Lissencephaly spectrum disorders

Summary

Lissencephaly spectrum disorders (MONDO:0018838) is a disease (an umbrella term covering 15 Mondo subtypes) caused by DCX (GenCC Definitive), with 22 cohort genes. The dominant Reactome pathway is Recruitment of NuMA to mitotic centrosomes (9 cohort genes).

At a glance

• Causal gene: DCX (GenCC Definitive)
• Umbrella term: 15 Mondo subtypes
• Cohort genes: 22
• ClinVar variants: 79

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	lissencephaly spectrum disorders
Mondo ID	MONDO:0018838
MeSH	D054082
OMIM	607432
Orphanet	48471
DOID	DOID:0050453
NCIT	C103921
SNOMED CT	204036008
UMLS	C0266463
MedGen	78604
GARD	0012291
MedDRA	10048911
NORD	1374
Is cancer (heuristic)	no

Also known as: Broad gyri of cerebrum · large gyri of cerebrum · Lissencephaly · lissencephaly · lissencephaly (disease) · lissencephaly spectrum disorders · macrogyria · pachygyria

Data availability: 79 ClinVar variants · 2 GenCC gene-disease records · 1 HPO phenotype · 2 cell lines.

Disease family

An umbrella term covering 15 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › lissencephaly spectrum disorders

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, 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, 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 (15): craniotelencephalic dysplasia, X-linked lissencephaly with abnormal genitalia, lissencephaly 7 with cerebellar hypoplasia, lissencephaly 8, classic lissencephaly, lissencephaly type 3, microlissencephaly, Warburg micro syndrome, Baraitser-Winter cerebrofrontofacial syndrome, cobblestone lissencephaly, lissencephaly with cerebellar hypoplasia, lissencephaly 10, cortical dysplasia, complex, with other brain malformations 9, massa casaer ceulemans syndrome, lissencephaly spectrum disorder with complex brainstem malformation

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

79 retrieved; paginated sample, class counts are floors:

27 likely pathogenic, 19 pathogenic, 12 pathogenic/likely pathogenic, 12 uncertain significance, 8 conflicting classifications of pathogenicity, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
997077	GRCh37/hg19 Xp22.33(chrX:61091-787353)		Pathogenic	criteria provided, single submitter
29589	NM_001614.5(ACTG1):c.760C>T (p.Arg254Trp)	ACTG1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
29590	NM_001614.5(ACTG1):c.766C>T (p.Arg256Trp)	ACTG1	Pathogenic	criteria provided, single submitter
643176	NM_018136.5(ASPM):c.9324del (p.Leu3109fs)	ASPM	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1077140	NM_001042475.3(CEP85L):c.232+2T>A	CEP85L	Pathogenic	criteria provided, single submitter
1320300	NM_001042475.3(CEP85L):c.3G>T (p.Met1Ile)	CEP85L	Pathogenic	criteria provided, single submitter
523261	GRCh37/hg19 17p13.3(chr17:2339561-2826073)	CLUH	Pathogenic	criteria provided, single submitter
1819	NM_018451.5(CPAP):c.3243_3246del (p.Ser1081fs)	CPAP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
158443	NM_001195553.2(DCX):c.233G>T (p.Arg78Leu)	DCX	Pathogenic	criteria provided, multiple submitters, no conflicts
158511	NM_001195553.2(DCX):c.907C>T (p.Arg303Ter)	DCX	Pathogenic	criteria provided, multiple submitters, no conflicts
209107	NM_001376.5(DYNC1H1):c.926G>A (p.Arg309His)	DYNC1H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
209108	NM_001376.5(DYNC1H1):c.1706G>C (p.Arg569Pro)	DYNC1H1	Pathogenic/Likely pathogenic	no assertion criteria provided
246393	NM_001376.5(DYNC1H1):c.10420C>T (p.Arg3474Trp)	DYNC1H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
424046	NM_001376.5(DYNC1H1):c.4868G>A (p.Arg1623Gln)	DYNC1H1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
55855	NM_001376.5(DYNC1H1):c.10031G>A (p.Arg3344Gln)	DYNC1H1	Pathogenic	criteria provided, multiple submitters, no conflicts
996573	NM_001376.5(DYNC1H1):c.10030C>T (p.Arg3344Trp)	DYNC1H1	Pathogenic	criteria provided, multiple submitters, no conflicts
31691	NM_016042.4(EXOSC3):c.92G>C (p.Gly31Ala)	EXOSC3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
523260	GRCh37/hg19 17p13.3(chr17:1361431-2573023)	INPP5K	Pathogenic	criteria provided, single submitter
586948	NM_001394062.1(MACF1):c.21707G>T (p.Cys7236Phe)	MACF1	Pathogenic	criteria provided, single submitter
586953	NM_001394062.1(MACF1):c.20293G>C (p.Gly6765Arg)	MACF1	Pathogenic/Likely pathogenic	no assertion criteria provided
6940	NM_002485.5(NBN):c.657_661del (p.Lys219fs)	NBN	Pathogenic	criteria provided, multiple submitters, no conflicts
523262	GRCh37/hg19 17p13.3-13.2(chr17:2339561-3447162)	OR3A1	Pathogenic	criteria provided, single submitter
159494	NM_000430.4(PAFAH1B1):c.1111C>T (p.Arg371Ter)	PAFAH1B1	Pathogenic	criteria provided, multiple submitters, no conflicts
21182	NM_000430.4(PAFAH1B1):c.569-10T>C	PAFAH1B1	Pathogenic	criteria provided, multiple submitters, no conflicts
8081	NM_000430.4(PAFAH1B1):c.22C>T (p.Arg8Ter)	PAFAH1B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
160146	NM_006009.4(TUBA1A):c.1204C>T (p.Arg402Cys)	TUBA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208490	NM_006009.4(TUBA1A):c.1226T>C (p.Val409Ala)	TUBA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7070	NM_006009.4(TUBA1A):c.790C>T (p.Arg264Cys)	TUBA1A	Pathogenic	criteria provided, multiple submitters, no conflicts
7071	NM_006009.4(TUBA1A):c.1205G>A (p.Arg402His)	TUBA1A	Pathogenic	criteria provided, multiple submitters, no conflicts
7077	NM_006009.4(TUBA1A):c.1265G>A (p.Arg422His)	TUBA1A	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 41 · 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
DCX	Definitive	X-linked	lissencephaly spectrum disorders	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DCX	Orphanet:2148	Lissencephaly type 1 due to doublecortin gene mutation
DCX	Orphanet:99796	Subcortical band heterotopia
TUBG1	Orphanet:261183	15q11.2 microdeletion syndrome
MACF1	Orphanet:572013	Posterior-predominant lissencephaly-broad flat pons and medulla-midline crossing defects syndrome
ACTG1	Orphanet:2995	Baraitser-Winter cerebrofrontofacial syndrome
ACTG1	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
ACTG1	Orphanet:98942	Coloboma of choroid and retina
ACTG1	Orphanet:98944	Coloboma of iris
CPAP	Orphanet:2512	Autosomal recessive primary microcephaly
CPAP	Orphanet:808	Seckel syndrome
EXOSC3	Orphanet:2254	Pontocerebellar hypoplasia type 1
ASPM	Orphanet:2512	Autosomal recessive primary microcephaly
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
TUBB3	Orphanet:300570	Cortical dysgenesis with pontocerebellar hypoplasia due to TUBB3 mutation
TUBB3	Orphanet:45358	Congenital fibrosis of extraocular muscles
TUBB3	Orphanet:467166	Tubulinopathy-associated dysgyria
TUBB	Orphanet:2505	Multiple benign circumferential skin creases on limbs
CEP85L	Orphanet:572013	Posterior-predominant lissencephaly-broad flat pons and medulla-midline crossing defects syndrome
DYNC1H1	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
DYNC1H1	Orphanet:209341	DYNC1H1-related autosomal dominant childhood-onset proximal spinal muscular atrophy
DYNC1H1	Orphanet:284232	Autosomal dominant Charcot-Marie-Tooth disease type 2O
TUBB2B	Orphanet:1766	Dysequilibrium syndrome
TUBB2B	Orphanet:300573	Polymicrogyria due to TUBB2B mutation
TUBB2B	Orphanet:45358	Congenital fibrosis of extraocular muscles
TUBB2B	Orphanet:467166	Tubulinopathy-associated dysgyria
INPP5K	Orphanet:662184	Congenital muscular dystrophy-cataract-intellectual disability syndrome
FOXG1	Orphanet:261144	FOXG1 syndrome due to 14q12 microdeletion
FOXG1	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
FOXG1	Orphanet:598164	FOXG1 syndrome due to intragenic alteration
NBN	Orphanet:1331	Familial prostate cancer
NBN	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
NBN	Orphanet:647	Nijmegen breakage syndrome
PAFAH1B1	Orphanet:217385	17p13.3 microduplication syndrome
PAFAH1B1	Orphanet:531	Miller-Dieker syndrome
PAFAH1B1	Orphanet:95232	Lissencephaly due to LIS1 mutation
PAFAH1B1	Orphanet:99796	Subcortical band heterotopia
RELN	Orphanet:101046	Epilepsy with auditory features
RELN	Orphanet:89844	Lissencephaly syndrome, Norman-Roberts type

Cohort genes → proteins

22 cohort genes, 22 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	22

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DCX	HGNC:2714	ENSG00000077279	O43602	Neuronal migration protein doublecortin	gencc,clinvar
TUBG1	HGNC:12417	ENSG00000131462	P23258	Tubulin gamma-1 chain	clinvar
MACF1	HGNC:13664	ENSG00000127603	O94854	Microtubule-actin cross-linking factor 1, isoforms 6/7	clinvar
ACTG1	HGNC:144	ENSG00000184009	P63261	Actin, cytoplasmic 2	clinvar
CPAP	HGNC:17272	ENSG00000151849	Q9HC77	Centrosomal P4.1-associated protein	clinvar
EXOSC3	HGNC:17944	ENSG00000107371	Q9NQT5	Exosome complex component RRP40	clinvar
PDZD2	HGNC:18486	ENSG00000133401	O15018	PDZ domain-containing protein 2	clinvar
ASPM	HGNC:19048	ENSG00000066279	Q8IZT6	Abnormal spindle-like microcephaly-associated protein	clinvar
TUBA1A	HGNC:20766	ENSG00000167552	Q71U36	Tubulin alpha-1A chain	clinvar
TUBB3	HGNC:20772	ENSG00000258947	Q13509	Tubulin beta-3 chain	clinvar
TUBB	HGNC:20778	ENSG00000196230	P07437	Tubulin beta chain	clinvar
CEP85L	HGNC:21638	ENSG00000111860	Q5SZL2	Centrosomal protein of 85 kDa-like	clinvar
MZT2B	HGNC:25886	ENSG00000152082	Q6NZ67	Mitotic-spindle organizing protein 2B	clinvar
CLUH	HGNC:29094	ENSG00000132361	O75153	Clustered mitochondria protein homolog	clinvar
DYNC1H1	HGNC:2961	ENSG00000197102	Q14204	Cytoplasmic dynein 1 heavy chain 1	clinvar
TUBB2B	HGNC:30829	ENSG00000137285	Q9BVA1	Tubulin beta-2B chain	clinvar
INPP5K	HGNC:33882	ENSG00000132376	Q9BT40	Inositol polyphosphate 5-phosphatase K	clinvar
FOXG1	HGNC:3811	ENSG00000176165	P55316	Forkhead box protein G1	clinvar
NBN	HGNC:7652	ENSG00000104320	O60934	Nibrin	clinvar
OR3A1	HGNC:8282	ENSG00000180090	P47881	Olfactory receptor 3A1	clinvar
PAFAH1B1	HGNC:8574	ENSG00000007168	P43034	Platelet-activating factor acetylhydrolase IB subunit beta	clinvar
RELN	HGNC:9957	ENSG00000189056	P78509	Reelin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DCX	Neuronal migration protein doublecortin	Microtubule-associated protein required for initial steps of neuronal dispersion and cortex lamination during cerebral cortex development.
TUBG1	Tubulin gamma-1 chain	Tubulin is the major constituent of microtubules, protein filaments consisting of alpha- and beta-tubulin heterodimers.
ACTG1	Actin, cytoplasmic 2	Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
CPAP	Centrosomal P4.1-associated protein	Plays an important role in cell division and centrosome function by participating in centriole duplication.
EXOSC3	Exosome complex component RRP40	Non-catalytic component of the RNA exosome complex which has 3’->5’ exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events.
ASPM	Abnormal spindle-like microcephaly-associated protein	Involved in mitotic spindle regulation and coordination of mitotic processes.
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.
TUBB3	Tubulin beta-3 chain	Tubulin is the major constituent of microtubules, protein filaments consisting of alpha- and beta-tubulin heterodimers.
TUBB	Tubulin beta chain	Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers.
CEP85L	Centrosomal protein of 85 kDa-like	Plays an essential role in neuronal cell migration.
MZT2B	Mitotic-spindle organizing protein 2B	Required for the recruitment and the assembly of the gamma-tubulin ring complex (gTuRC) at the centrosome.
CLUH	Clustered mitochondria protein homolog	mRNA-binding protein involved in proper cytoplasmic distribution of mitochondria.
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.
TUBB2B	Tubulin beta-2B chain	Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers.
INPP5K	Inositol polyphosphate 5-phosphatase K	Inositol 5-phosphatase which acts on inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate.
FOXG1	Forkhead box protein G1	Transcription repression factor which plays an important role in the establishment of the regional subdivision of the developing brain and in the development of the telencephalon.
NBN	Nibrin	Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis.
OR3A1	Olfactory receptor 3A1	Odorant receptor.
PAFAH1B1	Platelet-activating factor acetylhydrolase IB subunit beta	Regulatory subunit (beta subunit) of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)), an enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and participate…
RELN	Reelin	Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment.

Protein-family classification

Druggable: 4 · Difficult: 4 · Unknown: 14 · Druggable fraction: 0.18

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	3	2.4×	0.731
Antibody/Immunoglobulin	1	1.3×	0.731
Other/Unknown	14	1.1×	0.731
Enzyme (other)	2	1.1×	0.731
GPCR	1	1.1×	0.731
Transcription factor	1	0.4×	0.942

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DCX	Other/Unknown	no		Doublecortin_dom, DCX_chordates, Doublecortin_dom_sf
TUBG1	Enzyme (other)	yes	3.6.5.6	Tubulin, Gamma_tubulin, Tubulin_FtsZ_GTPase
MACF1	Scaffold/PPI	no		Spectrin_repeat, EF_hand_dom, GAR_dom
ACTG1	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS
CPAP	Other/Unknown	no		CENPJ_C_dom, TCP10L/CENPJ, Tcp10_C_sf
EXOSC3	Other/Unknown	no		KH_dom_type_1, NA-bd_OB-fold, Exosome_RNA_bind1/RRP40/RRP4
PDZD2	Scaffold/PPI	no		PDZ, PDZ_sf
ASPM	Antibody/Immunoglobulin	yes		IQ_motif_EF-hand-BS, CH_dom, ARM-like
TUBA1A	Other/Unknown	no		Tubulin, Alpha_tubulin, Tubulin_FtsZ_GTPase
TUBB3	Other/Unknown	no		Tubulin, Beta_tubulin, Tubulin_FtsZ_GTPase
TUBB	Other/Unknown	no		Tubulin, Beta_tubulin, Tubulin_FtsZ_GTPase
CEP85L	Other/Unknown	no		Cep85/Cep85L, CC4_CEP85
MZT2B	Other/Unknown	no		MOZART2
CLUH	Other/Unknown	no		TPR-like_helical_dom_sf, GSKIP_dom_sf, CLU_dom
DYNC1H1	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
TUBB2B	Other/Unknown	no		Tubulin, Beta_tubulin, Tubulin_FtsZ_GTPase
INPP5K	Enzyme (other)	yes	3.1.3.56	IPPc, Endo/exonu/phosph_ase_sf, SKICH
FOXG1	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_1, TF_fork_head_CS_2
NBN	Other/Unknown	no		FHA_dom, BRCT_dom, SMAD_FHA_dom_sf
OR3A1	GPCR	yes		GPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
PAFAH1B1	Scaffold/PPI	no		WD40_rpt, LisH, WD40/YVTN_repeat-like_dom_sf
RELN	Other/Unknown	no		EGF, Reeler_dom, EGF_extracell

Expression context

Cohort genes with no expression data: 0.

