NOTUM

Chr 17

notum, palmitoleoyl-protein carboxylesterase

Also known as: hNOTUM

NCBI Gene: 147111ENSG00000185269UniProt: Q6P988

Enables palmitoleyl hydrolase activity. Involved in negative regulation of Wnt signaling pathway and protein depalmitoleylation. Acts upstream of or within bone development and regulation of bone mineralization. Predicted to be located in endoplasmic reticulum lumen and extracellular region. [provided by Alliance of Genome Resources, Jul 2025]

0
Active trials
22
Pathogenic / LP
113
ClinVar variants
7
Pubs (1 yr)
1.4
Missense Z
0.58
LOEUF
Clinical Summary— NOTUM
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 84 VUS of 113 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.58LOEUF
pLI 0.002
Z-score 3.30
OE 0.34 (0.21–0.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.44Z-score
OE missense 0.77 (0.69–0.86)
235 obs / 305.8 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.0.34 (0.21–0.58)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.69–0.86)
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.1.10
0≤1.21.6
LoF obs/exp: 10 / 29.2Missense obs/exp: 235 / 305.8Syn Z: -0.90

ClinVar Variant Classifications

113 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic3
VUS84
Likely Benign5
Benign2
19
Pathogenic
3
Likely Pathogenic
84
VUS
5
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
0
3
0
3
VUS
0
80
4
0
84
Likely Benign
0
2
0
3
5
Benign
0
1
1
0
2
Total083273113

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

View in ClinVar →

Protein Context — Lollipop Plot

NOTUM · 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.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
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 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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