PLXNA1
protein-codingplexin A1, the group of Plexins|IPT domain containing
Gene summary
Contributes to semaphorin receptor activity. Involved in T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell and semaphorin-plexin signaling pathway. Located in extracellular exosome. Is active in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]
- PLXN1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~54.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0859260
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0859260
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0859260
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0100038
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0859260
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Dermatologic; Neurologic; Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PLXNA1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032242.4. 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 | 13 | 407 | 16 | 436 | ||
| missense | 5 | 683 | 32 | 3 | 723 | |
| nonsense | 2 | 3 | 9 | 14 | ||
| start loss | 0 | |||||
| frameshift | 2 | 5 | 10 | 17 | ||
| splice donor/acceptor (+/-2bp) | 1 | 3 | 11 | 15 | ||
| Total | 5 | 16 | 726 | 439 | 19 | 1205 |
Highest pathogenic variant AF is 0.0000130197195
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_115618.3 | 31 | MANE Select | |
| Ensembl | ENSP00000377061.2 | 31 | MANE Select | |
| Ensembl | ENSP00000507976.1 | 1 | Standard | |
| Ensembl | ENSP00000811617.1 | 31 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| plxna1b | Danio rerio | Structure: epithelial cell Quality: protruding out of 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
- Other semaphorin interactions
Biological Process
- negative regulation of cell adhesion
- multicellular organism development
- regulation of cell shape
- regulation of smooth muscle cell migration
- regulation of cell migration
Molecular Function
- semaphorin receptor activity
- signaling receptor activity
Cellular Component
- semaphorin receptor complex
- plasma membrane
- integral component of plasma membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000393409
- Coding exons
- 31
- Length
- 48799
- Individuals with no LoFs
- 125719
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 29
- Defined
- 125748
- p
- 0.000115
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.45 | 928 | 1.27e+3 | 0.728 | 0.0000933 | 12203 |
| Missense (PolyPhen) | 344 | 606.06 | 0.5676 | 6042 | ||
| Synonymous | -1.34 | 617 | 576 | 1.07 | 0.0000457 | 3956 |
| Loss of Function | 7.21 | 15 | 88.1 | 0.170 | 0.00000468 | 917 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0.000096 | 0.000092 | rare |
| European (Non-Finnish) | 0.00015 | 0.00014 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Coreceptor for SEMA3A, SEMA3C, SEMA3F and SEMA6D. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration. 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 (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.178
Intolerance Scores
- LoFtool
- 0.361
- RVIS EVS
- -4.39
- RVIS percentile EVS
- 0.09
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.800
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |