Mowat-Wilson syndrome

Summary

Mowat-Wilson syndrome (MONDO:0009341) is a disease caused by ZEB2 (GenCC Definitive), with 3 cohort genes and 2 clinical trials.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: ZEB2 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 1,292
• Phenotypes (HPO): 140
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 100 000	1.7	Europe	Validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0031936	Delayed ability to walk	Frequent (30-79%)
HP:0040082	Happy demeanor	Frequent (30-79%)
HP:0000047	Hypospadias	Frequent (30-79%)
HP:0000179	Thick lower lip vermilion	Frequent (30-79%)
HP:0000194	Open mouth	Frequent (30-79%)
HP:0000232	Everted lower lip vermilion	Frequent (30-79%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000276	Long face	Frequent (30-79%)
HP:0000303	Mandibular prognathia	Frequent (30-79%)
HP:0000307	Pointed chin	Frequent (30-79%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0000358	Posteriorly rotated ears	Frequent (30-79%)
HP:0000403	Recurrent otitis media	Frequent (30-79%)
HP:0000431	Wide nasal bridge	Frequent (30-79%)
HP:0000437	Depressed nasal tip	Frequent (30-79%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0000490	Deeply set eye	Frequent (30-79%)
HP:0000506	Telecanthus	Frequent (30-79%)
HP:0000733	Abnormal repetitive mannerisms	Frequent (30-79%)
HP:0000767	Pectus excavatum	Frequent (30-79%)
HP:0000768	Pectus carinatum	Frequent (30-79%)
HP:0001159	Syndactyly	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001274	Agenesis of corpus callosum	Frequent (30-79%)
HP:0001371	Flexion contracture	Frequent (30-79%)
HP:0001510	Growth delay	Frequent (30-79%)
HP:0001627	Abnormal heart morphology	Frequent (30-79%)
HP:0001643	Patent ductus arteriosus	Frequent (30-79%)
HP:0001671	Abnormal cardiac septum morphology	Frequent (30-79%)
HP:0001763	Pes planus	Frequent (30-79%)
HP:0001822	Hallux valgus	Frequent (30-79%)
HP:0002011	Morphological central nervous system abnormality	Frequent (30-79%)
HP:0002079	Hypoplasia of the corpus callosum	Frequent (30-79%)
HP:0002136	Broad-based gait	Frequent (30-79%)
HP:0002251	Aganglionic megacolon	Frequent (30-79%)
HP:0002342	Intellectual disability, moderate	Frequent (30-79%)
HP:0002360	Sleep abnormality	Frequent (30-79%)
HP:0002427	Motor aphasia	Frequent (30-79%)
HP:0002607	Bowel incontinence	Frequent (30-79%)
HP:0002650	Scoliosis	Frequent (30-79%)
HP:0002750	Delayed skeletal maturation	Frequent (30-79%)
HP:0002857	Genu valgum	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0004325	Decreased body weight	Frequent (30-79%)
HP:0005274	Prominent nasal tip	Frequent (30-79%)
HP:0007328	Impaired pain sensation	Frequent (30-79%)
HP:0009487	Ulnar deviation of the hand	Frequent (30-79%)
HP:0009765	Low hanging columella	Frequent (30-79%)
HP:0009909	Uplifted earlobe	Frequent (30-79%)
HP:0010055	Broad hallux	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Mowat-Wilson syndrome
Mondo ID	MONDO:0009341
MeSH	C536990
OMIM	235730
Orphanet	2152
DOID	DOID:0060485
ICD-11	1985672762
NCIT	C74999
SNOMED CT	703535000
UMLS	C1856113
MedGen	341067
GARD	0009673
NORD	1456
Is cancer (heuristic)	no

Also known as: Hirschsprung disease intellectual disability syndrome · Hirschsprung disease-intellectual disability syndrome · Hirschsprung disease-mental retardation syndrome · intellectual disability, microcephaly, and distinct facial features with or without Hirschsprung disease · mental retardation, microcephaly, and distinct facial features with or without Hirschsprung disease · microcephaly, intellectual disability, and distinct facial featrues, with or without Hirschprung disease · microcephaly, mental retardation, and distinct Facial features, with or without Hirschsprung disease · Mowat-Wilson syndrome · MOWS

Data availability: 1,292 ClinVar variants · 4 GenCC gene-disease records · 4 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › Mowat-Wilson syndrome

Related subtypes (216): polymicrogyria, congenital myasthenic syndrome with tubular aggregates, prenatal-onset spinal muscular atrophy with congenital bone fractures, anencephaly, cerebral cavernous malformation, meningocele, progressive external ophthalmoplegia, congenital nystagmus, congenital toxoplasmosis, congenital contractural arachnodactyly, congenital trigeminal anesthesia, familial congenital palsy of trochlear nerve, Myhre syndrome, Aase-Smith syndrome, KBG syndrome, autosomal dominant primary microcephaly, Mobius syndrome, MYH7-related skeletal myopathy, congenital stationary night blindness autosomal dominant 2, Prader-Willi syndrome, congenital myopathy 7A, myosin storage, autosomal dominant, Smith-Magenis syndrome, spina bifida, Freeman-Sheldon syndrome, isolated cerebellar hypoplasia/agenesis, Chediak-Higashi syndrome, Cohen syndrome, multiple pterygium-malignant hyperthermia syndrome, corpus callosum, agenesis of, congenital lactic acidosis, Saguenay-Lac-Saint-Jean type, facial dysmorphism-macrocephaly-myopia-Dandy-Walker malformation syndrome, diastematomyelia, EEM syndrome, Johanson-Blizzard syndrome, intellectual disability, Buenos-Aires type, myasthenia, congenital, refractory to acetylcholinesterase inhibitors, congenital myasthenic syndrome 6, Bailey-Bloch congenital myopathy, congenital stationary night blindness 1B, radioulnar synostosis-developmental delay-hypotonia syndrome, Schinzel-Giedion syndrome, schizencephaly, intellectual disability, Wolff type, X-linked intellectual disability-plagiocephaly syndrome, X-linked adrenal hypoplasia congenita, syndromic X-linked intellectual disability 7, syndromic X-linked intellectual disability Shashi type, syndromic X-linked intellectual disability Lubs type, syndromic X-linked intellectual disability Abidi type, syndromic X-linked intellectual disability Siderius type, X-linked intellectual disability, Cabezas type, X-linked intellectual disability-cubitus valgus-dysmorphism syndrome, syndromic X-linked intellectual disability Claes-Jensen type, moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome, multiple congenital anomalies-hypotonia-seizures syndrome 2, developmental and epileptic encephalopathy, 36, blepharophimosis - intellectual disability syndrome, MKB type, X-linked intellectual disability-short stature-overweight syndrome, intellectual disability, X-linked, syndromic 33, syndromic X-linked intellectual disability 34, infantile-onset X-linked spinal muscular atrophy, syndromic X-linked intellectual disability 5, holoprosencephaly-hypokinesia-congenital contractures syndrome, X-linked intellectual disability with marfanoid habitus, Wieacker-Wolff syndrome, MERRF syndrome, macrocephaly-spastic paraplegia-dysmorphism syndrome, intellectual disability-sparse hair-brachydactyly syndrome, myofibrillar myopathy 1, isolated hereditary congenital facial paralysis, fibrosis of extraocular muscles, congenital, 2, Pierpont syndrome, congenital cataracts-facial dysmorphism-neuropathy syndrome, Bohring-Opitz syndrome, PHACE syndrome, B4GALT1-congenital disorder of glycosylation, developmental malformations-deafness-dystonia syndrome, sensory ataxic neuropathy, dysarthria, and ophthalmoparesis, AICA-ribosiduria, myofibrillar myopathy 3, fibrosis of extraocular muscles, congenital, 3c, myofibrillar myopathy 4, myofibrillar myopathy 5, cone-rod synaptic disorder, congenital nonprogressive, congenital stationary night blindness autosomal dominant 3, congenital stationary night blindness autosomal dominant 1, intellectual disability, autosomal recessive 12, progressive myoclonic epilepsy type 3, chromosome 15q13.3 microdeletion syndrome, combined pituitary hormone deficiencies, genetic form, congenital stationary night blindness 1D, DYRK1A-related intellectual disability syndrome, Pitt-Hopkins-like syndrome 2, developmental and epileptic encephalopathy, 15, Schuurs-Hoeijmakers syndrome, severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome, severe intellectual disability-progressive spastic diplegia syndrome, hypotonia, infantile, with psychomotor retardation and characteristic facies, developmental and epileptic encephalopathy, 18, CTCF-related neurodevelopmental disorder, autism spectrum disorder due to AUTS2 deficiency, developmental and epileptic encephalopathy, 23, ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder, Bardet-Biedl syndrome 11, cerebellar-facial-dental syndrome, fibrosis of extraocular muscles, congenital, 5, congenital myasthenic syndrome 15, lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome, autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome, congenital myasthenic