ENTPD8

protein-coding

ectonucleoside triphosphate diphosphohydrolase 8, the group of Ectonucleoside triphosphate diphosphohydrolase family

Gene summary

Enables apyrase activity. Involved in ribonucleoside diphosphate catabolic process and ribonucleoside triphosphate catabolic process. Predicted to be located in membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001033113.2

Inheritance

—

ClinVar variants

U:117B:13

Top phenotype

Microcephaly

gnomAD constraint

pLI —, LoF o/e 0.84

Max pathogenic AF

—

Genomic locus

chr9:137,434,364-137,441,816

External References & Databases

Ensembl (ENSG00000188833)

Transcript & Mutation Effects

hg38 • Region Span ~7.5 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 ENTPD8 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 123

not providedTotal: 3

MicrocephalyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001033113.2. 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			114 clinvar	9 clinvar	1 clinvar	124
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	117	11	2	130

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001033113.2	RefSeq	NP_001028285.1	9	MANE Select
ENST00000371506.7	Ensembl	ENSP00000360561.2	9	MANE Select
NM_198585.3	RefSeq	NP_940987.2	8	Standard
ENST00000344119.6	Ensembl	ENSP00000344089.2	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pyrimidine metabolism - Homo sapiens (human)
Purine metabolism - Homo sapiens (human)
Epstein-Barr virus infection - Homo sapiens (human)
Purine Nucleoside Phosphorylase Deficiency
Mercaptopurine Action Pathway

Biological Process

nucleoside monophosphate biosynthetic process
nucleoside diphosphate biosynthetic process
nucleobase-containing small molecule catabolic process

Molecular Function

ATP binding
nucleoside-diphosphatase activity
nucleoside-triphosphatase activity
metal ion binding
dATP phosphohydrolase activity

Cellular Component

plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371506
Coding exons: 9
Length: 7453
Individuals with no LoFs: 125387
Homozygous LoFs: 1
Heterozygous LoFs: 230
Defined: 125618
p: 0.000920

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.229	321	310	1.04	0.0000194	3151
Missense (PolyPhen)		88	89.841	0.97951		1033
Synonymous	-0.0334	149	148	1.00	0.0000103	1059
Loss of Function	0.705	19	22.6	0.840	0.00000105	235

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.0012	0.0012	notable
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00065	0.00065	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.0014	0.0014	notable
South Asian	0.00013	0.00013	rare
Other	0.00098	0.00098	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Canalicular ectonucleoside NTPDase responsible for the main hepatic NTPDase activity. Ectonucleoside NTPDases catalyze the hydrolysis of gamma- and beta-phosphate residues of nucleotides, playing a central role in concentration of extracellular nucleotides. Has activity toward ATP, ADP, UTP and UDP, but not toward AMP. {ECO:0000269|PubMed:16752921, ECO:0000269|PubMed:17095758}.;

Recessive Scores

pRec: 0.142

Intolerance Scores

LoFtool: 0.864
RVIS EVS: -1.06
RVIS percentile EVS: 7.48

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0408

Gene Damage Prediction

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