ENPP2

ectonucleotide pyrophosphatase/phosphodiesterase 2, the group of Ectonucleotide pyrophosphatase/phosphodiesterase family

Basic information

Region (hg38): 8:119557086-119673453

Previous symbols: [ "PDNP2" ]

Links

ENSG00000136960 ∙ NCBI:5168 ∙ OMIM:601060 ∙ HGNC:3357 ∙ Uniprot:Q13822 ∙ 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 ENPP2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ENPP2 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	1	3
missense			45	2	2	49
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding						0
Total	0	0	46	3	3

Variants in ENPP2

This is a list of pathogenic ClinVar variants found in the ENPP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-119557556-T-C		not specified	Uncertain significance (Dec 13, 2023)
8-119557583-G-A			Benign/Likely benign (Jul 01, 2023)
8-119557630-C-T		not specified	Uncertain significance (Jul 19, 2022)
8-119562882-C-T		not specified	Uncertain significance (Mar 30, 2022)
8-119562883-G-A		not specified	Uncertain significance (Jun 21, 2021)
8-119562897-A-G		not specified	Uncertain significance (Mar 24, 2023)
8-119562967-T-C		not specified	Uncertain significance (Jun 22, 2023)
8-119562970-T-C		not specified	Uncertain significance (Dec 19, 2022)
8-119564816-C-T			Benign (Jun 06, 2018)
8-119564836-C-T		not specified	Uncertain significance (Apr 22, 2022)
8-119564847-T-C		not specified	Uncertain significance (Sep 16, 2021)
8-119564862-T-G		not specified	Uncertain significance (Jan 27, 2022)
8-119568238-G-A		not specified	Uncertain significance (Apr 22, 2024)
8-119569347-G-C		not specified	Likely benign (Dec 28, 2022)
8-119570803-G-A		not specified	Uncertain significance (Dec 13, 2022)
8-119570814-G-T		not specified	Uncertain significance (Sep 16, 2021)
8-119572182-T-G			Uncertain significance (Dec 01, 2022)
8-119580119-C-T		not specified	Uncertain significance (Jan 31, 2024)
8-119580143-G-A		not specified	Uncertain significance (Jul 16, 2021)
8-119580166-T-C			Benign (May 18, 2018)
8-119582495-G-C		not specified	Uncertain significance (Jun 16, 2023)
8-119582510-C-G		not specified	Uncertain significance (Aug 28, 2023)
8-119582519-T-A		not specified	Uncertain significance (May 31, 2023)
8-119582539-C-A		not specified	Uncertain significance (Jun 07, 2024)
8-119582552-T-G		not specified	Uncertain significance (Jun 07, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ENPP2	protein_coding	protein_coding	ENST00000259486	26	116368

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00279	0.997	125718	0	30	125748	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.38	425	513	0.828	0.0000275	6033
Missense in Polyphen		136	217.6	0.625		2417
Synonymous	-0.0713	183	182	1.01	0.0000102	1646
Loss of Function	4.98	16	56.4	0.284	0.00000294	690

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000208	0.000208
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000116	0.000114
Middle Eastern	0.00	0.00
South Asian	0.000296	0.000294
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Hydrolyzes lysophospholipids to produce the signaling molecule lysophosphatidic acid (LPA) in extracellular fluids (PubMed:15769751, PubMed:26371182, PubMed:27754931). Major substrate is lysophosphatidylcholine (PubMed:12176993, PubMed:27754931). Also can act on sphingosylphosphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility. Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP (PubMed:15769751, PubMed:12176993). Involved in several motility-related processes such as angiogenesis and neurite outgrowth. Acts as an angiogenic factor by stimulating migration of smooth muscle cells and microtubule formation (PubMed:11559573). Stimulates migration of melanoma cells, probably via a pertussis toxin-sensitive G protein (PubMed:1733949). May have a role in induction of parturition (PubMed:12176993). Possible involvement in cell proliferation and adipose tissue development (Probable). Tumor cell motility- stimulating factor (PubMed:1733949, PubMed:11559573). {ECO:0000269|PubMed:11559573, ECO:0000269|PubMed:12176993, ECO:0000269|PubMed:15769751, ECO:0000269|PubMed:1733949, ECO:0000269|PubMed:21240271, ECO:0000269|PubMed:26371182, ECO:0000269|PubMed:27754931, ECO:0000305|PubMed:15700135}.
• Pathway: Ether lipid metabolism - Homo sapiens (human);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: 0.196

Intolerance Scores

• loftool: 0.650
• rvis_EVS: 0.16
• rvis_percentile_EVS: 64.96

Haploinsufficiency Scores

• pHI: 0.460
• hipred: N
• hipred_score: 0.372
• ghis: 0.428

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.825

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Enpp2
• 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); normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); embryo phenotype; immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: enpp2
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: receptor-mediated endocytosis;chemotaxis;immune response;phospholipid catabolic process;positive regulation of epithelial cell migration;regulation of cell migration;phosphatidylcholine catabolic process;regulation of angiogenesis;cell motility;positive regulation of peptidyl-tyrosine phosphorylation;nucleic acid phosphodiester bond hydrolysis;positive regulation of lamellipodium morphogenesis
• Cellular component: extracellular space;plasma membrane
• Molecular function: nucleic acid binding;phosphodiesterase I activity;nucleotide diphosphatase activity;lysophospholipase activity;scavenger receptor activity;calcium ion binding;transcription factor binding;zinc ion binding;hydrolase activity;polysaccharide binding;alkylglycerophosphoethanolamine phosphodiesterase activity