SCUBE1

Chr 22

signal peptide, CUB domain and EGF like domain containing 1

NCBI Gene: 80274ENSG00000159307UniProt: Q8IWY4

This gene encodes a cell surface glycoprotein that is a member of the SCUBE (signal peptide, CUB domain, EGF (epidermal growth factor)-like protein) family. Family members have an amino-terminal signal peptide, nine copies of EGF-like repeats and a CUB domain at the carboxyl terminus. This protein is expressed in platelets and endothelial cells and may play an important role in vascular biology. [provided by RefSeq, Oct 2011]

242
ClinVar variants
45
Pathogenic / LP
0.96
pLI score· haploinsufficient
0
Active trials
Clinical Summary— SCUBE1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
45 Pathogenic / Likely Pathogenic· 168 VUS of 242 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.31LOEUF
pLI 0.961
Z-score 5.56
OE 0.18 (0.11–0.31)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
1.98Z-score
OE missense 0.78 (0.72–0.84)
496 obs / 636.4 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.0.18 (0.11–0.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.72–0.84)
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.1.03
0≤1.21.6
LoF obs/exp: 10 / 54.2Missense obs/exp: 496 / 636.4Syn Z: -0.35

ClinVar Variant Classifications

242 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic45
VUS168
Likely Benign9
Benign7
45
Pathogenic
168
VUS
9
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
45
0
45
Likely Pathogenic
0
0
0
0
0
VUS
0
162
6
0
168
Likely Benign
0
6
1
2
9
Benign
0
1
2
4
7
Total0169546229

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

View in ClinVar →

Protein Context — Lollipop Plot

SCUBE1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Machine learning-driven discovery of novel therapeutic targets in diabetic foot ulcers.
Yu X et al.·Mol Med
2024
The biology of SCUBE.
Lin YC et al.·J Biomed Sci
2023Review
Predictive Value of Combined Plasma D-Dimer, SCUBE1, and Right Ventricular Tei Index for the Prognosis of Elderly Patients with Acute Pulmonary Thromboembolism.
Yang M et al.·Rejuvenation Res
2023Cohort
The role of SCUBE1 in the pathogenesis of no-reflow phenomenon presenting with ST segment elevation myocardial infarction.
Bolayır HA et al.·Anatol J Cardiol
2017
The role of SCUBE1 in the development of late stent thrombosis presenting with ST-elevation myocardial infarction.
Bolayır HA et al.·Rev Port Cardiol (Engl Ed)
2018
Are There Non-Invasive Biomarker(s) That Would Facilitate the Detection of Ovarian Torsion? A Systematic Review and Meta-Analysis.
Naylor M et al.·Int J Mol Sci
2024Meta-analysis
Genome-wide association study (GWAS) for molar-incisor hypomineralization (MIH).
Kühnisch J et al.·Clin Oral Investig
2014
The diagnostic and prognostic significance of SCUBE1 levels in Crimean-Congo hemorrhagic fever.
Menteşe A et al.·Int J Infect Dis
2013
The value of signal peptide-CUB-EGF domain-containing protein-1 (SCUBE1) in the diagnosis of pulmonary embolism: a preliminary study.
Turkmen S et al.·Acad Emerg Med
2015
New marker of platelet activation, SCUBE1, is elevated in hypertensive patients.
Özkan G et al.·Am J Hypertens
2013Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools