PLD1-related congenital heart disease

Summary

PLD1-related congenital heart disease (MONDO:1010144) is a disease caused by PLD1 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: PLD1 (GenCC Definitive)
• Cohort genes: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	PLD1-related congenital heart disease
Mondo ID	MONDO:1010144
Is cancer (heuristic)	no

Also known as: PLD1-related congenital heart disease

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › congenital heart disease › PLD1-related congenital heart disease

Related subtypes (22): congenital heart defects, multiple types, heart septal defect, tetralogy of fallot, heart defects-limb shortening syndrome, tricuspid atresia, patent ductus arteriosus, coronary artery congenital malformation, mitral atresia disorder, persistent truncus arteriosus, dextro-looped transposition of the great arteries, aortic valve atresia, congenital pulmonary veins anomaly, mehta lewis patton syndrome, structural congenital heart disease, multiple types - GATA4, GATA6-related congenital heart disease with or without pancreatic agenesis or neonatal diabetes, GATA5-related congenital heart defects, RBFOX2-related congenital heart disorder, syndromic congenital heart disease, ACTC1-related distal arthrogryposis with congenital heart disease, HAND1 related congenital heart defect, HAND2 related congenital heart defect, TFAP2B-related congenital heart disease spectrum disorder

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 15 · Orphanet: 1 · 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
PLD1	Definitive	Autosomal recessive	PLD1-related congenital heart disease	5
PRKCSH	Definitive	Autosomal recessive	PLD1-related congenital heart disease	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PRKCSH	Orphanet:2924	Isolated polycystic liver disease

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PLD1	HGNC:9067	ENSG00000075651	Q13393	Phospholipase D1	gencc
PRKCSH	HGNC:9411	ENSG00000130175	P14314	Glucosidase 2 subunit beta	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PLD1	Phospholipase D1	Function as phospholipase selective for phosphatidylcholine.
PRKCSH	Glucosidase 2 subunit beta	Regulatory subunit of glucosidase II that cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

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
Scaffold/PPI	1	8.6×	0.160
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PLD1	Scaffold/PPI	no	3.1.4.4	PX_dom, PLipase_D/transphosphatidylase, PH_domain
PRKCSH	Enzyme (other)	yes	3.2.1.207	EF_hand_dom, Man6P_isomerase_rcpt-bd_dom_sf, EF-hand-dom_pair

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adrenal tissue	1
gall bladder	1
right adrenal gland cortex	1
olfactory bulb	1
stromal cell of endometrium	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PLD1	260	broad	marker	gall bladder, adrenal tissue, right adrenal gland cortex
PRKCSH	288	ubiquitous	marker	stromal cell of endometrium, type B pancreatic cell, olfactory bulb

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PLD1	2,282
PRKCSH	1,922

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PLD1	Q13393	2
PRKCSH	P14314	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Maturation of spike protein	1	951.7×	0.011	PRKCSH
Synthesis of PG	1	634.4×	0.011	PLD1
Advanced glycosylation endproduct receptor signaling	1	356.9×	0.011	PRKCSH
Calnexin/calreticulin cycle	1	356.9×	0.011	PRKCSH
Role of phospholipids in phagocytosis	1	228.4×	0.013	PLD1
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	1	211.5×	0.013	PRKCSH
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	1	167.9×	0.013	PRKCSH
Synthesis of PA	1	146.4×	0.013	PLD1
Maturation of spike protein	1	132.8×	0.013	PRKCSH
RHOG GTPase cycle	1	74.2×	0.022	PLD1
Post-translational protein phosphorylation	1	50.1×	0.029	PRKCSH
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	43.3×	0.031	PRKCSH
RHOA GTPase cycle	1	37.3×	0.031	PLD1
CDC42 GTPase cycle	1	36.1×	0.031	PLD1
RAC1 GTPase cycle	1	30.5×	0.035	PLD1
Neutrophil degranulation	1	11.5×	0.085	PLD1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of microvillus assembly	1	1203.7×	0.005	PLD1
cellular response to nutrient	1	1053.2×	0.005	PLD1
phospholipid catabolic process	1	601.9×	0.005	PLD1
regulation of vesicle-mediated transport	1	561.7×	0.005	PLD1
regulation of synaptic vesicle cycle	1	561.7×	0.005	PLD1
N-glycan processing	1	366.4×	0.006	PRKCSH
phosphatidic acid biosynthetic process	1	255.3×	0.007	PLD1
positive regulation of translation	1	113.9×	0.013	PLD1
liver development	1	110.9×	0.013	PRKCSH
Ras protein signal transduction	1	102.8×	0.013	PLD1
small GTPase-mediated signal transduction	1	91.6×	0.013	PLD1
chemotaxis	1	68.0×	0.016	PLD1
intracellular signal transduction	1	19.1×	0.052	PRKCSH

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
PLD1	RALOXIFENE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PLD1	2	4
PRKCSH	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RALOXIFENE	4	PLD1
HALOPEMIDE	2	PLD1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PLD1	33	Binding:29, Functional:4
PRKCSH	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PLD1	3.1.4.4	phospholipase D
PRKCSH	3.2.1.207	mannosyl-oligosaccharide alpha-1,3-glucosidase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

2 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.

Compound	Max phase	Cohort target (bioactivity)
RALOXIFENE	4	PLD1
HALOPEMIDE	2	PLD1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PLD1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	PRKCSH
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)
PRKCSH	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.