Juvenile polyposis syndrome

Summary

Juvenile polyposis syndrome (MONDO:0017380) is a disease caused by variants in BMPR1A and SMAD4, with 7 cohort genes and 11 clinical trials.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal genes: BMPR1A (GenCC Definitive), SMAD4 (GenCC Strong)
• Cohort genes: 7
• ClinVar variants: 3,583
• Phenotypes (HPO): 52
• Clinical trials: 11

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 100 000	3.85	Europe	Validated

Signs & symptoms

Clinical features (HPO)

52 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0012198	Juvenile colonic polyposis	Obligate (100%)
HP:0100896	Rectal polyposis	Obligate (100%)
HP:0004784	Juvenile gastrointestinal polyposis	Obligate (100%)
HP:0005266	Intestinal polyp	Very frequent (80-99%)
HP:0001903	Anemia	Frequent (30-79%)
HP:0002027	Abdominal pain	Frequent (30-79%)
HP:0004390	Hamartomatous polyposis	Frequent (30-79%)
HP:0030256	Small intestinal polyposis	Frequent (30-79%)
HP:0004795	Hamartomatous stomach polyps	Occasional (5-29%)
HP:0002573	Hematochezia	Occasional (5-29%)
HP:0002576	Intussusception	Occasional (5-29%)
HP:0002014	Diarrhea	Occasional (5-29%)
HP:0100822	Rectocele	Occasional (5-29%)
HP:0001510	Growth delay	Occasional (5-29%)
HP:0000969	Edema	Occasional (5-29%)
HP:0002239	Gastrointestinal hemorrhage	Occasional (5-29%)
HP:0012432	Chronic fatigue	Occasional (5-29%)
HP:0000256	Macrocephaly	Occasional (5-29%)
HP:0001999	Abnormal facial shape	Occasional (5-29%)
HP:0002003	Large forehead	Occasional (5-29%)
HP:0000331	Short chin	Occasional (5-29%)
HP:0001256	Intellectual disability, mild	Occasional (5-29%)
HP:0004406	Spontaneous, recurrent epistaxis	Occasional (5-29%)
HP:0003003	Colon cancer	Occasional (5-29%)
HP:0012126	Stomach cancer	Occasional (5-29%)
HP:0100833	Neoplasm of the small intestine	Occasional (5-29%)
HP:0001508	Failure to thrive	Occasional (5-29%)
HP:0100759	Clubbing of fingers	Occasional (5-29%)
HP:0007378	Neoplasm of the gastrointestinal tract	Occasional (5-29%)
HP:0002243	Protein-losing enteropathy	Very rare (<1-4%)
HP:0001012	Multiple lipomas	Very rare (<1-4%)
HP:0010797	Hemangioblastoma	Very rare (<1-4%)
HP:0000316	Hypertelorism	Very rare (<1-4%)
HP:0000494	Downslanted palpebral fissures	Very rare (<1-4%)
HP:0005280	Depressed nasal bridge	Very rare (<1-4%)
HP:0000369	Low-set ears	Very rare (<1-4%)
HP:0000160	Narrow mouth	Very rare (<1-4%)
HP:0100579	Mucosal telangiectasiae	Very rare (<1-4%)
HP:0100761	Visceral angiomatosis	Very rare (<1-4%)
HP:0002326	Transient ischemic attack	Very rare (<1-4%)
HP:0030049	Brain abscess	Very rare (<1-4%)
HP:0004941	Extrahepatic portal hypertension	Very rare (<1-4%)
HP:0002092	Pulmonary arterial hypertension	Very rare (<1-4%)
HP:0002894	Neoplasm of the pancreas	Very rare (<1-4%)
HP:0012050	Anasarca	Very rare (<1-4%)
HP:0003075	Hypoproteinemia	Very rare (<1-4%)
HP:0000421	Epistaxis	Very rare (<1-4%)
HP:0100026	Arteriovenous malformation	Very rare (<1-4%)
HP:0006548	Pulmonary arteriovenous malformation	Very rare (<1-4%)
HP:0006574	Hepatic arteriovenous malformation	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	juvenile polyposis syndrome
Mondo ID	MONDO:0017380
OMIM	174900
Orphanet	2929
ICD-11	1020795563
NCIT	C7754
SNOMED CT	9273005
UMLS	C0345893
MedGen	87518
GARD	0003065
NORD	280170
Is cancer (heuristic)	no

Also known as: JIP · JPS · jPS · juvenile gastrointestinal polyposis · juvenile intestinal polyposis · juvenile multiple polyps syndrome · juvenile polyposis · juvenile polyposis syndrome · PJI · polyposis familial of entire gastrointestinal tract · polyposis juvenile intestinal · polyposis, juvenile intestinal

Data availability: 3,583 ClinVar variants · 6 GenCC gene-disease records.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › juvenile polyposis syndrome

Related subtypes (30): benign digestive system neoplasm, autoimmune disorder of gastrointestinal tract, gastrointestinal mucositis, diarrheal disease, pancreas disorder, hepatobiliary disorder, digestive system cancer, peptic ulcer disease, stomach disorder, intestinal disorder, Meckel diverticulum, Cronkhite-Canada syndrome, diverticulosis, small-intestinal, diverticulosis of bowel, hernia, and retinal detachment, congenital enteropathy due to enteropeptidase deficiency, hereditary mixed polyposis syndrome, caudal duplication, Moyamoya disease with early-onset achalasia, hyperplastic polyposis syndrome, thoraco-abdominal enteric duplication, digestive duplication, umbilical cord ulceration-intestinal atresia syndrome, growth retardation-mild developmental delay-chronic hepatitis syndrome, common mesentery, neoplasm of oropharynx, gastrointestinal polyp, digestive system neuroendocrine neoplasm, digestive system infectious disorder, upper digestive tract disorder, congenital peritoneal encapsulation

Subtypes (3): generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis of infancy, BMPR1A-related juvenile polyposis syndrome

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

600 retrieved; paginated sample, class counts are floors:

311 uncertain significance, 84 likely benign, 76 benign/likely benign, 62 pathogenic, 48 conflicting classifications of pathogenicity, 12 likely pathogenic, 5 pathogenic/likely pathogenic, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1068879	NC_000010.10:g.(?88683123)(89725321_?)del	ADIRF	Pathogenic	criteria provided, single submitter
1018119	NM_004329.3(BMPR1A):c.1473+2T>C	BMPR1A	Pathogenic	criteria provided, single submitter
1068878	NC_000010.10:g.(?88651874)(88651996_?)del	BMPR1A	Pathogenic	criteria provided, single submitter
1068880	NC_000010.10:g.(?_88669791)_88681457del	BMPR1A	Pathogenic	criteria provided, single submitter
1071410	NM_004329.3(BMPR1A):c.156_165del (p.Glu53fs)	BMPR1A	Pathogenic	criteria provided, single submitter
1072349	NM_004329.3(BMPR1A):c.1119dup (p.Gly374fs)	BMPR1A	Pathogenic	criteria provided, single submitter
1073369	NM_004329.3(BMPR1A):c.394C>T (p.Gln132Ter)	BMPR1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1075137	NM_004329.3(BMPR1A):c.1151dup (p.Val385fs)	BMPR1A	Pathogenic	criteria provided, single submitter
1075317	NM_004329.3(BMPR1A):c.813del (p.Trp271fs)	BMPR1A	Pathogenic	criteria provided, single submitter
1075769	NM_004329.3(BMPR1A):c.127_137del (p.Lys43fs)	BMPR1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1076984	NC_000010.10:g.(?88598623)(88635852_?)del	BMPR1A	Pathogenic	criteria provided, single submitter
1076985	NC_000010.10:g.(?88598623)(88659889_?)del	BMPR1A	Pathogenic	criteria provided, single submitter
1353523	NM_004329.3(BMPR1A):c.530+3A>G	BMPR1A	Pathogenic	criteria provided, single submitter
1375333	NM_004329.3(BMPR1A):c.1255A>T (p.Lys419Ter)	BMPR1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1393823	NM_004329.3(BMPR1A):c.1101_1102dup (p.Ile368fs)	BMPR1A	Pathogenic	criteria provided, single submitter
1416153	NM_004329.3(BMPR1A):c.357_360del (p.Arg120fs)	BMPR1A	Pathogenic	criteria provided, single submitter
141674	NM_004329.3(BMPR1A):c.826_827del (p.Glu276fs)	BMPR1A	Pathogenic	criteria provided, multiple submitters, no conflicts
142329	NM_004329.3(BMPR1A):c.371G>A (p.Cys124Tyr)	BMPR1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
142351	NM_004329.3(BMPR1A):c.817C>T (p.Arg273Ter)	BMPR1A	Pathogenic	criteria provided, multiple submitters, no conflicts
142484	NM_004329.3(BMPR1A):c.355C>T (p.Arg119Cys)	BMPR1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
142735	NM_004329.3(BMPR1A):c.682C>T (p.Arg228Ter)	BMPR1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1435228	NM_004329.3(BMPR1A):c.1372dup (p.Tyr458fs)	BMPR1A	Pathogenic	criteria provided, single submitter
1437360	NM_004329.3(BMPR1A):c.1022del (p.Gly341fs)	BMPR1A	Pathogenic	criteria provided, single submitter
1446949	NM_004329.3(BMPR1A):c.97dup (p.Thr33fs)	BMPR1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1452517	NM_004329.3(BMPR1A):c.1064del (p.Lys355fs)	BMPR1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1452995	NM_004329.3(BMPR1A):c.1193dup (p.Leu398fs)	BMPR1A	Pathogenic	criteria provided, single submitter
1455939	NC_000010.10:g.(?88678919)(88679236_?)del	BMPR1A	Pathogenic	criteria provided, single submitter
1456917	NM_004329.3(BMPR1A):c.924del (p.Thr309fs)	BMPR1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1457449	NM_004329.3(BMPR1A):c.1461G>A (p.Trp487Ter)	BMPR1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1457588	NM_004329.3(BMPR1A):c.1057C>T (p.Gln353Ter)	BMPR1A	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 32 · Orphanet: 19 · 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
BMPR1A	Definitive	Autosomal dominant	generalized juvenile polyposis/juvenile polyposis coli	12
SMAD4	Definitive	Autosomal dominant	juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome	14
ENG	Limited	Autosomal dominant	juvenile polyposis syndrome	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SMAD4	Orphanet:1333	Familial pancreatic carcinoma
SMAD4	Orphanet:2588	Myhre syndrome
SMAD4	Orphanet:329971	Generalized juvenile polyposis/juvenile polyposis coli
SMAD4	Orphanet:774	Hereditary hemorrhagic telangiectasia
SMAD4	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
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
ENG	Orphanet:231160	Familial cerebral saccular aneurysm
ENG	Orphanet:275777	Heritable pulmonary arterial hypertension
ENG	Orphanet:329971	Generalized juvenile polyposis/juvenile polyposis coli
ENG	Orphanet:774	Hereditary hemorrhagic telangiectasia
LDB3	Orphanet:154	Familial isolated dilated cardiomyopathy
LDB3	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
LDB3	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
LDB3	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
LDB3	Orphanet:54260	Left ventricular noncompaction
LDB3	Orphanet:98912	Late-onset distal myopathy, Markesbery-Griggs type

Cohort genes → proteins

7 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SMAD4	HGNC:6770	ENSG00000141646	Q13485	SMAD family member 4	gencc,clinvar,civic_evidence
BMPR1A	HGNC:1076	ENSG00000107779	P36894	Bone morphogenetic protein receptor type-1A	gencc,clinvar
ENG	HGNC:3349	ENSG00000106991	P17813	Endoglin	gencc,clinvar
SLC12A1	HGNC:10910	ENSG00000074803	Q13621	Solute carrier family 12 member 1	clinvar
LDB3	HGNC:15710	ENSG00000122367	O75112	LIM domain-binding protein 3	clinvar
ADIRF	HGNC:24043	ENSG00000148671	Q15847	Adipogenesis regulatory factor	clinvar
DUT-AS1	HGNC:55420	ENSG00000259488		DUT antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SMAD4	SMAD family member 4	In muscle physiology, plays a central role in the balance between atrophy and hypertrophy.
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.
ENG	Endoglin	Vascular endothelium glycoprotein that plays an important role in the regulation of angiogenesis.
SLC12A1	Solute carrier family 12 member 1	Renal sodium, potassium and chloride non-electrogenic ion symporter that mediates the transepithelial NaCl reabsorption in the thick ascending limb and plays an essential role in the urinary concentration and volume regulation.
LDB3	LIM domain-binding protein 3	May function as an adapter in striated muscle to couple protein kinase C-mediated signaling via its LIM domains to the cytoskeleton.
ADIRF	Adipogenesis regulatory factor	Plays a role in fat cell development; promotes adipogenic differentiation and stimulates transcription initiation of master adipogenesis factors like PPARG and CEBPA at early stages of preadipocyte differentiation.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 5 · Druggable fraction: 0.14

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	1	4.0×	0.499
Other/Unknown	5	1.3×	0.499
Transcription factor	1	1.2×	0.595

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SMAD4	Other/Unknown	no		SMAD_dom, MAD_homology1_Dwarfin-type, SMAD_FHA_dom_sf
BMPR1A	Kinase	yes	2.7.10.2	TGFB_receptor, Activin_recp, Prot_kinase_dom
ENG	Other/Unknown	no		TGFBR3/Endoglin-like_N
SLC12A1	Other/Unknown	no		SLC12A1/SLC12A2, Slc12a1, AA-permease/SLC12A_dom
LDB3	Transcription factor	no		PDZ, Znf_LIM, Zasp-like_motif
ADIRF	Other/Unknown	no		ADIRF
DUT-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

7 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)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	2
ganglionic eminence	1
ventricular zone	1
saphenous vein	1
secondary oocyte	1
cardiac atrium	1
right atrium auricular region	1
right lung	1
metanephros cortex	1
nephron tubule	1
renal medulla	1
apex of heart	1
hindlimb stylopod muscle	1
skeletal muscle tissue of biceps brachii	1
left coronary artery	1
popliteal artery	1
tibial artery	1
bone marrow cell	1
colonic epithelium	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SMAD4	288	ubiquitous	marker	ventricular zone, ganglionic eminence, calcaneal tendon
BMPR1A	284	ubiquitous	marker	secondary oocyte, calcaneal tendon, saphenous vein
ENG	265	ubiquitous	marker	right lung, right atrium auricular region, cardiac atrium
SLC12A1	185	tissue_specific	marker	renal medulla, nephron tubule, metanephros cortex
LDB3	247	broad	marker	skeletal muscle tissue of biceps brachii, hindlimb stylopod muscle, apex of heart
ADIRF	280	ubiquitous	marker	popliteal artery, tibial artery, left coronary artery
DUT-AS1	132		marker	sural nerve, colonic epithelium, bone marrow cell

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMAD4	7,320
BMPR1A	3,316
ENG	3,236
SLC12A1	1,448
LDB3	1,275
ADIRF	594
DUT-AS1	0

Intra-cohort edges

A	B	Sources
BMPR1A	SMAD4	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 2 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SMAD4	Q13485	12
BMPR1A	P36894	11
ENG	P17813	3
LDB3	O75112	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC12A1	Q13621	78.39
ADIRF	Q15847	74.15

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 57. Enrichment computed across 7 evidence-associated genes (4 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 4 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	178.4×	0.003	SMAD4, BMPR1A
Defective SLC12A1 causes Bartter syndrome 1 (BS1)	1	2855.0×	0.006	SLC12A1
Adipogenesis	2	78.2×	0.006	SMAD4, ADIRF
Signaling by TGFB family members	2	57.7×	0.006	SMAD4, BMPR1A
Loss of Function of SMAD4 in Cancer	1	951.7×	0.009	SMAD4
SMAD4 MH2 Domain Mutants in Cancer	1	951.7×	0.009	SMAD4
SMAD2/3 MH2 Domain Mutants in Cancer	1	951.7×	0.009	SMAD4
RUNX3 regulates BCL2L11 (BIM) transcription	1	571.0×	0.012	SMAD4
Loss of Function of SMAD2/3 in Cancer	1	475.8×	0.012	SMAD4
Signaling by TGF-beta Receptor Complex in Cancer	1	475.8×	0.012	SMAD4
Cation-coupled Chloride cotransporters	1	407.9×	0.012	SLC12A1
RUNX3 regulates CDKN1A transcription	1	407.9×	0.012	SMAD4
Transcriptional regulation of brown and beige adipocyte differentiation	1	285.5×	0.015	SMAD4
RUNX2 regulates bone development	1	203.9×	0.018	SMAD4
Signaling by Activin	1	190.3×	0.018	SMAD4
Formation of definitive endoderm	1	178.4×	0.018	SMAD4
FOXO-mediated transcription of cell cycle genes	1	167.9×	0.018	SMAD4
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	1	167.9×	0.018	SMAD4
Germ layer formation at gastrulation	1	167.9×	0.018	SMAD4
Transcriptional regulation of pluripotent stem cells	1	135.9×	0.021	SMAD4
Signaling by NODAL	1	124.1×	0.022	SMAD4
TGFBR3 expression	1	114.2×	0.022	SMAD4
Cardiogenesis	1	105.7×	0.022	SMAD4
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes	1	95.2×	0.022	SMAD4
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	1	95.2×	0.022	SMAD4
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1	92.1×	0.022	SMAD4
Downregulation of SMAD2/3:SMAD4 transcriptional activity	1	92.1×	0.022	SMAD4
Signaling by TGFBR3	1	92.1×	0.022	SMAD4
FOXO-mediated transcription	1	84.0×	0.023	SMAD4
TGF-beta receptor signaling activates SMADs	1	81.6×	0.023	SMAD4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
outflow tract septum morphogenesis	3	324.1×	1e-05	SMAD4, BMPR1A, ENG
positive regulation of SMAD protein signal transduction	3	191.5×	3e-05	SMAD4, BMPR1A, ENG
dorsal aorta morphogenesis	2	702.2×	1e-04	BMPR1A, ENG
BMP signaling pathway	3	100.3×	1e-04	SMAD4, BMPR1A, ENG
mesendoderm development	2	624.1×	1e-04	SMAD4, BMPR1A
transforming growth factor beta receptor signaling pathway	3	79.5×	1e-04	SMAD4, BMPR1A, ENG
epithelial to mesenchymal transition involved in endocardial cushion formation	2	468.1×	2e-04	SMAD4, ENG
cardiac conduction system development	2	351.1×	3e-04	SMAD4, BMPR1A
ventricular trabecula myocardium morphogenesis	2	351.1×	3e-04	BMPR1A, ENG
endocardial cushion morphogenesis	2	280.9×	4e-04	BMPR1A, ENG
developmental growth	2	244.2×	5e-04	SMAD4, BMPR1A
cellular response to BMP stimulus	2	187.2×	7e-04	SMAD4, BMPR1A
ventricular septum morphogenesis	2	144.0×	0.001	SMAD4, BMPR1A
embryonic digit morphogenesis	2	100.3×	0.002	SMAD4, BMPR1A
positive regulation of miRNA transcription	2	96.8×	0.002	SMAD4, BMPR1A
obsolete positive regulation of cell proliferation involved in heart valve morphogenesis	1	2808.7×	0.003	SMAD4
neural plate mediolateral regionalization	1	2808.7×	0.003	BMPR1A
paraxial mesoderm structural organization	1	2808.7×	0.003	BMPR1A
female gonad morphogenesis	1	2808.7×	0.003	SMAD4
positive regulation of cardiac ventricle development	1	2808.7×	0.003	BMPR1A
fibrous ring of heart morphogenesis	1	2808.7×	0.003	BMPR1A
negative regulation of cardiac myofibril assembly	1	2808.7×	0.003	SMAD4
positive regulation of transcription by RNA polymerase II	4	9.9×	0.003	SMAD4, BMPR1A, ENG, ADIRF
detection of hypoxia	1	1404.3×	0.005	ENG
nephrogenic mesenchyme morphogenesis	1	1404.3×	0.005	SMAD4
positive regulation of vascular associated smooth muscle cell differentiation	1	1404.3×	0.005	ENG
cell differentiation	3	14.6×	0.005	SMAD4, BMPR1A, ADIRF
positive regulation of transforming growth factor beta2 production	1	936.2×	0.006	BMPR1A
regulation of lateral mesodermal cell fate specification	1	936.2×	0.006	BMPR1A
metanephric mesenchyme morphogenesis	1	936.2×	0.006	SMAD4

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 6

Druggability breadth: 4 of 7 evidence-associated genes (57%) 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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BMPR1A	11	4
SMAD4	0	0
ENG	0	0
SLC12A1	0	0
LDB3	0	0
ADIRF	0	0
DUT-AS1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	BMPR1A
GILTERITINIB	4	BMPR1A
DASATINIB	4	BMPR1A
SARACATINIB	3	BMPR1A
LESTAURTINIB	3	BMPR1A
AT-9283	2	BMPR1A
ZILURGISERTIB	2	BMPR1A
KER-047	2	BMPR1A
KW-2449	1	BMPR1A
XL-228	1	BMPR1A
Y-39983	1	BMPR1A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
BMPR1A	169	Binding:166, ADMET:3
SMAD4	6	Binding:6

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BMPR1A	2.7.10.2	non-specific protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BMPR1A	169

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

11 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
SARACATINIB	3	BMPR1A
LESTAURTINIB	3	BMPR1A
AT-9283	2	BMPR1A
ZILURGISERTIB	2	BMPR1A
KER-047	2	BMPR1A
KW-2449	1	BMPR1A
XL-228	1	BMPR1A
Y-39983	1	BMPR1A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	BMPR1A
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	6	SMAD4, ENG, SLC12A1, LDB3, ADIRF, DUT-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SMAD4	6	—
ENG	0	—
SLC12A1	0	—
LDB3	0	—
ADIRF	0	—
DUT-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 11.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	10
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05421312	PHASE4	UNKNOWN	Periarticular Penetration of Cefazolin and Clindamycin in Second Stage Revision Arthroplasty of the Hip
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT06666023	Not specified	RECRUITING	Paper-based Electrochemical Point-of-care Device in Diagnostic of Orthopedic Infections
NCT00633607	Not specified	COMPLETED	Hereditary Colorectal and Associated Tumor Registry Study
NCT05254145	Not specified	UNKNOWN	Joint Microbiome Study for the Knee
NCT05320354	Not specified	UNKNOWN	Diagnosis and Bacterial Identification of Periprosthetic Joint Infection With Microbial-ID
NCT06153446	Not specified	COMPLETED	Infection Consortium Study#1
NCT06784414	Not specified	COMPLETED	Analysis of Risk Factors for Recurrence of Periprosthetic Infection in Megaprostheses Implanted for Sarcoma of Bone
NCT06806449	Not specified	COMPLETED	Results of Silver-coated Resection Prostheses in the Treatment of Periprosthetic Knee Infections with Bone Deficiency
NCT07398742	Not specified	COMPLETED	Incidence and Microbial Profiles of Periprosthetic Joint Infection After Total Knee Arthroplasty in Obese vs Non-Obese Patients
NCT07453329	Not specified	COMPLETED	Assessment of Functional Outcomes of Custom-made Articulating Spacers in Two Stage Arthroplasty for Treatment of Infected Hip Joint