PLXNA3
protein-codingplexin A3, the group of Plexins|IPT domain containing
Gene summary
This gene encodes a member of the plexin class of proteins. The encoded protein is a class 3 semaphorin receptor, and may be involved in cytoskeletal remodeling and as well as apoptosis. Studies of a similar gene in zebrafish suggest that it is important for axon pathfinding in the developing nervous system. This gene may be associated with tumor progression. [provided by RefSeq, Aug 2013]
- PLXN4
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~19.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: XL
Disease ID:MONDO:0018555
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PLXNA3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017514.5. 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 | 29 | 328 | 12 | 369 | ||
| missense | 645 | 57 | 11 | 713 | ||
| nonsense | 14 | 14 | ||||
| start loss | 0 | |||||
| frameshift | 8 | 8 | ||||
| splice donor/acceptor (+/-2bp) | 28 | 28 | ||||
| Total | 0 | 0 | 724 | 385 | 23 | 1132 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_059984.3 | 32 | MANE Select | |
| Ensembl | ENSP00000358696.3 | 32 | MANE Select | |
| Ensembl | ENSP00000607865.1 | 32 | Standard | |
| Ensembl | ENSP00000607865.1 | 32 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| plxna3 | Danio rerio | Structure: primary motor neuron Quality: spatial pattern abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Axon guidance - Homo sapiens (human)
- Developmental Biology
- SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion
- Sema3A PAK dependent Axon repulsion
- Semaphorin interactions
Biological Process
- negative regulation of cell adhesion
- multicellular organism development
- regulation of cell shape
- facial nerve structural organization
- trigeminal nerve structural organization
Molecular Function
- transmembrane signaling receptor activity
- protein binding
- semaphorin receptor activity
Cellular Component
- semaphorin receptor complex
- nucleus
- plasma membrane
- integral component of plasma membrane
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000369682
- Coding exons
- 32
- Length
- 15369
- Individuals with no LoFs
- 125706
- Homozygous LoFs
- 15
- Heterozygous LoFs
- 13
- Defined
- 125734
- p
- 0.000111
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.676 | 853 | 910 | 0.937 | 0.0000874 | 12137 |
| Missense (PolyPhen) | 331 | 425.32 | 0.77823 | 5763 | ||
| Synonymous | -4.98 | 538 | 410 | 1.31 | 0.0000411 | 3893 |
| Loss of Function | 5.39 | 15 | 60.1 | 0.250 | 0.00000472 | 885 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00016 | 0.00012 | rare |
| Latino/Admixed American | 0.00011 | 0.000087 | rare |
| Ashkenazi Jewish | 0.00013 | 0.000099 | rare |
| East Asian | 0.000074 | 0.000054 | rare |
| Finnish | 0.000063 | 0.000046 | rare |
| European (Non-Finnish) | 0.00023 | 0.00015 | rare |
| South Asian | 0.00016 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Coreceptor for SEMA3A and SEMA3F. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance in the developing nervous system. Regulates the migration of sympathetic neurons, but not of neural crest precursors. Required for normal dendrite spine morphology in pyramidal neurons. May play a role in regulating semaphorin-mediated programmed cell death in the developing nervous system. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm.;
Recessive Scores
- pRec
- 0.141
Intolerance Scores
- LoFtool
- 0.284
- RVIS EVS
- -2.49
- RVIS percentile EVS
- 0.94
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.239
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |