ENTPD8

Chr 9

ectonucleoside triphosphate diphosphohydrolase 8

Also known as: E-NTPDase, GLSR2492, NTPDase-8, UNQ2492

NCBI Gene: 377841ENSG00000188833UniProt: Q5MY95OMIM: 616748

ENTPD8 encodes a canalicular ectonucleoside triphosphate diphosphohydrolase that hydrolyzes nucleoside triphosphates and diphosphates to regulate extracellular nucleotide levels, with primary expression and activity in the liver. The gene is not well-constrained against loss-of-function variants, and no definitive human disease associations have been established in the provided data. Inheritance pattern and clinical phenotypes remain to be determined.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.23
Clinical Summary— ENTPD8
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
22 unique Pathogenic / Likely Pathogenic· 60 VUS of 100 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.23LOEUF
pLI 0.000
Z-score 0.71
OE 0.84 (0.58–1.23)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.23Z-score
OE missense 1.04 (0.94–1.14)
321 obs / 309.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.84 (0.58–1.23)
0≤0.351.4
Missense OE1.04 (0.94–1.14)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 19 / 22.6Missense obs/exp: 321 / 309.7Syn Z: -0.03
DN
0.6258th %ile
GOF
0.6346th %ile
LOF
0.2678th %ile

The Badonyi & Marsh model scores gain-of-function highest, but genomic evidence most strongly supports dominant-negative as the primary mechanism.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
VUS60
Likely Benign8
22
Pathogenic
60
VUS
8
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
0
0
0
VUS
0
59
1
0
60
Likely Benign
0
6
0
2
8
Benign
0
0
0
0
0
Total06523290

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ENTPD8 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients