ENTPD2

Chr 9

ectonucleoside triphosphate diphosphohydrolase 2

Also known as: CD39L1, NTPDase-2

NCBI Gene: 954ENSG00000054179UniProt: Q9Y5L3OMIM: 602012

The ENTPD2 protein is an integral membrane ecto-nucleotidase that hydrolyzes extracellular nucleoside triphosphates and diphosphates, particularly ATP, to regulate extracellular nucleotide levels. Mutations cause autosomal dominant spastic paraplegia with early childhood onset, affecting motor function and gait. The gene shows low constraint against loss-of-function variants (high LOEUF score of 1.47).

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.47
Clinical Summary— ENTPD2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
49 unique Pathogenic / Likely Pathogenic· 50 VUS of 134 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
1.47LOEUF
pLI 0.000
Z-score -0.09
OE 1.02 (0.72–1.47)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.66Z-score
OE missense 1.11 (1.01–1.23)
299 obs / 268.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.02 (0.72–1.47)
0≤0.351.4
Missense OE1.11 (1.01–1.23)
0≤0.61.4
Synonymous OE1.05
0≤1.21.6
LoF obs/exp: 21 / 20.5Missense obs/exp: 299 / 268.6Syn Z: -0.45
DN
0.6550th %ile
GOF
0.5954th %ile
LOF
0.2970th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

134 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47
Likely Pathogenic2
VUS50
Likely Benign2
47
Pathogenic
2
Likely Pathogenic
50
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
47
0
47
Likely Pathogenic
1
0
1
0
2
VUS
0
49
1
0
50
Likely Benign
0
1
0
1
2
Benign
0
0
0
0
0
Total150491101

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

View in ClinVar →

Protein Context — Lollipop Plot

ENTPD2 · 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
Proteomics profiling and association with cardiorenal complications in type 2 diabetes subtypes in Asian population.
Gurung RL et al.·Diabetes Res Clin Pract
2024
Hypoxia inducible factor HIF-1 promotes myeloid-derived suppressor cells accumulation through ENTPD2/CD39L1 in hepatocellular carcinoma.
Chiu DK et al.·Nat Commun
2017
Immune landscape and a promising immune prognostic model associated with TP53 in early-stage lung adenocarcinoma.
Wu C et al.·Cancer Med
2021Functional
Molecular Signaling and Dysfunction of the Human Reactive Enteric Glial Cell Phenotype: Implications for GI Infection, IBD, POI, Neurological, Motility, and GI Disorders.
Liñán-Rico A et al.·Inflamm Bowel Dis
2016
Expression of Ecto-nucleoside Triphosphate Diphosphohydrolases-2 and -3 in the Enteric Nervous System Affects Inflammation in Experimental Colitis and Crohn's Disease.
Feldbrügge L et al.·J Crohns Colitis
2017
Top 5 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