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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
PLXNA2
plexin A2
Chromosome 1 Β· 1q32.2
NCBI Gene: 5362Ensembl: ENSG00000076356.8HGNC: HGNC:9100UniProt: O75051
55PubMed Papers
20Diseases
0Drugs
2Pathogenic Variants
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingsemaphorin receptor activitysynapse assemblysemaphorin-plexin signaling pathwayneurodegenerative diseasevertebral column disorderAbnormality of the skeletal systemrestless legs syndrome
✦AI Summary

PLXNA2 encodes plexin A2, a transmembrane receptor protein that serves as a coreceptor for semaphorin guidance molecules, particularly SEMA3A and SEMA6A 1. The protein plays critical roles in neurodevelopment through axon guidance, cell migration, and cytoskeletal remodeling 2. PLXNA2 functions by forming complexes with neuropilins to bind class 3 semaphorins, with its cytoplasmic domain containing a GTPase activating (GAP) domain that is essential for downstream signaling through FARP2 and FYN pathways 3. In human chondrocytes, SEMA3A signaling through plexin A2 increases protein content and suppresses PTH-R1 expression, suggesting roles in skeletal development 1. Disease associations include schizophrenia susceptibility in some populations 4 and autism spectrum disorder, where PLXNA2 variants cause protein mislocalization and reduced interactions with LRRC40 2. In cancer contexts, PLXNA2 promotes glioblastoma cell proliferation and tumor formation through AKT signaling, making it a potential therapeutic target 3. The protein's broad roles in neural development, skeletal biology, and oncology highlight its importance in multiple physiological and pathological processes.

Sources cited
1
PLXNA2 serves as a coreceptor for SEMA3A and functions in human chondrocytes to suppress PTH-R1 expression
PMID: 30271602
2
PLXNA2 participates in neurodevelopment and variants cause protein mislocalization in autism spectrum disorder
PMID: 33749153
3
PLXNA2 contains a GAP domain and promotes glioblastoma proliferation through FARP2/FYN pathways and AKT signaling
PMID: 36658114
4
PLXNA2 variants show association with schizophrenia susceptibility in Japanese populations
PMID: 18065206
5
PLXNA2 functions in axonal repulsion, attraction, cell migration, axon pruning, and synaptic plasticity
PMID: 17346868
Disease Associationsβ“˜20
neurodegenerative diseaseOpen Targets
0.55Moderate
vertebral column disorderOpen Targets
0.41Moderate
Abnormality of the skeletal systemOpen Targets
0.36Weak
restless legs syndromeOpen Targets
0.35Weak
Abruptio PlacentaeOpen Targets
0.34Weak
health study participationOpen Targets
0.32Weak
infectious meningitisOpen Targets
0.31Weak
systemic lupus erythematosusOpen Targets
0.28Weak
polypOpen Targets
0.27Weak
trauma complicationOpen Targets
0.27Weak
cataractOpen Targets
0.27Weak
rectal diseaseOpen Targets
0.27Weak
obesityOpen Targets
0.27Weak
rectosigmoid junction neoplasmOpen Targets
0.27Weak
Abnormality of the gastrointestinal tractOpen Targets
0.26Weak
cervical carcinomaOpen Targets
0.25Weak
risk-taking behaviourOpen Targets
0.25Weak
smoking initiationOpen Targets
0.25Weak
smoking behaviorOpen Targets
0.20Weak
overnutritionOpen Targets
0.20Weak
Pathogenic Variants2
NM_025179.4(PLXNA2):c.3640-1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_025179.4(PLXNA2):c.2206G>A (p.Gly736Ser)Likely pathogenic
atypical cerebral palsy
β˜…β˜†β˜†β˜†β†’ Residue 736
View on ClinVar β†—
Related Genes
DPYSL2Protein interaction100%DPYSL3Protein interaction100%SEMA3BProtein interaction100%SEMA6AProtein interaction100%SEMA3EProtein interaction100%RAC3Protein interaction98%
Tissue Expression6 tissues
Lung
100%
Ovary
98%
Heart
47%
Brain
33%
Liver
22%
Bone Marrow
4%
Gene Interaction Network
Click a node to explore
PLXNA2DPYSL2DPYSL3SEMA3BSEMA6ASEMA3ERAC3
PROTEIN STRUCTURE
Preparing viewer…
PDB3Q3J Β· 1.97 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.53Moderately Constrained
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.44 [0.36–0.53]
RankingsWhere PLXNA2 stands among ~20K protein-coding genes
  • #8,237of 20,598
    Most Researched55
  • #4,419of 5,498
    Most Pathogenic Variants2
  • #3,268of 17,882
    Most Constrained (LOEUF)0.53 Β· top quartile
Genes detectedPLXNA2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Genetic examination of the PLXNA2 gene in Japanese and Chinese people with schizophrenia.
PMID: 18065206
Schizophr Res Β· 2008
1.00
2
Failure to confirm an association between the PLXNA2 gene and schizophrenia in a Japanese population.
PMID: 17346868
Prog Neuropsychopharmacol Biol Psychiatry Β· 2007
0.90
3
A susceptibility gene signature for ERBB2-driven mammary tumour development and metastasis in collaborative cross mice.
PMID: 39067134
EBioMedicine Β· 2024
0.80
4
PMID: 30271602
Biomed Rep Β· 2018
0.70
5
PLXNA2 and LRRC40 as candidate genes in autism spectrum disorder.
PMID: 33749153
Autism Res Β· 2021
0.60