PLXNA1

plexin A1, the group of Plexins|IPT domain containing

Basic information

Region (hg38): 3:126982692-127037389

Previous symbols: [ "PLXN1" ]

Links

ENSG00000114554 ∙ NCBI:5361 ∙ OMIM:601055 ∙ HGNC:9099 ∙ Uniprot:Q9UIW2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Dworschak-Punetha neurodevelopmental syndrome (Limited), mode of inheritance: AR
• Dworschak-Punetha neurodevelopmental syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dworschak-Punetha neurodevelopmental syndrome	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Dermatologic; Neurologic; Ophthalmologic	34054129

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLXNA1 gene.

• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLXNA1 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			4	164	25	193
missense		2	227	20	1	250
nonsense	1					1
start loss						0
frameshift	1	1	1			3
inframe indel			2			2
splice donor/acceptor (+/-2bp)		1				1
splice region			4	21	4	29
non coding			1	28	11	40
Total	2	4	235	212	37

Highest pathogenic variant AF is 0.00000657

Variants in PLXNA1

This is a list of pathogenic ClinVar variants found in the PLXNA1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-126988598-C-A		Seizure;Intellectual disability	Uncertain significance (Feb 21, 2020)
3-126988598-C-T		PLXNA1-related disorder	Likely benign (Dec 20, 2021)
3-126988607-C-T			Benign (Dec 24, 2022)
3-126988608-G-A		PLXNA1-related disorder	Likely benign (Dec 09, 2022)
3-126988608-G-T		PLXNA1-related disorder	Likely benign (May 01, 2023)
3-126988609-C-T		PLXNA1-related disorder	Likely benign (Jul 17, 2023)
3-126988610-G-A		not specified	Uncertain significance (Feb 15, 2023)
3-126988613-G-T		PLXNA1-related disorder	Benign/Likely benign (Dec 30, 2022)
3-126988626-C-T		PLXNA1-related disorder	Likely benign (May 22, 2023)
3-126988642-T-C		PLXNA1-related disorder	Likely benign (Jul 03, 2023)
3-126988658-C-T		PLXNA1-related disorder	Uncertain significance (Nov 06, 2023)
3-126988659-G-A		PLXNA1-related disorder	Likely benign (Aug 28, 2019)
3-126988679-G-C		PLXNA1-related disorder	Uncertain significance (Jul 20, 2023)
3-126988691-C-T		not specified	Uncertain significance (May 02, 2024)
3-126988696-G-A		PLXNA1-related disorder	Uncertain significance (Feb 05, 2024)
3-126988708-C-A		not specified	Uncertain significance (Jul 29, 2023)
3-126988708-C-T		PLXNA1-related disorder	Uncertain significance (Nov 03, 2022)
3-126988711-C-G		PLXNA1-related disorder	Likely benign (May 23, 2019)
3-126988712-C-A		PLXNA1-related disorder	Uncertain significance (May 02, 2023)
3-126988712-C-G			Likely benign (Oct 17, 2022)
3-126988712-C-T		PLXNA1-related disorder	Uncertain significance (Jan 29, 2024)
3-126988713-C-T		PLXNA1-related disorder	Likely benign (Sep 08, 2022)
3-126988717-C-T		PLXNA1-related disorder	Uncertain significance (Jun 16, 2023)
3-126988727-C-T		PLXNA1-related disorder	Uncertain significance (Aug 10, 2023)
3-126988728-G-A			Likely benign (Nov 17, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLXNA1	protein_coding	protein_coding	ENST00000393409	31	48799

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000491	125719	0	29	125748	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.45	928	1.27e+3	0.728	0.0000933	12203
Missense in Polyphen		344	606.06	0.5676		6042
Synonymous	-1.34	617	576	1.07	0.0000457	3956
Loss of Function	7.21	15	88.1	0.170	0.00000468	917

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000305	0.000304
Ashkenazi Jewish	0.000201	0.000198
East Asian	0.0000545	0.0000544
Finnish	0.0000957	0.0000924
European (Non-Finnish)	0.000145	0.000141
Middle Eastern	0.0000545	0.0000544
South Asian	0.0000655	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Coreceptor for SEMA3A, SEMA3C, SEMA3F and SEMA6D. Necessary for signaling by 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}.
• Pathway: Axon guidance - Homo sapiens (human);Developmental Biology;SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion;Sema3A PAK dependent Axon repulsion;Other semaphorin interactions;Semaphorin interactions;Axon guidance;CRMPs in Sema3A signaling (Consensus)

Recessive Scores

• pRec: 0.178

Intolerance Scores

• loftool: 0.361
• rvis_EVS: -4.39
• rvis_percentile_EVS: 0.09

Haploinsufficiency Scores

• pHI: 0.0675
• hipred: Y
• hipred_score: 0.685
• ghis: 0.621

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.800

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Plxna1
• Phenotype: hematopoietic system 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); skeleton phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: plxna1b
• Affected structure: epithelial cell
• Phenotype tag: abnormal
• Phenotype quality: protruding out of

Gene ontology

• Biological process: negative regulation of cell adhesion;multicellular organism development;regulation of cell shape;regulation of smooth muscle cell migration;regulation of cell migration;regulation of GTPase activity;positive regulation of axonogenesis;dichotomous subdivision of terminal units involved in salivary gland branching;semaphorin-plexin signaling pathway involved in axon guidance;neuron projection extension
• Cellular component: semaphorin receptor complex;plasma membrane;integral component of plasma membrane;extracellular exosome
• Molecular function: semaphorin receptor activity;signaling receptor activity