Polyposis syndrome, hereditary mixed, 2

Summary

Polyposis syndrome, hereditary mixed, 2 (MONDO:0012405) is a disease caused by BMPR1A (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

• Causal gene: BMPR1A (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 196
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	polyposis syndrome, hereditary mixed, 2
Mondo ID	MONDO:0012405
MeSH	C566451
OMIM	610069
DOID	DOID:0111686
UMLS	C1864730
MedGen	350500
GARD	0018276
Is cancer (heuristic)	no

Also known as: BMPR1A hereditary mixed polyposis syndrome · hereditary mixed polyposis syndrome caused by mutation in BMPR1A · HMPS2 · polyposis syndrome, hereditary mixed, 2 · polyposis syndrome, hereditary mixed, type 2

Data availability: 196 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › digestive system disorder › hereditary mixed polyposis syndrome › polyposis syndrome, hereditary mixed, 2

Related subtypes (1): polyposis syndrome, hereditary mixed, 1

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

196 retrieved; paginated sample, class counts are floors:

106 uncertain significance, 65 conflicting classifications of pathogenicity, 7 benign/likely benign, 6 likely pathogenic, 4 pathogenic, 4 pathogenic/likely pathogenic, 3 benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1075769	NM_004329.3(BMPR1A):c.127_137del (p.Lys43fs)	BMPR1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1793638	NM_004329.3(BMPR1A):c.25A>T (p.Arg9Ter)	BMPR1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
183728	NM_004329.3(BMPR1A):c.1081C>T (p.Arg361Ter)	BMPR1A	Pathogenic	criteria provided, multiple submitters, no conflicts
2584111	NM_004329.3(BMPR1A):c.528C>A (p.Tyr176Ter)	BMPR1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2851621	NM_004329.3(BMPR1A):c.67+1G>A	BMPR1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
411642	NM_004329.3(BMPR1A):c.949_952del (p.Leu317fs)	BMPR1A	Pathogenic	criteria provided, multiple submitters, no conflicts
578684	NM_004329.3(BMPR1A):c.1374C>A (p.Tyr458Ter)	BMPR1A	Pathogenic	criteria provided, multiple submitters, no conflicts
8234	NM_004329.3(BMPR1A):c.370T>C (p.Cys124Arg)	BMPR1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2583147	NM_004329.3(BMPR1A):c.974dup (p.Leu326fs)	BMPR1A	Likely pathogenic	criteria provided, single submitter
2680204	NM_004329.3(BMPR1A):c.702del (p.Gln235fs)	BMPR1A	Likely pathogenic	criteria provided, single submitter
2680205	NM_004329.3(BMPR1A):c.79_83del (p.Asp27fs)	BMPR1A	Likely pathogenic	criteria provided, single submitter
3256737	NM_004329.3(BMPR1A):c.67G>C (p.Gly23Arg)	BMPR1A	Likely pathogenic	no assertion criteria provided
3338064	NM_004329.3(BMPR1A):c.868+2dup	BMPR1A	Likely pathogenic	no assertion criteria provided
825638	NM_004329.3(BMPR1A):c.531-1G>T	BMPR1A	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1016290	NM_004329.3(BMPR1A):c.103A>G (p.Met35Val)	BMPR1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127900	NM_004329.3(BMPR1A):c.1300G>A (p.Gly434Ser)	BMPR1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127902	NM_004329.3(BMPR1A):c.676G>T (p.Val226Phe)	BMPR1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127903	NM_004329.3(BMPR1A):c.953A>G (p.Tyr318Cys)	BMPR1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1332675	NM_004329.3(BMPR1A):c.1166+2T>C	BMPR1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
133717	NM_004329.3(BMPR1A):c.1327C>T (p.Arg443Cys)	BMPR1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
133718	NM_004329.3(BMPR1A):c.437T>C (p.Phe146Ser)	BMPR1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
136051	NM_004329.3(BMPR1A):c.569A>G (p.Asn190Ser)	BMPR1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
136054	NM_004329.3(BMPR1A):c.749T>C (p.Met250Thr)	BMPR1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
141022	NM_004329.3(BMPR1A):c.478A>G (p.Met160Val)	BMPR1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
141060	NM_004329.3(BMPR1A):c.1420G>C (p.Val474Leu)	BMPR1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
141113	NM_004329.3(BMPR1A):c.1333A>G (p.Ile445Val)	BMPR1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
141138	NM_004329.3(BMPR1A):c.1215A>C (p.Lys405Asn)	BMPR1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
141179	NM_004329.3(BMPR1A):c.118G>A (p.Asp40Asn)	BMPR1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
141898	NM_004329.3(BMPR1A):c.989C>T (p.Ala330Val)	BMPR1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
141942	NM_004329.3(BMPR1A):c.733T>A (p.Tyr245Asn)	BMPR1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 4 · 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

