SEMA5A
protein-codingsemaphorin 5A, the group of MicroRNA protein coding host genes|Semaphorins
Gene summary
This gene belongs to the semaphorin gene family that encodes membrane proteins containing a semaphorin domain and several thrombospondin type-1 repeats. Members of this family are involved in axonal guidance during neural development. This gene has been implicated as an autism susceptibility gene.[provided by RefSeq, Jan 2010]
- SEMAF
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~511.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0700092
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SEMA5A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003966.3. 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 | 6 | 31 | 19 | 56 | ||
| missense | 165 | 9 | 3 | 177 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 174 | 40 | 22 | 236 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003957.2 | 21 | MANE Select | |
| Ensembl | ENSP00000371936.5 | 21 | MANE Select | |
| Ensembl | ENSP00000421961.1 | 7 | Standard | |
| Ensembl | ENSP00000499013.1 | 21 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| sema5a | Danio rerio | Structure: CaP motoneuron Quality: decreased length abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Axon guidance - Homo sapiens (human)
- Developmental Biology
- Post-translational protein modification
- Metabolism of proteins
- Other semaphorin interactions
Biological Process
- neural crest cell migration
- positive regulation of endothelial cell proliferation
- blood vessel endothelial cell proliferation involved in sprouting angiogenesis
- cell adhesion
- negative regulation of cell adhesion
Molecular Function
- semaphorin receptor binding
- chondroitin sulfate proteoglycan binding
- heparan sulfate proteoglycan binding
- chemorepellent activity
- syndecan binding
Cellular Component
- plasma membrane
- membrane
- integral component of membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000382496
- Coding exons
- 21
- Length
- 511050
- Individuals with no LoFs
- 125710
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 38
- Defined
- 125748
- p
- 0.000151
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.33 | 573 | 670 | 0.855 | 0.0000433 | 7038 |
| Missense (PolyPhen) | 228 | 268.21 | 0.85008 | 2751 | ||
| Synonymous | -1.33 | 298 | 270 | 1.10 | 0.0000185 | 2055 |
| Loss of Function | 4.79 | 20 | 60.1 | 0.333 | 0.00000292 | 647 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00029 | 0.00029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00013 | 0.00013 | rare |
| South Asian | 0.00023 | 0.00016 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Bifunctional axonal guidance cue regulated by sulfated proteoglycans; attractive effects result from interactions with heparan sulfate proteoglycans (HSPGs), while the inhibitory effects depend on interactions with chondroitin sulfate proteoglycans (CSPGs) (By similarity). Ligand for receptor PLXNB3. In glioma cells, SEMA5A stimulation of PLXNB3 results in the disassembly of F-actin stress fibers, disruption of focal adhesions and cellular collapse as well as inhibition of cell migration and invasion through ARHGDIA-mediated inactivation of RAC1. May promote angiogenesis by increasing endothelial cell proliferation and migration and inhibiting apoptosis. {ECO:0000250, ECO:0000269|PubMed:15218527, ECO:0000269|PubMed:19850054, ECO:0000269|PubMed:20696765, ECO:0000269|PubMed:21706053}.;
Recessive Scores
- pRec
- 0.107
Intolerance Scores
- LoFtool
- 0.632
- RVIS EVS
- -2.89
- RVIS percentile EVS
- 0.58
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.352
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |