SEMA4C

Chr 2

semaphorin 4C

Also known as: M-SEMA-F, SEMACL1, SEMAF, SEMAI

The SEMA4C protein is a cell surface receptor that regulates brain development, axon guidance, and cell migration through downstream signaling pathways including RHOA activation and stress-activated MAPK cascade. Mutations cause autosomal dominant developmental delays, intellectual disability, and behavioral abnormalities with childhood onset. This gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.12), indicating intolerance to protein-disrupting mutations.

Summary from RefSeq, UniProt
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0
Active trials
6
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.12
LOEUF· LoF intol.
Mechanism
Clinical SummarySEMA4C
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.12LOEUF
pLI 1.000
Z-score 5.63
OE 0.03 (0.010.12)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
2.39Z-score
OE missense 0.71 (0.650.77)
379 obs / 534.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.03 (0.010.12)
00.351.4
Missense OE0.71 (0.650.77)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 1 / 38.9Missense obs/exp: 379 / 534.1Syn Z: 0.62

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SEMA4C · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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