PLXNA1

plexin A1, the group of Plexins|IPT domain containing

Basic information

Region (hg38): 3:126982693-127037389

Previous symbols: [ "PLXN1" ]

Links

ENSG00000114554 ∙ NCBI:5361 ∙ OMIM:601055 ∙ HGNC:9099 ∙ Uniprot:Q9UIW2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Dworschak-Punetha neurodevelopmental syndrome (Limited), mode of inheritance: AR
• Dworschak-Punetha neurodevelopmental syndrome (Strong), mode of inheritance: AR
• Dworschak-Punetha neurodevelopmental syndrome (Limited), mode of inheritance: AR
• complex neurodevelopmental disorder (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dworschak-Punetha neurodevelopmental syndrome	AR	General	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	Craniofacial; Dermatologic; Neurologic; Ophthalmologic	34054129

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLXNA1 gene.

• PLXNA1-related_disorder (638 variants)
• not_specified (251 variants)
• not_provided (247 variants)
• Dworschak-Punetha_neurodevelopmental_syndrome (27 variants)
• Neurodevelopmental_disorder (12 variants)
• Parkinson_disease (1 variants)
• PLXNA1-related_Neurodevelopmental_disorder_with_variable_cerebral_and_eye_anomalies (1 variants)
• Parkinsonian_disorder (1 variants)
• PLXNA1-associated_encephalopathy (1 variants)
• See_cases (1 variants)
• HP:0000750%3B_HP:0001263%3B_HP:0001513 (1 variants)
• PLXNA1-related_neurodevelopmental_disorder (1 variants)
• Vascular_parkinsonism (1 variants)
• Neurodevelopmental_disorder_with_variable_cerebral_and_eye_anomalies (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLXNA1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000032242.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			10	302	21	333
missense		7	465	28	4	504
nonsense	1	2	3			6
start loss						0
frameshift	1	3	1			5
splice donor/acceptor (+/-2bp)		2	6			8
Total	2	14	485	330	25

Highest pathogenic variant AF is 0.000032230473

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLXNA1	protein_coding	protein_coding	ENST00000393409	31	48799

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000491	125719	0	29	125748	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.45	928	1.27e+3	0.728	0.0000933	12203
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000305	0.000304
Ashkenazi Jewish	0.000201	0.000198
East Asian	0.0000545	0.0000544
Finnish	0.0000957	0.0000924
European (Non-Finnish)	0.000145	0.000141
Middle Eastern	0.0000545	0.0000544
South Asian	0.0000655	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: Axon guidance - Homo sapiens (human);Developmental Biology;SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion;Sema3A PAK dependent Axon repulsion;Other semaphorin interactions;Semaphorin interactions;Axon guidance;CRMPs in Sema3A signaling (Consensus)

Recessive Scores

• pRec: 0.178

Intolerance Scores

• loftool: 0.361
• rvis_EVS: -4.39
• rvis_percentile_EVS: 0.09

Haploinsufficiency Scores

• pHI: 0.0675
• hipred: Y
• hipred_score: 0.685
• ghis: 0.621

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.800

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Plxna1
• Phenotype: hematopoietic system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: plxna1b
• Affected structure: epithelial cell
• Phenotype tag: abnormal
• Phenotype quality: protruding out of

Gene ontology

• Biological process: negative regulation of cell adhesion;multicellular organism development;regulation of cell shape;regulation of smooth muscle cell migration;regulation of cell migration;regulation of GTPase activity;positive regulation of axonogenesis;dichotomous subdivision of terminal units involved in salivary gland branching;semaphorin-plexin signaling pathway involved in axon guidance;neuron projection extension
• Cellular component: semaphorin receptor complex;plasma membrane;integral component of plasma membrane;extracellular exosome
• Molecular function: semaphorin receptor activity;signaling receptor activity