lissencephaly due to TUBA1A mutation

Summary

lissencephaly due to TUBA1A mutation (MONDO:0012703) is a disease caused by TUBA1A (GenCC Definitive), with 3 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: TUBA1A (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 140
• Phenotypes (HPO): 29

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		15	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

29 HPO clinical features (Orphanet curated; top 29 by frequency):

HPO ID	Term	Frequency
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0002119	Ventriculomegaly	Very frequent (80-99%)
HP:0025102	Dysgenesis of the basal ganglia	Very frequent (80-99%)
HP:0000252	Microcephaly	Frequent (30-79%)
HP:0000308	Microretrognathia	Frequent (30-79%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001257	Spasticity	Frequent (30-79%)
HP:0001274	Agenesis of corpus callosum	Frequent (30-79%)
HP:0001320	Cerebellar vermis hypoplasia	Frequent (30-79%)
HP:0001339	Lissencephaly	Frequent (30-79%)
HP:0002069	Bilateral tonic-clonic seizure	Frequent (30-79%)
HP:0002079	Hypoplasia of the corpus callosum	Frequent (30-79%)
HP:0002198	Dilated fourth ventricle	Frequent (30-79%)
HP:0002365	Hypoplasia of the brainstem	Frequent (30-79%)
HP:0025101	Dysgenesis of the hippocampus	Frequent (30-79%)
HP:0034051	Hypoplastic anterior limbs of the internal capsule	Frequent (30-79%)
HP:0000609	Optic nerve hypoplasia	Occasional (5-29%)
HP:0000639	Nystagmus	Occasional (5-29%)
HP:0001302	Pachygyria	Occasional (5-29%)
HP:0001338	Partial agenesis of the corpus callosum	Occasional (5-29%)
HP:0002126	Polymicrogyria	Occasional (5-29%)
HP:0006989	Dysplastic corpus callosum	Occasional (5-29%)
HP:0007359	Focal-onset seizure	Occasional (5-29%)
HP:0012469	Infantile spasms	Occasional (5-29%)
HP:0012650	Perisylvian polymicrogyria	Occasional (5-29%)
HP:0025517	Hypoplastic hippocampus	Occasional (5-29%)
HP:0031882	Agyria	Occasional (5-29%)
HP:0002251	Aganglionic megacolon	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	lissencephaly due to TUBA1A mutation
Mondo ID	MONDO:0012703
MeSH	C566908
OMIM	611603
Orphanet	171680
NCIT	C148461
UMLS	C4305153
MedGen	930822
GARD	0017066
Is cancer (heuristic)	no

Also known as: LIS3 · lissencephaly 3

Data availability: 140 ClinVar variants · 5 GenCC gene-disease records · 5 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › lissencephaly spectrum disorders › lissencephaly type 3 › lissencephaly due to TUBA1A mutation

Related subtypes (3): Neu-Laxova syndrome, lissencephaly type 3-metacarpal bone dysplasia syndrome, lissencephaly type 3-familial fetal akinesia sequence 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

140 retrieved; paginated sample, class counts are floors:

44 likely pathogenic, 30 uncertain significance, 26 pathogenic/likely pathogenic, 19 conflicting classifications of pathogenicity, 16 pathogenic, 2 benign/likely benign, 2 benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1012610	NM_006009.4(TUBA1A):c.236G>A (p.Arg79His)	TUBA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065497	NM_006009.4(TUBA1A):c.1288_1302del (p.Lys430_Glu434del)	TUBA1A	Pathogenic	criteria provided, single submitter
1164064	NM_006009.4(TUBA1A):c.431G>T (p.Gly144Val)	TUBA1A	Pathogenic	no assertion criteria provided
1394747	NM_006009.4(TUBA1A):c.657T>G (p.Ile219Met)	TUBA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
160143	NM_006009.4(TUBA1A):c.1148C>T (p.Ala383Val)	TUBA1A	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
160147	NM_006009.4(TUBA1A):c.1205G>T (p.Arg402Leu)	TUBA1A	Pathogenic	criteria provided, multiple submitters, no conflicts
160148	NM_006009.4(TUBA1A):c.1274T>A (p.Met425Lys)	TUBA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
160158	NM_006009.4(TUBA1A):c.481T>G (p.Tyr161Asp)	TUBA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
160161	NM_006009.4(TUBA1A):c.5G>A (p.Arg2His)	TUBA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
160164	NM_006009.4(TUBA1A):c.808G>T (p.Ala270Ser)	TUBA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
160167	NM_006009.4(TUBA1A):c.986A>G (p.Asn329Ser)	TUBA1A	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
212488	NM_006009.4(TUBA1A):c.1105G>A (p.Ala369Thr)	TUBA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217023	NM_006009.4(TUBA1A):c.352G>A (p.Val118Met)	TUBA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
265378	NM_006009.4(TUBA1A):c.367C>T (p.Arg123Cys)	TUBA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
287392	NM_006009.4(TUBA1A):c.791G>A (p.Arg264His)	TUBA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3255105	NM_006009.4(TUBA1A):c.4C>T (p.Arg2Cys)	TUBA1A	Pathogenic	criteria provided, single submitter
372542	NM_006009.4(TUBA1A):c.641G>A (p.Arg214His)	TUBA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4072026	NM_006009.4(TUBA1A):c.955T>A (p.Tyr319Asn)	TUBA1A	Pathogenic	criteria provided, single submitter
418531	NM_006009.4(TUBA1A):c.1168C>T (p.Arg390Cys)	TUBA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
420581	NM_006009.4(TUBA1A):c.190C>T (p.Arg64Trp)	TUBA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
423490	NM_006009.4(TUBA1A):c.1169G>C (p.Arg390Pro)	TUBA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
437122	NM_006009.4(TUBA1A):c.368G>A (p.Arg123His)	TUBA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
438589	NM_006009.4(TUBA1A):c.920C>T (p.Pro307Leu)	TUBA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
488628	NM_006009.4(TUBA1A):c.1169G>A (p.Arg390His)	TUBA1A	Pathogenic	criteria provided, multiple submitters, no conflicts
521647	NM_006009.4(TUBA1A):c.959G>A (p.Arg320His)	TUBA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
625504	NM_006009.4(TUBA1A):c.1225G>A (p.Val409Ile)	TUBA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
625513	NM_006009.4(TUBA1A):c.167C>T (p.Thr56Met)	TUBA1A	Pathogenic	criteria provided, multiple submitters, no conflicts
625515	NM_006009.4(TUBA1A):c.302A>G (p.Asn101Ser)	TUBA1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 17 · 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
TUBA1A	Definitive	Autosomal dominant	lissencephaly due to TUBA1A mutation	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
NKX2-5	Orphanet:101351	Familial isolated congenital asplenia
NKX2-5	Orphanet:1479	Atrial septal defect-atrioventricular conduction defects syndrome
NKX2-5	Orphanet:1627	Deletion 5q35 syndrome
NKX2-5	Orphanet:2248	Hypoplastic left heart syndrome
NKX2-5	Orphanet:3303	Tetralogy of Fallot
NKX2-5	Orphanet:334	Hereditary atrial fibrillation
NKX2-5	Orphanet:402075	Familial bicuspid aortic valve
NKX2-5	Orphanet:871	Hereditary progressive cardiac conduction defect
NKX2-5	Orphanet:95712	Thyroid ectopia
NKX2-5	Orphanet:95713	Athyreosis
NKX2-5	Orphanet:99103	Atrial septal defect, ostium secundum type
AIPL1	Orphanet:1872	Cone rod dystrophy
AIPL1	Orphanet:65	Leber congenital amaurosis

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TUBA1A	HGNC:20766	ENSG00000167552	Q71U36	Tubulin alpha-1A chain	gencc,clinvar
NKX2-5	HGNC:2488	ENSG00000183072	P52952	Homeobox protein Nkx-2.5	clinvar
AIPL1	HGNC:359	ENSG00000129221	Q9NZN9	Aryl-hydrocarbon-interacting protein-like 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
NKX2-5	Homeobox protein Nkx-2.5	Transcription factor required for the development of the heart and the spleen.
AIPL1	Aryl-hydrocarbon-interacting protein-like 1	May be important in protein trafficking and/or protein folding and stabilization.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 2 · 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
Transcription factor	1	2.8×	0.587
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TUBA1A	Other/Unknown	no		Tubulin, Alpha_tubulin, Tubulin_FtsZ_GTPase
NKX2-5	Transcription factor	no		HD, Homeodomain-like_sf, Homeobox_CS
AIPL1	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, AIP/AIPL1/TTC9

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
endothelial cell	1
ganglionic eminence	1
apex of heart	1
cardiac atrium	1
right atrium auricular region	1
buccal mucosa cell	1
pancreatic ductal cell	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TUBA1A	288	ubiquitous	marker	endothelial cell, cortical plate, ganglionic eminence
NKX2-5	98	broad	yes	apex of heart, right atrium auricular region, cardiac atrium
AIPL1	62	tissue_specific	marker	buccal mucosa cell, pancreatic ductal cell, tendon of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NKX2-5	2,355
TUBA1A	1,436
AIPL1	891

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TUBA1A	Q71U36	15
AIPL1	Q9NZN9	6
NKX2-5	P52952	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 96. Enrichment computed across 3 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

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

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
YAP1- and WWTR1 (TAZ)-stimulated gene expression	1	380.7×	0.031	NKX2-5
Physiological factors	1	335.9×	0.031	NKX2-5
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	1	271.9×	0.031	TUBA1A
Transport of connexons to the plasma membrane	1	271.9×	0.031	TUBA1A
Gap junction trafficking and regulation	1	237.9×	0.031	TUBA1A
Gap junction trafficking	1	237.9×	0.031	TUBA1A
Post-chaperonin tubulin folding pathway	1	237.9×	0.031	TUBA1A
Formation of tubulin folding intermediates by CCT/TriC	1	211.5×	0.031	TUBA1A
Cardiogenesis	1	211.5×	0.031	NKX2-5
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	1	203.9×	0.031	TUBA1A
Prefoldin mediated transfer of substrate to CCT/TriC	1	196.9×	0.031	TUBA1A
Activation of AMPK downstream of NMDARs	1	190.3×	0.031	TUBA1A
RHO GTPases activate IQGAPs	1	173.0×	0.031	TUBA1A
Sealing of the nuclear envelope (NE) by ESCRT-III	1	173.0×	0.031	TUBA1A
HCMV Infection	1	163.1×	0.031	TUBA1A
Chaperonin-mediated protein folding	1	150.3×	0.031	TUBA1A
Gap junction assembly	1	146.4×	0.031	TUBA1A
Nuclear Envelope (NE) Reassembly	1	146.4×	0.031	TUBA1A
Selective autophagy	1	139.3×	0.031	TUBA1A
Protein folding	1	129.8×	0.031	TUBA1A
Centrosome maturation	1	126.9×	0.031	TUBA1A
Assembly and cell surface presentation of NMDA receptors	1	126.9×	0.031	TUBA1A
Cargo trafficking to the periciliary membrane	1	124.1×	0.031	TUBA1A
Aggrephagy	1	124.1×	0.031	TUBA1A
Carboxyterminal post-translational modifications of tubulin	1	119.0×	0.031	TUBA1A
Recycling pathway of L1	1	112.0×	0.031	TUBA1A
COPI-independent Golgi-to-ER retrograde traffic	1	103.8×	0.031	TUBA1A
Post NMDA receptor activation events	1	102.0×	0.031	TUBA1A
Intraflagellar transport	1	100.2×	0.031	TUBA1A
Antimicrobial mechanism of IFN-stimulated genes	1	98.5×	0.031	TUBA1A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
Purkinje myocyte differentiation	1	5617.3×	0.005	NKX2-5
septum secundum development	1	5617.3×	0.005	NKX2-5
right ventricular cardiac muscle tissue morphogenesis	1	2808.7×	0.005	NKX2-5
atrioventricular node cell fate commitment	1	2808.7×	0.005	NKX2-5
cardiac ventricle formation	1	1872.4×	0.005	NKX2-5
apoptotic process involved in heart morphogenesis	1	1872.4×	0.005	NKX2-5
proepicardium development	1	1872.4×	0.005	NKX2-5
pulmonary myocardium development	1	1872.4×	0.005	NKX2-5
protein farnesylation	1	1872.4×	0.005	AIPL1
ventricular cardiac myofibril assembly	1	1872.4×	0.005	NKX2-5
atrial cardiac muscle cell development	1	1872.4×	0.005	NKX2-5
bundle of His development	1	1404.3×	0.005	NKX2-5
atrial cardiac muscle tissue development	1	1404.3×	0.005	NKX2-5
positive regulation of cardioblast differentiation	1	1404.3×	0.005	NKX2-5
atrioventricular node cell development	1	1404.3×	0.005	NKX2-5
pyramidal neuron differentiation	1	1123.5×	0.005	TUBA1A
regulation of cardiac muscle cell proliferation	1	1123.5×	0.005	NKX2-5
atrioventricular node development	1	936.2×	0.006	NKX2-5
cerebellar cortex morphogenesis	1	936.2×	0.006	TUBA1A
embryonic heart tube left/right pattern formation	1	936.2×	0.006	NKX2-5
positive regulation of heart contraction	1	702.2×	0.007	NKX2-5
neuron projection arborization	1	624.1×	0.007	TUBA1A
regulation of opsin-mediated signaling pathway	1	561.7×	0.007	AIPL1
response to L-glutamate	1	561.7×	0.007	TUBA1A
ventricular cardiac muscle cell development	1	510.7×	0.007	NKX2-5
forebrain morphogenesis	1	468.1×	0.007	TUBA1A
cardiac muscle tissue morphogenesis	1	468.1×	0.007	NKX2-5
phototransduction, visible light	1	432.1×	0.007	AIPL1
atrial septum morphogenesis	1	432.1×	0.007	NKX2-5
adult heart development	1	401.2×	0.007	NKX2-5

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) 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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TUBA1A	22	4
NKX2-5	0	0
AIPL1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
COLCHICINE	4	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
PATUPILONE	3	TUBA1A
ABT-751	2	TUBA1A
MAYTANSINE	2	TUBA1A
DOLASTATIN-10	2	TUBA1A
INDIBULIN	2	TUBA1A
PARBENDAZOLE	2	TUBA1A
NOCODAZOLE	2	TUBA1A
MOLIBRESIB	2	TUBA1A
COMBRETASTATIN	1	TUBA1A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TUBA1A	1,696	Binding:1655, Functional:35, ADMET:6
AIPL1	1	Binding:1

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

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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
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
PATUPILONE	3	TUBA1A
ABT-751	2	TUBA1A
MAYTANSINE	2	TUBA1A
DOLASTATIN-10	2	TUBA1A
INDIBULIN	2	TUBA1A
PARBENDAZOLE	2	TUBA1A
NOCODAZOLE	2	TUBA1A
MOLIBRESIB	2	TUBA1A
COMBRETASTATIN	1	TUBA1A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TUBA1A
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	2	NKX2-5, AIPL1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
NKX2-5	0	—
AIPL1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.