syndrome 18, autosomal recessive spinocerebellar ataxia 20, Houge-Janssens syndrome 1, intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome, congenital stationary night blindness 1G, hypomyelinating leukodystrophy 10, developmental and epileptic encephalopathy, 50, congenital insensitivity to pain-hypohidrosis syndrome, macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome, SLC39A8-CDG, spastic paraplegia-severe developmental delay-epilepsy syndrome, cardiac anomalies - developmental delay - facial dysmorphism syndrome, severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome, intellectual disability, autosomal recessive 53, TELO2-related intellectual disability-neurodevelopmental disorder, micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome, autosomal recessive limb-girdle muscular dystrophy type 2Y, myofibrillar myopathy 7, short stature-brachydactyly-obesity-global developmental delay syndrome, autosomal recessive limb-girdle muscular dystrophy type 2R1, severe microbrachycephaly-intellectual disability-athetoid cerebral palsy syndrome, congenital laryngeal palsy, congenital or early infantile CACH syndrome, congenital epulis, severe congenital nemaline myopathy, intermediate nemaline myopathy, typical nemaline myopathy, childhood-onset nemaline myopathy, adult-onset nemaline myopathy, qualitative or quantitative defects of protein involved in O-glycosylation of alpha-dystroglycan, holoprosencephaly, congenital insensitivity to pain with hyperhidrosis, congenital hydrocephalus, familial congenital mirror movements, macrocephaly-short stature-paraplegia syndrome, cephalocele, mitochondrial neurogastrointestinal encephalomyopathy, X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome, 7p22.1 microduplication syndrome, congenital achiasma, congenital retinal arteriovenous communication, 3q27.3 microdeletion syndrome, Prader-Willi-like syndrome, 9q31.1q31.3 microdeletion syndrome, congenital oculomotor nerve palsy, congenital abducens nerve palsy, neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, congenital insensitivity to pain with severe intellectual disability, X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, lissencephaly spectrum disorders, hyaline body myopathy, 22q11.2 deletion syndrome, craniorachischisis, Leber congenital amaurosis, Ritscher-Schinzel syndrome, Rubinstein-Taybi syndrome, X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome, X-linked intellectual disability-epilepsy-progressive joint contractures-dysmorphism syndrome, X-linked intellectual disability, Pai type, X-linked intellectual disability, Stevenson type, X-linked intellectual disability, Stoll type, congenital muscular dystrophy, congenital vitreoretinal dysplasia, periventricular nodular heterotopia, postsynaptic congenital myasthenic syndrome, subcortical band heterotopia, congenital fibrosis of extraocular muscles type 1, Al Gazali Khidr Prem Chandran syndrome, distal arthrogryposis Moore weaver type, congenital myotonic dystrophy, myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive, intellectual disability, autosomal dominant 47, intellectual disability, autosomal dominant 48, spondyloepiphyseal dysplasia, sensorineural hearing loss, impaired intellectual development, and leber congenital amaurosis, myasthenic syndrome, congenital, 23, presynaptic, myasthenic syndrome, congenital, 24, presynaptic, myasthenic syndrome, congenital, 25, presynaptic, developmental and epileptic encephalopathy, 77, night blindness, congenital stationary, type1i, neuropathy, congenital hypomelinating, congenital axonal neuropathy with encephalopathy, developmental and epileptic encephalopathy, 73, PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome, isolated exencephaly, myasthenic syndrome, congenital, 22, intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, 9q33.3q34.11 microdeletion syndrome, congenital labioscrotal agenesis-cerebellar malformation-corneal dystrophy-facial dysmorphism syndrome, early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome, SIN3A-related intellectual disability syndrome, childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder, X-linked congenital stationary night blindness, neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, FOXG1 disorder, alpha-actinopathy, TPM3-related myopathy, X-linked recessive mitochondrial myopathy, RYR1-related myopathy, TTN-related myopathy, TPM2-related myopathy, myopathy caused by variation in POMGNT1, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, segmental spinal dysgenesis, myopathy, myofibrillar, 13, with rimmed vacuoles, congenital neuronal ceroid lipofuscinosis 10

