ENTPD1

Chr 10AR

ectonucleoside triphosphate diphosphohydrolase 1

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

The encoded protein is a plasma membrane enzyme that hydrolyzes extracellular ATP and ADP to AMP, regulating nucleotide levels and preventing platelet aggregation to support blood flow. Biallelic mutations cause spastic paraplegia 64, an autosomal recessive disorder affecting the motor system. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.602).

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 0.601 OMIM phenotype
Clinical SummaryENTPD1
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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.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.60LOEUF
pLI 0.008
Z-score 3.02
OE 0.33 (0.200.60)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.83Z-score
OE missense 0.86 (0.770.96)
226 obs / 264.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.33 (0.200.60)
00.351.4
Missense OE0.86 (0.770.96)
00.61.4
Synonymous OE0.86
01.21.6
LoF obs/exp: 8 / 24.0Missense obs/exp: 226 / 264.1Syn Z: 1.09
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedENTPD1-related intellectual developmental disorderOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7230th %ile
GOF
0.5759th %ile
LOF
0.1994th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold
Clinical Literature
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