ENPP7

Chr 17

ectonucleotide pyrophosphatase/phosphodiesterase 7

Also known as: ALK-SMase, E-NPP 7, NPP-7, NPP7

NCBI Gene: 339221ENSG00000182156UniProt: Q6UWV6

The encoded protein functions as an intestinal alkaline sphingomyelin phosphodiesterase that hydrolyzes sphingomyelin to ceramide and phosphocholine, playing a critical role in sphingomyelin digestion, ceramide formation, and fatty acid absorption in the gastrointestinal tract. The protein also exhibits phospholipase C activity and can inactivate platelet-activating factor by cleaving phosphocholine from lysophosphatidylcholine substrates. No associated human diseases have been reported for ENPP7 mutations based on the provided clinical data.

Summary from RefSeq, UniProt, Mechanism
Research Assistant →
0
Active trials
0
Pubs (1 yr)
17
P/LP submissions
0%
P/LP missense
1.79
LOEUF
DN
Mechanism· predicted
Clinical Summary— ENPP7
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 91 VUS of 125 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.79LOEUF
pLI 0.000
Z-score -0.96
OE 1.27 (0.88–1.79)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.48Z-score
OE missense 1.08 (0.98–1.18)
326 obs / 302.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.27 (0.88–1.79)
0≤0.351.4
Missense OE1.08 (0.98–1.18)
0≤0.61.4
Synonymous OE0.96
0≤1.21.6
LoF obs/exp: 19 / 15.0Missense obs/exp: 326 / 302.6Syn Z: 0.33
DN
0.6743th %ile
GOF
0.6345th %ile
LOF
0.3258th %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

125 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic2
VUS91
Likely Benign15
15
Pathogenic
2
Likely Pathogenic
91
VUS
15
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
15
0
15
Likely Pathogenic
0
0
2
0
2
VUS
0
86
5
0
91
Likely Benign
0
13
0
2
15
Benign
0
0
0
0
0
Total099222123

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

View in ClinVar →

Protein Context — Lollipop Plot

ENPP7 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

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