SEMA4D

Chr 9

semaphorin 4D

ENSG00000187764UniProt: Q92854

The protein functions as a cell surface receptor for PLXNB1 and PLXNB2, regulating GABAergic synapse development and promoting inhibitory synapse formation, while also modulating neurite complexity and arborization in hippocampal neurons and promoting cerebellar granule cell migration. SEMA4D mutations cause autosomal dominant neurodevelopmental disorders through loss-of-function mechanisms, as indicated by the gene's extreme intolerance to protein-truncating variants (pLI 0.97) and constraint against missense variation (LOEUF 0.31).

Summary from RefSeq, UniProt
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0
Active trials
37
Pubs (1 yr)
0
P/LP submissions
—
P/LP missense
0.31
LOEUF· LoF intol.
—
Mechanism
Clinical Summary— SEMA4D
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
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Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.31LOEUF
pLI 0.975
Z-score 4.79
OE 0.16 (0.09–0.31)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.00Z-score
OE missense 0.88 (0.81–0.95)
460 obs / 524.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.16 (0.09–0.31)
0≤0.351.4
Missense OE0.88 (0.81–0.95)
0≤0.61.4
Synonymous OE0.96
0≤1.21.6
LoF obs/exp: 6 / 37.8Missense obs/exp: 460 / 524.2Syn Z: 0.45

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SEMA4D · 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.

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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 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
METTL1 Aggravates Periodontitis Progression by Inhibiting Osteoblast Differentiation via m7G modification of SEMA4D.
Huang YS et al.·Int Dent J
2026
Tumor-Derived Exosomal TAGLN2 Promotes Metastasis by Inducing Vascular Permeability and Angiogenesis via the NRP1/SEMA4D/YAP Axis.
Yu S et al.·Adv Sci (Weinh)
2026
[The Role of Sema4D in Immune Abnormalities Mediated by IgA Secreted by B Lymphocytes in Children with Henoch-Schonlein Purpura].
Su D et al.·Zhongguo Shi Yan Xue Ye Xue Za Zhi
2025
Soluble Sema4D From γδ T Cells Exerts Osteoblast Inhibition via Plexin-B/mTOR Signalling Contributing to Pathogenesis of Bisphosphonate-Related Osteonecrosis of the Jaws.
Ou L et al.·Cell Prolif
2025
Sema4D combined with electrocardiographic parameters for predicting STEMI prognosis: Development and validation of a nomogram model.
Li D et al.·Medicine (Baltimore)
2025Open AccessFunctional
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