Corpus callosum, agenesis of

Summary

Corpus callosum, agenesis of (MONDO:0009022) is a disease caused by PAK3 (GenCC Definitive), with 30 cohort genes and 10 clinical trials. Top therapeutic interventions include pembrolizumab, dovitinib, and nevanimibe.

At a glance

• Prevalence: Unknown (United States) [Orphanet-validated]
• Causal gene: PAK3 (GenCC Definitive)
• Cohort genes: 30
• ClinVar variants: 52
• Phenotypes (HPO): 13
• Clinical trials: 10

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 100 000	1.37	United States	Validated
Prevalence at birth	1-9 / 100 000	3.2	Hungary	Validated

Signs & symptoms

Clinical features (HPO)

13 HPO clinical features (Orphanet curated; top 13 by frequency):

HPO ID	Term	Frequency
HP:0001274	Agenesis of corpus callosum	Very frequent (80-99%)
HP:0000736	Short attention span	Occasional (5-29%)
HP:0000750	Delayed speech and language development	Occasional (5-29%)
HP:0001252	Hypotonia	Occasional (5-29%)
HP:0001328	Specific learning disability	Occasional (5-29%)
HP:0002015	Dysphagia	Occasional (5-29%)
HP:0002342	Intellectual disability, moderate	Occasional (5-29%)
HP:0002370	Poor coordination	Occasional (5-29%)
HP:0002463	Language impairment	Occasional (5-29%)
HP:0010522	Dyslexia	Occasional (5-29%)
HP:0010864	Intellectual disability, severe	Occasional (5-29%)
HP:0031843	Bradyphrenia	Occasional (5-29%)
HP:6000915	Dysorthography	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	corpus callosum, agenesis of
Mondo ID	MONDO:0009022
MeSH	D061085
OMIM	217990
Orphanet	200
NCIT	C98905
SNOMED CT	5102002
UMLS	C0175754
MedGen	104498
GARD	0027261
Is cancer (heuristic)	no

Also known as: ACC · agenesis of corpus callosum · agenesis of the corpus callosum · corpus callosum agenesis · corpus callosum, agenesis of · isolated corpus callosum agenesis

Data availability: 52 ClinVar variants · 3 GenCC gene-disease records.

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 › corpus callosum, agenesis of

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, 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, 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): calloso-genital dysplasia, Kozlowski Ouvrier syndrome

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

52 retrieved; paginated sample, class counts are floors:

18 pathogenic, 14 pathogenic/likely pathogenic, 8 likely pathogenic, 8 uncertain significance, 4 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
375288	NM_005215.3:c.[3649A>G;3748G>A]		Pathogenic	no assertion criteria provided
997077	GRCh37/hg19 Xp22.33(chrX:61091-787353)		Pathogenic	criteria provided, single submitter
279598	NM_001282531.3(ADNP):c.2188C>T (p.Arg730Ter)	ADNP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374179	NM_001374828.1(ARID1B):c.1861C>T (p.Gln621Ter)	ARID1B	Pathogenic	criteria provided, multiple submitters, no conflicts
1077119	NM_139058.3(ARX):c.994C>T (p.Arg332Cys)	ARX	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
632586	NM_022893.4(BCL11A):c.295del (p.Val99fs)	BCL11A	Pathogenic/Likely pathogenic	no assertion criteria provided
804251	NM_001792.5(CDH2):c.2027A>G (p.Tyr676Cys)	CDH2	Pathogenic	criteria provided, multiple submitters, no conflicts
805759	NM_001792.5(CDH2):c.1789G>A (p.Asp597Asn)	CDH2	Pathogenic/Likely pathogenic	no assertion criteria provided
805760	NM_001792.5(CDH2):c.1789G>T (p.Asp597Tyr)	CDH2	Pathogenic	no assertion criteria provided
805761	NM_001792.5(CDH2):c.1802A>C (p.Asn601Thr)	CDH2	Pathogenic	no assertion criteria provided
805762	NM_001792.5(CDH2):c.1839C>G (p.Cys613Trp)	CDH2	Pathogenic	criteria provided, single submitter
805763	NM_001792.5(CDH2):c.1880A>G (p.Asp627Gly)	CDH2	Pathogenic/Likely pathogenic	no assertion criteria provided
805764	NM_001792.5(CDH2):c.2563_2564del (p.Leu855fs)	CDH2	Pathogenic/Likely pathogenic	no assertion criteria provided
805765	NM_001792.5(CDH2):c.2564_2567dup (p.Leu856fs)	CDH2	Pathogenic/Likely pathogenic	no assertion criteria provided
1047876	GRCh37/hg19 1q43-44(chr1:240554955-247342593)	CEP170	Pathogenic	criteria provided, single submitter
1077129	NM_001845.6(COL4A1):c.388-1G>C	COL4A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1047867	GRCh37/hg19 16p13.3(chr16:3784414-3821324)	CREBBP	Pathogenic	criteria provided, single submitter
694759	NM_004380.3(CREBBP):c.1108C>T (p.Arg370Ter)	CREBBP	Pathogenic	criteria provided, multiple submitters, no conflicts
997058	GRCh37/hg19 2q24.3(chr2:165903672-166666206)	CSRNP3	Pathogenic	criteria provided, single submitter
187796	NM_005215.4(DCC):c.823C>T (p.Arg275Ter)	DCC	Pathogenic	criteria provided, multiple submitters, no conflicts
375281	NM_005215.4(DCC):c.925del (p.Thr309fs)	DCC	Pathogenic	no assertion criteria provided
375282	NM_005215.4(DCC):c.2378T>G (p.Val793Gly)	DCC	Pathogenic	no assertion criteria provided
375283	NM_005215.4(DCC):c.2414G>A (p.Gly805Glu)	DCC	Pathogenic	no assertion criteria provided
375284	NM_005215.4(DCC):c.1790G>C (p.Arg597Pro)	DCC	Pathogenic	no assertion criteria provided
375287	NM_005215.4(DCC):c.2677G>A (p.Ala893Thr)	DCC	Pathogenic	no assertion criteria provided
691931	NM_003587.5(DHX16):c.1744T>A (p.Phe582Ile)	DHX16	Pathogenic/Likely pathogenic	no assertion criteria provided
996695	NM_003680.4(YARS1):c.806T>C (p.Phe269Ser)	LOC126805688	Pathogenic/Likely pathogenic	no assertion criteria provided
11520	NM_005120.3(MED12):c.2881C>T (p.Arg961Trp)	MED12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
388568	NM_014159.7(SETD2):c.5218C>T (p.Arg1740Trp)	SETD2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
523557	NM_001365088.1(SLC12A6):c.752dup (p.Ser252fs)	SLC12A6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 19 · Orphanet: 74 · 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
PAK3	Definitive	X-linked	corpus callosum, agenesis of	6
ZEB1	Moderate	Autosomal dominant	corpus callosum, agenesis of	8
CDK5RAP2	Limited	Autosomal recessive	corpus callosum, agenesis of	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ZEB1	Orphanet:98973	Posterior polymorphous corneal dystrophy
ZEB1	Orphanet:98974	Fuchs endothelial corneal dystrophy
CDK5RAP2	Orphanet:2512	Autosomal recessive primary microcephaly
PAK3	Orphanet:528084	Non-specific syndromic intellectual disability
SLC12A6	Orphanet:1496	Corpus callosum agenesis-neuronopathy syndrome
MED12	Orphanet:1415	Hardikar syndrome
MED12	Orphanet:293707	Blepharophimosis-intellectual disability syndrome, MKB type
MED12	Orphanet:776	Lujan-Fryns syndrome
MED12	Orphanet:777	X-linked non-syndromic intellectual disability
MED12	Orphanet:93932	FG syndrome type 1
BCL11A	Orphanet:251380	Hereditary persistence of fetal hemoglobin-sickle cell disease syndrome
BCL11A	Orphanet:619233	Hereditary persistence of fetal hemoglobin-intellectual disability syndrome
AUTS2	Orphanet:352490	Autism spectrum disorder due to AUTS2 deficiency
AUTS2	Orphanet:641372	B-lymphoblastic leukemia/lymphoma with t(7;9)(q11.2;p13.2)
ADNP	Orphanet:404448	Helsmoortel-Van der Aa syndrome
CDH2	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
ARID1B	Orphanet:1465	Coffin-Siris syndrome
ARID1B	Orphanet:251056	6q25.2q25.3 microdeletion syndrome
ARX	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
ARX	Orphanet:2508	Corpus callosum agenesis-abnormal genitalia syndrome
ARX	Orphanet:3175	X-linked spasticity-intellectual disability-epilepsy syndrome
ARX	Orphanet:364063	Infantile epileptic-dyskinetic encephalopathy
ARX	Orphanet:452	X-linked lissencephaly with abnormal genitalia
ARX	Orphanet:697160	Infantile epileptic spasms syndrome
ARX	Orphanet:777	X-linked non-syndromic intellectual disability
ARX	Orphanet:94083	Partington syndrome
SETD2	Orphanet:597738	Luscan-Lumish syndrome
SETD2	Orphanet:597743	SETD2-related microcephaly-severe intellectual disability-multiple congenital anomalies syndrome
ARMC9	Orphanet:475	Isolated Joubert syndrome
TUBA1A	Orphanet:171680	Lissencephaly due to TUBA1A mutation
TUBA1A	Orphanet:45358	Congenital fibrosis of extraocular muscles
TUBA1A	Orphanet:467166	Tubulinopathy-associated dysgyria
TUBA1A	Orphanet:994	Fetal akinesia deformation sequence
BCOR	Orphanet:2712	Oculofaciocardiodental syndrome
BCOR	Orphanet:457246	Clear cell sarcoma of kidney
BCOR	Orphanet:520	Acute promyelocytic leukemia
BCOR	Orphanet:568	Microphthalmia, Lenz type
COL4A1	Orphanet:36383	COL4A1/2-related familial vascular leukoencephalopathy
COL4A1	Orphanet:477749	Pontine autosomal dominant microangiopathy with leukoencephalopathy
COL4A1	Orphanet:481986	Familial schizencephaly
COL4A1	Orphanet:73229	HANAC syndrome
COL4A1	Orphanet:75326	Familial isolated retinal arteriolar tortuosity
COL4A1	Orphanet:899	Walker-Warburg syndrome
COL4A1	Orphanet:99810	Familial porencephaly
CREBBP	Orphanet:353277	Rubinstein-Taybi syndrome due to CREBBP mutations
CREBBP	Orphanet:353281	Rubinstein-Taybi syndrome due to 16p13.3 microdeletion
CREBBP	Orphanet:370026	Acute myeloid leukemia with t(8;16)(p11;p13) translocation
CREBBP	Orphanet:592574	Menke-Hennekam syndrome
DCC	Orphanet:238722	Familial congenital mirror movements
DCC	Orphanet:2744	Horizontal gaze palsy with progressive scoliosis

Cohort genes → proteins

30 cohort genes, 30 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	30

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ZEB1	HGNC:11642	ENSG00000148516	P37275	Zinc finger E-box-binding homeobox 1	gencc
CDK5RAP2	HGNC:18672	ENSG00000136861	Q96SN8	CDK5 regulatory subunit-associated protein 2	gencc
PAK3	HGNC:8592	ENSG00000077264	O75914	Serine/threonine-protein kinase PAK 3	gencc
SLC12A6	HGNC:10914	ENSG00000140199	Q9UHW9	Solute carrier family 12 member 6	clinvar
MED12	HGNC:11957	ENSG00000184634	Q93074	Mediator of RNA polymerase II transcription subunit 12	clinvar
BCL11A	HGNC:13221	ENSG00000119866	Q9H165	BCL11 transcription factor A	clinvar
KIF4A	HGNC:13339	ENSG00000090889	O95239	Chromosome-associated kinesin KIF4A	clinvar
AUTS2	HGNC:14262	ENSG00000158321	Q8WXX7	Autism susceptibility gene 2 protein	clinvar
ADNP	HGNC:15766	ENSG00000101126	Q9H2P0	Activity-dependent neuroprotector homeobox protein	clinvar
TMEM242	HGNC:17206	ENSG00000215712	Q9NWH2	Transmembrane protein 242	clinvar
CDH2	HGNC:1759	ENSG00000170558	P19022	Cadherin-2	clinvar
BORCS5	HGNC:17950	ENSG00000165714	Q969J3	BLOC-1-related complex subunit 5	clinvar
ARID1B	HGNC:18040	ENSG00000049618	Q8NFD5	AT-rich interactive domain-containing protein 1B	clinvar
ARX	HGNC:18060	ENSG00000004848	Q96QS3	Homeobox protein ARX	clinvar
TMLHE	HGNC:18308	ENSG00000185973	Q9NVH6	Trimethyllysine dioxygenase, mitochondrial	clinvar
SETD2	HGNC:18420	ENSG00000181555	Q9BYW2	Histone-lysine N-methyltransferase SETD2	clinvar
ARMC9	HGNC:20730	ENSG00000135931	Q7Z3E5	LisH domain-containing protein ARMC9	clinvar
TUBA1A	HGNC:20766	ENSG00000167552	Q71U36	Tubulin alpha-1A chain	clinvar
BCOR	HGNC:20893	ENSG00000183337	Q6W2J9	BCL-6 corepressor	clinvar
COL4A1	HGNC:2202	ENSG00000187498	P02462	Collagen alpha-1(IV) chain	clinvar
CREBBP	HGNC:2348	ENSG00000005339	Q92793	CREB-binding protein	clinvar
DCC	HGNC:2701	ENSG00000187323	P43146	Netrin receptor DCC	clinvar
DHX16	HGNC:2739	ENSG00000204560	O60231	Pre-mRNA-splicing factor ATP-dependent RNA helicase DHX16	clinvar
CEP170	HGNC:28920	ENSG00000143702	Q5SW79	Centrosomal protein of 170 kDa	clinvar
DYNC1H1	HGNC:2961	ENSG00000197102	Q14204	Cytoplasmic dynein 1 heavy chain 1	clinvar
CSRNP3	HGNC:30729	ENSG00000178662	Q8WYN3	Cysteine/serine-rich nuclear protein 3	clinvar
EP300	HGNC:3373	ENSG00000100393	Q09472	Histone acetyltransferase p300	clinvar
ERCC2	HGNC:3434	ENSG00000104884	P18074	General transcription and DNA repair factor IIH helicase subunit XPD	clinvar
FZD3	HGNC:4041	ENSG00000104290	Q9NPG1	Frizzled-3	clinvar
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ZEB1	Zinc finger E-box-binding homeobox 1	Acts as a transcriptional repressor.
CDK5RAP2	CDK5 regulatory subunit-associated protein 2	Potential regulator of CDK5 activity via its interaction with CDK5R1.
PAK3	Serine/threonine-protein kinase PAK 3	Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, or cell cycle regulation.
SLC12A6	Solute carrier family 12 member 6	Mediates electroneutral potassium-chloride cotransport when activated by cell swelling.
MED12	Mediator of RNA polymerase II transcription subunit 12	Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.
BCL11A	BCL11 transcription factor A	Transcription factor.
KIF4A	Chromosome-associated kinesin KIF4A	Iron-sulfur (Fe-S) cluster binding motor protein that has a role in chromosome segregation during mitosis.
AUTS2	Autism susceptibility gene 2 protein	Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development.
ADNP	Activity-dependent neuroprotector homeobox protein	May be involved in transcriptional regulation.
TMEM242	Transmembrane protein 242	Scaffold protein that participates in the c-ring assembly of mitochondrial ATP synthase (F(1)F(0) ATP synthase or complex V) by facilitating the membrane insertion and oligomer formation of the subunit c/ATP5MC3.
CDH2	Cadherin-2	Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell.
BORCS5	BLOC-1-related complex subunit 5	As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery.
ARID1B	AT-rich interactive domain-containing protein 1B	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
ARX	Homeobox protein ARX	Transcription factor.
TMLHE	Trimethyllysine dioxygenase, mitochondrial	Converts trimethyllysine (TML) into hydroxytrimethyllysine (HTML).
SETD2	Histone-lysine N-methyltransferase SETD2	Histone methyltransferase that specifically trimethylates ‘Lys-36’ of histone H3 (H3K36me3) using dimethylated ‘Lys-36’ (H3K36me2) as substrate.
ARMC9	LisH domain-containing protein ARMC9	Involved in ciliogenesis.
TUBA1A	Tubulin alpha-1A chain	Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers.
BCOR	BCL-6 corepressor	Transcriptional corepressor.
COL4A1	Collagen alpha-1(IV) chain	Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen.
CREBBP	CREB-binding protein	Acetylates histones, giving a specific tag for transcriptional activation.
DCC	Netrin receptor DCC	Receptor for netrin required for axon guidance.
DHX16	Pre-mRNA-splicing factor ATP-dependent RNA helicase DHX16	Required for pre-mRNA splicing as a component of the spliceosome.
CEP170	Centrosomal protein of 170 kDa	Plays a role in microtubule organization.
DYNC1H1	Cytoplasmic dynein 1 heavy chain 1	Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules.
CSRNP3	Cysteine/serine-rich nuclear protein 3	Binds to the consensus sequence 5’-AGAGTG-3’ and has transcriptional activator activity.
EP300	Histone acetyltransferase p300	Functions as a histone acetyltransferase and regulates transcription via chromatin remodeling.
ERCC2	General transcription and DNA repair factor IIH helicase subunit XPD	ATP-dependent 5’-3’ DNA helicase.
FZD3	Frizzled-3	Receptor for Wnt proteins.
PIK3CA	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.

Protein-family classification

Druggable: 7 · Difficult: 8 · Unknown: 15 · Druggable fraction: 0.23

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	2	1.9×	0.796
Transcription factor	6	1.6×	0.796
Enzyme (other)	3	1.2×	0.796
Scaffold/PPI	2	1.1×	0.796
Antibody/Immunoglobulin	1	1.0×	0.796
Other/Unknown	15	0.9×	0.796
GPCR	1	0.8×	0.796

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ZEB1	Transcription factor	no		HD, Di19_Zn-bd, Homeodomain-like_sf
CDK5RAP2	Other/Unknown	no		Cnn_1N, CDK5RAP2, CDK5RAP2_MYOME_CC
PAK3	Kinase	yes	2.7.11.1	CRIB_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
SLC12A6	Other/Unknown	no		KCL_cotranspt, AA-permease/SLC12A_dom, SLC12A_fam
MED12	Other/Unknown	no		Mediator_Med12, Mediator_Med12_catenin-bd, Mediator_Med12_LCEWAV
BCL11A	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Dev/Hematopoietic_TF
KIF4A	Other/Unknown	no		Kinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase
AUTS2	Other/Unknown	no		AUTS2
ADNP	Transcription factor	no		HD, Homeodomain-like_sf, Znf_C2H2_type
TMEM242	Other/Unknown	no		TMEM242
CDH2	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin_pro_dom
BORCS5	Other/Unknown	no		TBORCS5
ARID1B	Other/Unknown	no		ARID_dom, BAF250/Osa, BAF250_C
ARX	Transcription factor	no		HD, OAR_dom, Homeodomain-like_sf
TMLHE	Enzyme (other)	yes	1.14.11.8	TauD/TfdA-like, GBBH-like_N, Trimethyllysine_dOase
SETD2	Scaffold/PPI	no	2.1.1.359	WW_dom, SET_dom, Post-SET_dom
ARMC9	Other/Unknown	no		LisH, ARM-like, ARM-type_fold
TUBA1A	Other/Unknown	no		Tubulin, Alpha_tubulin, Tubulin_FtsZ_GTPase
BCOR	Scaffold/PPI	no		Ankyrin_rpt, BCOR, PUFD
COL4A1	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold
CREBBP	Transcription factor	no	2.3.1.48	Znf_TAZ, Znf_ZZ, Bromodomain
DCC	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
DHX16	Enzyme (other)	yes	3.6.4.13	Helicase_C-like, DNA/RNA_helicase_DEAH_CS, Helicase-assoc_dom
CEP170	Other/Unknown	no		FHA_dom, SMAD_FHA_dom_sf, CEP170_C
DYNC1H1	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
CSRNP3	Other/Unknown	no		Cys/Ser-rich_nuc_prot, CSRNP_N
EP300	Transcription factor	no	2.3.1.48	Znf_TAZ, Znf_ZZ, Bromodomain
ERCC2	Enzyme (other)	yes	3.6.4.12	RAD3/XPD, DNA/RNA_helicase_DEAH_CS, Helicase-like_DEXD_c2
FZD3	GPCR	yes		Frizzled/Smoothened_7TM, Frizzled/SFRP, GPCR_2-like_7TM
PIK3CA	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom

Expression context

Cohort genes with no expression data: 0.

29 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)	30
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	8
ganglionic eminence	7
sural nerve	5
ventricular zone	5
colonic epithelium	4
secondary oocyte	4
Brodmann (1909) area 23	3
endothelial cell	3
stromal cell of endometrium	3
calcaneal tendon	2
tendon	2
right coronary artery	2
middle temporal gyrus	2
left ovary	2
right adrenal gland	2
oocyte	2
tibia	2
buccal mucosa cell	2
bone marrow cell	2
left testis	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ZEB1	287	ubiquitous	marker	calcaneal tendon, colonic epithelium, tendon
CDK5RAP2	272	ubiquitous	marker	sural nerve, ventricular zone, right coronary artery
PAK3	214	broad	marker	middle temporal gyrus, Brodmann (1909) area 23, endothelial cell
SLC12A6	274	ubiquitous	marker	esophagus squamous epithelium, blood, secondary oocyte
MED12	281	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, left ovary
BCL11A	247	ubiquitous	marker	cortical plate, ganglionic eminence, primary visual cortex
KIF4A	179	broad	marker	oocyte, secondary oocyte, ventricular zone
AUTS2	292	ubiquitous	marker	cortical plate, tibia, ganglionic eminence
ADNP	295	ubiquitous	marker	ganglionic eminence, cortical plate, ventricular zone
TMEM242	262	ubiquitous	marker	buccal mucosa cell, vena cava, decidua
CDH2	233	ubiquitous	marker	heart right ventricle, ventricular zone, stromal cell of endometrium
BORCS5	139	ubiquitous	yes	sural nerve, primordial germ cell in gonad, prefrontal cortex
ARID1B	256	ubiquitous	marker	bone marrow cell, colonic epithelium, sural nerve
ARX	162	broad	marker	left ovary, ovary, right ovary
TMLHE	136	ubiquitous	marker	skeletal muscle tissue, hindlimb stylopod muscle, muscle of leg
SETD2	291	ubiquitous	marker	tendon of biceps brachii, endothelial cell, colonic epithelium
ARMC9	244	ubiquitous	marker	stromal cell of endometrium, secondary oocyte, oocyte
TUBA1A	288	ubiquitous	marker	endothelial cell, cortical plate, ganglionic eminence
BCOR	265	ubiquitous	marker	buccal mucosa cell, ganglionic eminence, cortical plate
COL4A1	283	ubiquitous	marker	visceral pleura, placenta, right coronary artery
CREBBP	297	ubiquitous	marker	sural nerve, tibia, amniotic fluid
DCC	154	broad	marker	cortical plate, right testis, left testis
DHX16	134	ubiquitous	marker	sural nerve, granulocyte, left testis
CEP170	134	ubiquitous	marker	cortical plate, ganglionic eminence, corpus callosum
DYNC1H1	290	ubiquitous	marker	cortical plate, ganglionic eminence, ventricular zone
CSRNP3	226	broad	marker	Brodmann (1909) area 23, middle temporal gyrus, entorhinal cortex
EP300	292	ubiquitous	marker	colonic epithelium, adrenal tissue, bone marrow cell
ERCC2	184	ubiquitous	marker	stromal cell of endometrium, right adrenal gland, left adrenal gland
FZD3	257	ubiquitous	marker	Brodmann (1909) area 23, secondary oocyte, corpus epididymis
PIK3CA	284	ubiquitous	marker	calcaneal tendon, adrenal tissue, tendon

Protein interactions among cohort

Intra-cohort edges: 7.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EP300	10,122
CREBBP	6,959
CDH2	5,623
PIK3CA	5,157
SETD2	4,668
DYNC1H1	4,215
ZEB1	4,171
MED12	3,322
DHX16	3,279
COL4A1	2,909

Intra-cohort edges

A	B	Sources
ADNP	ARID1B	string_interaction
ARX	SETD2	biogrid_interaction, intact
AUTS2	EP300	biogrid_interaction, intact
CDH2	ZEB1	string_interaction
CREBBP	EP300	string_interaction
EP300	ZEB1	biogrid_interaction, string_interaction
KIF4A	TUBA1A	intact

Structural data

PDB: 21 · AlphaFold-only: 9 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CREBBP	Q92793	144
PIK3CA	P42336	135
DYNC1H1	Q14204	97
EP300	Q09472	60
ERCC2	P18074	51
SETD2	Q9BYW2	43
BCL11A	Q9H165	17
TUBA1A	Q71U36	15
DHX16	O60231	12
DCC	P43146	9
SLC12A6	Q9UHW9	8
BCOR	Q6W2J9	5
CDK5RAP2	Q96SN8	4
COL4A1	P02462	4
FZD3	Q9NPG1	4
MED12	Q93074	3
ARID1B	Q8NFD5	2
ZEB1	P37275	1
PAK3	O75914	1
KIF4A	O95239	1
CEP170	Q5SW79	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TMLHE	Q9NVH6	89.10
BORCS5	Q969J3	80.54
CDH2	P19022	79.68
TMEM242	Q9NWH2	72.63
ARMC9	Q7Z3E5	71.71
CSRNP3	Q8WYN3	60.42
ADNP	Q9H2P0	57.07
ARX	Q96QS3	56.51
AUTS2	Q8WXX7	41.89

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 387. Enrichment computed across 30 evidence-associated genes (23 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 23 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	2	198.6×	0.004	CREBBP, EP300
NFE2L2 regulating inflammation associated genes	2	198.6×	0.004	CREBBP, EP300
NFE2L2 regulating ER-stress associated genes	2	198.6×	0.004	CREBBP, EP300
CD209 (DC-SIGN) signaling	3	67.7×	0.004	CREBBP, EP300, PAK3
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	3	39.2×	0.004	AUTS2, ARID1B, EP300
NFE2L2 regulates pentose phosphate pathway genes	2	124.1×	0.005	CREBBP, EP300
NFE2L2 regulating MDR associated enzymes	2	124.1×	0.005	CREBBP, EP300
Regulation of NFE2L2 gene expression	2	124.1×	0.005	CREBBP, EP300
Regulation of FOXO transcriptional activity by acetylation	2	99.3×	0.007	CREBBP, EP300
Regulation of gene expression by Hypoxia-inducible Factor	2	82.8×	0.008	CREBBP, EP300
Activation of the TFAP2 (AP-2) family of transcription factors	2	82.8×	0.008	CREBBP, EP300
NFE2L2 regulating tumorigenic genes	2	82.8×	0.008	CREBBP, EP300
Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition	2	76.4×	0.009	ZEB1, CDH2
RUNX3 regulates NOTCH signaling	2	70.9×	0.009	CREBBP, EP300
TRAF3-dependent IRF activation pathway	2	66.2×	0.009	CREBBP, EP300
Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells	2	62.1×	0.009	CREBBP, EP300
FOXO-mediated transcription of cell death genes	2	62.1×	0.009	CREBBP, EP300
Loss of Nlp from mitotic centrosomes	3	20.7×	0.009	CDK5RAP2, TUBA1A, DYNC1H1
Loss of proteins required for interphase microtubule organization from the centrosome	3	20.7×	0.009	CDK5RAP2, TUBA1A, DYNC1H1
AURKA Activation by TPX2	3	19.9×	0.009	CDK5RAP2, TUBA1A, DYNC1H1
Transcriptional regulation by RUNX1	3	19.1×	0.009	AUTS2, ARID1B, CREBBP
Zygotic genome activation (ZGA)	2	58.4×	0.009	CREBBP, EP300
Recruitment of mitotic centrosome proteins and complexes	3	17.7×	0.010	CDK5RAP2, TUBA1A, DYNC1H1
NOTCH4 Intracellular Domain Regulates Transcription	2	49.6×	0.011	CREBBP, EP300
Transcriptional regulation of white adipocyte differentiation	3	16.9×	0.011	MED12, CREBBP, EP300
Regulation of PLK1 Activity at G2/M Transition	3	16.6×	0.011	CDK5RAP2, TUBA1A, DYNC1H1
NFE2L2 regulating anti-oxidant/detoxification enzymes	2	47.3×	0.011	CREBBP, EP300
Recruitment of NuMA to mitotic centrosomes	3	15.2×	0.013	CDK5RAP2, TUBA1A, DYNC1H1
MITF-M-regulated melanocyte development	3	14.9×	0.013	CDH2, ARID1B, CREBBP
Anchoring of the basal body to the plasma membrane	3	14.8×	0.013	CDK5RAP2, TUBA1A, DYNC1H1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 29 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
N-terminal peptidyl-lysine acetylation	2	387.4×	0.002	CREBBP, EP300
stimulatory C-type lectin receptor signaling pathway	3	75.8×	0.002	CREBBP, EP300, PAK3
negative regulation of dendrite development	2	145.3×	0.011	BCL11A, DCC
negative regulation of collateral sprouting	2	105.7×	0.015	BCL11A, DCC
protein acetylation	2	96.8×	0.015	CREBBP, EP300
organelle transport along microtubule	2	83.0×	0.017	BORCS5, TUBA1A
regulation of cellular response to heat	2	72.6×	0.020	CREBBP, EP300
glial cell differentiation	2	61.2×	0.022	CDH2, TUBA1A
positive regulation of transcription by RNA polymerase II	8	4.1×	0.022	ZEB1, MED12, BCL11A, AUTS2, ARX, CREBBP, CSRNP3, EP300
behavioral defense response	1	581.1×	0.023	EP300
regulation of mesenchymal cell proliferation	1	581.1×	0.023	ZEB1
response to muscle inactivity	1	581.1×	0.023	PIK3CA
negative regulation of protein oligomerization	1	581.1×	0.023	EP300
swimming	1	581.1×	0.023	EP300
peptidyl-lysine propionylation	1	581.1×	0.023	EP300
specification of axis polarity	1	581.1×	0.023	BCOR
regulation of tubulin deacetylation	1	581.1×	0.023	EP300
peptidyl-lysine crotonylation	1	581.1×	0.023	EP300
peptidyl-lysine butyrylation	1	581.1×	0.023	EP300
response to butyrate	1	581.1×	0.023	PIK3CA
negative regulation of neuron remodeling	1	581.1×	0.023	BCL11A
negative regulation of branching morphogenesis of a nerve	1	581.1×	0.023	BCL11A
blood vessel morphogenesis	2	55.3×	0.023	CDH2, COL4A1
post-anal tail morphogenesis	2	50.5×	0.023	MED12, FZD3
positive regulation of lamellipodium assembly	2	41.5×	0.023	AUTS2, PIK3CA
positive regulation of transforming growth factor beta receptor signaling pathway	2	36.3×	0.023	CREBBP, EP300
spinal cord development	2	35.2×	0.023	MED12, ERCC2
insulin-like growth factor receptor signaling pathway	2	34.2×	0.023	ERCC2, PIK3CA
cellular response to nutrient levels	2	32.3×	0.023	CREBBP, EP300
positive regulation of neuron projection development	3	14.2×	0.023	BCL11A, ADNP, EP300

Therapeutics

Drug target analysis

Approved (phase 4): 5 · Phase ≥3: 6 · Phased (≥1): 9 · Undrugged: 21

Druggability breadth: 15 of 30 evidence-associated genes (50%) 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
PAK3	BOSUTINIB
TUBA1A	COLCHICINE
CREBBP	COLCHICINE
ERCC2	SUNITINIB
PIK3CA	IDELALISIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PIK3CA	67	4
TUBA1A	22	4
PAK3	17	4
ERCC2	16	4
CREBBP	13	4
EP300	9	3
SETD2	3	2
MED12	1	2
DYNC1H1	1	2
ZEB1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BOSUTINIB	4	PAK3
NINTEDANIB	4	PAK3
SUNITINIB	4	ERCC2, PAK3, PIK3CA
QUIZARTINIB	4	PAK3
MIDOSTAURIN	4	PAK3, PIK3CA
COLCHICINE	4	CREBBP, TUBA1A
VINBLASTINE	4	TUBA1A
LEVOFLOXACIN ANHYDROUS	4	TUBA1A
DOCETAXEL	4	TUBA1A
NOSCAPINE	4	TUBA1A
VINBLASTINE SULFATE	4	TUBA1A
PACLITAXEL	4	TUBA1A
LEVOFLOXACIN	4	TUBA1A
VINORELBINE	4	TUBA1A
TIRBANIBULIN	4	TUBA1A
PODOFILOX	4	TUBA1A
VINCRISTINE	4	TUBA1A
DOCETAXEL ANHYDROUS	4	TUBA1A
ALTRETAMINE	4	CREBBP
IDELALISIB	4	PIK3CA
ALPELISIB	4	PIK3CA
DUVELISIB	4	PIK3CA
COPANLISIB	4	PIK3CA
FEDRATINIB	4	PIK3CA
ROMIDEPSIN	4	PIK3CA
COPANLISIB HYDROCHLORIDE	4	PIK3CA
LENIOLISIB	4	PIK3CA
BELINOSTAT	4	PIK3CA
INAVOLISIB	4	PIK3CA
DASATINIB	4	PIK3CA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 8.

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

Symbol	Assays	Type breakdown
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
TUBA1A	1,696	Binding:1655, Functional:35, ADMET:6
EP300	767	Binding:763, Functional:3, ADMET:1
CREBBP	687	Binding:644, Functional:43
PAK3	240	Binding:240
SETD2	64	Binding:64
KIF4A	20	Binding:20
DYNC1H1	7	Binding:7
MED12	6	Binding:6
CDH2	4	Binding:3, Functional:1
ERCC2	3	Binding:3
BCOR	2	Binding:2
CEP170	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PAK3	2.7.11.1	non-specific serine/threonine protein kinase
TMLHE	1.14.11.8	trimethyllysine dioxygenase
SETD2	2.1.1.359	[histone H3]-lysine36 N-trimethyltransferase
CREBBP	2.3.1.48	histone acetyltransferase
DHX16	3.6.4.13	RNA helicase
EP300	2.3.1.48	histone acetyltransferase
ERCC2	3.6.4.12	DNA helicase
PIK3CA	2.7.1.137, 2.7.1.153, 2.7.11.1	phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PAK3	240
TUBA1A	1,696
CREBBP	687
EP300	767
PIK3CA	2,034

Pharmacogenomics

Cohort genes with a PharmGKB record: 30; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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)
BOSUTINIB	4	PAK3
NINTEDANIB	4	PAK3
SUNITINIB	4	ERCC2, PAK3, PIK3CA
QUIZARTINIB	4	PAK3
MIDOSTAURIN	4	PAK3, PIK3CA
COLCHICINE	4	CREBBP, TUBA1A
VINBLASTINE	4	TUBA1A
LEVOFLOXACIN ANHYDROUS	4	TUBA1A
DOCETAXEL	4	TUBA1A
NOSCAPINE	4	TUBA1A
VINBLASTINE SULFATE	4	TUBA1A
PACLITAXEL	4	TUBA1A
LEVOFLOXACIN	4	TUBA1A
VINORELBINE	4	TUBA1A
TIRBANIBULIN	4	TUBA1A
PODOFILOX	4	TUBA1A
VINCRISTINE	4	TUBA1A
DOCETAXEL ANHYDROUS	4	TUBA1A
ALTRETAMINE	4	CREBBP
IDELALISIB	4	PIK3CA
ALPELISIB	4	PIK3CA
DUVELISIB	4	PIK3CA
COPANLISIB	4	PIK3CA
FEDRATINIB	4	PIK3CA
ROMIDEPSIN	4	PIK3CA
COPANLISIB HYDROCHLORIDE	4	PIK3CA
LENIOLISIB	4	PIK3CA
BELINOSTAT	4	PIK3CA
INAVOLISIB	4	PIK3CA
DASATINIB	4	PIK3CA

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	5	PAK3, TUBA1A, CREBBP, ERCC2, PIK3CA
B	Phased (≥1) drug, not yet approved	4	MED12, SETD2, DYNC1H1, EP300
C	Druggable family + PDB, no drug	3	DCC, DHX16, FZD3
D	Druggable family + AlphaFold only, no drug	1	TMLHE
E	Difficult family or no structure, no drug	17	ZEB1, CDK5RAP2, SLC12A6, BCL11A, KIF4A, AUTS2, ADNP, TMEM242, CDH2, BORCS5 (+7 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ZEB1	0	—
CDK5RAP2	0	—
SLC12A6	0	—
BCL11A	0	—
KIF4A	20	—
AUTS2	0	—
ADNP	0	—
TMEM242	0	—
CDH2	4	—
BORCS5	0	—
ARID1B	0	—
ARX	0	—
TMLHE	0	—
ARMC9	0	—
BCOR	2	—
COL4A1	0	—
DCC	0	—
DHX16	0	—
CEP170	1	—
CSRNP3	0	—
FZD3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 10.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	6
PHASE2	2
PHASE1/PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06066333	PHASE2	RECRUITING	Study of Radiotherapy and Pembrolizumab in People With Adrenocortical Carcinoma
NCT01262235	PHASE1/PHASE2	COMPLETED	A Dose Finding Study of TKM-080301 Infusion in Neuroendocrine Tumors (NET) and Adrenocortical Carcinoma (ACC) Patients
NCT01678105	PHASE2	COMPLETED	A Phase II Study of Dovitinib in Recurrent and/or Metastatic Adenoid Cystic Carcinoma of the Salivary Glands
NCT01898715	PHASE1	COMPLETED	Phase 1 Study of ATR-101 in Subjects With Advanced Adrenocortical Carcinoma
NCT00170326	Not specified	COMPLETED	Progressive Ventricular Dysfunction Prevention in Pacemaker Patients
NCT01117792	Not specified	COMPLETED	Subcutaneous Implantable Defibrillator (S-ICD) System - CE Clinical Investigation
NCT02267161	Not specified	COMPLETED	Infants With Agenesis of the Corpus Callosum
NCT02826824	Not specified	UNKNOWN	BECOME CHILDREN OF HOLDERS Corpus Callosum Agenesis Screened IN PERIOD Antenatal
NCT05843110	Not specified	UNKNOWN	Decision-making Process of Couples Confronted With Prenatal Diagnosis of an Isolated CCA
NCT06262152	Not specified	UNKNOWN	Sleep Profile of Patients With Septo-optic Dysplasia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PEMBROLIZUMAB	4	1
DOVITINIB	3	1
NEVANIMIBE	2	2
CHEMBL4578973	0	1