Congenital heart defects, multiple types, 9

Summary

Congenital heart defects, multiple types, 9 (MONDO:0859532) is a disease caused by PLXND1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: PLXND1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 13

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital heart defects, multiple types, 9
Mondo ID	MONDO:0859532
OMIM	620294
UMLS	C5830367
MedGen	1841003
Is cancer (heuristic)	no

Data availability: 13 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › congenital heart disease › congenital heart defects, multiple types › congenital heart defects, multiple types, 9

Related subtypes (7): congenital heart defects, multiple types, 6, congenital heart defects, multiple types, 3, congenital heart defects, multiple types, 2, congenital heart defects, multiple types, 4, congenital heart defects, multiple types, 5, MYH-6 related congenital heart defects, congenital heart defects, multiple types, 8, with or without heterotaxy

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

13 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 5 pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2445604	NM_015103.3(PLXND1):c.5323A>T (p.Ile1775Phe)	LOC112872301	Pathogenic	no assertion criteria provided
2445603	NM_015103.3(PLXND1):c.3895C>T (p.Arg1299Cys)	PLXND1	Pathogenic	no assertion criteria provided
2445605	NM_015103.3(PLXND1):c.652A>T (p.Ser218Cys)	PLXND1	Pathogenic	no assertion criteria provided
2445606	NM_015103.3(PLXND1):c.2733C>G (p.Ile911Met)	PLXND1	Pathogenic	no assertion criteria provided
2445607	NM_015103.3(PLXND1):c.880_881del (p.Gln294fs)	PLXND1	Pathogenic	criteria provided, single submitter
1810414	NM_015103.3(PLXND1):c.5629A>G (p.Ile1877Val)	PLXND1	Uncertain significance	criteria provided, single submitter
2689791	NM_015103.3(PLXND1):c.2240C>T (p.Thr747Met)	PLXND1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2920786	NM_015103.3(PLXND1):c.2870C>T (p.Pro957Leu)	PLXND1	Uncertain significance	criteria provided, single submitter
4079751	NM_015103.3(PLXND1):c.2734C>T (p.Arg912Ter)	PLXND1	Uncertain significance	criteria provided, single submitter
4819667	NM_015103.3(PLXND1):c.1629G>T (p.Arg543Ser)	PLXND1	Uncertain significance	criteria provided, single submitter
4819668	NM_015103.3(PLXND1):c.121dup (p.Ala41fs)	PLXND1	Uncertain significance	criteria provided, single submitter
978156	NM_015103.3(PLXND1):c.5081A>G (p.His1694Arg)	PLXND1	Uncertain significance	criteria provided, multiple submitters, no conflicts
773447	NM_015103.3(PLXND1):c.2263A>G (p.Thr755Ala)	PLXND1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
PLXND1	Strong	Autosomal recessive	congenital heart defects, multiple types, 9	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PLXND1	Orphanet:3384	Common arterial trunk
PLXND1	Orphanet:570	Moebius syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PLXND1	HGNC:9107	ENSG00000004399	Q9Y4D7	Plexin-D1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PLXND1	Plexin-D1	Cell surface receptor for SEMA4A and for class 3 semaphorins, such as SEMA3A, SEMA3C and SEMA3E.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PLXND1	Antibody/Immunoglobulin	yes		Semap_dom, Plexin_repeat, IPT_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right coronary artery	1
right lung	1
upper lobe of left lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PLXND1	278	ubiquitous	marker	upper lobe of left lung, right coronary artery, right lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PLXND1	1,454

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PLXND1	Q9Y4D7	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Other semaphorin interactions	1	601.0×	0.003	PLXND1
NOTCH3 Intracellular Domain Regulates Transcription	1	439.2×	0.003	PLXND1
RND2 GTPase cycle	1	259.6×	0.004	PLXND1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
synaptic target recognition	1	8426.0×	0.002	PLXND1
dichotomous subdivision of terminal units involved in salivary gland branching	1	4213.0×	0.002	PLXND1
cardiac septum development	1	1685.2×	0.004	PLXND1
coronary vasculature development	1	624.1×	0.004	PLXND1
positive regulation of axonogenesis	1	581.1×	0.004	PLXND1
aorta development	1	561.7×	0.004	PLXND1
branching involved in blood vessel morphogenesis	1	526.6×	0.004	PLXND1
regulation of angiogenesis	1	421.3×	0.004	PLXND1
endothelial cell migration	1	411.0×	0.004	PLXND1
semaphorin-plexin signaling pathway	1	401.2×	0.004	PLXND1
negative regulation of cell adhesion	1	383.0×	0.004	PLXND1
outflow tract morphogenesis	1	306.4×	0.005	PLXND1
synapse assembly	1	230.8×	0.006	PLXND1
regulation of cell migration	1	157.5×	0.008	PLXND1
kidney development	1	140.4×	0.009	PLXND1
regulation of cell shape	1	123.0×	0.009	PLXND1
negative regulation of neuron apoptotic process	1	110.9×	0.010	PLXND1
angiogenesis	1	62.4×	0.016	PLXND1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PLXND1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	PLXND1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
PLXND1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.