SEMA4C
protein-codingsemaphorin 4C, the group of Immunoglobulin like domain containing|Semaphorins
Gene summary
Predicted to enable chemorepellent activity; neuropilin binding activity; and semaphorin receptor binding activity. Involved in muscle cell differentiation and positive regulation of stress-activated MAPK cascade. Located in obsolete extracellular space. [provided by Alliance of Genome Resources, Jun 2026]
- SEMAI
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SEMA4C variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017789.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 122 | 4 | 126 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 129 | 5 | 0 | 134 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060259.4 | 14 | MANE Select | |
| Ensembl | ENSP00000306844.5 | 14 | MANE Select | |
| Ensembl | ENSP00000393498.1 | 6 | Standard | |
| Ensembl | ENSP00000391094.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Axon guidance - Homo sapiens (human)
Biological Process
- neural crest cell migration
- neural tube closure
- cell migration in hindbrain
- cerebellum development
- positive regulation of cell migration
Molecular Function
- protein binding
- semaphorin receptor binding
- neuropilin binding
- chemorepellent activity
Cellular Component
- extracellular space
- integral component of plasma membrane
- postsynaptic density
- cell junction
- synaptic vesicle membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000305476
- Coding exons
- 14
- Length
- 11042
- Individuals with no LoFs
- 119147
- Homozygous LoFs
- 815
- Heterozygous LoFs
- 5768
- Defined
- 125730
- p
- 0.0265
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.39 | 379 | 534 | 0.710 | 0.0000349 | 5303 |
| Missense (PolyPhen) | 100 | 207.39 | 0.48219 | 2159 | ||
| Synonymous | 0.622 | 222 | 234 | 0.948 | 0.0000150 | 1800 |
| Loss of Function | 5.63 | 1 | 38.9 | 0.0257 | 0.00000185 | 418 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0020 | 0.0020 | notable |
| Latino/Admixed American | 0.21 | 0.20 | notable |
| Ashkenazi Jewish | 0.0021 | 0.0021 | notable |
| East Asian | 0.0039 | 0.0039 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00013 | 0.00012 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.023 | 0.022 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cell surface receptor for PLXNB2 that plays an important role in cell-cell signaling. PLXNB2 binding promotes downstream activation of RHOA and phosphorylation of ERBB2 at 'Tyr-1248'. Required for normal brain development, axon guidance and cell migration (By similarity). Probable signaling receptor which may play a role in myogenic differentiation through activation of the stress-activated MAPK cascade. {ECO:0000250, ECO:0000269|PubMed:17498836}.;
Recessive Scores
- pRec
- 0.156
Intolerance Scores
- LoFtool
- 0.163
- RVIS EVS
- -0.78
- RVIS percentile EVS
- 13.05
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.813
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |