PLXNA2

protein-coding

plexin A2, the group of Plexins|IPT domain containing

Gene summary

This gene encodes a member of the plexin-A family of semaphorin co-receptors. Semaphorins are a large family of secreted or membrane-bound proteins that mediate repulsive effects on axon pathfinding during nervous system development. A subset of semaphorins are recognized by plexin-A/neuropilin transmembrane receptor complexes, triggering a cellular signal transduction cascade that leads to axon repulsion. This plexin-A family member is thought to transduce signals from semaphorin-3A and -3C. [provided by RefSeq, Jul 2008]

Previous symbols:

PLXN2

MANE transcript

NM_025179.4

Inheritance

AD, AR

ClinVar variants

P:2U:713B:368

Top phenotype

PLXNA2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr1:208,022,242-208,244,384

External References & Databases

Ensembl (ENSG00000076356)

Transcript & Mutation Effects

hg38 • Region Span ~222.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

complex neurodevelopmental disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: PanelApp Australia

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PLXNA2 variants in ClinVar

5 Conditions Cataloged

PLXNA2-related disorderTotal: 860

not providedTotal: 557

not specifiedTotal: 237

AutismTotal: 2

atypical cerebral palsyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_025179.4. 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			10 clinvar	325 clinvar	21 clinvar	356
missense		1 clinvar	678 clinvar	15 clinvar	7 clinvar	701
nonsense			11 clinvar			11
start loss						0
frameshift			8 clinvar			8
splice donor/acceptor (+/-2bp)		1 clinvar	6 clinvar			7
Total	0	2	713	340	28	1083

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_025179.4	RefSeq	NP_079455.3	31	MANE Select
ENST00000367033.4	Ensembl	ENSP00000356000.3	31	MANE Select
ENST00000866340.1	Ensembl	ENSP00000536399.1	31	Standard
ENST00000866340.2	Ensembl	ENSP00000536399.1	31	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
plxna2	Danio rerio	Structure: optic cup Quality: decreased occurrence abnormal

Gene / Model

Organism

Observed Phenotype

plxna2

Danio rerio

Structure: optic cup

Quality: decreased occurrence

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Axon guidance - Homo sapiens (human)
Spinal Cord Injury
Ectoderm Differentiation
Developmental Biology
SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion

Biological Process

somitogenesis
negative regulation of cell adhesion
regulation of cell shape
neural tube development
cerebellar granule cell precursor tangential migration

Molecular Function

protein binding
semaphorin receptor activity
identical protein binding

Cellular Component

semaphorin receptor complex
plasma membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367033
Coding exons: 31
Length: 222079
Individuals with no LoFs: 125702
Homozygous LoFs: 0
Heterozygous LoFs: 46
Defined: 125748
p: 0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.93	889	1.17e+3	0.759	0.0000756	12378
Missense (PolyPhen)		389	594.17	0.6547		6245
Synonymous	-0.431	514	502	1.02	0.0000340	3853
Loss of Function	5.94	28	88.3	0.317	0.00000461	955

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00016	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00024	0.00022	rare
South Asian	0.00017	0.00016	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Coreceptor for SEMA3A and SEMA6A. Necessary for signaling by SEMA6A and 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, ECO:0000269|PubMed:10520995}.;

Recessive Scores

pRec: 0.154

Intolerance Scores

LoFtool: 0.424
RVIS EVS: -1.48
RVIS percentile EVS: 3.64

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.422

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High