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

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
BMPR1A	HGNC:1076	ENSG00000107779	P36894	Bone morphogenetic protein receptor type-1A	gencc,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.

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BMPR1A	Kinase	yes	2.7.10.2	TGFB_receptor, Activin_recp, Prot_kinase_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
calcaneal tendon	1
saphenous vein	1
secondary oocyte	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BMPR1A	3,316

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BMPR1A	P36894	11

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
Signaling by BMP	1	356.9×	0.008	BMPR1A
Signaling by TGFB family members	1	115.3×	0.013	BMPR1A
Signal Transduction	1	10.2×	0.098	BMPR1A

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
neural plate mediolateral regionalization	1	16852.0×	0.001	BMPR1A
paraxial mesoderm structural organization	1	16852.0×	0.001	BMPR1A
positive regulation of cardiac ventricle development	1	16852.0×	0.001	BMPR1A
fibrous ring of heart morphogenesis	1	16852.0×	0.001	BMPR1A
positive regulation of transforming growth factor beta2 production	1	5617.3×	0.002	BMPR1A
regulation of lateral mesodermal cell fate specification	1	5617.3×	0.002	BMPR1A
atrioventricular valve development	1	4213.0×	0.002	BMPR1A
lateral mesoderm development	1	4213.0×	0.002	BMPR1A
atrioventricular node cell development	1	4213.0×	0.002	BMPR1A
Mullerian duct regression	1	3370.4×	0.002	BMPR1A
tricuspid valve morphogenesis	1	3370.4×	0.002	BMPR1A
regulation of cardiac muscle cell proliferation	1	3370.4×	0.002	BMPR1A
heart formation	1	3370.4×	0.002	BMPR1A
hindlimb morphogenesis	1	2808.7×	0.002	BMPR1A
anti-Mullerian hormone receptor signaling pathway	1	2808.7×	0.002	BMPR1A
ventricular compact myocardium morphogenesis	1	2407.4×	0.002	BMPR1A
dorsal aorta morphogenesis	1	2106.5×	0.002	BMPR1A
mesendoderm development	1	1872.4×	0.002	BMPR1A
mitral valve morphogenesis	1	1685.2×	0.002	BMPR1A
negative regulation of muscle cell differentiation	1	1685.2×	0.002	BMPR1A
pharyngeal arch artery morphogenesis	1	1685.2×	0.002	BMPR1A
dorsal/ventral axis specification	1	1532.0×	0.002	BMPR1A
negative regulation of smooth muscle cell migration	1	1532.0×	0.002	BMPR1A
cardiac right ventricle morphogenesis	1	1404.3×	0.002	BMPR1A
endocardial cushion formation	1	1404.3×	0.002	BMPR1A
regulation of cellular senescence	1	1404.3×	0.002	BMPR1A
ectoderm development	1	1203.7×	0.002	BMPR1A
cardiac conduction system development	1	1053.2×	0.002	BMPR1A
ventricular trabecula myocardium morphogenesis	1	1053.2×	0.002	BMPR1A
positive regulation of dendrite development	1	991.3×	0.002	BMPR1A

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
BMPR1A	MOMELOTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BMPR1A	11	4

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

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: 1; 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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06447961	Not specified	RECRUITING	PSYLIVED: the Psychological Impacts of Living With an Inherited Colorectal Cancer Predisposition Syndrome