ENTPD4
Chr 8ectonucleoside triphosphate diphosphohydrolase 4
Also known as: LALP70, LAP70, LYSAL1, NTPDase-4, UDPase
The protein functions as an endo-apyrase that catalyzes the hydrolysis of nucleoside triphosphates and diphosphates in a calcium- or magnesium-dependent manner, with preference for pyrimidines like UTP and TTP, and may be involved in nucleotide salvage from lysosomes. Mutations cause spastic paraplegia 35, an autosomal recessive hereditary spastic paraplegia presenting with progressive lower limb spasticity. The gene shows no constraint against loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
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
214 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 77 | 0 | 77 |
Likely Pathogenic | 0 | 0 | 4 | 0 | 4 |
VUS | 0 | 105 | 4 | 0 | 109 |
Likely Benign | 0 | 5 | 0 | 1 | 6 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 110 | 85 | 1 | 196 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ENTPD4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools