SEMA4B

Chr 15

semaphorin 4B

Also known as: SEMAC, SemC

NCBI Gene: 10509ENSG00000185033UniProt: Q9NPR2

Predicted to enable chemorepellent activity; neuropilin binding activity; and semaphorin receptor binding activity. Predicted to be involved in several processes, including axon guidance; neural crest cell migration; and semaphorin-plexin signaling pathway. Predicted to be located in membrane and synapse. Predicted to be active in glutamatergic synapse and postsynaptic density membrane. [provided by Alliance of Genome Resources, Apr 2025]

194
ClinVar variants
39
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SEMA4B
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
📋
ClinVar Variants
39 Pathogenic / Likely Pathogenic· 143 VUS of 194 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.
0.53LOEUF
pLI 0.001
Z-score 3.83
OE 0.34 (0.22–0.53)
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.
0.96Z-score
OE missense 0.88 (0.81–0.95)
430 obs / 489.5 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 (0.22–0.53)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.81–0.95)
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.1.11
0≤1.21.6
LoF obs/exp: 13 / 38.8Missense obs/exp: 430 / 489.5Syn Z: -1.28

ClinVar Variant Classifications

194 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic4
VUS143
Likely Benign11
Conflicting1
35
Pathogenic
4
Likely Pathogenic
143
VUS
11
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
35
0
35
Likely Pathogenic
0
0
4
0
4
VUS
0
139
4
0
143
Likely Benign
0
10
1
0
11
Benign
0
0
0
0
0
Conflicting
—1
Total0149440194

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

View in ClinVar →

Protein Context — Lollipop Plot

SEMA4B · 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
SEMAPHORIN 4B; SEMA4B
MIM #617029 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Semaphorin4B is elevated in rheumatoid arthritis and enhances the inflammatory phenotype of macrophages and fibroblast-like synoviocytes.
Martínez-Ramos S et al.·Arthritis Res Ther
2025
Gene-Environment Interaction Between CYP1B1 and Oral Contraception on Frontal Fibrosing Alopecia.
Rayinda T et al.·JAMA Dermatol
2024
Identification and Validation of Signature Genes and Their Correlations with Infiltrated Immune Cells in Neonatal Sepsis.
Zhu H et al.·Altern Ther Health Med
2023
Discovery and Validation of Salivary Extracellular RNA Biomarkers for Noninvasive Detection of Gastric Cancer.
Li F et al.·Clin Chem
2018
Label-free quantitative proteomics and N-glycoproteomics analysis of KRAS-activated human bronchial epithelial cells.
Sudhir PR et al.·Mol Cell Proteomics
2012
Evaluation of predictive role of carcinoembryonic antigen and salivary mRNA biomarkers in gastric cancer detection.
Xu F et al.·Medicine (Baltimore)
2020
Regulation of antitumor miR-144-5p targets oncogenes: Direct regulation of syndecan-3 and its clinical significance.
Yamada Y et al.·Cancer Sci
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Astrocyte-to-microglia communication via Sema4B-Plexin-B2 modulates injury-induced reactivity of microglia.
Casden N et al.·Proc Natl Acad Sci U S A
2024🔓 Open Access
Effects of the SEMA4B gene on hexavalent chromium [Cr(VI)]-induced malignant transformation of human bronchial epithelial cells.
Qin Y et al.·Toxicol Res (Camb)
2024
[Retracted] Long non‑coding RNA NEAT1 promotes the malignancy of laryngeal squamous cell carcinoma by regulating the microRNA‑204‑5p/SEMA4B axis.
Han L et al.·Oncol Lett
2024🔓 Open Access
CircSEMA4B inhibits the progression of breast cancer by encoding a novel protein SEMA4B-211aa and regulating AKT phosphorylation.
Wang X et al.·Cell Death Dis
2022🔓 Open Access
Long non-coding RNA NEAT1 promotes the malignancy of laryngeal squamous cell carcinoma by regulating the microRNA-204-5p/SEMA4B axis.
Han L et al.·Oncol Lett
2021🔓 Open Access
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