Acromesomelic dysplasia 3

Summary

Acromesomelic dysplasia 3 (MONDO:0012274) is a disease caused by BMPR1B (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: BMPR1B (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 246

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	acromesomelic dysplasia 3
Mondo ID	MONDO:0012274
MeSH	C537913
OMIM	609441
DOID	DOID:0081237
UMLS	C4225404
MedGen	904735
GARD	0010077
Is cancer (heuristic)	no

Also known as: acromesomelic dysplasia 3 · acromesomelic dysplasia, Demirhan type · AMDD · chondrodysplasia acromesomelic with genital anomalies · chondrodysplasia, acromesomelic, with or without genital anomalies

Data availability: 246 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone development disease › osteochondrodysplasia › acromesomelic dysplasia › acromesomelic dysplasia 3

Related subtypes (7): Osebold-Remondini syndrome, acromesomelic dysplasia 2A, acromesomelic dysplasia 2C, Hunter-Thompson type, acromesomelic dysplasia 2B, acromesomelic dysplasia 1, Maroteaux type, acromesomelic dysplasia, Campailla Martinelli type, acromesomelic dysplasia 4

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

246 retrieved; paginated sample, class counts are floors:

116 uncertain significance, 82 likely benign, 17 conflicting classifications of pathogenicity, 12 benign, 10 pathogenic, 7 benign/likely benign, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
217254	NM_001203.3(BMPR1B):c.157T>C (p.Cys53Arg)	BMPR1B	Pathogenic	no assertion criteria provided
217255	NM_001203.3(BMPR1B):c.657G>A (p.Trp219Ter)	BMPR1B	Pathogenic	no assertion criteria provided
217256	NM_001203.3(BMPR1B):c.91C>T (p.Arg31Cys)	BMPR1B	Pathogenic	no assertion criteria provided
2926869	NM_001203.3(BMPR1B):c.402_405del (p.Cys135fs)	BMPR1B	Pathogenic	criteria provided, single submitter
3246657	NC_000004.11:g.(?96025576)(96036958_?)del	BMPR1B	Pathogenic	criteria provided, single submitter
3752436	NM_001203.3(BMPR1B):c.1111C>T (p.Arg371Ter)	BMPR1B	Pathogenic	criteria provided, single submitter
4309267	NM_001203.3(BMPR1B):c.247-2A>G	BMPR1B	Pathogenic	criteria provided, single submitter
446284	NM_001203.3(BMPR1B):c.640C>A (p.Arg214Ser)	BMPR1B	Pathogenic	no assertion criteria provided
6556	NM_001203.3(BMPR1B):c.1456C>T (p.Arg486Trp)	BMPR1B	Pathogenic	criteria provided, multiple submitters, no conflicts
6557	NM_001203.3(BMPR1B):c.361_368del (p.Gly121fs)	BMPR1B	Pathogenic	no assertion criteria provided
2921762	NM_001203.3(BMPR1B):c.585+1G>C	BMPR1B	Likely pathogenic	criteria provided, multiple submitters, no conflicts
689613	NM_001203.3(BMPR1B):c.988C>T (p.His330Tyr)	BMPR1B	Likely pathogenic	criteria provided, single submitter
1043555	NM_001203.3(BMPR1B):c.16G>A (p.Ala6Thr)	BMPR1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1133408	NM_001203.3(BMPR1B):c.229T>G (p.Ser77Ala)	BMPR1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1357550	NM_001203.3(BMPR1B):c.892G>A (p.Ala298Thr)	BMPR1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1383565	NM_001203.3(BMPR1B):c.1367G>A (p.Arg456Gln)	BMPR1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1512018	NM_001203.3(BMPR1B):c.43A>G (p.Lys15Glu)	BMPR1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1551029	NM_001203.3(BMPR1B):c.896A>G (p.Lys299Arg)	BMPR1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1914196	NM_001203.3(BMPR1B):c.1239A>T (p.Arg413Ser)	BMPR1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2048766	NM_001203.3(BMPR1B):c.1394A>G (p.Gln465Arg)	BMPR1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2055357	NM_001203.3(BMPR1B):c.85G>T (p.Val29Phe)	BMPR1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
285442	NM_001203.3(BMPR1B):c.289A>G (p.Thr97Ala)	BMPR1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3134594	NM_001203.3(BMPR1B):c.121G>T (p.Asp41Tyr)	BMPR1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
350117	NM_001203.3(BMPR1B):c.671G>A (p.Arg224His)	BMPR1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
350120	NM_001203.3(BMPR1B):c.762G>T (p.Arg254Ser)	BMPR1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
350124	NM_001203.3(BMPR1B):c.1105A>G (p.Asn369Asp)	BMPR1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
595516	NM_001203.3(BMPR1B):c.468A>G (p.Arg156=)	BMPR1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
663972	NM_001203.3(BMPR1B):c.251C>T (p.Thr84Ile)	BMPR1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
906582	NM_001203.3(BMPR1B):c.11G>A (p.Arg4Gln)	BMPR1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1001619	NM_001203.3(BMPR1B):c.508A>G (p.Ile170Val)	BMPR1B	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 17 · Orphanet: 5 · 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
BMPR1B	Strong	Autosomal recessive	acromesomelic dysplasia 3	17

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BMPR1B	Orphanet:2098	Acromesomelic dysplasia, Grebe type
BMPR1B	Orphanet:2639	Fibular aplasia-complex brachydactyly syndrome
BMPR1B	Orphanet:93384	Brachydactyly type C
BMPR1B	Orphanet:93388	Brachydactyly type A1
BMPR1B	Orphanet:93396	Brachydactyly type A2

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
BMPR1B	HGNC:1077	ENSG00000138696	O00238	Bone morphogenetic protein receptor type-1B	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BMPR1B	Bone morphogenetic protein receptor type-1B	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)
BMPR1B	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
bronchial epithelial cell	1
calcaneal tendon	1
cauda epididymis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BMPR1B	239	broad	marker	calcaneal tendon, bronchial epithelial cell, cauda epididymis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BMPR1B	116

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BMPR1B	O00238	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
Signaling by BMP	1	356.9×	0.008	BMPR1B
Signaling by TGFB family members	1	115.3×	0.013	BMPR1B
Signal Transduction	1	10.2×	0.098	BMPR1B

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
ovarian cumulus expansion	1	4213.0×	0.002	BMPR1B
endochondral bone morphogenesis	1	4213.0×	0.002	BMPR1B
negative regulation of chondrocyte proliferation	1	4213.0×	0.002	BMPR1B
ovulation cycle	1	2407.4×	0.003	BMPR1B
positive regulation of extrinsic apoptotic signaling pathway via death domain receptors	1	1404.3×	0.003	BMPR1B
chondrocyte development	1	936.2×	0.003	BMPR1B
positive regulation of cartilage development	1	936.2×	0.003	BMPR1B
proteoglycan biosynthetic process	1	842.6×	0.003	BMPR1B
positive regulation of chondrocyte differentiation	1	802.5×	0.003	BMPR1B
cartilage condensation	1	766.0×	0.003	BMPR1B
retinal ganglion cell axon guidance	1	766.0×	0.003	BMPR1B
central nervous system neuron differentiation	1	601.9×	0.004	BMPR1B
cellular response to BMP stimulus	1	561.7×	0.004	BMPR1B
dorsal/ventral pattern formation	1	421.3×	0.004	BMPR1B
positive regulation of bone mineralization	1	391.9×	0.004	BMPR1B
eye development	1	351.1×	0.005	BMPR1B
cellular response to growth factor stimulus	1	318.0×	0.005	BMPR1B
retina development in camera-type eye	1	255.3×	0.006	BMPR1B
positive regulation of osteoblast differentiation	1	224.7×	0.006	BMPR1B
BMP signaling pathway	1	200.6×	0.006	BMPR1B
MAPK cascade	1	153.2×	0.008	BMPR1B
osteoblast differentiation	1	121.2×	0.010	BMPR1B
positive regulation of gene expression	1	38.7×	0.029	BMPR1B
inflammatory response	1	37.7×	0.029	BMPR1B
cell differentiation	1	29.1×	0.036	BMPR1B
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	BMPR1B

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
BMPR1B	MOMELOTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BMPR1B	28	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	BMPR1B
FEDRATINIB	4	BMPR1B
AXITINIB	4	BMPR1B
RUXOLITINIB	4	BMPR1B
VANDETANIB	4	BMPR1B
GILTERITINIB	4	BMPR1B
PAZOPANIB	4	BMPR1B
SUNITINIB	4	BMPR1B
DASATINIB	4	BMPR1B
QUIZARTINIB	4	BMPR1B
CRIZOTINIB	4	BMPR1B
SARACATINIB	3	BMPR1B
LINIFANIB	3	BMPR1B
CANERTINIB	3	BMPR1B
ALVOCIDIB	3	BMPR1B
LESTAURTINIB	3	BMPR1B
SU-014813	2	BMPR1B
R-406	2	BMPR1B
AT-9283	2	BMPR1B
ZILURGISERTIB	2	BMPR1B
TOZASERTIB	2	BMPR1B
KER-047	2	BMPR1B
TAK-285	1	BMPR1B
KW-2449	1	BMPR1B
MLN-8054	1	BMPR1B
XL-228	1	BMPR1B
ASP-3026	1	BMPR1B
AEW-541	1	BMPR1B

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
BMPR1B	166	Binding:164, ADMET:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BMPR1B	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
BMPR1B	166

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

28 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	BMPR1B
FEDRATINIB	4	BMPR1B
AXITINIB	4	BMPR1B
RUXOLITINIB	4	BMPR1B
VANDETANIB	4	BMPR1B
GILTERITINIB	4	BMPR1B
PAZOPANIB	4	BMPR1B
SUNITINIB	4	BMPR1B
DASATINIB	4	BMPR1B
QUIZARTINIB	4	BMPR1B
CRIZOTINIB	4	BMPR1B
SARACATINIB	3	BMPR1B
LINIFANIB	3	BMPR1B
CANERTINIB	3	BMPR1B
ALVOCIDIB	3	BMPR1B
LESTAURTINIB	3	BMPR1B
SU-014813	2	BMPR1B
R-406	2	BMPR1B
AT-9283	2	BMPR1B
ZILURGISERTIB	2	BMPR1B
TOZASERTIB	2	BMPR1B
KER-047	2	BMPR1B
TAK-285	1	BMPR1B
KW-2449	1	BMPR1B
MLN-8054	1	BMPR1B
XL-228	1	BMPR1B
ASP-3026	1	BMPR1B
AEW-541	1	BMPR1B

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	BMPR1B
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: 0.