Frontotemporal dementia with motor neuron disease

Summary

Frontotemporal dementia with motor neuron disease (MONDO:0017161) is a disease (an umbrella term covering 7 Mondo subtypes) with 5 cohort genes. The dominant Reactome pathway is Selective autophagy (3 cohort genes).

At a glance

• Prevalence: Unknown (Worldwide)
• Umbrella term: 7 Mondo subtypes
• Cohort genes: 5
• Phenotypes (HPO): 35

Clinical features

Signs & symptoms

Clinical features (HPO)

35 HPO clinical features (Orphanet curated; top 35 by frequency):

HPO ID	Term	Frequency
HP:0002366	Abnormal lower motor neuron morphology	Very frequent (80-99%)
HP:0002127	Abnormal upper motor neuron morphology	Very frequent (80-99%)
HP:0002145	Frontotemporal dementia	Very frequent (80-99%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0000716	Depression	Frequent (30-79%)
HP:0000738	Hallucinations	Frequent (30-79%)
HP:0000741	Apathy	Frequent (30-79%)
HP:0001260	Dysarthria	Frequent (30-79%)
HP:0001300	Parkinsonism	Frequent (30-79%)
HP:0002015	Dysphagia	Frequent (30-79%)
HP:0002071	Abnormality of extrapyramidal motor function	Frequent (30-79%)
HP:0002073	Progressive cerebellar ataxia	Frequent (30-79%)
HP:0002171	Gliosis	Frequent (30-79%)
HP:0002186	Apraxia	Frequent (30-79%)
HP:0002273	Tetraparesis	Frequent (30-79%)
HP:0002314	Degeneration of the lateral corticospinal tracts	Frequent (30-79%)
HP:0002385	Paraparesis	Frequent (30-79%)
HP:0002442	Dyscalculia	Frequent (30-79%)
HP:0002460	Distal muscle weakness	Frequent (30-79%)
HP:0003700	Generalized amyotrophy	Frequent (30-79%)
HP:0003701	Proximal muscle weakness	Frequent (30-79%)
HP:0007190	Neuronal loss in the cerebral cortex	Frequent (30-79%)
HP:0010549	Weakness due to upper motor neuron dysfunction	Frequent (30-79%)
HP:0000605	Supranuclear gaze palsy	Occasional (5-29%)
HP:0000734	Disinhibition	Occasional (5-29%)
HP:0001265	Hyporeflexia	Occasional (5-29%)
HP:0001283	Bulbar palsy	Occasional (5-29%)
HP:0002283	Global brain atrophy	Occasional (5-29%)
HP:0002300	Mutism	Occasional (5-29%)
HP:0002380	Fasciculations	Occasional (5-29%)
HP:0003487	Babinski sign	Occasional (5-29%)
HP:0008322	Abnormal mitochondrial morphology	Occasional (5-29%)
HP:0008619	Bilateral sensorineural hearing impairment	Occasional (5-29%)
HP:0030223	Perseveration	Occasional (5-29%)
HP:0000508	Ptosis	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	frontotemporal dementia with motor neuron disease
Mondo ID	MONDO:0017161
MeSH	C566288
OMIM	105550
Orphanet	275872
ICD-11	1171850356
UMLS	C3888102
MedGen	854771
GARD	0017273
Is cancer (heuristic)	no

Also known as: frontotemporal dementia with ALS · frontotemporal dementia with amyotrophic lateral sclerosis · FTD-ALS · FTD-MND · FTDALS

Data availability: 5 GenCC gene-disease records · 266 cell lines.

Disease family

An umbrella term covering 7 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › movement disorder › frontotemporal dementia with motor neuron disease

Related subtypes (53): cerebellar ataxia, chronic tic disorder, choreatic disease, extrapyramidal and movement disease, benign shuddering attacks, transient tic disorder, essential tremor, lingual-facial-buccal dyskinesia, kuru, inherited Creutzfeldt-Jakob disease, Tourette syndrome, clonic hemifacial spasm, Huntington disease, multiple system atrophy, spinal muscular atrophy-progressive myoclonic epilepsy syndrome, benign paroxysmal tonic upgaze of childhood with ataxia, hereditary geniospasm, tremor-nystagmus-duodenal ulcer syndrome, arthrogryposis, Lafora disease, Unverricht-Lundborg syndrome, neuronal intranuclear inclusion disease, Huntington disease-like 3, brain-lung-thyroid syndrome, myoclonus, familial, proximal myopathy with extrapyramidal signs, progressive myoclonic epilepsy type 7, progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome, progressive non-fluent aphasia, opsoclonus-myoclonus syndrome, isolated facial myokymia, primary orthostatic tremor, familial congenital mirror movements, neuroacanthocytosis, behavioral variant of frontotemporal dementia, hyperekplexia, intellectual disability-hyperkinetic movement-truncal ataxia syndrome, neurodegeneration with brain iron accumulation, Huntington disease-like syndrome due to C9ORF72 expansions, variably protease-sensitive prionopathy, corticobasal syndrome, sensorineural hearing loss-early graying-essential tremor syndrome, progressive supranuclear palsy, Sandifer syndrome, psychogenic movement disorders, epilepsy with myoclonic absences, infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome, childhood-onset benign chorea with striatal involvement, childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder, PRRT2-associated paroxysmal movement disorder, SLC6A3-related dopamine transporter deficiency syndrome, dyskinesia with orofacial involvement, autosomal dominant, complex movement disorder with or without neurodevelopmental features

Subtypes (7): frontotemporal dementia and/or amyotrophic lateral sclerosis 1, amyotrophic lateral sclerosis type 6, amyotrophic lateral sclerosis type 10, frontotemporal dementia and/or amyotrophic lateral sclerosis 6, frontotemporal dementia and/or amyotrophic lateral sclerosis 2, frontotemporal dementia and/or amyotrophic lateral sclerosis 3, frontotemporal dementia and/or amyotrophic lateral sclerosis 4

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 48 · Orphanet: 22 · 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
TBK1	Definitive	Autosomal dominant	frontotemporal dementia and/or amyotrophic lateral sclerosis 4	6
VCP	Definitive	Autosomal dominant	inclusion body myopathy with Paget disease of bone and frontotemporal dementia	13
CHCHD10	Strong	Autosomal dominant	frontotemporal dementia and/or amyotrophic lateral sclerosis 2	10
SQSTM1	Strong	Autosomal dominant	frontotemporal dementia and/or amyotrophic lateral sclerosis 3	13
TARDBP	Supportive	Autosomal dominant	frontotemporal dementia with motor neuron disease	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SQSTM1	Orphanet:275864	Behavioral variant of frontotemporal dementia
SQSTM1	Orphanet:275872	Frontotemporal dementia with motor neuron disease
SQSTM1	Orphanet:603	Distal myopathy, Welander type
SQSTM1	Orphanet:803	Amyotrophic lateral sclerosis
TARDBP	Orphanet:275872	Frontotemporal dementia with motor neuron disease
TARDBP	Orphanet:700154	TARDBP-related predominantly upper-limb distal myopathy
TARDBP	Orphanet:803	Amyotrophic lateral sclerosis
TBK1	Orphanet:1930	Herpes simplex virus encephalitis
TBK1	Orphanet:275872	Frontotemporal dementia with motor neuron disease
TBK1	Orphanet:803	Amyotrophic lateral sclerosis
VCP	Orphanet:100070	Progressive non-fluent aphasia
VCP	Orphanet:275864	Behavioral variant of frontotemporal dementia
VCP	Orphanet:275872	Frontotemporal dementia with motor neuron disease
VCP	Orphanet:329475	Spastic paraplegia-Paget disease of bone syndrome
VCP	Orphanet:329478	Adult-onset distal myopathy due to VCP mutation
VCP	Orphanet:435387	Autosomal dominant Charcot-Marie-Tooth disease type 2Y
VCP	Orphanet:52430	Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
VCP	Orphanet:803	Amyotrophic lateral sclerosis
CHCHD10	Orphanet:275872	Frontotemporal dementia with motor neuron disease
CHCHD10	Orphanet:276435	Lower motor neuron syndrome with late-adult onset
CHCHD10	Orphanet:457050	Autosomal dominant mitochondrial myopathy with exercise intolerance
CHCHD10	Orphanet:803	Amyotrophic lateral sclerosis

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SQSTM1	HGNC:11280	ENSG00000161011	Q13501	Sequestosome-1	gencc
TARDBP	HGNC:11571	ENSG00000120948	Q13148	TAR DNA-binding protein 43	gencc
TBK1	HGNC:11584	ENSG00000183735	Q9UHD2	Serine/threonine-protein kinase TBK1	gencc
VCP	HGNC:12666	ENSG00000165280	P55072	Transitional endoplasmic reticulum ATPase	gencc
CHCHD10	HGNC:15559	ENSG00000250479	Q8WYQ3	Coiled-coil-helix-coiled-coil-helix domain-containing protein 10, mitochondrial	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SQSTM1	Sequestosome-1	Molecular adapter required for selective macroautophagy (aggrephagy) by acting as a bridge between polyubiquitinated proteins and autophagosomes.
TARDBP	TAR DNA-binding protein 43	RNA-binding protein that is involved in various steps of RNA biogenesis and processing.
TBK1	Serine/threonine-protein kinase TBK1	Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents.
VCP	Transitional endoplasmic reticulum ATPase	Necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis.
CHCHD10	Coiled-coil-helix-coiled-coil-helix domain-containing protein 10, mitochondrial	May be involved in the maintenance of mitochondrial organization and mitochondrial cristae structure.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.4

