PLXNA4

protein-coding

plexin A4, the group of Plexins|IPT domain containing

Gene summary

Predicted to enable semaphorin receptor activity. Predicted to be involved in nervous system development; regulation of cell migration; and semaphorin-plexin signaling pathway. Predicted to act upstream of or within nervous system development; regulation of axon extension involved in axon guidance; and regulation of negative chemotaxis. Predicted to be located in membrane. Predicted to be part of semaphorin receptor complex. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

PLXNA4A
PLXNA4B

MANE transcript

NM_020911.2

Inheritance

—

ClinVar variants

U:520B:325

Top phenotype

PLXNA4-related disorder

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr7:132,123,340-132,648,688

External References & Databases

Ensembl (ENSG00000221866)

Transcript & Mutation Effects

hg38 • Region Span ~525.3 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 PLXNA4 variants in ClinVar

3 Conditions Cataloged

PLXNA4-related disorderTotal: 888

not specifiedTotal: 99

not providedTotal: 31

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020911.2. 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	295 clinvar	8 clinvar	313
missense			487 clinvar	16 clinvar	6 clinvar	509
nonsense			6 clinvar			6
start loss			1 clinvar			1
frameshift			6 clinvar			6
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	0	0	520	311	14	845

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020911.2	RefSeq	NP_065962.1	31	MANE Select
ENST00000321063.9	Ensembl	ENSP00000323194.4	31	MANE Select
NM_001105543.2	RefSeq	NP_001099013.1	3	Standard
NM_001393897.1	RefSeq	NP_001380826.1	31	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Axon guidance - Homo sapiens (human)
Developmental Biology
SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion
Sema3A PAK dependent Axon repulsion
Other semaphorin interactions

Biological Process

negative regulation of cell adhesion
regulation of cell shape
facial nerve structural organization
glossopharyngeal nerve morphogenesis
trigeminal nerve structural organization

Molecular Function

semaphorin receptor activity

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: ENST00000359827
Coding exons: 31
Length: 525357
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 19
Defined: 125748
p: 0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.80	788	1.15e+3	0.685	0.0000722	12422
Missense (PolyPhen)		291	562.39	0.51744		6094
Synonymous	-2.89	568	487	1.17	0.0000331	3723
Loss of Function	7.32	12	84.8	0.142	0.00000439	983

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.00016	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Coreceptor for SEMA3A. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance 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 (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.191
RVIS EVS: -0.19
RVIS percentile EVS: 39.21

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.132

Gene Damage Prediction

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