ENPP5

protein-coding

ectonucleotide pyrophosphatase/phosphodiesterase family member 5, the group of Ectonucleotide pyrophosphatase/phosphodiesterase family

Gene summary

This gene encodes a type-I transmembrane glycoprotein. Studies in rat suggest the encoded protein may play a role in neuronal cell communications. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2014]

MANE transcript

NM_001290072.2

Inheritance

—

ClinVar variants

U:64B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.96

Max pathogenic AF

—

Genomic locus

chr6:46,159,185-46,170,980

External References & Databases

Ensembl (ENSG00000112796)

Transcript & Mutation Effects

hg38 • Region Span ~11.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ENPP5 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 64

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001290072.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	1 clinvar		3
missense			61 clinvar	3 clinvar		64
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	64	4	0	68

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001290072.2	RefSeq	NP_001277001.1	3	MANE Select
ENST00000371383.7	Ensembl	ENSP00000360436.1	3	MANE Select
NM_001290073.2	RefSeq	NP_001277002.1	3	Standard
NM_021572.6	RefSeq	NP_067547.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cell communication

Molecular Function

hydrolase activity
metal ion binding

Cellular Component

extracellular region
plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371383
Coding exons: 3
Length: 11785
Individuals with no LoFs: 125671
Homozygous LoFs: 0
Heterozygous LoFs: 76
Defined: 125747
p: 0.000302

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0436	254	256	0.992	0.0000127	3173
Missense (PolyPhen)		100	100.64	0.99363		1250
Synonymous	0.669	86	94.3	0.912	0.00000526	890
Loss of Function	0.153	15	15.7	0.958	7.32e-7	204

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00024	0.00023	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00016	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00035	0.00033	rare
South Asian	0.00070	0.00069	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Can hydrolyze NAD but cannot hydrolyze nucleotide di- and triphosphates. Lacks lysopholipase D activity. May play a role in neuronal cell communication. {ECO:0000250|UniProtKB:P84039, ECO:0000250|UniProtKB:Q9EQG7}.;

Recessive Scores

pRec: 0.0878

Intolerance Scores

LoFtool: 0.728
RVIS EVS: 0.18
RVIS percentile EVS: 66.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.202

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High