22 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)	1
broad (>20)	21
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	7
ganglionic eminence	6
ventricular zone	6
secondary oocyte	3
right lung	2
right lobe of thyroid gland	2
sperm	2
oocyte	2
endothelial cell	2
apex of heart	2
adult organism	1
left testis	1
right testis	1
dorsal motor nucleus of vagus nerve	1
inferior olivary complex	1
amniotic fluid	1
ileal mucosa	1
left lobe of thyroid gland	1
tendon of biceps brachii	1
dorsal root ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DCX	114	broad	marker	cortical plate, ganglionic eminence, ventricular zone
TUBG1	289	ubiquitous	marker	left testis, right testis, adult organism
MACF1	303	ubiquitous	marker	inferior olivary complex, dorsal motor nucleus of vagus nerve, right lung
ACTG1	288	ubiquitous	marker	ileal mucosa, ventricular zone, amniotic fluid
CPAP	246	ubiquitous	marker	sperm, left lobe of thyroid gland, right lobe of thyroid gland
EXOSC3	246	ubiquitous	marker	oocyte, secondary oocyte, tendon of biceps brachii
PDZD2	281	broad	marker	trigeminal ganglion, dorsal root ganglion, upper leg skin
ASPM	176	ubiquitous	marker	oocyte, ventricular zone, secondary oocyte
TUBA1A	288	ubiquitous	marker	endothelial cell, cortical plate, ganglionic eminence
TUBB3	144	ubiquitous	marker	cortical plate, ganglionic eminence, embryo
TUBB	133	ubiquitous	marker	cortical plate, ganglionic eminence, ventricular zone
CEP85L	248	ubiquitous	marker	thymus, tibialis anterior, pylorus
MZT2B	285	ubiquitous	marker	apex of heart, anterior cingulate cortex, cingulate cortex
CLUH	283	ubiquitous	marker	gingival epithelium, apex of heart, right lobe of liver
DYNC1H1	290	ubiquitous	marker	cortical plate, ganglionic eminence, ventricular zone
TUBB2B	265	ubiquitous	marker	cortical plate, ganglionic eminence, ventricular zone
INPP5K	283	ubiquitous	marker	pigmented layer of retina, right lung, right lobe of thyroid gland
FOXG1	100	broad	marker	cortical plate, endothelial cell, Brodmann (1909) area 23
NBN	299	ubiquitous	marker	endometrium epithelium, mammary duct, cauda epididymis
OR3A1	14		marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, primordial germ cell in gonad
PAFAH1B1	295	ubiquitous	marker	sperm, male germ cell, middle temporal gyrus
RELN	254	broad	marker	olfactory bulb, cerebellar vermis, cerebellum

Protein interactions among cohort

Intra-cohort edges: 14.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TUBB3	6,797
TUBB2B	4,736
DYNC1H1	4,215
PAFAH1B1	3,181
TUBG1	3,048
ASPM	2,949
EXOSC3	2,330
RELN	2,305
CPAP	2,242
DCX	2,112

Intra-cohort edges

A	B	Sources
ASPM	CPAP	string_interaction
CEP85L	TUBA1A	intact
CPAP	TUBG1	string_interaction
DCX	PAFAH1B1	string_interaction
DYNC1H1	PAFAH1B1	biogrid_interaction
DYNC1H1	TUBB2B	string_interaction
DYNC1H1	TUBG1	string_interaction
MZT2B	TUBG1	biogrid_interaction, intact
PAFAH1B1	RELN	string_interaction
TUBA1A	TUBB	intact
TUBA1A	TUBB2B	intact
TUBA1A	TUBB3	intact
TUBB	TUBB3	intact
TUBB2B	TUBB3	biogrid_interaction

Structural data

PDB: 17 · AlphaFold-only: 5 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DYNC1H1	Q14204	97
TUBG1	P23258	32
TUBB3	Q13509	28
TUBB	P07437	21
PAFAH1B1	P43034	21
TUBA1A	Q71U36	15
DCX	O43602	14
ACTG1	P63261	10
EXOSC3	Q9NQT5	8
NBN	O60934	7
CPAP	Q9HC77	6
MACF1	O94854	3
TUBB2B	Q9BVA1	3
MZT2B	Q6NZ67	1
INPP5K	Q9BT40	1
FOXG1	P55316	1
RELN	P78509	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
OR3A1	P47881	87.02
CLUH	O75153	83.11
CEP85L	Q5SZL2	64.98
PDZD2	O15018
ASPM	Q8IZT6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 208. Enrichment computed across 22 evidence-associated genes (17 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 17 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Recruitment of NuMA to mitotic centrosomes	9	61.7×	8e-13	TUBG1, CPAP, TUBA1A, TUBB3, TUBB, MZT2B, DYNC1H1, TUBB2B (+1 more)
Recruitment of mitotic centrosome proteins and complexes	7	56.0×	1e-09	TUBG1, CPAP, TUBA1A, TUBB, MZT2B, DYNC1H1, PAFAH1B1
Mitotic G2-G2/M phases	7	52.2×	1e-09	TUBG1, TUBA1A, TUBB3, TUBB, MZT2B, TUBB2B, PAFAH1B1
G2/M Transition	7	52.2×	1e-09	TUBG1, TUBA1A, TUBB3, TUBB, MZT2B, TUBB2B, PAFAH1B1
Mitotic Prometaphase	8	32.6×	1e-09	TUBG1, TUBA1A, TUBB3, TUBB, MZT2B, DYNC1H1, TUBB2B, PAFAH1B1
Loss of Nlp from mitotic centrosomes	6	56.0×	2e-08	TUBG1, CPAP, TUBA1A, TUBB, DYNC1H1, PAFAH1B1
Loss of proteins required for interphase microtubule organization from the centrosome	6	56.0×	2e-08	TUBG1, CPAP, TUBA1A, TUBB, DYNC1H1, PAFAH1B1
AURKA Activation by TPX2	6	53.7×	2e-08	TUBG1, CPAP, TUBA1A, TUBB, DYNC1H1, PAFAH1B1
Regulation of PLK1 Activity at G2/M Transition	6	44.8×	5e-08	TUBG1, CPAP, TUBA1A, TUBB, DYNC1H1, PAFAH1B1
M Phase	7	27.2×	6e-08	TUBG1, TUBA1A, TUBB3, TUBB, MZT2B, TUBB2B, PAFAH1B1
Centrosome maturation	5	74.6×	8e-08	TUBG1, TUBA1A, TUBB, MZT2B, PAFAH1B1
Anchoring of the basal body to the plasma membrane	6	39.9×	8e-08	TUBG1, CPAP, TUBA1A, TUBB, DYNC1H1, PAFAH1B1
Cilium Assembly	6	38.4×	9e-08	TUBG1, TUBA1A, TUBB3, TUBB, TUBB2B, PAFAH1B1
Cell Cycle	8	16.9×	9e-08	TUBG1, TUBA1A, TUBB3, TUBB, MZT2B, TUBB2B, NBN, PAFAH1B1
COPI-independent Golgi-to-ER retrograde traffic	5	61.1×	2e-07	TUBA1A, TUBB3, DYNC1H1, TUBB2B, PAFAH1B1
Cell Cycle, Mitotic	7	19.8×	3e-07	TUBG1, TUBA1A, TUBB3, TUBB, MZT2B, TUBB2B, PAFAH1B1
Gap junction trafficking and regulation	4	112.0×	4e-07	ACTG1, TUBA1A, TUBB3, TUBB2B
Gap junction trafficking	4	112.0×	4e-07	ACTG1, TUBA1A, TUBB3, TUBB2B
RHO GTPases Activate Formins	6	27.4×	5e-07	ACTG1, TUBA1A, TUBB3, DYNC1H1, TUBB2B, PAFAH1B1
Organelle biogenesis and maintenance	6	23.3×	1e-06	TUBG1, TUBA1A, TUBB3, TUBB, TUBB2B, PAFAH1B1
RHO GTPases activate IQGAPs	4	81.4×	1e-06	ACTG1, TUBA1A, TUBB3, TUBB2B
Aggrephagy	4	58.4×	5e-06	TUBA1A, TUBB3, DYNC1H1, TUBB2B
EML4 and NUDC in mitotic spindle formation	5	27.3×	7e-06	TUBA1A, TUBB3, DYNC1H1, TUBB2B, PAFAH1B1
Recycling pathway of L1	4	52.7×	7e-06	ACTG1, TUBA1A, TUBB3, TUBB2B
Resolution of Sister Chromatid Cohesion	5	25.4×	9e-06	TUBA1A, TUBB3, DYNC1H1, TUBB2B, PAFAH1B1
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	4	45.5×	1e-05	TUBA1A, TUBB3, DYNC1H1, TUBB2B
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	3	96.0×	3e-05	TUBA1A, TUBB3, TUBB2B
Transport of connexons to the plasma membrane	3	96.0×	3e-05	TUBA1A, TUBB3, TUBB2B
Translocation of SLC2A4 (GLUT4) to the plasma membrane	4	36.3×	3e-05	ACTG1, TUBA1A, TUBB3, TUBB2B
RHO GTPase Effectors	5	20.0×	3e-05	ACTG1, TUBA1A, TUBB3, TUBB2B, PAFAH1B1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 21 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
neuron migration	7	44.6×	3e-08	DCX, ASPM, TUBA1A, CEP85L, TUBB2B, PAFAH1B1, RELN
microtubule-based process	4	188.8×	6e-07	TUBA1A, TUBB, TUBB2B, PAFAH1B1
microtubule cytoskeleton organization	6	34.6×	1e-06	TUBG1, TUBA1A, TUBB3, TUBB, TUBB2B, PAFAH1B1
mitotic cell cycle	5	31.8×	3e-05	TUBG1, TUBA1A, TUBB3, TUBB, TUBB2B
cerebral cortex development	4	39.1×	2e-04	ASPM, TUBA1A, TUBB2B, PAFAH1B1
maintenance of centrosome location	2	267.5×	1e-03	ASPM, PAFAH1B1
neuroblast proliferation	3	52.3×	1e-03	FOXG1, NBN, PAFAH1B1
positive regulation of spindle assembly	2	200.6×	0.001	CPAP, DYNC1H1
retrograde axonal transport	2	145.9×	0.002	DYNC1H1, PAFAH1B1
interneuron migration	2	145.9×	0.002	PAFAH1B1, RELN
reelin-mediated signaling pathway	2	114.6×	0.003	PAFAH1B1, RELN
layer formation in cerebral cortex	2	107.0×	0.004	PAFAH1B1, RELN
cytoskeleton-dependent intracellular transport	2	89.2×	0.004	TUBA1A, TUBB
glial cell differentiation	2	84.5×	0.004	TUBA1A, RELN
microtubule polymerization	2	84.5×	0.004	CPAP, TUBA1A
positive regulation of dendritic spine morphogenesis	2	84.5×	0.004	PAFAH1B1, RELN
isotype switching	2	80.2×	0.004	EXOSC3, NBN
regulation of mitotic spindle organization	2	80.2×	0.004	CPAP, DYNC1H1
modulation of chemical synaptic transmission	3	26.2×	0.004	TUBB2B, PAFAH1B1, RELN
nuclear migration	2	69.8×	0.005	DYNC1H1, PAFAH1B1
regulation of synapse organization	2	61.7×	0.006	TUBA1A, TUBB
microtubule nucleation	2	59.4×	0.006	TUBG1, CPAP
regulation of focal adhesion assembly	2	57.3×	0.007	MACF1, ACTG1
positive regulation of neuroblast proliferation	2	55.3×	0.007	ASPM, FOXG1
positive regulation of axon extension	2	48.6×	0.008	MACF1, PAFAH1B1
cell division	4	8.8×	0.010	CPAP, TUBA1A, TUBB, DYNC1H1
spinal cord patterning	1	802.5×	0.011	RELN
astral microtubule nucleation	1	802.5×	0.011	CPAP
negative regulation of asymmetric cell division	1	802.5×	0.011	ASPM
positive regulation of lateral motor column neuron migration	1	802.5×	0.011	RELN

