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.995

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Acp5
• Phenotype: hematopoietic system phenotype; immune system phenotype; skeleton phenotype; limbs/digits/tail phenotype

Gene ontology

• Biological process: ossification;riboflavin metabolic process;dephosphorylation;response to lipopolysaccharide;negative regulation of interleukin-1 beta production;negative regulation of interleukin-12 production;negative regulation of tumor necrosis factor production;negative regulation of superoxide anion generation;response to cytokine;negative regulation of nitric oxide biosynthetic process;bone resorption;negative regulation of inflammatory response;defense response to Gram-positive bacterium;bone morphogenesis
• Cellular component: lysosome;cytosol;integral component of membrane
• Molecular function: acid phosphatase activity;ferrous iron binding;ferric iron binding