ENTPD4

protein-coding

ectonucleoside triphosphate diphosphohydrolase 4, the group of Ectonucleoside triphosphate diphosphohydrolase family

Gene summary

This gene encodes a member of the apyrase protein family. Apyrases are enzymes that catalyze the hydrolysis of nucleotide diphosphates and triphosphates in a calcium or magnesium-dependent manner. The encoded protein is an endo-apyrase and may play a role in salvaging nucleotides from lysosomes. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and these isoforms may differ in divalent cation dependence and substrate specificity. [provided by RefSeq, Sep 2011]

Previous symbols:

LYSAL1

MANE transcript

NM_004901.5

Inheritance

—

ClinVar variants

U:117B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.75

Max pathogenic AF

—

Genomic locus

chr8:23,385,783-23,457,695

External References & Databases

Ensembl (ENSG00000197217)

Transcript & Mutation Effects

hg38 • Region Span ~71.9 kb

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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 ENTPD4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 111

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004901.5. 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			112 clinvar	5 clinvar		117
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	117	6	0	123

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004901.5	RefSeq	NP_004892.1	12	MANE Select
ENST00000358689.9	Ensembl	ENSP00000351520.4	12	MANE Select
NM_001128930.3	RefSeq	NP_001122402.1	12	Standard
ENST00000356206.10	Ensembl	ENSP00000348536.6	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pyrimidine metabolism - Homo sapiens (human)
Lysosome - Homo sapiens (human)
Purine metabolism - Homo sapiens (human)
Nucleobase catabolism
Metabolism of nucleotides

Biological Process

UDP catabolic process
nucleobase-containing small molecule catabolic process

Molecular Function

nucleoside-diphosphatase activity
nucleoside-triphosphatase activity
uridine-diphosphatase activity

Cellular Component

Golgi membrane
integral component of Golgi membrane
cytoplasmic vesicle
integral component of autophagosome membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000358689
Coding exons: 12
Length: 71913
Individuals with no LoFs: 125549
Homozygous LoFs: 0
Heterozygous LoFs: 199
Defined: 125748
p: 0.000792

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.723	403	364	1.11	0.0000212	4029
Missense (PolyPhen)		180	169.26	1.0635		1880
Synonymous	-0.658	152	142	1.07	0.00000874	1215
Loss of Function	1.47	30	40.0	0.750	0.00000287	351

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00076	0.00069	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00044	0.00044	rare
Finnish	0.00056	0.00055	rare
European (Non-Finnish)	0.0010	0.0010	notable
South Asian	0.00094	0.00091	rare
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Hydrolyzes preferentially nucleoside 5'-diphosphates, nucleoside 5'-triphosphates are hydrolyzed only to a minor extent. The order of activity with different substrates is UDP >> GDP = CDP = TDP, AMP, ADP, ATP and UMP are not substrates. Preferred substrates for isoform 2 are CTP, UDP, CDP, GTP and GDP, while isoform 1 utilizes UTP and TTP.;

Recessive Scores

pRec: 0.157

Intolerance Scores

LoFtool: 0.948
RVIS EVS: -0.66
RVIS percentile EVS: 15.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.779

Gene Damage Prediction

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