ENPP3

ectonucleotide pyrophosphatase/phosphodiesterase 3, the group of CD molecules|Ectonucleotide pyrophosphatase/phosphodiesterase family

Basic information

Region (hg38): 6:131628441-131747418

Previous symbols: [ "PDNP3" ]

Links

ENSG00000154269 ∙ NCBI:5169 ∙ OMIM:602182 ∙ HGNC:3358 ∙ Uniprot:O14638 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ENPP3 gene.

• Inborn genetic diseases (89 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ENPP3 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				1		1
missense			34	2	2	38
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			53	1		54
Total	0	0	87	4	2

Variants in ENPP3

This is a list of pathogenic ClinVar variants found in the ENPP3 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-131637410-C-T		not specified	Likely benign (Oct 25, 2023)
6-131637451-A-G		not specified	Uncertain significance (Nov 10, 2022)
6-131641480-T-C		not specified	Uncertain significance (Jun 09, 2022)
6-131650057-C-T		not specified	Uncertain significance (Dec 21, 2022)
6-131652607-T-C		not specified	Uncertain significance (Jan 03, 2024)
6-131652863-A-T		not specified	Uncertain significance (Feb 07, 2023)
6-131652887-G-A		not specified	Uncertain significance (Jun 06, 2023)
6-131658328-A-T		not specified	Uncertain significance (Oct 29, 2021)
6-131658418-T-C		not specified	Uncertain significance (Dec 21, 2023)
6-131671285-G-A		not specified	Uncertain significance (Nov 12, 2021)
6-131674172-C-T		not specified	Uncertain significance (Nov 10, 2022)
6-131674181-A-G		not specified	Uncertain significance (Dec 11, 2023)
6-131674272-T-A		not specified	Likely benign (Nov 17, 2022)
6-131674272-T-G		not specified	Likely benign (Jan 26, 2022)
6-131674285-T-C			Likely benign (Jun 23, 2018)
6-131675099-A-G		not specified	Uncertain significance (Aug 14, 2023)
6-131677878-T-C		not specified	Uncertain significance (Jul 10, 2023)
6-131683076-T-C		not specified	Uncertain significance (Sep 12, 2023)
6-131683100-T-C		not specified	Uncertain significance (Mar 02, 2023)
6-131685367-T-C		not specified	Uncertain significance (Jun 02, 2023)
6-131685418-G-A		not specified	Uncertain significance (Jan 06, 2023)
6-131685441-G-A		not specified	Uncertain significance (Nov 30, 2022)
6-131685448-C-T		not specified	Uncertain significance (Jan 03, 2022)
6-131685456-C-T		not specified	Uncertain significance (Sep 07, 2022)
6-131685463-G-A		not specified	Uncertain significance (Apr 05, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ENPP3	protein_coding	protein_coding	ENST00000414305	25	118972

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.47e-23	0.0532	125073	1	672	125746	0.00268

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0744	463	468	0.990	0.0000229	5805
Missense in Polyphen		175	192.54	0.90889		2439
Synonymous	-0.491	169	161	1.05	0.00000805	1557
Loss of Function	1.40	41	51.9	0.790	0.00000260	647

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00482	0.00482
Ashkenazi Jewish	0.000697	0.000695
East Asian	0.00158	0.00152
Finnish	0.00208	0.00208
European (Non-Finnish)	0.00278	0.00277
Middle Eastern	0.00158	0.00152
South Asian	0.00504	0.00494
Other	0.00261	0.00261

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Hydrolase that metabolizes extracellular nucleotides, including ATP, GTP, UTP and CTP (PubMed:29717535). Limits mast cell and basophil responses during inflammation and during the chronic phases of allergic responses by eliminating the extracellular ATP that functions as signaling molecule and activates basophils and mast cells and induces the release of inflammatory cytokines. Metabolizes extracellular ATP in the lumen of the small intestine, and thereby prevents ATP-induced apoptosis of intestinal plasmacytoid dendritic cells (By similarity). Has also alkaline phosphodiesterase activity (PubMed:11342463). {ECO:0000250|UniProtKB:Q6DYE8, ECO:0000269|PubMed:11342463, ECO:0000269|PubMed:29717535}.
• Pathway: Pyrimidine metabolism - Homo sapiens (human);Nicotinate and nicotinamide metabolism - Homo sapiens (human);Starch and sucrose metabolism - Homo sapiens (human);Pantothenate and CoA biosynthesis - Homo sapiens (human);Riboflavin metabolism - Homo sapiens (human);Purine metabolism - Homo sapiens (human);IL-3 Signaling Pathway;Pathways in clear cell renal cell carcinoma;Pyrimidine metabolism;Vitamin B2 (riboflavin) metabolism;Vitamin B3 (nicotinate and nicotinamide) metabolism;Vitamin B5 - CoA biosynthesis from pantothenate;Nicotinate Nicotinamide metabolism;Pyrimidine metabolism (Consensus)

Recessive Scores

• pRec: 0.423

Intolerance Scores

• loftool: 0.935
• rvis_EVS: 0.39
• rvis_percentile_EVS: 75.68

Haploinsufficiency Scores

• pHI: 0.130
• hipred: N
• hipred_score: 0.254
• ghis: 0.379

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.599

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Enpp3
• Phenotype: digestive/alimentary phenotype; immune system phenotype; respiratory system phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype

Gene ontology

• Biological process: basophil activation involved in immune response;pyrimidine nucleotide metabolic process;phosphate-containing compound metabolic process;receptor-mediated endocytosis;nucleoside triphosphate catabolic process;inorganic diphosphate transport;negative regulation of mast cell activation involved in immune response;ATP metabolic process;negative regulation of inflammatory response;negative regulation of mast cell proliferation;nucleic acid phosphodiester bond hydrolysis
• Cellular component: external side of plasma membrane;integral component of membrane;apical plasma membrane;perinuclear region of cytoplasm;extracellular exosome
• Molecular function: nucleic acid binding;phosphodiesterase I activity;scavenger receptor activity;calcium ion binding;zinc ion binding;polysaccharide binding;NADH pyrophosphatase activity;nucleoside-triphosphate diphosphatase activity