ENPP6

ectonucleotide pyrophosphatase/phosphodiesterase 6, the group of Ectonucleotide pyrophosphatase/phosphodiesterase family

Basic information

Region (hg38): 4:184088705-184221230

Links

ENSG00000164303 ∙ NCBI:133121 ∙ OMIM:616983 ∙ HGNC:23409 ∙ Uniprot:Q6UWR7 ∙ 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 ENPP6 gene.

• Inborn genetic diseases (26 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ENPP6 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	2
missense			26			26
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	26	1	2

Variants in ENPP6

This is a list of pathogenic ClinVar variants found in the ENPP6 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-184091217-T-A		not specified	Uncertain significance (Jun 21, 2023)
4-184091251-G-A		not specified	Uncertain significance (Oct 26, 2022)
4-184091301-G-A		not specified	Uncertain significance (Nov 03, 2023)
4-184091323-A-G		not specified	Uncertain significance (May 17, 2023)
4-184091338-C-T		not specified	Uncertain significance (Sep 22, 2023)
4-184091362-C-G		not specified	Uncertain significance (Oct 12, 2022)
4-184097271-C-T		not specified	Uncertain significance (Apr 22, 2022)
4-184097287-C-T		not specified	Uncertain significance (Sep 29, 2022)
4-184112730-T-C		not specified	Uncertain significance (Oct 05, 2023)
4-184112758-C-G		not specified	Uncertain significance (Oct 16, 2023)
4-184112767-C-G		not specified	Uncertain significance (Jan 17, 2023)
4-184112799-T-C		not specified	Uncertain significance (Oct 02, 2023)
4-184116873-G-C		not specified	Uncertain significance (Aug 22, 2023)
4-184116976-G-C		not specified	Uncertain significance (Jun 14, 2023)
4-184117023-G-T		not specified	Uncertain significance (Dec 06, 2021)
4-184117790-G-A		not specified	Uncertain significance (Sep 17, 2021)
4-184117800-C-T		not specified	Uncertain significance (Sep 27, 2021)
4-184117862-C-T		not specified	Uncertain significance (May 17, 2023)
4-184117893-G-A		not specified	Uncertain significance (Oct 03, 2022)
4-184124179-T-A		not specified	Uncertain significance (Dec 16, 2023)
4-184124242-G-T		not specified	Uncertain significance (Jan 05, 2022)
4-184153545-C-T			Benign (May 30, 2018)
4-184153578-T-G		not specified	Uncertain significance (Jan 26, 2022)
4-184153601-A-T		not specified	Uncertain significance (Jan 19, 2024)
4-184153642-G-T		not specified	Uncertain significance (May 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ENPP6	protein_coding	protein_coding	ENST00000296741	8	132525

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.75e-9	0.444	125712	0	36	125748	0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.311	256	270	0.947	0.0000158	2889
Missense in Polyphen		98	114.06	0.8592		1217
Synonymous	-0.837	118	107	1.10	0.00000678	854
Loss of Function	0.955	15	19.6	0.767	8.76e-7	227

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000150	0.000149
Middle Eastern	0.000272	0.000272
South Asian	0.000261	0.000261
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Choline-specific glycerophosphodiester phosphodiesterase. The preferred substrate may be lysosphingomyelin (By similarity). Hydrolyzes lysophosphatidylcholine (LPC) to form monoacylglycerol and phosphorylcholine but not lysophosphatidic acid, showing it has a lysophospholipase C activity. Has a preference for LPC with short (12:0 and 14:0) or polyunsaturated (18:2 and 20:4) fatty acids. Also hydrolyzes glycerophosphorylcholine and sphingosylphosphorylcholine efficiently. Hydrolyzes the classical substrate for phospholipase C, p-nitrophenyl phosphorylcholine in vitro, while it does not hydrolyze the classical nucleotide phosphodiesterase substrate, p-nitrophenyl thymidine 5'- monophosphate. Does not hydrolyze diacyl phospholipids such as phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidylglycerol and phosphatidic acid. {ECO:0000250, ECO:0000269|PubMed:15788404}.
• Pathway: Ether lipid metabolism - Homo sapiens (human);Metabolism of lipids;Metabolism;Glycerophospholipid catabolism;PI Metabolism;Phospholipid metabolism (Consensus)

Intolerance Scores

• loftool: 0.649
• rvis_EVS: -0.35
• rvis_percentile_EVS: 29.49

Haploinsufficiency Scores

• pHI: 0.145
• hipred: N
• hipred_score: 0.289
• ghis: 0.498

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.924

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Enpp6

Gene ontology

• Biological process: lipid metabolic process;choline metabolic process;glycerophospholipid catabolic process
• Cellular component: extracellular region;plasma membrane;anchored component of membrane;extracellular exosome
• Molecular function: phosphoric diester hydrolase activity;glycerophosphodiester phosphodiesterase activity;glycerophosphocholine cholinephosphodiesterase activity