PLXND1

plexin D1, the group of Plexins|IPT domain containing

Basic information

Region (hg38): 3:129555214-129606676

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
Mobius syndrome (Limited), mode of inheritance: AD

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_specified (255 variants)
not_provided (112 variants)
PLXND1-related_disorder (42 variants)
Congenital_heart_defects,_multiple_types,_9 (11 variants)
Kleine-Levin_syndrome (2 variants)
Oromandibular-limb_hypogenesis_spectrum (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. These statistics are base on transcript: NM_000015103.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				54 clinvar	8 clinvar	62
missense	4 clinvar		260 clinvar	17 clinvar	11 clinvar	292
nonsense			1 clinvar			1
start loss						0
frameshift	1 clinvar		2 clinvar			3
splice donor/acceptor (+/-2bp)						0
Total	5	0	263	71	19

Highest pathogenic variant AF is 0.0000025611835

Loading clinvar variants...

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