autosomal dominant Robinow syndrome

Summary

autosomal dominant Robinow syndrome (MONDO:0008389) is a disease with 4 cohort genes. The dominant Reactome pathway is WNT5:FZD7-mediated leishmania damping (3 cohort genes).

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 4
• ClinVar variants: 1
• Phenotypes (HPO): 80

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		100	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0000316	Hypertelorism	Very frequent (80-99%)
HP:0000431	Wide nasal bridge	Very frequent (80-99%)
HP:0000445	Wide nose	Very frequent (80-99%)
HP:0000463	Anteverted nares	Very frequent (80-99%)
HP:0001156	Brachydactyly	Very frequent (80-99%)
HP:0002983	Micromelia	Very frequent (80-99%)
HP:0003196	Short nose	Very frequent (80-99%)
HP:0004279	Short palm	Very frequent (80-99%)
HP:0008736	Hypoplasia of penis	Very frequent (80-99%)
HP:0011800	Midface retrusion	Very frequent (80-99%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000059	Hypoplastic labia majora	Frequent (30-79%)
HP:0000060	Clitoral hypoplasia	Frequent (30-79%)
HP:0000064	Hypoplastic labia minora	Frequent (30-79%)
HP:0000168	Abnormality of the gingiva	Frequent (30-79%)
HP:0000212	Gingival overgrowth	Frequent (30-79%)
HP:0000256	Macrocephaly	Frequent (30-79%)
HP:0000278	Retrognathia	Frequent (30-79%)
HP:0000286	Epicanthus	Frequent (30-79%)
HP:0000343	Long philtrum	Frequent (30-79%)
HP:0000347	Micrognathia	Frequent (30-79%)
HP:0000520	Proptosis	Frequent (30-79%)
HP:0000527	Long eyelashes	Frequent (30-79%)
HP:0000582	Upslanted palpebral fissure	Frequent (30-79%)
HP:0000637	Long palpebral fissure	Frequent (30-79%)
HP:0000767	Pectus excavatum	Frequent (30-79%)
HP:0001537	Umbilical hernia	Frequent (30-79%)
HP:0002007	Frontal bossing	Frequent (30-79%)
HP:0002705	High, narrow palate	Frequent (30-79%)
HP:0002714	Downturned corners of mouth	Frequent (30-79%)
HP:0002937	Hemivertebrae	Frequent (30-79%)
HP:0003312	Abnormal form of the vertebral bodies	Frequent (30-79%)
HP:0003510	Severe short stature	Frequent (30-79%)
HP:0004209	Clinodactyly of the 5th finger	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0005280	Depressed nasal bridge	Frequent (30-79%)
HP:0007665	Curly eyelashes	Frequent (30-79%)
HP:0010297	Bifid tongue	Frequent (30-79%)
HP:0010807	Open bite	Frequent (30-79%)
HP:0011220	Prominent forehead	Frequent (30-79%)
HP:0012905	Euryblepharon	Frequent (30-79%)
HP:0009099	Median cleft palate	Frequent (30-79%)
HP:0000023	Inguinal hernia	Occasional (5-29%)
HP:0000036	Abnormality of the penis	Occasional (5-29%)
HP:0000039	Epispadias	Occasional (5-29%)
HP:0000047	Hypospadias	Occasional (5-29%)
HP:0000322	Short philtrum	Occasional (5-29%)
HP:0000358	Posteriorly rotated ears	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000369	Low-set ears	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant Robinow syndrome
Mondo ID	MONDO:0008389
Orphanet	3107
ICD-11	807338758
SNOMED CT	76520005
UMLS	C5200540
MedGen	1675001
GARD	0016620
Is cancer (heuristic)	no

Also known as: autosomal dominant Robinow syndrome · Robinow syndrome, autosomal dominant · Robinow syndrome, autosomal dominant type

Data availability: 1 ClinVar variant · 5 GenCC gene-disease records.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › autosomal dominant Robinow syndrome

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid syndrome

Subtypes (3): autosomal dominant Robinow syndrome 2, autosomal dominant Robinow syndrome 3, autosomal dominant Robinow syndrome 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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3773755	NM_003392.7(WNT5A):c.992G>A (p.Gly331Asp)	WNT5A	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 20 · 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
DVL1	Definitive	Autosomal dominant	autosomal dominant Robinow syndrome 2	4
DVL3	Definitive	Autosomal dominant	autosomal dominant Robinow syndrome 3	4
WNT5A	Definitive	Autosomal dominant	autosomal dominant Robinow syndrome 1	7
FZD2	Supportive	Autosomal dominant	autosomal dominant Robinow syndrome	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WNT5A	Orphanet:3107	Autosomal dominant Robinow syndrome
DVL1	Orphanet:3107	Autosomal dominant Robinow syndrome
DVL3	Orphanet:3107	Autosomal dominant Robinow syndrome
FZD2	Orphanet:3107	Autosomal dominant Robinow syndrome
FZD2	Orphanet:93328	Autosomal dominant omodysplasia

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
WNT5A	HGNC:12784	ENSG00000114251	P41221	Protein Wnt-5a	gencc,clinvar
DVL1	HGNC:3084	ENSG00000107404	O14640	Segment polarity protein dishevelled homolog DVL-1	gencc
DVL3	HGNC:3087	ENSG00000161202	Q92997	Segment polarity protein dishevelled homolog DVL-3	gencc
FZD2	HGNC:4040	ENSG00000180340	Q14332	Frizzled-2	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
WNT5A	Protein Wnt-5a	Ligand for members of the frizzled family of seven transmembrane receptors.
DVL1	Segment polarity protein dishevelled homolog DVL-1	Participates in Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors.
DVL3	Segment polarity protein dishevelled homolog DVL-3	Involved in the signal transduction pathway mediated by multiple Wnt genes.
FZD2	Frizzled-2	Receptor for Wnt proteins.

Protein-family classification

Druggable: 1 · Difficult: 2 · Unknown: 1 · Druggable fraction: 0.25

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	8.6×	0.056
GPCR	1	6.0×	0.235
Other/Unknown	1	0.5×	0.962

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
WNT5A	Other/Unknown	no		Wnt, Wnt_CS, Wnt_C
DVL1	Scaffold/PPI	no		DEP_dom, DIX, PDZ
DVL3	Scaffold/PPI	no		DEP_dom, DIX, PDZ
FZD2	GPCR	yes		Frizzled/Smoothened_7TM, Frizzled/SFRP, GPCR_2-like_7TM

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
stromal cell of endometrium	2
decidua	1
parotid gland	1
gastrocnemius	1
hindlimb stylopod muscle	1
lower esophagus mucosa	1
ganglionic eminence	1
mucosa of stomach	1
dorsal root ganglion	1
embryo	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
WNT5A	258	ubiquitous	marker	stromal cell of endometrium, parotid gland, decidua
DVL1	290	ubiquitous	marker	hindlimb stylopod muscle, gastrocnemius, lower esophagus mucosa
DVL3	287	ubiquitous	marker	stromal cell of endometrium, ganglionic eminence, mucosa of stomach
FZD2	197	ubiquitous	marker	ventricular zone, embryo, dorsal root ganglion

Protein interactions among cohort

Intra-cohort edges: 5.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WNT5A	3,799
DVL3	3,185
DVL1	2,949
FZD2	1,764

Intra-cohort edges

A	B	Sources
DVL1	DVL3	intact
DVL1	FZD2	string_interaction
DVL1	WNT5A	string_interaction
DVL3	WNT5A	string_interaction
FZD2	WNT5A	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DVL3	Q92997	9
FZD2	Q14332	5
DVL1	O14640	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
WNT5A	P41221	88.23

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. Enrichment computed across 4 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
WNT5:FZD7-mediated leishmania damping	3	713.8×	4e-08	WNT5A, DVL1, DVL3
TCF dependent signaling in response to WNT	4	117.7×	4e-08	WNT5A, DVL1, DVL3, FZD2
Disassembly of the destruction complex and recruitment of AXIN to the membrane	3	267.7×	5e-07	DVL1, DVL3, FZD2
PCP/CE pathway	3	225.4×	6e-07	WNT5A, DVL1, DVL3
Negative regulation of TCF-dependent signaling by DVL-interacting proteins	2	1142.0×	3e-06	DVL1, DVL3
WNT mediated activation of DVL	2	713.8×	7e-06	DVL1, DVL3
WNT5A-dependent internalization of FZD2, FZD5 and ROR2	2	439.2×	2e-05	WNT5A, FZD2
Degradation of DVL	2	119.0×	2e-04	DVL1, DVL3
Asymmetric localization of PCP proteins	2	102.0×	3e-04	WNT5A, FZD2
Class B/2 (Secretin family receptors)	2	95.2×	3e-04	WNT5A, FZD2
Ca2+ pathway	2	89.2×	3e-04	WNT5A, FZD2
RHO GTPases Activate Formins	2	38.8×	0.001	DVL1, DVL3
WNT5A-dependent internalization of FZD4	1	190.3×	0.007	WNT5A
Negative regulation of TCF-dependent signaling by WNT ligand antagonists	1	178.4×	0.007	WNT5A
WNT ligand biogenesis and trafficking	1	105.7×	0.011	WNT5A
Cargo recognition for clathrin-mediated endocytosis	1	26.2×	0.040	WNT5A
Clathrin-mediated endocytosis	1	21.3×	0.046	WNT5A

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
non-canonical Wnt signaling pathway	4	581.1×	1e-09	WNT5A, DVL1, DVL3, FZD2
Wnt signaling pathway, planar cell polarity pathway	4	455.5×	2e-09	WNT5A, DVL1, DVL3, FZD2
positive regulation of neuron projection arborization	3	1579.9×	2e-08	WNT5A, DVL1, DVL3
canonical Wnt signaling pathway	4	153.2×	8e-08	WNT5A, DVL1, DVL3, FZD2
cochlea morphogenesis	3	435.8×	6e-07	WNT5A, DVL1, FZD2
presynapse assembly	2	601.9×	1e-04	WNT5A, DVL1
regulation of postsynapse organization	2	263.3×	5e-04	WNT5A, DVL1
outflow tract morphogenesis	2	153.2×	0.001	DVL1, FZD2
heart looping	2	133.8×	0.002	WNT5A, DVL1
regulation of protein localization	2	102.8×	0.002	DVL1, DVL3
positive regulation of DNA-templated transcription	3	21.0×	0.003	WNT5A, DVL3, FZD2
chemoattraction of serotonergic neuron axon	1	4213.0×	0.003	WNT5A
negative regulation of cell proliferation in midbrain	1	4213.0×	0.003	WNT5A
positive regulation of JNK cascade	2	81.8×	0.003	WNT5A, DVL3
optic cup formation involved in camera-type eye development	1	2106.5×	0.003	WNT5A
chemorepulsion of dopaminergic neuron axon	1	2106.5×	0.003	WNT5A
hypophysis morphogenesis	1	2106.5×	0.003	WNT5A
positive regulation of timing of anagen	1	2106.5×	0.003	WNT5A
convergent extension involved in organogenesis	1	2106.5×	0.003	WNT5A
cervix development	1	2106.5×	0.003	WNT5A
lateral sprouting involved in mammary gland duct morphogenesis	1	2106.5×	0.003	WNT5A
postsynapse assembly	1	2106.5×	0.003	WNT5A
regulation of postsynaptic cytosolic calcium ion concentration	1	2106.5×	0.003	WNT5A
positive regulation of protein localization to presynapse	1	2106.5×	0.003	DVL1
positive regulation of neuron projection development	2	68.5×	0.003	WNT5A, DVL1
primary heart field specification	1	1404.3×	0.004	WNT5A
olfactory bulb interneuron development	1	1404.3×	0.004	WNT5A
convergent extension involved in neural plate elongation	1	1404.3×	0.004	DVL1
mesenchymal-epithelial cell signaling	1	1404.3×	0.004	WNT5A
mesodermal to mesenchymal transition involved in gastrulation	1	1404.3×	0.004	WNT5A

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 4 evidence-associated genes (75%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
WNT5A	0	0
DVL1	0	0
DVL3	0	0
FZD2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
FZD2	18	Functional:18
DVL1	11	Binding:10, Functional:1
DVL3	3	Binding:2, Functional:1

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	FZD2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	WNT5A, DVL1, DVL3

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)
WNT5A	0	—
DVL1	11	—
DVL3	3	—
FZD2	18	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.