autosomal recessive Robinow syndrome

Summary

autosomal recessive Robinow syndrome (MONDO:0009999) is a disease caused by ROR2 (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: ROR2 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 361
• 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:0000154	Wide mouth	Very frequent (80-99%)
HP:0000164	Abnormality of the dentition	Very frequent (80-99%)
HP:0000316	Hypertelorism	Very frequent (80-99%)
HP:0000431	Wide nasal bridge	Very frequent (80-99%)
HP:0000463	Anteverted nares	Very frequent (80-99%)
HP:0001156	Brachydactyly	Very frequent (80-99%)
HP:0002714	Downturned corners of mouth	Very frequent (80-99%)
HP:0003027	Mesomelia	Very frequent (80-99%)
HP:0003196	Short nose	Very frequent (80-99%)
HP:0003422	Vertebral segmentation defect	Very frequent (80-99%)
HP:0004209	Clinodactyly of the 5th finger	Very frequent (80-99%)
HP:0008736	Hypoplasia of penis	Very frequent (80-99%)
HP:0008873	Disproportionate short-limb short stature	Very frequent (80-99%)
HP:0009882	Short distal phalanx of finger	Very frequent (80-99%)
HP:0010807	Open bite	Very frequent (80-99%)
HP:0011800	Midface retrusion	Very frequent (80-99%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000212	Gingival overgrowth	Frequent (30-79%)
HP:0000256	Macrocephaly	Frequent (30-79%)
HP:0000286	Epicanthus	Frequent (30-79%)
HP:0000343	Long philtrum	Frequent (30-79%)
HP:0000347	Micrognathia	Frequent (30-79%)
HP:0000365	Hearing impairment	Frequent (30-79%)
HP:0000389	Chronic otitis media	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:0000902	Rib fusion	Frequent (30-79%)
HP:0001537	Umbilical hernia	Frequent (30-79%)
HP:0002007	Frontal bossing	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0002808	Kyphosis	Frequent (30-79%)
HP:0003042	Elbow dislocation	Frequent (30-79%)
HP:0005280	Depressed nasal bridge	Frequent (30-79%)
HP:0010059	Broad hallux phalanx	Frequent (30-79%)
HP:0010296	Ankyloglossia	Frequent (30-79%)
HP:0010297	Bifid tongue	Frequent (30-79%)
HP:0010804	Tented upper lip vermilion	Frequent (30-79%)
HP:0011304	Broad thumb	Frequent (30-79%)
HP:0012815	Hypoplastic female external genitalia	Frequent (30-79%)
HP:0100798	Fingernail dysplasia	Frequent (30-79%)
HP:0000358	Posteriorly rotated ears	Frequent (30-79%)
HP:0001641	Abnormal pulmonary valve morphology	Occasional (5-29%)
HP:0001679	Abnormal aortic morphology	Occasional (5-29%)
HP:0001702	Abnormal tricuspid valve morphology	Occasional (5-29%)
HP:0001770	Toe syndactyly	Occasional (5-29%)
HP:0001852	Sandal gap	Occasional (5-29%)
HP:0002205	Recurrent respiratory infections	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive Robinow syndrome
Mondo ID	MONDO:0009999
MeSH	C535863
OMIM	268310
Orphanet	1507
DOID	DOID:0060764
ICD-11	793292660
UMLS	C5399974
MedGen	1770070
GARD	0016568
Is cancer (heuristic)	no

Also known as: costovertebral segmentation defect with mesomelia · costovertebral segmentation defect-mesomelia syndrome · COVESDEM syndrome · Covesdem syndrome · Robinow syndrome, autosomal recessive · RRS

Data availability: 361 ClinVar variants · 6 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 › autosomal recessive Robinow syndrome

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, acromesomelic dysplasia 2B, 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, 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

361 retrieved; paginated sample, class counts are floors:

196 uncertain significance, 66 conflicting classifications of pathogenicity, 25 likely pathogenic, 20 likely benign, 20 benign/likely benign, 19 benign, 14 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1188826	NM_004560.4(ROR2):c.1353_1360del (p.Met452fs)	ROR2	Pathogenic	no assertion criteria provided
1455301	NM_004560.4(ROR2):c.1582C>T (p.Arg528Ter)	ROR2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1679220	NM_004560.4(ROR2):c.1184-1G>T	ROR2	Pathogenic	criteria provided, single submitter
7307	NM_004560.4(ROR2):c.1504C>T (p.Gln502Ter)	ROR2	Pathogenic	no assertion criteria provided
7309	NM_004560.4(ROR2):c.2160G>A (p.Trp720Ter)	ROR2	Pathogenic	no assertion criteria provided
7310	NM_004560.4(ROR2):c.613C>T (p.Arg205Ter)	ROR2	Pathogenic	no assertion criteria provided
7313	NM_004560.4(ROR2):c.1937_1943del (p.Tyr646fs)	ROR2	Pathogenic	no assertion criteria provided
7314	NM_004560.4(ROR2):c.355C>T (p.Arg119Ter)	ROR2	Pathogenic	criteria provided, multiple submitters, no conflicts
7315	NM_004560.4(ROR2):c.622+762_1184-1036del	ROR2	Pathogenic	no assertion criteria provided
7318	NM_004560.4(ROR2):c.1324C>T (p.Arg442Ter)	ROR2	Pathogenic	criteria provided, multiple submitters, no conflicts
983452	NM_004560.4(ROR2):c.2T>G (p.Met1Arg)	ROR2	Pathogenic	no assertion criteria provided
983455	NM_004560.4(ROR2):c.1189C>T (p.Arg397Ter)	ROR2	Pathogenic	criteria provided, multiple submitters, no conflicts
983457	NM_004560.4(ROR2):c.79_80del (p.Ser29fs)	ROR2	Pathogenic	no assertion criteria provided
983461	NM_004560.4(ROR2):c.675del (p.Gln225fs)	ROR2	Pathogenic	no assertion criteria provided
984982	NM_004560.4(ROR2):c.990del (p.Thr331fs)	ROR2	Pathogenic	criteria provided, single submitter
1066325	NM_004560.4(ROR2):c.175+1G>A	ROR2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1077069	NM_004560.4(ROR2):c.950A>G (p.Tyr317Cys)	ROR2	Likely pathogenic	no assertion criteria provided
2412792	NM_004560.4(ROR2):c.640G>C (p.Gly214Arg)	ROR2	Likely pathogenic	criteria provided, single submitter
2502303	NM_004560.4(ROR2):c.854A>G (p.Lys285Arg)	ROR2	Likely pathogenic	criteria provided, single submitter
3597717	NM_004560.4(ROR2):c.2353del (p.Arg785fs)	ROR2	Likely pathogenic	criteria provided, single submitter
3597728	NM_004560.4(ROR2):c.2018C>G (p.Ser673Ter)	ROR2	Likely pathogenic	criteria provided, single submitter
3597736	NM_004560.4(ROR2):c.1855del (p.Arg619fs)	ROR2	Likely pathogenic	criteria provided, single submitter
3597756	NM_004560.4(ROR2):c.1137del (p.Gln380fs)	ROR2	Likely pathogenic	criteria provided, single submitter
3597761	NM_004560.4(ROR2):c.1083dup (p.His362fs)	ROR2	Likely pathogenic	criteria provided, single submitter
3597771	NM_004560.4(ROR2):c.799G>T (p.Glu267Ter)	ROR2	Likely pathogenic	criteria provided, single submitter
627538	NM_004560.4(ROR2):c.1565_1569delinsTGTA (p.Arg522fs)	ROR2	Likely pathogenic	criteria provided, single submitter
627539	NM_004560.4(ROR2):c.323G>A (p.Arg108Gln)	ROR2	Likely pathogenic	criteria provided, single submitter
7308	NM_004560.4(ROR2):c.550C>T (p.Arg184Cys)	ROR2	Likely pathogenic	criteria provided, single submitter
983453	NM_004560.4(ROR2):c.494+4_494+7del	ROR2	Likely pathogenic	no assertion criteria provided
983454	NM_004560.4(ROR2):c.1100A>T (p.Asn367Ile)	ROR2	Likely pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 3 · 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
ROR2	Definitive	Autosomal recessive	autosomal recessive Robinow syndrome	9
NXN	Strong	Autosomal recessive	robinow syndrome, autosomal recessive 2	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ROR2	Orphanet:1507	Autosomal recessive Robinow syndrome
ROR2	Orphanet:572385	Brachydactyly type B1
NXN	Orphanet:1507	Autosomal recessive Robinow syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ROR2	HGNC:10257	ENSG00000169071	Q01974	Tyrosine-protein kinase transmembrane receptor ROR2	gencc,clinvar
NXN	HGNC:18008	ENSG00000167693	Q6DKJ4	Nucleoredoxin	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ROR2	Tyrosine-protein kinase transmembrane receptor ROR2	Tyrosine-protein kinase receptor which may be involved in the early formation of the chondrocytes.
NXN	Nucleoredoxin	Functions as a redox-dependent negative regulator of the Wnt signaling pathway, possibly by preventing ubiquitination of DVL3 by the BCR(KLHL12) complex.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ROR2	Kinase	yes	2.7.10.1	Kringle, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
NXN	Other/Unknown	no		Thioredoxin-like_fold, Thioredoxin_domain, Thioredoxin-like_sf

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of uterus	1
mucosa of stomach	1
muscle layer of sigmoid colon	1
cervix squamous epithelium	1
hair follicle	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ROR2	188	ubiquitous	marker	muscle layer of sigmoid colon, mucosa of stomach, body of uterus
NXN	279	ubiquitous	marker	cervix squamous epithelium, hair follicle, skeletal muscle tissue of rectus abdominis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ROR2	1,813
NXN	911

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ROR2	Q01974	6

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NXN	Q6DKJ4	90.37

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 2 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
WNT5A-dependent internalization of FZD2, FZD5 and ROR2	1	878.5×	0.006	ROR2
PCP/CE pathway	1	300.5×	0.006	ROR2
Beta-catenin independent WNT signaling	1	292.8×	0.006	ROR2
Signaling by WNT	1	112.0×	0.011	ROR2
Signal Transduction	1	10.2×	0.098	ROR2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
Wnt signaling pathway	2	99.7×	9e-04	ROR2, NXN
circulatory system development	1	702.2×	0.006	NXN
negative regulation of Wnt signaling pathway	1	172.0×	0.016	NXN
negative regulation of protein ubiquitination	1	142.8×	0.016	NXN
cell surface receptor protein tyrosine kinase signaling pathway	1	86.9×	0.021	ROR2
in utero embryonic development	1	36.0×	0.041	NXN
positive regulation of cell migration	1	30.9×	0.041	ROR2
cell differentiation	1	14.6×	0.076	NXN
signal transduction	1	8.0×	0.121	ROR2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ROR2	0	0
NXN	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ROR2	4	Binding:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ROR2	2.7.10.1	receptor protein-tyrosine kinase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	ROR2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	NXN

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ROR2	4	—
NXN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.