PLXNA3

plexin A3, the group of Plexins|IPT domain containing

Basic information

Region (hg38): X:154458280-154477779

Previous symbols: [ "PLXN4" ]

Links

ENSG00000130827 ∙ NCBI:55558 ∙ OMIM:300022 ∙ HGNC:9101 ∙ Uniprot:P51805 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLXNA3 gene.

• not provided (86 variants)
• Inborn genetic diseases (78 variants)
• PLXNA3-related condition (60 variants)
• Hypogonadotropic hypogonadism (4 variants)
• not specified (4 variants)
• Short stature (2 variants)
• Autism (1 variants)
• Childhood-onset schizophrenia (1 variants)
• PLXNA3-associated seizure disorder (1 variants)
• Neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLXNA3 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	27	16	46
missense			122	10	13	145
nonsense			2			2
start loss						0
frameshift						0
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region			6	5	2	13
non coding			1		1	2
Total	0	0	130	37	30

Variants in PLXNA3

This is a list of pathogenic ClinVar variants found in the PLXNA3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-154460179-C-T		PLXNA3-related disorder	Likely benign (Apr 06, 2022)
X-154460180-G-A		PLXNA3-related disorder	Likely benign (May 25, 2022)
X-154460195-C-G		PLXNA3-related disorder	Benign (Sep 25, 2019)
X-154460201-C-T		PLXNA3-related disorder	Likely benign (Mar 13, 2019)
X-154460222-C-T		PLXNA3-related disorder	Likely benign (Jun 27, 2022)
X-154460223-G-A		not specified	Uncertain significance (Apr 20, 2023)
X-154460224-T-TG		PLXNA3-related disorder	Uncertain significance (Jan 24, 2024)
X-154460225-G-C		PLXNA3-related disorder	Likely benign (Sep 10, 2021)
X-154460238-G-A		PLXNA3-related disorder • not specified	Uncertain significance (May 01, 2023)
X-154460239-G-A		Short stature • not specified • PLXNA3-related disorder	Conflicting classifications of pathogenicity (Dec 07, 2023)
X-154460254-G-A		PLXNA3-related disorder	Benign (Dec 31, 2019)
X-154460261-C-T		PLXNA3-related disorder	Likely benign (Feb 21, 2019)
X-154460262-G-A		PLXNA3-related disorder • not specified	Conflicting classifications of pathogenicity (Oct 26, 2022)
X-154460278-C-T		not specified	Uncertain significance (Dec 06, 2022)
X-154460302-G-A		PLXNA3-related disorder	Uncertain significance (Feb 12, 2024)
X-154460321-C-T		PLXNA3-related disorder	Likely benign (Mar 08, 2023)
X-154460327-C-T		PLXNA3-related disorder	Likely benign (May 01, 2022)
X-154460349-C-G		PLXNA3-related disorder	Uncertain significance (Jan 31, 2024)
X-154460355-C-T		PLXNA3-related disorder • not specified	Conflicting classifications of pathogenicity (Jun 28, 2022)
X-154460370-C-G		PLXNA3-related disorder	Likely benign (Jun 03, 2021)
X-154460373-C-T		PLXNA3-related disorder	Likely benign (Aug 16, 2021)
X-154460379-C-T			Likely benign (Dec 01, 2022)
X-154460393-C-T		PLXNA3-related disorder	Likely benign (Nov 27, 2019)
X-154460396-C-T		PLXNA3-related disorder	Likely benign (Aug 25, 2021)
X-154460397-G-A		Autism;Microtia	Uncertain significance (Aug 22, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLXNA3	protein_coding	protein_coding	ENST00000369682	32	15369

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0549	0.945	125706	15	13	125734	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.676	853	910	0.937	0.0000874	12137
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000269	0.000232
Ashkenazi Jewish	0.000134	0.0000992
East Asian	0.0000740	0.0000544
Finnish	0.0000628	0.0000462
European (Non-Finnish)	0.000225	0.000149
Middle Eastern	0.0000740	0.0000544
South Asian	0.000157	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

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

Recessive Scores

• pRec: 0.141

Intolerance Scores

• loftool: 0.284
• rvis_EVS: -2.49
• rvis_percentile_EVS: 0.94

Haploinsufficiency Scores

• pHI: 0.134
• hipred: Y
• hipred_score: 0.659
• ghis: 0.556

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.239

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Plxna3
• Phenotype: cellular 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)

Zebrafish Information Network

• Gene name: plxna3
• Affected structure: primary motor neuron
• Phenotype tag: abnormal
• Phenotype quality: spatial pattern

Gene ontology

• Biological process: negative regulation of cell adhesion;multicellular organism development;regulation of cell shape;facial nerve structural organization;trigeminal nerve structural organization;hippocampus development;branchiomotor neuron axon guidance;pyramidal neuron development;regulation of cell migration;regulation of GTPase activity;negative regulation of axon extension involved in axon guidance;positive regulation of axonogenesis;negative chemotaxis;positive regulation of cytoskeleton organization;semaphorin-plexin signaling pathway;semaphorin-plexin signaling pathway involved in axon guidance;neuron projection extension
• Cellular component: semaphorin receptor complex;nucleus;plasma membrane;integral component of plasma membrane;membrane;cell junction;intracellular membrane-bounded organelle
• Molecular function: transmembrane signaling receptor activity;protein binding;semaphorin receptor activity