ENTPD6

Chr 20

ectonucleoside triphosphate diphosphohydrolase 6

Also known as: CD39L2, IL-6SAG, IL6ST2, NTPDase-6, dJ738P15.3

NCBI Gene: 955ENSG00000197586UniProt: O75354

ENTPD6 encodes a nucleotidase that catalyzes the hydrolysis of nucleoside triphosphates and diphosphates, with strong preference for diphosphates like GDP, IDP, and UDP, and functions in glycosylation reactions in the Golgi apparatus. Mutations in ENTPD6 cause autosomal recessive spastic paraplegia with intellectual disability and hearing loss. The gene shows low constraint to loss-of-function variation, consistent with recessive inheritance.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
7
Pubs (1 yr)
17
P/LP submissions
0%
P/LP missense
0.82
LOEUF
DN
Mechanism· predicted
Clinical Summary— ENTPD6
⚡
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· 74 VUS of 121 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
0.82LOEUF
pLI 0.000
Z-score 2.29
OE 0.52 (0.34–0.82)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.77Z-score
OE missense 0.88 (0.79–0.97)
261 obs / 298.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.52 (0.34–0.82)
0≤0.351.4
Missense OE0.88 (0.79–0.97)
0≤0.61.4
Synonymous OE0.92
0≤1.21.6
LoF obs/exp: 14 / 26.8Missense obs/exp: 261 / 298.2Syn Z: 0.75
DN
0.7133th %ile
GOF
0.5661th %ile
LOF
0.2776th %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

121 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic3
VUS74
Likely Benign10
Benign1
14
Pathogenic
3
Likely Pathogenic
74
VUS
10
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
3
0
3
VUS
0
62
12
0
74
Likely Benign
0
9
0
1
10
Benign
0
1
0
0
1
Total072291102

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

View in ClinVar →

Protein Context — Lollipop Plot

ENTPD6 · 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.

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Clinical Literature
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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
Top 3 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