Therapeutics

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 4 · Phased (≥1): 5 · Undrugged: 17

Druggability breadth: 9 of 22 evidence-associated genes (41%) 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
TUBA1A	COLCHICINE
TUBB3	COLCHICINE
TUBB	COLCHICINE
TUBB2B	COLCHICINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TUBA1A	22	4
TUBB	22	4
TUBB3	21	4
TUBB2B	21	4
DYNC1H1	1	2
DCX	0	0
TUBG1	0	0
MACF1	0	0
ACTG1	0	0
CPAP	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
COLCHICINE	4	TUBA1A, TUBB, TUBB2B, TUBB3
VINBLASTINE	4	TUBA1A, TUBB, TUBB2B, TUBB3
LEVOFLOXACIN ANHYDROUS	4	TUBA1A, TUBB, TUBB2B, TUBB3
DOCETAXEL	4	TUBA1A, TUBB, TUBB2B, TUBB3
NOSCAPINE	4	TUBA1A, TUBB, TUBB2B, TUBB3
VINBLASTINE SULFATE	4	TUBA1A, TUBB, TUBB2B, TUBB3
PACLITAXEL	4	TUBA1A, TUBB, TUBB2B, TUBB3
LEVOFLOXACIN	4	TUBA1A, TUBB, TUBB2B, TUBB3
VINORELBINE	4	TUBA1A, TUBB, TUBB2B, TUBB3
TIRBANIBULIN	4	TUBA1A, TUBB, TUBB2B, TUBB3
PODOFILOX	4	TUBA1A, TUBB, TUBB2B, TUBB3
VINCRISTINE	4	TUBA1A, TUBB, TUBB2B, TUBB3
DOCETAXEL ANHYDROUS	4	TUBA1A, TUBB, TUBB2B, TUBB3
PATUPILONE	3	TUBA1A, TUBB, TUBB2B, TUBB3
ABT-751	2	TUBA1A, TUBB, TUBB2B, TUBB3
MAYTANSINE	2	TUBA1A, TUBB, TUBB2B, TUBB3
DOLASTATIN-10	2	TUBA1A, TUBB, TUBB2B, TUBB3
INDIBULIN	2	TUBA1A, TUBB, TUBB2B, TUBB3
PARBENDAZOLE	2	TUBA1A, TUBB, TUBB2B, TUBB3
NOCODAZOLE	2	TUBA1A, TUBB, TUBB2B, TUBB3
MOLIBRESIB	2	DYNC1H1, TUBA1A, TUBB
COMBRETASTATIN	1	TUBA1A, TUBB, TUBB2B, TUBB3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
TUBB3	1,781	Binding:1741, Functional:34, ADMET:6
TUBB	1,780	Binding:1740, Functional:34, ADMET:6
TUBB2B	1,757	Binding:1717, Functional:34, ADMET:6
TUBA1A	1,696	Binding:1655, Functional:35, ADMET:6
DYNC1H1	7	Binding:7
NBN	2	Binding:2
DCX	1	Binding:1
CLUH	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TUBG1	3.6.5.6	tubulin GTPase
INPP5K	3.1.3.56	inositol-polyphosphate 5-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TUBA1A	1,696
TUBB3	1,781
TUBB	1,780
TUBB2B	1,757

