SEMA3E

Chr 7

semaphorin 3E

NCBI Gene: 9723ENSG00000170381UniProt: O15041

Plays an important role in signaling via the cell surface receptor PLXND1. Mediates reorganization of the actin cytoskeleton, leading to the retraction of cell projections. Promotes focal adhesion disassembly and inhibits adhesion of endothelial cells to the extracellular matrix. Regulates angiogenesis, both during embryogenesis and after birth. Can down-regulate sprouting angiogenesis. Required for normal vascular patterning during embryogenesis. Plays an important role in ensuring the specificity of synapse formation (By similarity)

593
ClinVar variants
5
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SEMA3E
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
5 Pathogenic / Likely Pathogenic· 362 VUS of 593 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.68LOEUF
pLI 0.000
Z-score 3.27
OE 0.47 (0.33–0.68)
Tolerant

Typical tolerance to LoF variation

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.
0.46Z-score
OE missense 0.94 (0.86–1.02)
408 obs / 435.3 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.0.47 (0.33–0.68)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.86–1.02)
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.1.23
0≤1.21.6
LoF obs/exp: 21 / 44.5Missense obs/exp: 408 / 435.3Syn Z: -2.28

ClinVar Variant Classifications

593 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
VUS362
Likely Benign218
Benign4
Conflicting4
5
Pathogenic
362
VUS
218
Likely Benign
4
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
0
0
0
VUS
15
312
30
5
362
Likely Benign
0
2
96
120
218
Benign
0
0
4
0
4
Conflicting
—4
Total15314135125593

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

View in ClinVar →

Protein Context — Lollipop Plot

SEMA3E · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — SEMA3E
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of plasma SEMA3E as the diagnostic biomarker for human epilepsy based on integrated bioinformatics analysis.
Yang X et al.·Neurotherapeutics
2025
Prevalence of pathogenic variants and digenic disease in patients diagnosed with normosmic hypogonadotropic hypogonadism/Kallmann Syndrome.
Poch A et al.·Mol Cell Endocrinol
2024Cohort
Bilateral Testicular Regression Syndrome and Optic Nerve Atrophy: Clinical Aspects of a Child with a SEMA3E Loss-of-Function Variant.
Wankanit S et al.·Sex Dev
2025Case report
A Novel Loss-of-Function SEMA3E Mutation in a Patient with Severe Intellectual Disability and Cognitive Regression.
Paganoni AJJ et al.·Int J Mol Sci
2022Case report
Sema3E is required for migration of cranial neural crest cells in zebrafish: Implications for the pathogenesis of CHARGE syndrome.
Liu ZZ et al.·Int J Exp Pathol
2019Functional
Exploring the Role of Chemokine-Related Gene Deregulation and Immune Infiltration in Ischemic Stroke: Insights into CXCL16 and SEMA3E as Potential Biomarkers.
Yu T et al.·J Mol Neurosci
2024
Sema3E-Plexin D1 signaling drives human cancer cell invasiveness and metastatic spreading in mice.
Casazza A et al.·J Clin Invest
2010
Tumour growth inhibition and anti-metastatic activity of a mutated furin-resistant Semaphorin 3E isoform.
Casazza A et al.·EMBO Mol Med
2012
Sema-3E/PlexinD1 axis modulates dendritic cell phenotypes and functions: Current status and future implications.
Alamri A·Hum Immunol
2024Review
Association of Increased Serum Sema3E with TRIB3 Q84R Polymorphism and Carotid Atherosclerosis in Metabolic Syndrome.
Qin RR et al.·Ann Clin Lab Sci
2017
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