Severe intellectual disability-progressive spastic diplegia syndrome

Summary

Severe intellectual disability-progressive spastic diplegia syndrome (MONDO:0014035) is a disease caused by CTNNB1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: CTNNB1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 114
• Phenotypes (HPO): 32

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

32 HPO clinical features (Orphanet curated; top 32 by frequency):

HPO ID	Term	Frequency
HP:0000252	Microcephaly	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001257	Spasticity	Very frequent (80-99%)
HP:0001270	Motor delay	Very frequent (80-99%)
HP:0001999	Abnormal facial shape	Very frequent (80-99%)
HP:0002465	Poor speech	Very frequent (80-99%)
HP:0008936	Axial hypotonia	Very frequent (80-99%)
HP:0000478	Abnormality of the eye	Frequent (30-79%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0002376	Developmental regression	Frequent (30-79%)
HP:0011451	Congenital microcephaly	Frequent (30-79%)
HP:0000219	Thin upper lip vermilion	Occasional (5-29%)
HP:0000319	Smooth philtrum	Occasional (5-29%)
HP:0000343	Long philtrum	Occasional (5-29%)
HP:0000430	Underdeveloped nasal alae	Occasional (5-29%)
HP:0000455	Broad nasal tip	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000540	Hypermetropia	Occasional (5-29%)
HP:0000545	Myopia	Occasional (5-29%)
HP:0000718	Aggressive behavior	Occasional (5-29%)
HP:0000729	Autistic behavior	Occasional (5-29%)
HP:0002079	Hypoplasia of the corpus callosum	Occasional (5-29%)
HP:0002119	Ventriculomegaly	Occasional (5-29%)
HP:0002144	Tethered cord	Occasional (5-29%)
HP:0002188	Delayed CNS myelination	Occasional (5-29%)
HP:0002360	Sleep abnormality	Occasional (5-29%)
HP:0003396	Syringomyelia	Occasional (5-29%)
HP:0009765	Low hanging columella	Occasional (5-29%)
HP:0025160	Abnormal temper tantrums	Occasional (5-29%)
HP:0100716	Self-injurious behavior	Occasional (5-29%)
HP:0000365	Hearing impairment	Very rare (<1-4%)
HP:0001250	Seizure	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	severe intellectual disability-progressive spastic diplegia syndrome
Mondo ID	MONDO:0014035
OMIM	615075
Orphanet	404473
DOID	DOID:0070049
ICD-10-CM	Q87.88
UMLS	C3554449
MedGen	767363
GARD	0003505
Is cancer (heuristic)	no

Also known as: autosomal dominant intellectual disability 19 · CTNNB1 syndrome · CTNNB1-related intellectual disability · intellectual disability, autosomal dominant 19 · intellectual disability, autosomal dominant type 19 · mental retardation, autosomal dominant 19 · mental retardation, autosomal dominant type 19 · MRD19 · neurodevelopmental disorder with spastic diplegia and visual defects · severe intellectual disability-progressive spastic diplegia syndrome

Data availability: 114 ClinVar variants · 5 GenCC gene-disease records · 7 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › severe intellectual disability-progressive spastic diplegia 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, Mowat-Wilson 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, 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

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

114 retrieved; paginated sample, class counts are floors:

67 pathogenic, 24 likely pathogenic, 14 uncertain significance, 5 pathogenic/likely pathogenic, 4 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1068620	NM_001904.4(CTNNB1):c.696dup (p.Lys233Ter)	CTNNB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1164027	NM_001904.4(CTNNB1):c.646G>A (p.Gly216Arg)	CTNNB1	Pathogenic	no assertion criteria provided
1174512	NM_001904.4(CTNNB1):c.1706del (p.Ile569fs)	CTNNB1	Pathogenic	no assertion criteria provided
1315504	NM_001904.4(CTNNB1):c.1924G>T (p.Glu642Ter)	CTNNB1	Pathogenic	criteria provided, single submitter
1320077	NM_001904.4(CTNNB1):c.163G>T (p.Glu55Ter)	CTNNB1	Pathogenic	criteria provided, single submitter
1320120	NM_001904.4(CTNNB1):c.1082-1G>C	CTNNB1	Pathogenic	criteria provided, multiple submitters, no conflicts
1320247	NM_001904.4(CTNNB1):c.2008dup (p.Tyr670fs)	CTNNB1	Pathogenic	criteria provided, single submitter
1329943	NM_001904.4(CTNNB1):c.564dup (p.Met189fs)	CTNNB1	Pathogenic	criteria provided, single submitter
133315	NM_001904.4(CTNNB1):c.705dup (p.Gly236fs)	CTNNB1	Pathogenic	no assertion criteria provided
1343152	NM_001904.4(CTNNB1):c.133del (p.Ser45fs)	CTNNB1	Pathogenic	criteria provided, single submitter
1699116	NM_001904.4(CTNNB1):c.1350dup (p.Val451fs)	CTNNB1	Pathogenic	criteria provided, single submitter
1708496	NM_001904.4(CTNNB1):c.999del (p.Thr332_Tyr333insTer)	CTNNB1	Pathogenic	criteria provided, single submitter
1727055	NM_001904.4(CTNNB1):c.1836_1837dup (p.Val613fs)	CTNNB1	Pathogenic	criteria provided, single submitter
1803714	NM_001904.4(CTNNB1):c.1612C>T (p.Gln538Ter)	CTNNB1	Pathogenic	criteria provided, single submitter
1805795	NM_001904.4(CTNNB1):c.1961_1962del (p.Tyr654fs)	CTNNB1	Pathogenic	criteria provided, single submitter
1805870	NM_001904.4(CTNNB1):c.242-3C>A	CTNNB1	Pathogenic	criteria provided, single submitter
1879576	NM_001904.4(CTNNB1):c.2083del (p.Asp695fs)	CTNNB1	Pathogenic	criteria provided, multiple submitters, no conflicts
1879838	NM_001904.4(CTNNB1):c.81dup (p.Gln28fs)	CTNNB1	Pathogenic	no assertion criteria provided
2025033	NM_001904.4(CTNNB1):c.1309_1316del (p.Met437fs)	CTNNB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208674	NM_001904.4(CTNNB1):c.1723G>A (p.Gly575Arg)	CTNNB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
225170	NM_001904.4(CTNNB1):c.1434_1435insC (p.Glu479fs)	CTNNB1	Pathogenic	no assertion criteria provided
2441921	NM_001904.4(CTNNB1):c.1183C>T (p.Gln395Ter)	CTNNB1	Pathogenic	criteria provided, multiple submitters, no conflicts
2499550	NM_001904.4(CTNNB1):c.1351dup (p.Val451fs)	CTNNB1	Pathogenic	criteria provided, single submitter
2506272	NM_001904.4(CTNNB1):c.1863dup (p.Ala622fs)	CTNNB1	Pathogenic	criteria provided, single submitter
253000	NM_001904.4(CTNNB1):c.268C>T (p.Arg90Ter)	CTNNB1	Pathogenic	criteria provided, multiple submitters, no conflicts
2579643	NM_001904.4(CTNNB1):c.1904dup (p.Ala636fs)	CTNNB1	Pathogenic	no assertion criteria provided
2635133	NM_001904.4(CTNNB1):c.865_869del (p.Thr289fs)	CTNNB1	Pathogenic	criteria provided, multiple submitters, no conflicts
2637892	NM_001904.4(CTNNB1):c.2125dup (p.Tyr709fs)	CTNNB1	Pathogenic	criteria provided, single submitter
265085	NM_001904.4(CTNNB1):c.1603C>T (p.Arg535Ter)	CTNNB1	Pathogenic	criteria provided, multiple submitters, no conflicts
265443	NM_001904.4(CTNNB1):c.283C>T (p.Arg95Ter)	CTNNB1	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 12 · 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
CTNNB1	Definitive	Autosomal dominant	severe intellectual disability-progressive spastic diplegia syndrome	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CTNNB1	Orphanet:1501	Adrenocortical carcinoma
CTNNB1	Orphanet:210159	Adult hepatocellular carcinoma
CTNNB1	Orphanet:2780	Osteopathia striata-cranial sclerosis syndrome
CTNNB1	Orphanet:33402	Pediatric hepatocellular carcinoma
CTNNB1	Orphanet:404473	Intellectual disability-eye abnormalities-microcephaly-peripheral spasticity syndrome
CTNNB1	Orphanet:54595	Craniopharyngioma
CTNNB1	Orphanet:569248	Microcystic stromal tumor
CTNNB1	Orphanet:689430	Adenoid ameloblastoma
CTNNB1	Orphanet:873	Desmoid tumor
CTNNB1	Orphanet:891	Familial exudative vitreoretinopathy
CTNNB1	Orphanet:91414	Pilomatrixoma
CTNNB1	Orphanet:952	Acrofacial dysostosis, Weyers type

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CTNNB1	HGNC:2514	ENSG00000168036	P35222	Catenin beta-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CTNNB1	Catenin beta-1	Key downstream component of the canonical Wnt signaling pathway.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CTNNB1	Other/Unknown	no		Armadillo, ARM-like, Beta-catenin

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adrenal tissue	1
periodontal ligament	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CTNNB1	295	ubiquitous	marker	adrenal tissue, ventricular zone, periodontal ligament

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CTNNB1	15,668

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CTNNB1	P35222	50

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 46. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production	1	2284.0×	0.004	CTNNB1
CDH11 homotypic and heterotypic interactions	1	1631.4×	0.004	CTNNB1
Regulation of CDH19 Expression and Function	1	1427.5×	0.004	CTNNB1
InlA-mediated entry of Listeria monocytogenes into host cells	1	1268.9×	0.004	CTNNB1
Binding of TCF/LEF:CTNNB1 to target gene promoters	1	1142.0×	0.004	CTNNB1
RUNX3 regulates WNT signaling	1	1142.0×	0.004	CTNNB1
Apoptotic cleavage of cell adhesion proteins	1	1038.2×	0.004	CTNNB1
Regulation of CDH11 function	1	1038.2×	0.004	CTNNB1
Regulation of CDH1 Function	1	951.7×	0.004	CTNNB1
Formation of axial mesoderm	1	815.7×	0.004	CTNNB1
Signaling by GSK3beta mutants	1	761.3×	0.004	CTNNB1
CTNNB1 S33 mutants aren’t phosphorylated	1	761.3×	0.004	CTNNB1
CTNNB1 S37 mutants aren’t phosphorylated	1	761.3×	0.004	CTNNB1
CTNNB1 S45 mutants aren’t phosphorylated	1	761.3×	0.004	CTNNB1
CTNNB1 T41 mutants aren’t phosphorylated	1	761.3×	0.004	CTNNB1
Formation of definitive endoderm	1	713.8×	0.004	CTNNB1
Beta-catenin phosphorylation cascade	1	671.8×	0.004	CTNNB1
Germ layer formation at gastrulation	1	671.8×	0.004	CTNNB1
Formation of the nephric duct	1	634.4×	0.004	CTNNB1
Specification of the neural plate border	1	634.4×	0.004	CTNNB1
Regulation of MITF-M-dependent genes involved in cell cycle and proliferation	1	571.0×	0.004	CTNNB1
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)	1	519.1×	0.004	CTNNB1
SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)	1	496.5×	0.004	CTNNB1
Cardiogenesis	1	423.0×	0.004	CTNNB1
VEGFR2 mediated vascular permeability	1	407.9×	0.004	CTNNB1
Formation of paraxial mesoderm	1	407.9×	0.004	CTNNB1
Myogenesis	1	380.7×	0.004	CTNNB1
Disassembly of the destruction complex and recruitment of AXIN to the membrane	1	356.9×	0.005	CTNNB1
RHO GTPases activate IQGAPs	1	346.1×	0.005	CTNNB1
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	1	335.9×	0.005	CTNNB1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
glial cell fate determination	1	16852.0×	0.001	CTNNB1
canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation	1	16852.0×	0.001	CTNNB1
cranial ganglion development	1	16852.0×	0.001	CTNNB1
neural plate development	1	8426.0×	0.001	CTNNB1
negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis	1	8426.0×	0.001	CTNNB1
regulation of centriole-centriole cohesion	1	8426.0×	0.001	CTNNB1
negative regulation of mitotic cell cycle, embryonic	1	8426.0×	0.001	CTNNB1
regulation of timing of anagen	1	8426.0×	0.001	CTNNB1
positive regulation of branching involved in lung morphogenesis	1	8426.0×	0.001	CTNNB1
renal vesicle formation	1	8426.0×	0.001	CTNNB1
renal inner medulla development	1	8426.0×	0.001	CTNNB1
renal outer medulla development	1	8426.0×	0.001	CTNNB1
nephron tubule formation	1	8426.0×	0.001	CTNNB1
regulation of nephron tubule epithelial cell differentiation	1	8426.0×	0.001	CTNNB1
mesenchymal stem cell differentiation	1	8426.0×	0.001	CTNNB1
positive regulation of determination of dorsal identity	1	8426.0×	0.001	CTNNB1
astrocyte-dopaminergic neuron signaling	1	5617.3×	0.001	CTNNB1
regulation of fibroblast proliferation	1	5617.3×	0.001	CTNNB1
oviduct development	1	5617.3×	0.001	CTNNB1
lung induction	1	5617.3×	0.001	CTNNB1
positive regulation of epithelial cell proliferation involved in prostate gland development	1	5617.3×	0.001	CTNNB1
fungiform papilla formation	1	5617.3×	0.001	CTNNB1
regulation of centromeric sister chromatid cohesion	1	5617.3×	0.001	CTNNB1
regulation of secondary heart field cardioblast proliferation	1	4213.0×	0.001	CTNNB1
metanephros morphogenesis	1	4213.0×	0.001	CTNNB1
positive regulation of heparan sulfate proteoglycan biosynthetic process	1	4213.0×	0.001	CTNNB1
embryonic skeletal limb joint morphogenesis	1	4213.0×	0.001	CTNNB1
central nervous system vasculogenesis	1	3370.4×	0.001	CTNNB1
genitalia morphogenesis	1	3370.4×	0.001	CTNNB1
epithelial cell differentiation involved in prostate gland development	1	3370.4×	0.001	CTNNB1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CTNNB1	DITHIAZANINE IODIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CTNNB1	4	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DITHIAZANINE IODIDE	4	CTNNB1
QUERCETIN	3	CTNNB1
SALINOMYCIN	2	CTNNB1
DALOSIRVAT	2	CTNNB1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CTNNB1	361	Binding:358, Functional:3

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CTNNB1	361

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

4 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)
DITHIAZANINE IODIDE	4	CTNNB1
QUERCETIN	3	CTNNB1
SALINOMYCIN	2	CTNNB1
DALOSIRVAT	2	CTNNB1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CTNNB1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.