acromesomelic dysplasia 2B

Summary

acromesomelic dysplasia 2B (MONDO:0009231) is a disease with 5 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 5
• ClinVar variants: 52
• Phenotypes (HPO): 15

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		16	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0000446	Narrow nasal bridge	Very frequent (80-99%)
HP:0001156	Brachydactyly	Very frequent (80-99%)
HP:0001172	Abnormal thumb morphology	Very frequent (80-99%)
HP:0001376	Limitation of joint mobility	Very frequent (80-99%)
HP:0002818	Abnormal morphology of the radius	Very frequent (80-99%)
HP:0002983	Micromelia	Very frequent (80-99%)
HP:0002992	Abnormality of tibia morphology	Very frequent (80-99%)
HP:0003272	Abnormality of the hip bone	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0005048	Synostosis of carpal bones	Very frequent (80-99%)
HP:0005930	Abnormality of epiphysis morphology	Very frequent (80-99%)
HP:0006492	Aplasia/Hypoplasia of the fibula	Very frequent (80-99%)
HP:0007598	Bilateral single transverse palmar creases	Very frequent (80-99%)
HP:0008368	Tarsal synostosis	Very frequent (80-99%)
HP:0040071	Abnormal morphology of ulna	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	acromesomelic dysplasia 2B
Mondo ID	MONDO:0009231
MeSH	C537931
OMIM	228900
Orphanet	2639
DOID	DOID:0050790
SNOMED CT	715474004
UMLS	C1856738
MedGen	346432
GARD	0009879
Is cancer (heuristic)	no

Also known as: acromesomelic dysplasia 2B · Du Pan syndrome · fibular hypoplasia and complex brachydactyly

Data availability: 52 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › acromesomelic dysplasia 2B

Related subtypes (218): immunodeficiency-centromeric instability-facial anomalies syndrome, hypercalcemia, infantile, Ochoa syndrome, autosomal recessive Ehlers-Danlos syndrome, vascular type, hydrolethalus syndrome, 3-M syndrome, isolated hyperchlorhidrosis, dacryocystitis-osteopoikilosis syndrome, Hutchinson-Gilford progeria syndrome, achalasia microcephaly syndrome, acrorenal syndrome, autosomal recessive, beta-ketothiolase deficiency, autosomal recessive Alport syndrome, Alstrom syndrome, microphthalmia with limb anomalies, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, Behr syndrome, bifid nose, autosomal recessive, Bloom syndrome, Bowen-Conradi syndrome, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, heart defects-limb shortening syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, COFS syndrome, craniometaphyseal dysplasia, autosomal recessive, Fraser syndrome, cystic fibrosis, polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly, persistent hyperplastic primary vitreous, autosomal recessive, Donnai-Barrow syndrome, Schöpf-Schulz-Passarge syndrome, cleft lip/palate-ectodermal dysplasia syndrome, Ellis-van Creveld syndrome, Wolcott-Rallison syndrome, autosomal recessive faciodigitogenital syndrome, brittle cornea syndrome, triple-A syndrome, autosomal recessive humeroradial synostosis, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, hydrocephalus, nonsyndromic, autosomal recessive 1, autosomal recessive hydrocephalus due to congenital stenosis of aqueduct of Sylvius, hypertelorism, microtia, facial clefting syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, Vici syndrome, Johanson-Blizzard syndrome, autosomal recessive Kenny-Caffey syndrome, Papillon-Lefevre disease, Haim-Munk syndrome, Laurence-Moon syndrome, Donohue syndrome, lipase deficiency, combined, autosomal recessive familial Mediterranean fever, thiamine-responsive megaloblastic anemia syndrome, cartilage-hair hypoplasia, Nijmegen breakage syndrome, pseudo-TORCH syndrome, Galloway-Mowat syndrome, mulibrey nanism, myotonia congenita, autosomal recessive, Schwartz-Jampel syndrome, proteosome-associated autoinflammatory syndrome, Netherton syndrome, Niemann-Pick disease type A, oculodentodigital dysplasia, autosomal recessive, odonto-onycho-dermal dysplasia, autosomal recessive omodysplasia, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, phenylketonuria, Bjornstad syndrome, Laron syndrome, autosomal recessive polycystic kidney disease, autosomal recessive inherited pseudoxanthoma elasticum, autosomal recessive multiple pterygium syndrome, rapadilino syndrome, short-rib thoracic dysplasia 9 with or without polydactyly, autosomal recessive Robinow syndrome, Sjogren-Larsson syndrome, scapuloperoneal spinal muscular atrophy, autosomal recessive, spondyloepiphyseal dysplasia tarda, autosomal recessive, inherited threoninemia, Pendred syndrome, autosomal recessive spondylocostal dysostosis, Werner syndrome, ABCD syndrome, Naxos disease, autosomal recessive amelia, human HOXA1 syndromes, sickle cell disease, autosomal recessive proximal renal tubular acidosis, hyper-IgM syndrome type 2, temtamy preaxial brachydactyly syndrome, TH-deficient dopa-responsive dystonia, craniosynostosis syndrome, autosomal recessive, Niemann-Pick disease type B, skin fragility-woolly hair-palmoplantar keratoderma syndrome, CoQ-responsive OXPHOS deficiency, familial adenomatous polyposis 2, Pierson syndrome, palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome, cardiomyopathy-hypotonia-lactic acidosis syndrome, PHARC syndrome, Kahrizi syndrome, cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies, congenital prothrombin deficiency, immunodeficiency 31B, dyskeratosis congenita, autosomal recessive 2, dyskeratosis congenita, autosomal recessive 3, Nestor-Guillermo progeria syndrome, leukoencephalopathy with calcifications and cysts, mitochondrial pyruvate carrier deficiency, branched-chain keto acid dehydrogenase kinase deficiency, dyskeratosis congenita, autosomal recessive 5, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome, alacrima, achalasia, and intellectual disability syndrome, hyperlipoproteinemia, type 1D, microcephaly and chorioretinopathy 2, congenital stationary night blindness 1G, combined oxidative phosphorylation deficiency 29, hypermanganesemia with dystonia 2, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, gnb5-related intellectual disability-cardiac arrhythmia syndrome, autosomal recessive spastic paraplegia type 78, autosomal recessive limb-girdle muscular dystrophy, Bardet-Biedl syndrome, autosomal recessive cerebellar ataxia, neuronopathy, distal hereditary motor, autosomal recessive, UV-sensitive syndrome, Ehlers-Danlos syndrome, kyphoscoliotic type 1, Cockayne syndrome, hyperphenylalaninemia due to tetrahydrobiopterin deficiency, leukoencephalopathy-palmoplantar keratoderma syndrome, autosomal recessive hypohidrotic ectodermal dysplasia, Warburg micro syndrome, autosomal recessive primary microcephaly, autosomal recessive progressive external ophthalmoplegia, Meier-Gorlin syndrome, autosomal recessive sideroblastic anemia, autosomal recessive intermediate Charcot-Marie-Tooth disease, Perrault syndrome, autosomal recessive hypophosphatemic rickets, de Barsy syndrome, leukocyte adhesion deficiency, Senior-Loken syndrome, autosomal recessive spastic ataxia, childhood-onset autosomal recessive myopathy with external ophthalmoplegia, autosomal recessive cerebral atrophy, GM3 synthase deficiency, autosomal recessive distal renal tubular acidosis, pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome, autosomal recessive brachyolmia, Aicardi-Goutieres syndrome, homocystinuria without methylmalonic aciduria, Niemann-Pick disease type C, nephronophthisis, autosomal recessive osteopetrosis, peroxisome biogenesis disorder, congenital non-bullous ichthyosiform erythroderma, Seckel syndrome, Usher syndrome, autosomal recessive cutis laxa type 1, autosomal recessive cutis laxa type 2, hearing loss, autosomal recessive, microcephaly, growth restriction, and increased sister chromatid exchange 2, encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1, congenital vertebral-cardiac-renal anomalies syndrome, hair defect with photosensitivity and intellectual disability syndrome, autosomal recessive severe congenital neutropenia, severe combined immunodeficiency due to CARMIL2 deficiency, extraoral halitosis due to methanethiol oxidase deficiency, neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, mitochondrial complex 2 deficiency, nuclear type 3, mitochondrial complex 2 deficiency, nuclear type 4, mismatch repair cancer syndrome, spondyloepimetaphyseal dysplasia with joint laxity, type 3, Kilquist syndrome, Duane anomaly-myopathy-scoliosis syndrome, autosomal recessive axonal charcot-marie-tooth disease due to copper metabolism defect, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome, congenital myopathy with reduced type 2 muscle fibers, NAD(P)HX dehydratase deficiency, autosomal recessive ocular albinism, ichthyosis linearis circumflexa, eosinophil peroxidase deficiency, hyperphenylalaninemia due to DNAJC12 deficiency, autosomal recessive epidermolytic ichthyosis, Ehlers-Danlos syndrome, classic-like, 2, joint laxity, short stature, and myopia, HELIX syndrome, auditory neuropathy-optic atrophy syndrome, glycosylphosphatidylinositol biosynthesis defect 15, neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, SCN4A-related myopathy, autosomal recessive, Uner Tan Syndrome, nephropathic cystinosis, Imerslund-Grasbeck syndrome type 1, Imerslund-Grasbeck syndrome type 2, permanent neonatal diabetes mellitus 1, growth hormone insensitivity with immune dysregulation 1, autosomal recessive, Rajab interstitial lung disease with brain calcifications 1, Roberts-SC phocomelia syndrome, neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, RPE65-related recessive retinopathy, GUCY2D-related recessive retinopathy, autosomal recessive titinopathy, intellectual disability, autosomal recessive, ALPL-related autosomal recessive hypophosphatasia, spastic paraplegia 18b, autosomal recessive, CEP164-related ciliopathy, RP1-related recessive retinopathy, pseudohypoaldosteronism, type IB2, autosomal recessive, pseudohypoaldosteronism, type IB3, autosomal recessive, spastic paraplegia 30B, autosomal recessive, cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, brain small vessel disease 2B, autosomal recessive, IMPG1-related recessive retinopathy, PROM1-related recessive retinopathy

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

52 retrieved; paginated sample, class counts are floors:

12 uncertain significance, 12 conflicting classifications of pathogenicity, 11 benign/likely benign, 10 benign, 5 pathogenic, 1 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
8387	NM_000557.5(GDF5):c.[1309_1311del;1315T>A1319A>T]		Pathogenic	no assertion criteria provided
446284	NM_001203.3(BMPR1B):c.640C>A (p.Arg214Ser)	BMPR1B	Pathogenic	no assertion criteria provided
817567	NM_000557.5(GDF5):c.788_810dup (p.Gly271Ter)	GDF5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8381	NM_000557.5(GDF5):c.1322T>C (p.Leu441Pro)	GDF5	Pathogenic	criteria provided, single submitter
8393	NM_000557.5(GDF5):c.1133G>A (p.Arg378Gln)	GDF5-AS1	Pathogenic	no assertion criteria provided
8394	NM_000557.5(GDF5):c.1306C>A (p.Pro436Thr)	GDF5-AS1	Pathogenic	no assertion criteria provided
3764682	NM_000557.5(GDF5):c.784del (p.Gln262fs)	GDF5	Likely pathogenic	criteria provided, single submitter
430720	NM_001148.6(ANK2):c.7951G>C (p.Val2651Leu)	ANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
338320	NM_000557.5(GDF5):c.855C>T (p.Gly285=)	GDF5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
338323	NM_000557.5(GDF5):c.168C>A (p.Asn56Lys)	GDF5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
895466	NM_000557.5(GDF5):c.*259G>C	GDF5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
895609	NM_000557.5(GDF5):c.631+6G>A	GDF5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
895673	NM_000557.5(GDF5):c.206C>G (p.Ala69Gly)	GDF5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
896024	NM_000557.5(GDF5):c.-134C>G	GDF5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
897014	NM_000557.5(GDF5):c.483G>A (p.Pro161=)	GDF5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
897561	NM_000557.5(GDF5):c.57G>T (p.Leu19=)	GDF5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2631825	NM_000557.5(GDF5):c.1420A>T (p.Ile474Phe)	GDF5-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
338317	NM_000557.5(GDF5):c.1104C>T (p.Thr368=)	GDF5-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
896867	NM_000557.5(GDF5):c.1374C>G (p.Pro458=)	GDF5-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1019956	NM_000557.5(GDF5):c.1198_1200dup (p.Cys400dup)	GDF5	Uncertain significance	criteria provided, multiple submitters, no conflicts
2143629	NM_000557.5(GDF5):c.519G>A (p.Met173Ile)	GDF5	Uncertain significance	criteria provided, multiple submitters, no conflicts
338327	NM_000557.5(GDF5):c.-220C>T	GDF5	Uncertain significance	criteria provided, single submitter
3893112	NM_000557.5(GDF5):c.71C>G (p.Thr24Ser)	GDF5	Uncertain significance	criteria provided, single submitter
595155	NM_000557.5(GDF5):c.25T>C (p.Phe9Leu)	GDF5	Uncertain significance	criteria provided, multiple submitters, no conflicts
895535	NM_000557.5(GDF5):c.1067A>G (p.Asn356Ser)	GDF5	Uncertain significance	criteria provided, multiple submitters, no conflicts
895610	NM_000557.5(GDF5):c.506C>A (p.Pro169His)	GDF5	Uncertain significance	criteria provided, single submitter
895672	NM_000557.5(GDF5):c.226G>T (p.Ala76Ser)	GDF5	Uncertain significance	criteria provided, single submitter
897084	NM_000557.5(GDF5):c.182G>A (p.Gly61Glu)	GDF5	Uncertain significance	criteria provided, single submitter
338315	NM_000557.5(GDF5):c.*166G>A	GDF5-AS1	Uncertain significance	criteria provided, single submitter
895743	NM_000557.5(GDF5):c.-97T>C	LOC109461476	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 37 · Orphanet: 15 · 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
GDF5	Definitive	Autosomal recessive	acromesomelic dysplasia 2A	20
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
GDF5	Orphanet:2098	Acromesomelic dysplasia, Grebe type
GDF5	Orphanet:2639	Fibular aplasia-complex brachydactyly syndrome
GDF5	Orphanet:3237	Multiple synostoses syndrome
GDF5	Orphanet:3250	Proximal symphalangism
GDF5	Orphanet:63442	Angel-shaped phalango-epiphyseal dysplasia
GDF5	Orphanet:93384	Brachydactyly type C
GDF5	Orphanet:93388	Brachydactyly type A1
GDF5	Orphanet:93396	Brachydactyly type A2
GDF5	Orphanet:968	Acromesomelic dysplasia, Hunter-Thompson type
ANK2	Orphanet:101016	Romano-Ward syndrome

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BMPR1B	HGNC:1077	ENSG00000138696	O00238	Bone morphogenetic protein receptor type-1B	gencc,clinvar
GDF5	HGNC:4220	ENSG00000125965	P43026	Growth/differentiation factor 5	gencc,clinvar
ANKRD36	HGNC:24079	ENSG00000135976	A6QL64	Ankyrin repeat domain-containing protein 36A	clinvar
GDF5-AS1	HGNC:33435	ENSG00000204183	Q5U4N7	Protein GDF5-AS1, mitochondrial	clinvar
ANK2	HGNC:493	ENSG00000145362	Q01484	Ankyrin-2	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.
GDF5	Growth/differentiation factor 5	Growth factor involved in bone and cartilage formation.
ANK2	Ankyrin-2	Plays an essential role in the localization and membrane stabilization of ion transporters and ion channels in several cell types, including cardiomyocytes, as well as in striated muscle cells.

Protein-family classification

Druggable: 1 · Difficult: 2 · Unknown: 2 · Druggable fraction: 0.2

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	2	6.9×	0.089
Kinase	1	5.5×	0.252
Other/Unknown	2	0.7×	0.877

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BMPR1B	Kinase	yes	2.7.10.2	TGFB_receptor, Activin_recp, Prot_kinase_dom
GDF5	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGF-beta-like
ANKRD36	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, CC144C-like_CC_dom
GDF5-AS1	Other/Unknown	no		GDF5OS
ANK2	Scaffold/PPI	no		Death_dom, ZU5_dom, Ankyrin_rpt

Expression context

Cohort genes with no expression data: 0.

3 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	2
bronchial epithelial cell	1
cauda epididymis	1
cartilage tissue	1
parotid gland	1
pericardium	1
corpus callosum	1
sural nerve	1
colonic epithelium	1
cortical plate	1
ventricular zone	1
lateral nuclear group of thalamus	1
substantia nigra pars compacta	1
substantia nigra pars reticulata	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
GDF5	116	broad	yes	parotid gland, pericardium, cartilage tissue
ANKRD36	137	ubiquitous	marker	corpus callosum, calcaneal tendon, sural nerve
GDF5-AS1	68		yes	colonic epithelium, cortical plate, ventricular zone
ANK2	281	ubiquitous	marker	substantia nigra pars compacta, lateral nuclear group of thalamus, substantia nigra pars reticulata

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ANK2	6,423
GDF5	1,486
ANKRD36	1,330
BMPR1B	116
GDF5-AS1	15

Intra-cohort edges

A	B	Sources
BMPR1B	GDF5	biogrid_interaction, intact

Structural data

PDB: 3 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GDF5	P43026	15
ANK2	Q01484	11
BMPR1B	O00238	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GDF5-AS1	Q5U4N7	58.79
ANKRD36	A6QL64	50.82

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. Enrichment computed across 5 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interaction between L1 and Ankyrins	1	122.8×	0.055	ANK2
Signaling by BMP	1	119.0×	0.055	BMPR1B
Molecules associated with elastic fibres	1	102.9×	0.055	GDF5
ER to Golgi Anterograde Transport	1	44.3×	0.061	ANK2
L1CAM interactions	1	40.1×	0.061	ANK2
Signaling by TGFB family members	1	38.5×	0.061	BMPR1B
COPI-mediated anterograde transport	1	36.6×	0.061	ANK2
Transport to the Golgi and subsequent modification	1	34.3×	0.061	ANK2
Asparagine N-linked glycosylation	1	20.0×	0.093	ANK2
Axon guidance	1	15.1×	0.106	ANK2
Nervous system development	1	14.3×	0.106	ANK2
Membrane Trafficking	1	12.4×	0.109	ANK2
Vesicle-mediated transport	1	11.6×	0.109	ANK2
Post-translational protein modification	1	6.4×	0.180	ANK2
Developmental Biology	1	4.8×	0.219	ANK2
Metabolism of proteins	1	4.1×	0.237	ANK2
Signal Transduction	1	3.4×	0.267	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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of chondrocyte differentiation	2	535.0×	4e-04	BMPR1B, GDF5
protein localization to T-tubule	1	5617.3×	0.003	ANK2
atrial cardiac muscle cell to AV node cell communication	1	5617.3×	0.003	ANK2
SA node cell to atrial cardiac muscle cell communication	1	5617.3×	0.003	ANK2
BMP signaling pathway	2	133.8×	0.003	BMPR1B, GDF5
protein localization to M-band	1	2808.7×	0.004	ANK2
ossification involved in bone remodeling	1	1872.4×	0.004	GDF5
regulation of atrial cardiac muscle cell action potential	1	1872.4×	0.004	ANK2
ovarian cumulus expansion	1	1404.3×	0.004	BMPR1B
endochondral bone morphogenesis	1	1404.3×	0.004	BMPR1B
negative regulation of chondrocyte proliferation	1	1404.3×	0.004	BMPR1B
chondroblast differentiation	1	1123.5×	0.004	GDF5
sarcoplasmic reticulum calcium ion transport	1	1123.5×	0.004	ANK2
membrane depolarization during SA node cell action potential	1	1123.5×	0.004	ANK2
positive regulation of potassium ion import across plasma membrane	1	1123.5×	0.004	ANK2
paranodal junction assembly	1	936.2×	0.004	ANK2
T-tubule organization	1	936.2×	0.004	ANK2
hindlimb morphogenesis	1	936.2×	0.004	GDF5
SA node cell action potential	1	936.2×	0.004	ANK2
regulation of SA node cell action potential	1	936.2×	0.004	ANK2
ovulation cycle	1	802.5×	0.004	BMPR1B
response to methylmercury	1	802.5×	0.004	ANK2
negative regulation of mesenchymal cell apoptotic process	1	802.5×	0.004	GDF5
atrial septum development	1	702.2×	0.004	ANK2
forelimb morphogenesis	1	702.2×	0.004	GDF5
protein localization to endoplasmic reticulum	1	702.2×	0.004	ANK2
atrial cardiac muscle cell action potential	1	561.7×	0.005	ANK2
mesenchymal cell apoptotic process	1	510.7×	0.005	GDF5
positive regulation of gene expression	2	25.8×	0.005	BMPR1B, ANK2
positive regulation of extrinsic apoptotic signaling pathway via death domain receptors	1	468.1×	0.006	BMPR1B

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 5 evidence-associated genes (20%) 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
GDF5	0	0
ANKRD36	0	0
GDF5-AS1	0	0
ANK2	0	0

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: 4; 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	4	GDF5, ANKRD36, GDF5-AS1, ANK2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GDF5	0	—
ANKRD36	0	—
GDF5-AS1	0	—
ANK2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.