Subtypes (2): Mowat-Wilson syndrome due to monosomy 2q22, Mowat-Wilson syndrome due to a ZEB2 point mutation

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

600 retrieved; paginated sample, class counts are floors:

184 likely benign, 166 uncertain significance, 123 pathogenic, 51 conflicting classifications of pathogenicity, 29 benign, 28 benign/likely benign, 16 likely pathogenic, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
160326	NM_014795.4(ZEB2):c.550_568del (p.Ser184fs)	LOC111721705	Pathogenic	criteria provided, single submitter
2687499	NM_014795.4(ZEB2):c.540del (p.Glu181fs)	LOC111721705	Pathogenic	criteria provided, single submitter
1029309	NM_014795.4(ZEB2):c.2886+1G>A	ZEB2	Pathogenic	criteria provided, multiple submitters, no conflicts
1069634	NM_014795.4(ZEB2):c.874A>T (p.Lys292Ter)	ZEB2	Pathogenic	criteria provided, single submitter
1071228	NM_014795.4(ZEB2):c.31del (p.Arg11fs)	ZEB2	Pathogenic	criteria provided, single submitter
1071230	NM_014795.4(ZEB2):c.2592del (p.Phe864fs)	ZEB2	Pathogenic	criteria provided, single submitter
1071821	NM_014795.4(ZEB2):c.3094del (p.Cys1032fs)	ZEB2	Pathogenic	criteria provided, single submitter
1072089	NC_000002.11:g.(?145147018)(145753167_?)del	ZEB2	Pathogenic	criteria provided, single submitter
1072214	NM_014795.4(ZEB2):c.818_821dup (p.Gln275fs)	ZEB2	Pathogenic	criteria provided, single submitter
1074356	NM_014795.4(ZEB2):c.1038_1039del (p.Asn346fs)	ZEB2	Pathogenic	criteria provided, single submitter
1076322	NM_014795.4(ZEB2):c.696C>A (p.Tyr232Ter)	ZEB2	Pathogenic	criteria provided, single submitter
1076838	NM_014795.4(ZEB2):c.876dup (p.Tyr293fs)	ZEB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1164069	NM_014795.4(ZEB2):c.3242G>A (p.Cys1081Tyr)	ZEB2	Pathogenic	no assertion criteria provided
1172771	NM_014795.4(ZEB2):c.2717del (p.Pro906fs)	ZEB2	Pathogenic	criteria provided, multiple submitters, no conflicts
1180834	NM_014795.4(ZEB2):c.625C>T (p.Gln209Ter)	ZEB2	Pathogenic	criteria provided, multiple submitters, no conflicts
1320072	NM_014795.4(ZEB2):c.73+1G>A	ZEB2	Pathogenic	criteria provided, multiple submitters, no conflicts
1320108	NM_014795.4(ZEB2):c.1209del (p.Met404fs)	ZEB2	Pathogenic	criteria provided, single submitter
1320148	NM_014795.4(ZEB2):c.769G>T (p.Glu257Ter)	ZEB2	Pathogenic	criteria provided, single submitter
1320156	NM_014795.4(ZEB2):c.1170del (p.Thr392fs)	ZEB2	Pathogenic	criteria provided, single submitter
1320255	NM_014795.4(ZEB2):c.1052del (p.Gly351fs)	ZEB2	Pathogenic	criteria provided, multiple submitters, no conflicts
1320262	NM_014795.4(ZEB2):c.2056G>T (p.Glu686Ter)	ZEB2	Pathogenic	criteria provided, single submitter
1323780	NM_014795.4(ZEB2):c.1200_1201del (p.Tyr400_Lys401delinsTer)	ZEB2	Pathogenic	criteria provided, single submitter
1350184	NM_014795.4(ZEB2):c.1866dup (p.Asn623fs)	ZEB2	Pathogenic	criteria provided, single submitter
1367594	NM_014795.4(ZEB2):c.1700_1703dup (p.Asp568_Asp569insTer)	ZEB2	Pathogenic	criteria provided, single submitter
1376989	NM_014795.4(ZEB2):c.1630_1631del (p.Thr544fs)	ZEB2	Pathogenic	criteria provided, single submitter
1377334	NM_014795.4(ZEB2):c.2745del (p.Ser916fs)	ZEB2	Pathogenic	criteria provided, single submitter
1418131	NM_014795.4(ZEB2):c.313del (p.Ala105fs)	ZEB2	Pathogenic	criteria provided, single submitter
1428527	NM_014795.4(ZEB2):c.3154G>T (p.Glu1052Ter)	ZEB2	Pathogenic	criteria provided, single submitter
1439087	NM_014795.4(ZEB2):c.2122del (p.Leu708fs)	ZEB2	Pathogenic	criteria provided, single submitter
1445094	NM_014795.4(ZEB2):c.712G>T (p.Glu238Ter)	ZEB2	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
ZEB2	Definitive	Autosomal dominant	Mowat-Wilson syndrome	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ZEB2	Orphanet:261537	Mowat-Wilson syndrome due to monosomy 2q22
ZEB2	Orphanet:261552	Mowat-Wilson syndrome due to a ZEB2 point mutation
ZEB2	Orphanet:626	Large/giant congenital melanocytic nevus

Cohort genes → proteins

3 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ZEB2	HGNC:14881	ENSG00000169554	O60315	Zinc finger E-box-binding homeobox 2	gencc,clinvar
ARHGAP15	HGNC:21030	ENSG00000075884	Q53QZ3	Rho GTPase-activating protein 15	clinvar
LINC01412	HGNC:50704	ENSG00000232606		long intergenic non-protein coding RNA 1412	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ZEB2	Zinc finger E-box-binding homeobox 2	Transcriptional inhibitor that binds to DNA sequence 5’-CACCT-3’ in different promoters.
ARHGAP15	Rho GTPase-activating protein 15	GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 1 · Druggable fraction: 0.0

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
Scaffold/PPI	1	5.8×	0.482
Transcription factor	1	2.8×	0.482
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ZEB2	Transcription factor	no		HD, Di19_Zn-bd, Homeodomain-like_sf
ARHGAP15	Scaffold/PPI	no		RhoGAP_dom, PH_domain, Rho_GTPase_activation_prot
LINC01412	Other/Unknown	no

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
monocyte	2
cortical plate	1
sural nerve	1
blood	1
bone marrow cell	1
granulocyte	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ZEB2	290	ubiquitous	marker	cortical plate, sural nerve, monocyte
ARHGAP15	207	broad	marker	blood, bone marrow cell, granulocyte
LINC01412	117	broad	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ZEB2	3,193
ARHGAP15	1,627
LINC01412	0

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ZEB2	O60315	1
ARHGAP15	Q53QZ3	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Formation of the posterior neural plate	1	571.0×	0.004	ZEB2
Regulation of CDH11 gene transcription	1	519.1×	0.004	ZEB2
Formation of the anterior neural plate	1	519.1×	0.004	ZEB2
Positive Regulation of CDH1 Gene Transcription	1	475.8×	0.004	ZEB2
Negative Regulation of CDH1 Gene Transcription	1	60.1×	0.020	ZEB2
RAC3 GTPase cycle	1	59.5×	0.020	ARHGAP15
RAC1 GTPase cycle	1	30.5×	0.032	ARHGAP15

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
mammillary axonal complex development	1	8426.0×	0.002	ZEB2
positive regulation of myofibroblast contraction	1	8426.0×	0.002	ZEB2
regulation of blood-brain barrier permeability	1	8426.0×	0.002	ZEB2
positive regulation of lens fiber cell differentiation	1	4213.0×	0.002	ZEB2
regulation of melanosome organization	1	4213.0×	0.002	ZEB2
regulation of myofibroblast cell apoptotic process	1	4213.0×	0.002	ZEB2
melanocyte migration	1	2808.7×	0.002	ZEB2
myofibroblast differentiation	1	1685.2×	0.003	ZEB2
positive regulation of melanocyte differentiation	1	1685.2×	0.003	ZEB2
corpus callosum morphogenesis	1	1203.7×	0.003	ZEB2
corticospinal tract morphogenesis	1	1203.7×	0.003	ZEB2
fibroblast activation	1	1203.7×	0.003	ZEB2
developmental pigmentation	1	1053.2×	0.003	ZEB2
response to oxygen-glucose deprivation	1	1053.2×	0.003	ZEB2
negative regulation of fibroblast migration	1	766.0×	0.003	ZEB2
positive regulation of melanin biosynthetic process	1	702.2×	0.003	ZEB2
cell proliferation in forebrain	1	648.1×	0.003	ZEB2
collateral sprouting	1	601.9×	0.004	ZEB2
astrocyte activation	1	495.6×	0.004	ZEB2
stress fiber assembly	1	383.0×	0.005	ZEB2
positive regulation of axonogenesis	1	290.6×	0.006	ZEB2
endothelial cell proliferation	1	271.8×	0.006	ZEB2
positive regulation of transforming growth factor beta receptor signaling pathway	1	263.3×	0.006	ZEB2
pyroptotic inflammatory response	1	255.3×	0.006	ZEB2
endothelial cell migration	1	205.5×	0.007	ZEB2
somitogenesis	1	187.2×	0.008	ZEB2
neural crest cell migration	1	168.5×	0.008	ZEB2
hippocampus development	1	115.4×	0.012	ZEB2
neural tube closure	1	93.6×	0.014	ZEB2
small GTPase-mediated signal transduction	1	91.6×	0.014	ARHGAP15

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 3 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ZEB2	0	0
ARHGAP15	0	0
LINC01412	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	ZEB2, ARHGAP15, LINC01412

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ZEB2	0	—
ARHGAP15	0	—
LINC01412	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT07476417	Not specified	NOT_YET_RECRUITING	Oral Health, Dento-facial Condition and OHRQoL in Subjects With Mowat-Wilson Syndrome: an Epidemiologic Study.