PLXNB2

protein-coding

plexin B2, the group of Plexins|IPT domain containing

Gene summary

Members of the B class of plexins, such as PLXNB2 are transmembrane receptors that participate in axon guidance and cell migration in response to semaphorins (Perrot et al. (2002) [PubMed 12183458]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_012401.4

Inheritance

ClinVar variants

P:8U:320B:67

Top phenotype

syndromic disease

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr22:50,274,979-50,307,646

External References & Databases

Ensembl (ENSG00000196576)

Transcript & Mutation Effects

hg38 • Region Span ~32.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

syndromic diseaseSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0002254

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PLXNB2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 289

not providedTotal: 75

See casesTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012401.4. 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	1 clinvar		4 clinvar	39 clinvar	5 clinvar	49
missense	3 clinvar		292 clinvar	22 clinvar	1 clinvar	318
nonsense	1 clinvar		4 clinvar			5
start loss						0
frameshift	2 clinvar		5 clinvar			7
splice donor/acceptor (+/-2bp)	1 clinvar		15 clinvar			16
Total	8	0	320	61	6	395

Highest pathogenic variant AF is 0.000004377944

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 88 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012401.4	RefSeq	NP_036533.2	35	MANE Select
ENST00000359337.9	Ensembl	ENSP00000352288.4	35	MANE Select
NM_001376864.1	RefSeq	NP_001363793.1	35	Standard
NM_001376865.1	RefSeq	NP_001363794.1	36	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
plxnb2a	Danio rerio	Structure: axial vasculature Quality: has fewer parts of type abnormal

Gene / Model

Organism

Observed Phenotype

plxnb2a

Danio rerio

Structure: axial vasculature

Quality: has fewer parts of type

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Axon guidance - Homo sapiens (human)

Biological Process

neural tube closure
regulation of protein phosphorylation
homophilic cell adhesion via plasma membrane adhesion molecules
negative regulation of cell adhesion
neuroblast proliferation

Molecular Function

protein binding
semaphorin receptor activity

Cellular Component

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

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000449103
Coding exons: 35
Length: 32649
Individuals with no LoFs: 124857
Homozygous LoFs: 0
Heterozygous LoFs: 28
Defined: 124885
p: 0.000112

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.36	896	1.23e+3	0.730	0.0000882	11907
Missense (PolyPhen)		276	546.14	0.50537		5638
Synonymous	-3.17	675	578	1.17	0.0000475	3710
Loss of Function	7.10	17	89.5	0.190	0.00000470	944

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.000059	0.000056	rare
Finnish	0.00029	0.00028	rare
European (Non-Finnish)	0.000036	0.000035	rare
South Asian	0.00016	0.00016	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cell surface receptor for SEMA4C, SEMA4D and SEMA4G that plays an important role in cell-cell signaling. Binding to class 4 semaphorins promotes downstream activation of RHOA and phosphorylation of ERBB2 at 'Tyr-1248'. Required for normal differentiation and migration of neuronal cells during brain corticogenesis and for normal embryonic brain development. Regulates the migration of cerebellar granule cells in the developing brain. Plays a role in RHOA activation and subsequent changes of the actin cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration. May modulate the activity of RAC1 and CDC42. Down-regulates macrophage migration in wound- healing assays (in vitro) (By similarity). {ECO:0000250, ECO:0000269|PubMed:12183458, ECO:0000269|PubMed:12533544, ECO:0000269|PubMed:15184888}.;

Recessive Scores

pRec: 0.124

Intolerance Scores

LoFtool: 0.335
RVIS EVS: -3.3
RVIS percentile EVS: 0.42

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.665

Gene Damage Prediction

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