PLXND1

plexin D1, the group of Plexins|IPT domain containing

Basic information

Region (hg38): 3:129555213-129606676

Links

ENSG00000004399 ∙ NCBI:23129 ∙ OMIM:604282 ∙ HGNC:9107 ∙ Uniprot:Q9Y4D7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Mobius syndrome (Supportive), mode of inheritance: AD
• persistent truncus arteriosus (Supportive), mode of inheritance: AR
• congenital heart defects, multiple types, 9 (Limited), mode of inheritance: AR
• congenital heart defects, multiple types, 9 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital heart defects, multiple types, 9	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular	24254849; 34791216; 35396997

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLXND1 gene.

• not provided (103 variants)
• Inborn genetic diseases (85 variants)
• not specified (2 variants)
• Congenital heart defects, multiple types, 9 (1 variants)
• Oromandibular-limb hypogenesis spectrum (1 variants)
• Kleine-Levin syndrome (1 variants)
• PLXND1-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLXND1 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				42	10	52
missense			92	13	14	119
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				11	3	14
non coding				3	4	7
Total	0	0	92	58	28

Variants in PLXND1

This is a list of pathogenic ClinVar variants found in the PLXND1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-129556323-T-C		not specified	Uncertain significance (Mar 25, 2022)
3-129556363-C-T		PLXND1-related disorder	Benign (Jun 06, 2019)
3-129556419-C-T			Likely benign (Dec 31, 2019)
3-129556632-C-T		PLXND1-related disorder	Likely benign (Jul 15, 2019)
3-129556637-C-T		not specified	Uncertain significance (Jun 11, 2021)
3-129556638-G-A		PLXND1-related disorder	Likely benign (Jun 11, 2019)
3-129556649-T-C		Kleine-Levin syndrome	Uncertain significance (Oct 19, 2017)
3-129557119-C-A		not specified	Uncertain significance (Jul 12, 2022)
3-129557121-C-T		not specified	Uncertain significance (May 23, 2023)
3-129557172-T-C		not specified	Uncertain significance (Jun 29, 2023)
3-129557179-C-T			Likely benign (Dec 31, 2019)
3-129557229-C-CAGAG		PLXND1-related disorder	Likely benign (Jul 08, 2019)
3-129558550-T-A		Congenital heart defects, multiple types, 9	Pathogenic (Mar 22, 2023)
3-129558550-T-C		not specified	Uncertain significance (Feb 24, 2022)
3-129559661-T-G			Likely benign (Aug 20, 2018)
3-129560322-G-A			Likely benign (May 15, 2018)
3-129560323-G-A			Likely benign (Mar 30, 2018)
3-129560382-T-C		not specified	Uncertain significance (May 04, 2022)
3-129560419-C-G		not specified	Uncertain significance (Jul 20, 2021)
3-129560420-G-A			Likely benign (Mar 30, 2018)
3-129560431-G-T		PLXND1-related disorder	Benign (Dec 31, 2019)
3-129560439-G-C			Likely benign (Jul 05, 2018)
3-129560727-T-C		PLXND1-related disorder	Benign (Jun 06, 2019)
3-129561636-C-T			Likely benign (Dec 26, 2018)
3-129561670-T-C		not specified	Uncertain significance (Feb 07, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLXND1	protein_coding	protein_coding	ENST00000324093	36	51644

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	4.40e-9	125727	0	21	125748	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.35	821	1.14e+3	0.721	0.0000733	12310
Missense in Polyphen		254	473.98	0.53588		5136
Synonymous	0.119	497	500	0.993	0.0000352	3922
Loss of Function	7.78	7	83.9	0.0835	0.00000415	920

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000889	0.0000889
Ashkenazi Jewish	0.000398	0.000397
East Asian	0.000111	0.000109
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.0000710	0.0000703
Middle Eastern	0.000111	0.000109
South Asian	0.0000988	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cell surface receptor for SEMA4A and for class 3 semaphorins, such as SEMA3A, SEMA3C and SEMA3E. Plays an important role in cell-cell signaling, and in regulating the migration of a wide spectrum of cell types. Regulates the migration of thymocytes in the medulla. Regulates endothelial cell migration. Plays an important role in ensuring the specificity of synapse formation. Required for normal development of the heart and vasculature (By similarity). Mediates anti-angiogenic signaling in response to SEMA3E. {ECO:0000250, ECO:0000269|PubMed:20385769}.
• Pathway: Angiogenesis overview;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;Developmental Biology;Signal Transduction;NOTCH3 Intracellular Domain Regulates Transcription;Signaling by NOTCH3;Signaling by NOTCH;Other semaphorin interactions;Semaphorin interactions;Plexin-D1 Signaling;Axon guidance (Consensus)

Recessive Scores

• pRec: 0.126

Intolerance Scores

• loftool: 0.160
• rvis_EVS: -1.31
• rvis_percentile_EVS: 4.88

Haploinsufficiency Scores

• pHI: 0.156
• hipred: Y
• hipred_score: 0.682
• ghis: 0.595

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.167

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Plxnd1
• Phenotype: hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; embryo phenotype; renal/urinary system phenotype; skeleton phenotype; immune system phenotype; vision/eye phenotype; digestive/alimentary phenotype; muscle 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); limbs/digits/tail phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype

Zebrafish Information Network

• Gene name: plxnd1
• Affected structure: fat cell
• Phenotype tag: abnormal
• Phenotype quality: increased process quality

Gene ontology

• Biological process: angiogenesis;branching involved in blood vessel morphogenesis;outflow tract morphogenesis;cardiac septum development;negative regulation of cell adhesion;positive regulation of transcription of Notch receptor target;synapse assembly;regulation of cell shape;regulation of cell migration;positive regulation of protein binding;aorta development;regulation of GTPase activity;endothelial cell migration;regulation of angiogenesis;positive regulation of axonogenesis;dichotomous subdivision of terminal units involved in salivary gland branching;coronary vasculature development;semaphorin-plexin signaling pathway;semaphorin-plexin signaling pathway involved in axon guidance
• Cellular component: semaphorin receptor complex;plasma membrane;integral component of plasma membrane;lamellipodium;lamellipodium membrane
• Molecular function: protein binding;semaphorin receptor activity;protein domain specific binding