PLXNB3

protein-coding

plexin B3, the group of Plexins|IPT domain containing

Gene summary

The protein encoded by this gene is a member of the plexin family. It functions as a receptor for semaphorin 5A, and plays a role in axon guidance, invasive growth and cell migration. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

Previous symbols:

PLXN6

MANE transcript

NM_005393.3

Inheritance

—

ClinVar variants

U:378B:79

Top phenotype

PLXNB3-related disorder

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chrX:153,764,196-153,779,346

External References & Databases

Ensembl (ENSG00000198753)

Transcript & Mutation Effects

hg38 • Region Span ~15.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PLXNB3 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 333

not providedTotal: 62

PLXNB3-related disorderTotal: 15

PLXNB3-related Congenital heart disease with neurodevelopmental disabilitiesTotal: 2

Neurodevelopmental disorderTotal: 1

Autism spectrum disorderTotal: 1

PLXNB3-related Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005393.3. 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			21 clinvar	14 clinvar	11 clinvar	46
missense			338 clinvar	47 clinvar	6 clinvar	391
nonsense			7 clinvar			7
start loss				1 clinvar		1
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	0	0	378	62	17	457

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005393.3	RefSeq	NP_005384.2	35	MANE Select
ENST00000361971.10	Ensembl	ENSP00000355378.5	35	MANE Select
NM_001163257.2	RefSeq	NP_001156729.1	35	Standard
ENST00000411613.5	Ensembl	ENSP00000391650.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Axon guidance - Homo sapiens (human)
Developmental Biology
Other semaphorin interactions
Semaphorin interactions
Axon guidance

Biological Process

positive regulation of endothelial cell proliferation
homophilic cell adhesion via plasma membrane adhesion molecules
negative regulation of cell adhesion
regulation of cell shape
negative regulation of lamellipodium assembly

Molecular Function

protein binding
semaphorin receptor activity
protein domain specific binding
Rho GDP-dissociation inhibitor binding
cell-cell adhesion mediator activity

Cellular Component

semaphorin receptor complex
plasma membrane
integral component of plasma membrane
cell surface

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000538966
Coding exons: 35
Length: 15151
Individuals with no LoFs: 125586
Homozygous LoFs: 14
Heterozygous LoFs: 16
Defined: 125616
p: 0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.227	805	823	0.978	0.0000752	12294
Missense (PolyPhen)		197	296.35	0.66474		4869
Synonymous	-4.49	496	384	1.29	0.0000375	4166
Loss of Function	5.30	13	55.7	0.234	0.00000385	921

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000079	0.000062	rare
Latino/Admixed American	0.000037	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00034	0.00023	rare
European (Non-Finnish)	0.00021	0.00014	rare
South Asian	0.00041	0.00023	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for SEMA5A that plays a role in axon guidance, invasive growth and cell migration. Stimulates neurite outgrowth and mediates Ca(2+)/Mg(2+)-dependent cell aggregation. In glioma cells, SEMA5A stimulation of PLXNB3 results in the disassembly of F-actin stress fibers, disruption of focal adhesions and cellular collapse as well as inhibition of cell migration and invasion through ARHGDIA-mediated inactivation of RAC1. {ECO:0000269|PubMed:15218527, ECO:0000269|PubMed:20696765, ECO:0000269|PubMed:21706053}.;

Recessive Scores

pRec: 0.127

Intolerance Scores

LoFtool: 0.441
RVIS EVS: -0.71
RVIS percentile EVS: 14.72

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.878

Gene Damage Prediction

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