Pharmacogenomics

Cohort genes with a PharmGKB record: 22; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

22 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)
COLCHICINE	4	TUBA1A, TUBB, TUBB2B, TUBB3
VINBLASTINE	4	TUBA1A, TUBB, TUBB2B, TUBB3
LEVOFLOXACIN ANHYDROUS	4	TUBA1A, TUBB, TUBB2B, TUBB3
DOCETAXEL	4	TUBA1A, TUBB, TUBB2B, TUBB3
NOSCAPINE	4	TUBA1A, TUBB, TUBB2B, TUBB3
VINBLASTINE SULFATE	4	TUBA1A, TUBB, TUBB2B, TUBB3
PACLITAXEL	4	TUBA1A, TUBB, TUBB2B, TUBB3
LEVOFLOXACIN	4	TUBA1A, TUBB, TUBB2B, TUBB3
VINORELBINE	4	TUBA1A, TUBB, TUBB2B, TUBB3
TIRBANIBULIN	4	TUBA1A, TUBB, TUBB2B, TUBB3
PODOFILOX	4	TUBA1A, TUBB, TUBB2B, TUBB3
VINCRISTINE	4	TUBA1A, TUBB, TUBB2B, TUBB3
DOCETAXEL ANHYDROUS	4	TUBA1A, TUBB, TUBB2B, TUBB3
PATUPILONE	3	TUBA1A, TUBB, TUBB2B, TUBB3
ABT-751	2	TUBA1A, TUBB, TUBB2B, TUBB3
MAYTANSINE	2	TUBA1A, TUBB, TUBB2B, TUBB3
DOLASTATIN-10	2	TUBA1A, TUBB, TUBB2B, TUBB3
INDIBULIN	2	TUBA1A, TUBB, TUBB2B, TUBB3
PARBENDAZOLE	2	TUBA1A, TUBB, TUBB2B, TUBB3
NOCODAZOLE	2	TUBA1A, TUBB, TUBB2B, TUBB3
MOLIBRESIB	2	DYNC1H1, TUBA1A, TUBB
COMBRETASTATIN	1	TUBA1A, TUBB, TUBB2B, TUBB3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	4	TUBA1A, TUBB3, TUBB, TUBB2B
B	Phased (≥1) drug, not yet approved	1	DYNC1H1
C	Druggable family + PDB, no drug	2	TUBG1, INPP5K
D	Druggable family + AlphaFold only, no drug	2	ASPM, OR3A1
E	Difficult family or no structure, no drug	13	DCX, MACF1, ACTG1, CPAP, EXOSC3, PDZD2, CEP85L, MZT2B, CLUH, FOXG1 (+3 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DCX	1	—
TUBG1	0	—
MACF1	0	—
ACTG1	0	—
CPAP	0	—
EXOSC3	0	—
PDZD2	0	—
ASPM	0	—
CEP85L	0	—
MZT2B	0	—
CLUH	1	—
INPP5K	0	—
FOXG1	0	—
NBN	2	—
OR3A1	0	—
PAFAH1B1	0	—
RELN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.