SEMA6A
protein-codingsemaphorin 6A, the group of Semaphorins
Gene summary
Predicted to enable several functions, including chemorepellent activity; identical protein binding activity; and semaphorin receptor binding activity. Involved in cellular response to vascular endothelial growth factor stimulus; negative regulation of cell adhesion involved in sprouting angiogenesis; and negative regulation of signal transduction. Predicted to be located in axon and membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]
- SEMAQ
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~131.3 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 SEMA6A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020796.5. 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 | 3 | 2 | 5 | 10 | ||
| missense | 1 | 160 | 6 | 167 | ||
| nonsense | 1 | 3 | 4 | |||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 2 | 172 | 8 | 5 | 187 |
Highest pathogenic variant AF is 0.0000013698049
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_065847.1 | 18 | MANE Select | |
| Ensembl | ENSP00000345512.6 | 18 | MANE Select | |
| RefSeq | NP_001287709.1 | 19 | Standard | |
| Ensembl | ENSP00000257414.8 | 19 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| sema6a | Danio rerio | Structure: optic cup Quality: decreased occurrence abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Axon guidance - Homo sapiens (human)
- Spinal Cord Injury
- Developmental Biology
- Other semaphorin interactions
- Semaphorin interactions
Biological Process
- neural crest cell migration
- apoptotic process
- cytoskeleton organization
- cell surface receptor signaling pathway
- nervous system development
Molecular Function
- protein binding
- semaphorin receptor binding
- chemorepellent activity
Cellular Component
- extracellular space
- integral component of plasma membrane
- integral component of membrane
- axon
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000343348
- Coding exons
- 18
- Length
- 131319
- Individuals with no LoFs
- 124630
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 15
- Defined
- 124645
- p
- 0.0000602
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.747 | 543 | 594 | 0.914 | 0.0000353 | 6744 |
| Missense (PolyPhen) | 209 | 278.27 | 0.75108 | 3108 | ||
| Synonymous | -1.23 | 269 | 244 | 1.10 | 0.0000165 | 2028 |
| Loss of Function | 5.39 | 4 | 41.4 | 0.0965 | 0.00000196 | 541 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000066 | 0.000065 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.000073 | 0.000071 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cell surface receptor for PLXNA2 that plays an important role in cell-cell signaling. Required for normal granule cell migration in the developing cerebellum. Promotes reorganization of the actin cytoskeleton and plays an important role in axon guidance in the developing central nervous system. Can act as repulsive axon guidance cue. Has repulsive action towards migrating granular neurons. May play a role in channeling sympathetic axons into the sympathetic chains and controlling the temporal sequence of sympathetic target innervation (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.470
Intolerance Scores
- LoFtool
- 0.133
- RVIS EVS
- -0.06
- RVIS percentile EVS
- 48.91
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.878
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |