Congenital heart defects, multiple types

disease

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Also known as CHTD

Summary

Congenital heart defects, multiple types (MONDO:0000119) is a disease (an umbrella term covering 8 Mondo subtypes) caused by RBFOX2 (GenCC Strong), with 13 cohort genes.

At a glance

Causal gene: RBFOX2 (GenCC Strong)
Umbrella term: 8 Mondo subtypes
Cohort genes: 13
ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital heart defects, multiple types
Mondo ID	MONDO:0000119
Is cancer (heuristic)	no

Also known as: CHTD

Data availability: 4 ClinVar variants · 11 GenCC gene-disease records.

Disease family

An umbrella term covering 8 Mondo subtypes.

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

Subtypes (8): 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, congenital heart defects, multiple types, 9

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

4 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
522571	NM_001492.6(GDF1):c.1091T>C (p.Met364Thr)	CERS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1508694	NM_080473.5(GATA5):c.875G>A (p.Arg292Gln)	GATA5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1511689	NM_080473.5(GATA5):c.664G>A (p.Val222Ile)	GATA5	Uncertain significance	criteria provided, multiple submitters, no conflicts
3377369	NM_080473.5(GATA5):c.209C>T (p.Ala70Val)	GATA5	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 72 · Orphanet: 21 · 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
FGF10	Strong	Autosomal dominant	congenital alveolar dysplasia due to FGF10	8
PRKD1	Strong	Autosomal dominant	congenital heart defects and ectodermal dysplasia	14
RBFOX2	Strong	Autosomal dominant	congenital heart defects, multiple types	3
CITED2	Moderate	Autosomal dominant	congenital heart defects, multiple types	4
HAND2	Moderate	Autosomal dominant	HAND2 related congenital heart defect	4
SMAD6	Supportive	Unknown	congenital radioulnar synostosis	14
ANKRD11	Limited	Autosomal dominant	congenital heart defects, multiple types	8
ASB17	Limited	Autosomal dominant	congenital heart defects, multiple types
BMPR1A	Limited	Autosomal dominant	congenital heart defects, multiple types	12
DLC1	Limited	Autosomal dominant	congenital heart defects, multiple types	3
MCTP2	Limited	Autosomal dominant	congenital heart defects, multiple types

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BMPR1A	Orphanet:157794	Hereditary mixed polyposis syndrome
BMPR1A	Orphanet:329971	Generalized juvenile polyposis/juvenile polyposis coli
BMPR1A	Orphanet:440437	Familial colorectal cancer Type X
BMPR1A	Orphanet:79076	Juvenile polyposis of infancy
CITED2	Orphanet:101063	Situs inversus totalis
CITED2	Orphanet:3303	Tetralogy of Fallot
CITED2	Orphanet:99103	Atrial septal defect, ostium secundum type
CITED2	Orphanet:99105	Atrial septal defect, sinus venosus type
ANKRD11	Orphanet:2332	KBG syndrome
ANKRD11	Orphanet:261250	16q24.3 microdeletion syndrome
MCTP2	Orphanet:1596	Distal deletion 15q syndrome
FGF10	Orphanet:2363	Lacrimoauriculodentodigital syndrome
FGF10	Orphanet:86815	Aplasia of lacrimal and salivary glands
HAND2	Orphanet:154	Familial isolated dilated cardiomyopathy
SMAD6	Orphanet:402075	Familial bicuspid aortic valve
PRKD1	Orphanet:276145	Malignant epithelial tumor of salivary glands
PRKD1	Orphanet:708019	Congenital heart defect-ectodermal dysplasia- brachydactyly-telangiectasia syndrome
CERS1	Orphanet:424027	Progressive myoclonic epilepsy type 8
GATA5	Orphanet:3303	Tetralogy of Fallot
GATA5	Orphanet:334	Hereditary atrial fibrillation
GATA5	Orphanet:402075	Familial bicuspid aortic valve

Cohort genes → proteins

13 cohort genes, 13 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	13

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BMPR1A	HGNC:1076	ENSG00000107779	P36894	Bone morphogenetic protein receptor type-1A	gencc
ASB17	HGNC:19769	ENSG00000154007	Q8WXJ9	Ankyrin repeat and SOCS box protein 17	gencc
CITED2	HGNC:1987	ENSG00000164442	Q99967	Cbp/p300-interacting transactivator 2	gencc
ANKRD11	HGNC:21316	ENSG00000167522	Q6UB99	Ankyrin repeat domain-containing protein 11	gencc
MCTP2	HGNC:25636	ENSG00000140563	Q6DN12	Multiple C2 and transmembrane domain-containing protein 2	gencc
DLC1	HGNC:2897	ENSG00000164741	Q96QB1	Rho GTPase-activating protein 7	gencc
FGF10	HGNC:3666	ENSG00000070193	O15520	Fibroblast growth factor 10	gencc
HAND2	HGNC:4808	ENSG00000164107	P61296	Heart- and neural crest derivatives-expressed protein 2	gencc
SMAD6	HGNC:6772	ENSG00000137834	O43541	SMAD family member 6	gencc
PRKD1	HGNC:9407	ENSG00000184304	Q15139	Serine/threonine-protein kinase D1	gencc
RBFOX2	HGNC:9906	ENSG00000100320	O43251	RNA binding protein fox-1 homolog 2	gencc
CERS1	HGNC:14253	ENSG00000223802	P27544	Ceramide synthase 1	clinvar
GATA5	HGNC:15802	ENSG00000130700	Q9BWX5	Transcription factor GATA-5	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BMPR1A	Bone morphogenetic protein receptor type-1A	On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases.
ASB17	Ankyrin repeat and SOCS box protein 17	May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
CITED2	Cbp/p300-interacting transactivator 2	Transcriptional coactivator of the p300/CBP-mediated transcription complex.
ANKRD11	Ankyrin repeat domain-containing protein 11	Chromatin regulator which modulates histone acetylation and gene expression in neural precursor cells.
MCTP2	Multiple C2 and transmembrane domain-containing protein 2	Might play a role in the development of cardiac outflow tract.
DLC1	Rho GTPase-activating protein 7	Functions as a GTPase-activating protein for the small GTPases RHOA, RHOB, RHOC and CDC42, terminating their downstream signaling.
FGF10	Fibroblast growth factor 10	Plays an important role in the regulation of embryonic development, cell proliferation and cell differentiation.
HAND2	Heart- and neural crest derivatives-expressed protein 2	Essential for cardiac morphogenesis, particularly for the formation of the right ventricle and of the aortic arch arteries.
SMAD6	SMAD family member 6	Transforming growth factor-beta superfamily receptors signaling occurs through the Smad family of intracellular mediators.
PRKD1	Serine/threonine-protein kinase D1	Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and tr…
RBFOX2	RNA binding protein fox-1 homolog 2	RNA-binding protein that regulates alternative splicing events by binding to 5’-UGCAUGU-3’ elements.
CERS1	Ceramide synthase 1	Ceramide synthase that catalyzes the transfer of the acyl chain from acyl-CoA to a sphingoid base, with high selectivity toward stearoyl-CoA (octadecanoyl-CoA; C18:0-CoA).
GATA5	Transcription factor GATA-5	Transcription factor required during cardiovascular development.

Protein-family classification

Druggable: 3 · Difficult: 4 · Unknown: 6 · Druggable fraction: 0.23

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
Kinase	2	4.3×	0.390
Scaffold/PPI	2	2.7×	0.428
Transcription factor	2	1.3×	0.798
Enzyme (other)	1	0.9×	0.837
Other/Unknown	6	0.8×	0.837

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BMPR1A	Kinase	yes	2.7.10.2	TGFB_receptor, Activin_recp, Prot_kinase_dom
ASB17	Scaffold/PPI	no		SOCS_box, SOCS_box-like_dom_sf, Ankyrin_rpt-contain_sf
CITED2	Other/Unknown	no		CITED
ANKRD11	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, ANKRD11
MCTP2	Other/Unknown	no		C2_dom, MCTP_C, C2_domain_sf
DLC1	Other/Unknown	no		RhoGAP_dom, SAM, START_lipid-bd_dom
FGF10	Other/Unknown	no		Fibroblast_GF_fam, IL1/FGF
HAND2	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, E-box_TF_Regulators
SMAD6	Other/Unknown	no		SMAD_dom, MAD_homology1_Dwarfin-type, SMAD_FHA_dom_sf
PRKD1	Kinase	yes	2.7.11.13	Prot_kinase_dom, PH_domain, PKC_DAG/PE
RBFOX2	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RBFOX1-3
CERS1	Enzyme (other)	yes	2.3.1.299	TLC-dom, Lag1/Lac1-like
GATA5	Transcription factor	no		Znf_GATA, GATA_N, Znf_NHR/GATA

Expression context

Cohort genes with no expression data: 0.

10 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)	13
unknown	0

Top tissues across cohort

Tissue	Cohort genes
secondary oocyte	2
stromal cell of endometrium	2
sural nerve	2
buccal mucosa cell	2
calcaneal tendon	1
saphenous vein	1
adult organism	1
male germ line stem cell (sensu Vertebrata) in testis	1
sperm	1
mucosa of stomach	1
type B pancreatic cell	1
tendon of biceps brachii	1
germinal epithelium of ovary	1
adrenal tissue	1
lower lobe of lung	1
endocervix	1
synovial joint	1
apex of heart	1
lower esophagus muscularis layer	1
muscle layer of sigmoid colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BMPR1A	284	ubiquitous	marker	secondary oocyte, calcaneal tendon, saphenous vein
ASB17	24	tissue_specific	yes	sperm, male germ line stem cell (sensu Vertebrata) in testis, adult organism
CITED2	284	ubiquitous	marker	stromal cell of endometrium, type B pancreatic cell, mucosa of stomach
ANKRD11	278	ubiquitous	marker	tendon of biceps brachii, sural nerve, stromal cell of endometrium
MCTP2	234	broad	marker	germinal epithelium of ovary, secondary oocyte, buccal mucosa cell
DLC1	268	ubiquitous	marker	adrenal tissue, lower lobe of lung, sural nerve
FGF10	169	broad	marker	buccal mucosa cell, synovial joint, endocervix
HAND2	147	broad	marker	muscle layer of sigmoid colon, apex of heart, lower esophagus muscularis layer
SMAD6	277	ubiquitous	marker	right lung, renal glomerulus, metanephric glomerulus
PRKD1	239	ubiquitous	marker	ventricular zone, seminal vesicle, thoracic aorta
RBFOX2	144	ubiquitous	marker	cortical plate, embryo, ganglionic eminence
CERS1	177	broad	yes	C1 segment of cervical spinal cord, right frontal lobe, spinal cord
GATA5	106	broad	yes	ileal mucosa, left uterine tube, jejunal mucosa

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FGF10	4,233
BMPR1A	3,316
GATA5	2,434
ANKRD11	2,384
RBFOX2	2,274
PRKD1	2,131
SMAD6	2,006
HAND2	1,828
CITED2	1,215
DLC1	1,128

Intra-cohort edges

A	B	Sources
GATA5	HAND2	string_interaction

Structural data

PDB: 6 · AlphaFold-only: 7 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BMPR1A	P36894	11
DLC1	Q96QB1	7
CITED2	Q99967	4
FGF10	O15520	2
MCTP2	Q6DN12	1
RBFOX2	O43251	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CERS1	P27544	88.95
ASB17	Q8WXJ9	86.18
SMAD6	O43541	72.34
PRKD1	Q15139	68.99
HAND2	P61296	67.30
GATA5	Q9BWX5	59.91
ANKRD11	Q6UB99	39.44

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 56. Enrichment computed across 13 evidence-associated genes (11 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 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by BMP	2	64.9×	0.015	BMPR1A, SMAD6
Sphingolipid de novo biosynthesis	2	51.9×	0.015	CERS1, PRKD1
Transcriptional regulation by RUNX2	2	46.1×	0.015	HAND2, SMAD6
TFAP2 (AP-2) family regulates transcription of other transcription factors	1	259.6×	0.044	CITED2
Signaling by TGFB family members	2	21.0×	0.044	BMPR1A, SMAD6
Regulation of gene expression in early pancreatic precursor cells	1	129.8×	0.053	FGF10
FGFR1b ligand binding and activation	1	115.3×	0.053	FGF10
FGFR2b ligand binding and activation	1	103.8×	0.053	FGF10
Regulation of gene expression by Hypoxia-inducible Factor	1	86.5×	0.053	CITED2
Activation of the TFAP2 (AP-2) family of transcription factors	1	86.5×	0.053	CITED2
FGFRL1 modulation of FGFR1 signaling	1	79.9×	0.053	FGF10
RUNX2 regulates bone development	1	74.2×	0.053	SMAD6
Developmental Lineage of Mammary Stem Cells	1	69.2×	0.053	FGF10
FOXO-mediated transcription of cell death genes	1	64.9×	0.053	CITED2
Activated point mutants of FGFR2	1	61.1×	0.053	FGF10
Phospholipase C-mediated cascade: FGFR1	1	61.1×	0.053	FGF10
Phospholipase C-mediated cascade; FGFR2	1	57.7×	0.053	FGF10
Developmental Lineage of Multipotent Pancreatic Progenitor Cells	1	54.6×	0.053	FGF10
Downstream signaling of activated FGFR1	1	49.4×	0.053	FGF10
PI-3K cascade:FGFR1	1	47.2×	0.053	FGF10
SHC-mediated cascade:FGFR1	1	45.1×	0.053	FGF10
PI-3K cascade:FGFR2	1	45.1×	0.053	FGF10
SHC-mediated cascade:FGFR2	1	43.3×	0.053	FGF10
FRS-mediated FGFR1 signaling	1	41.5×	0.053	FGF10
FRS-mediated FGFR2 signaling	1	39.9×	0.053	FGF10
FGFR2 alternative splicing	1	38.5×	0.053	RBFOX2
Cardiogenesis	1	38.5×	0.053	HAND2
Negative regulation of FGFR1 signaling	1	33.5×	0.057	FGF10
Negative regulation of FGFR2 signaling	1	33.5×	0.057	FGF10
PI3K Cascade	1	24.7×	0.073	FGF10

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 13 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
odontogenesis of dentin-containing tooth	4	92.6×	3e-05	BMPR1A, ANKRD11, FGF10, HAND2
thymus development	3	77.8×	0.001	CITED2, FGF10, HAND2
outflow tract morphogenesis	3	70.7×	0.001	BMPR1A, CITED2, HAND2
positive regulation of gene expression	5	14.9×	0.001	BMPR1A, GATA5, CITED2, HAND2, PRKD1
mitral valve morphogenesis	2	259.3×	0.002	BMPR1A, SMAD6
negative regulation of gene expression	4	21.2×	0.002	BMPR1A, GATA5, CITED2, HAND2
angiogenesis	4	19.2×	0.002	BMPR1A, FGF10, HAND2, PRKD1
negative regulation of cardiac muscle hypertrophy	2	172.8×	0.003	CERS1, GATA5
positive regulation of transcription by RNA polymerase II	6	6.9×	0.004	BMPR1A, GATA5, CITED2, FGF10, HAND2, PRKD1
outflow tract septum morphogenesis	2	99.7×	0.006	BMPR1A, SMAD6
pituitary gland development	2	99.7×	0.006	BMPR1A, FGF10
cranial nerve morphogenesis	1	1296.3×	0.007	CITED2
neural plate mediolateral regionalization	1	1296.3×	0.007	BMPR1A
embryonic genitalia morphogenesis	1	1296.3×	0.007	FGF10
regulation of activin receptor signaling pathway	1	1296.3×	0.007	FGF10
paraxial mesoderm structural organization	1	1296.3×	0.007	BMPR1A
urothelial cell proliferation	1	1296.3×	0.007	FGF10
positive regulation of urothelial cell proliferation	1	1296.3×	0.007	FGF10
bronchiole morphogenesis	1	1296.3×	0.007	FGF10
mesenchymal-epithelial cell signaling involved in lung development	1	1296.3×	0.007	FGF10
fibroblast growth factor receptor signaling pathway involved in mammary gland specification	1	1296.3×	0.007	FGF10
submandibular salivary gland formation	1	1296.3×	0.007	FGF10
semicircular canal fusion	1	1296.3×	0.007	FGF10
lung proximal/distal axis specification	1	1296.3×	0.007	FGF10
positive regulation of cardiac endothelial to mesenchymal transition	1	1296.3×	0.007	GATA5
positive regulation of hair follicle cell proliferation	1	1296.3×	0.007	FGF10
cellular response to dithiothreitol	1	1296.3×	0.007	CERS1
cell-cell junction disassembly	1	1296.3×	0.007	ASB17
positive regulation of cardiac ventricle development	1	1296.3×	0.007	BMPR1A
fibrous ring of heart morphogenesis	1	1296.3×	0.007	BMPR1A

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 11

Druggability breadth: 3 of 13 evidence-associated genes (23%) 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
BMPR1A	MOMELOTINIB
PRKD1	INGENOL MEBUTATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PRKD1	26	4
BMPR1A	11	4
ASB17	0	0
CITED2	0	0
ANKRD11	0	0
MCTP2	0	0
DLC1	0	0
FGF10	0	0
HAND2	0	0
SMAD6	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	BMPR1A
GILTERITINIB	4	BMPR1A
DASATINIB	4	BMPR1A
INGENOL MEBUTATE	4	PRKD1
MIDOSTAURIN	4	PRKD1
TAMOXIFEN	4	PRKD1
NERATINIB	4	PRKD1
BRIGATINIB	4	PRKD1
NINTEDANIB	4	PRKD1
SUNITINIB	4	PRKD1
CRIZOTINIB	4	PRKD1
GEFITINIB	4	PRKD1
SARACATINIB	3	BMPR1A
LESTAURTINIB	3	BMPR1A, PRKD1
SURAMIN	3	PRKD1
FASUDIL	3	PRKD1
ALVOCIDIB	3	PRKD1
AT-9283	2	BMPR1A, PRKD1
ZILURGISERTIB	2	BMPR1A
KER-047	2	BMPR1A
PHORBOL MYRISTATE ACETATE	2	PRKD1
EDELFOSINE	2	PRKD1
UPROSERTIB	2	PRKD1
UCN-01	2	PRKD1
SU-014813	2	PRKD1
BI-2536	2	PRKD1
KW-2449	1	BMPR1A, PRKD1
XL-228	1	BMPR1A
Y-39983	1	BMPR1A
BMS-387032	1	PRKD1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
PRKD1	660	Binding:650, Functional:10
BMPR1A	169	Binding:166, ADMET:3
CERS1	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BMPR1A	2.7.10.2	non-specific protein-tyrosine kinase
PRKD1	2.7.11.13	protein kinase C
CERS1	2.3.1.299	sphingoid base N-stearoyltransferase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
BMPR1A	169
PRKD1	660

Pharmacogenomics

Cohort genes with a PharmGKB record: 13; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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)
MOMELOTINIB	4	BMPR1A
GILTERITINIB	4	BMPR1A
DASATINIB	4	BMPR1A
INGENOL MEBUTATE	4	PRKD1
MIDOSTAURIN	4	PRKD1
TAMOXIFEN	4	PRKD1
NERATINIB	4	PRKD1
BRIGATINIB	4	PRKD1
NINTEDANIB	4	PRKD1
SUNITINIB	4	PRKD1
CRIZOTINIB	4	PRKD1
GEFITINIB	4	PRKD1
SARACATINIB	3	BMPR1A
LESTAURTINIB	3	BMPR1A, PRKD1
SURAMIN	3	PRKD1
FASUDIL	3	PRKD1
ALVOCIDIB	3	PRKD1
AT-9283	2	BMPR1A, PRKD1
ZILURGISERTIB	2	BMPR1A
KER-047	2	BMPR1A
PHORBOL MYRISTATE ACETATE	2	PRKD1
EDELFOSINE	2	PRKD1
UPROSERTIB	2	PRKD1
UCN-01	2	PRKD1
SU-014813	2	PRKD1
BI-2536	2	PRKD1
KW-2449	1	BMPR1A, PRKD1
XL-228	1	BMPR1A
Y-39983	1	BMPR1A
BMS-387032	1	PRKD1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	BMPR1A, PRKD1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	CERS1
E	Difficult family or no structure, no drug	10	ASB17, CITED2, ANKRD11, MCTP2, DLC1, FGF10, HAND2, SMAD6, RBFOX2, GATA5

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ASB17	0	—
CITED2	0	—
ANKRD11	0	—
MCTP2	0	—
DLC1	0	—
FGF10	0	—
HAND2	0	—
SMAD6	0	—
RBFOX2	0	—
CERS1	2	—
GATA5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: BMPR1A, ASB17, CITED2, ANKRD11, MCTP2, DLC1, FGF10, HAND2, SMAD6, PRKD1, RBFOX2, CERS1, GATA5