ENTPD1

Chr 10

ectonucleoside triphosphate diphosphohydrolase 1

Also known as: ATP-DPH, ATPDase, CD39, NTPDase-1, SPG64

NCBI Gene: 953ENSG00000138185UniProt: P49961

The protein encoded by this gene is a plasma membrane protein that hydrolyzes extracellular ATP and ADP to AMP. Inhibition of this protein's activity may confer anticancer benefits. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

Primary Disease Associations & Inheritance

UniProtSpastic paraplegia 64, autosomal recessive
287
ClinVar variants
37
Pathogenic / LP
0.01
pLI score
2
Active trials
Clinical Summary— ENTPD1
🧬
Gene-Disease Validity (ClinGen)
complex hereditary spastic paraplegia · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
37 Pathogenic / Likely Pathogenic· 114 VUS of 287 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.60LOEUF
pLI 0.008
Z-score 3.02
OE 0.33 (0.20–0.60)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.83Z-score
OE missense 0.86 (0.77–0.96)
226 obs / 264.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.33 (0.20–0.60)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.77–0.96)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.86
0≤1.21.6
LoF obs/exp: 8 / 24.0Missense obs/exp: 226 / 264.1Syn Z: 1.09

ClinVar Variant Classifications

287 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic7
VUS114
Likely Benign95
Benign30
Conflicting11
30
Pathogenic
7
Likely Pathogenic
114
VUS
95
Likely Benign
30
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
27
0
30
Likely Pathogenic
6
0
1
0
7
VUS
0
96
14
4
114
Likely Benign
0
2
44
49
95
Benign
0
1
27
2
30
Conflicting
—11
Total810011355287

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

View in ClinVar →

Protein Context — Lollipop Plot

ENTPD1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ENTPD1-related intellectual developmental disorder

limited
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — ENTPD1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Single-cell RNA sequencing reveals distinct cellular factors for response to immunotherapy targeting CD73 and PD-1 in colorectal cancer.
Kim M et al.·J Immunother Cancer
2021
Single-cell sequencing on CD8(+) TILs revealed the nature of exhausted T cells recognizing neoantigen and cancer/testis antigen in non-small cell lung cancer.
Komuro H et al.·J Immunother Cancer
2023
ENPP1 Immunobiology as a Therapeutic Target.
Ruiz-Fernández de Córdoba B et al.·Clin Cancer Res
2023Review
Fibrocyte Phenotype of ENTPD1+CD55+ Cells and Its Association with Pain in Osteoarthritic Synovium.
Tsuchiya M et al.·Int J Mol Sci
2024
Novel microRNAs modulating ecto-5'-nucleotidase expression.
Kordaß T et al.·Front Immunol
2023
Revealing and harnessing CD39 for the treatment of colorectal cancer and liver metastases by engineered T cells.
Potenza A et al.·Gut
2023
Bioinformatics-based identification of CTSS, DOK2, and ENTPD1 as potential blood biomarkers of schizophrenia.
Zhang L et al.·BMC Psychiatry
2025
Long-Term Clinical Characterization of ENTPD1-Related Spastic Paraplegia: A Novel Variant and Comprehensive Literature Review.
Erkan DD et al.·Int J Dev Neurosci
2025Review
Evaluation of non-invasive biomarkers of kidney allograft rejection in a prospective multicenter unselected cohort study (EU-TRAIN).
Goutaudier V et al.·Kidney Int
2024Cohort
KIR2DL2/DL3+NKs and Helios+Tregs in Peripheral Blood Predict Nivolumab Response in Patients with Metastatic Renal Cell Cancer.
Santagata S et al.·Clin Cancer Res
2024Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Bladder Cancer

Antitumor T Cell Responses in Patients With Bladder Cancer

NOT YET RECRUITING
NCT06334406Centre Hospitalier Universitaire de BesanconStarted 2024-04-02
Biological samples
Immune System ToleranceDepressionObesity

ESAN II - Energy Sensing in Depression

RECRUITING
NCT05432362Phase NAMedical University of GrazStarted 2019-02-25
Aronia JuicePlacebo

External Resources

Links to major genomics databases and tools