GeneBe

PLXND1

protein-coding

plexin D1, the group of Plexins|IPT domain containing

Gene summary

Enables protein domain specific binding activity. Predicted to be involved in several processes, including positive regulation of axonogenesis; semaphorin-plexin signaling pathway; and synapse assembly. Predicted to act upstream of or within circulatory system development; dichotomous subdivision of terminal units involved in salivary gland branching; and kidney development. Located in lamellipodium. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_015103.3

Inheritance

AD, AR

ClinVar variants

P:6U:325B:114

Top phenotype

Congenital heart defects, multiple types, 9

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr3:129,555,214-129,606,676

External References & Databases

Ensembl (ENSG00000004399)NCBI Gene (23129)OMIM (604282)HGNC:9107GenCCUniProt (Q9Y4D7)AlphaFoldClinVar (PLXND1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~51.5 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Moebius syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008006

Submitter: Orphanet

Moebius syndromeLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0008006

Submitter: G2P

persistent truncus arteriosusSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018072

Submitter: Orphanet

congenital heart defects, multiple types, 9STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859532

Submitter: G2P

congenital heart defects, multiple types, 9STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859532

Submitter: Labcorp Genetics (formerly Invitae)

congenital heart defects, multiple types, 9STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859532

Submitter: PanelApp Australia

congenital heart defects, multiple types, 9LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0859532

Submitter: Ambry Genetics

Moebius syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008006

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Congenital heart defects, multiple types, 9AR

Manifestation: Cardiovascular

Intervention: Cardiovascular

Rationale: The condition can involve congenital cardiac anomalies, and awareness may allow early management

Refs: 24254849; 34791216; 35396997Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PLXND1 variants in ClinVar

6 Conditions Cataloged
not specifiedTotal: 330
not providedTotal: 127
PLXND1-related disorderTotal: 43
Congenital heart defects, multiple types, 9Total: 16
Kleine-Levin syndromeTotal: 2
Oromandibular-limb hypogenesis spectrumTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015103.3. 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.

EffectPLPVUSLBBSum
synonymous
6
clinvar
78
clinvar
7
clinvar
 91
missense
4
clinvar
301
clinvar
21
clinvar
8
clinvar
 334
nonsense
2
clinvar
 2
start loss
0
frameshift
1
clinvar
1
clinvar
4
clinvar
 6
splice donor/acceptor (+/-2bp)
12
clinvar
 12
Total513259915445

Highest pathogenic variant AF is 0.0000025611835

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_015103.3RefSeqNP_055918.336MANE Select
ENST00000324093.9EnsemblENSP00000317128.436MANE Select
ENST00000504689.1EnsemblENSP00000426162.13Standard
ENST00000505237.2EnsemblENSP00000426241.24Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
plxnd1Danio rerio

Structure: fat cell

Quality: increased process quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Angiogenesis overview
  • miR-targeted genes in leukocytes - TarBase
  • miR-targeted genes in lymphocytes - TarBase
  • Developmental Biology
  • Signal Transduction

Biological Process

  • angiogenesis
  • branching involved in blood vessel morphogenesis
  • outflow tract morphogenesis
  • cardiac septum development
  • negative regulation of cell adhesion

Molecular Function

  • protein binding
  • semaphorin receptor activity
  • protein domain specific binding

Cellular Component

  • semaphorin receptor complex
  • plasma membrane
  • integral component of plasma membrane
  • lamellipodium
  • lamellipodium membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000324093
Coding exons
36
Length
51644
Individuals with no LoFs
125727
Homozygous LoFs
0
Heterozygous LoFs
21
Defined
125748
p
0.0000835
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense3.358211.14e+30.7210.000073312310
Missense (PolyPhen)254473.980.535885136
Synonymous0.1194975000.9930.00003523922
Loss of Function7.78783.90.08350.00000415920

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000890.000087rare
Ashkenazi Jewish0.000400.00040rare
East Asian0.000110.00011rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.0000710.000070rare
South Asian0.0000990.000098rare
Other00.0absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec
0.126

Intolerance Scores

LoFtool
0.160
RVIS EVS
-1.31
RVIS percentile EVS
4.88

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.167

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium
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