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	1	5.5×	0.634
Enzyme (other)	1	2.4×	0.634
Transcription factor	1	1.6×	0.634
Other/Unknown	2	0.7×	0.877

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SQSTM1	Transcription factor	no		PB1_dom, Znf_ZZ, UBA-like_sf
TARDBP	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RBD_domain_sf
TBK1	Kinase	yes		Prot_kinase_dom, Kinase-like_dom_sf, Protein_kinase_ATP_BS
VCP	Enzyme (other)	yes	3.6.4.6	CDC4_N-term_subdom, AAA+_ATPase, ATPase_AAA_core
CHCHD10	Other/Unknown	no		CHCH, CHCHD2/10-like

Expression context

Cohort genes with no expression data: 0.

5 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left adrenal gland	1
right adrenal gland	1
right adrenal gland cortex	1
ganglionic eminence	1
secondary oocyte	1
ventricular zone	1
calcaneal tendon	1
colonic epithelium	1
lateral nuclear group of thalamus	1
adrenal tissue	1
islet of Langerhans	1
stromal cell of endometrium	1
apex of heart	1
heart left ventricle	1
hindlimb stylopod muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SQSTM1	241	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland
TARDBP	301	ubiquitous	marker	secondary oocyte, ventricular zone, ganglionic eminence
TBK1	284	ubiquitous	marker	colonic epithelium, calcaneal tendon, lateral nuclear group of thalamus
VCP	294	ubiquitous	marker	stromal cell of endometrium, adrenal tissue, islet of Langerhans
CHCHD10	133	ubiquitous	marker	apex of heart, heart left ventricle, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
VCP	10,015
SQSTM1	7,269
TARDBP	7,245
TBK1	5,476
CHCHD10	1,344

Intra-cohort edges

A	B	Sources
CHCHD10	TARDBP	string_interaction
CHCHD10	VCP	string_interaction
SQSTM1	TBK1	biogrid_interaction
TARDBP	VCP	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
VCP	P55072	144
TARDBP	Q13148	44
SQSTM1	Q13501	26
TBK1	Q9UHD2	25
CHCHD10	Q8WYQ3	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 102. Enrichment computed across 5 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Selective autophagy	3	208.9×	2e-05	SQSTM1, TBK1, VCP
Autophagy	3	111.2×	6e-05	SQSTM1, TBK1, VCP
Macroautophagy	3	86.5×	9e-05	SQSTM1, TBK1, VCP
Mitophagy	2	519.1×	1e-04	SQSTM1, TBK1
PINK1-PRKN Mediated Mitophagy	2	178.4×	9e-04	SQSTM1, TBK1
Interleukin-1 family signaling	2	135.9×	0.001	SQSTM1, TBK1
SARS-CoV-1 Infection	2	71.4×	0.003	TBK1, VCP
Cellular response to chemical stress	2	71.4×	0.003	SQSTM1, VCP
Death Receptor Signaling	2	69.6×	0.003	SQSTM1, TBK1
KEAP1-NFE2L2 pathway	2	60.1×	0.004	SQSTM1, VCP
SARS-CoV-2 Infection	2	40.2×	0.008	TBK1, VCP
STAT6-mediated induction of chemokines	1	951.7×	0.009	TBK1
Attachment and Entry	1	713.8×	0.010	VCP
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	1	571.0×	0.010	VCP
DNA Damage Bypass	1	571.0×	0.010	VCP
Signaling by Interleukins	2	32.1×	0.010	SQSTM1, TBK1
Diseases of signal transduction by growth factor receptors and second messengers	2	28.4×	0.010	SQSTM1, VCP
SARS-CoV Infections	2	27.7×	0.010	TBK1, VCP
Disease	3	9.8×	0.010	SQSTM1, TBK1, VCP
Immune System	3	9.7×	0.010	SQSTM1, TBK1, VCP
IRF3 mediated activation of type 1 IFN	1	475.8×	0.010	TBK1
p75NTR signals via NF-kB	1	475.8×	0.010	SQSTM1
Neddylation	2	23.7×	0.011	SQSTM1, VCP
Hh mutants abrogate ligand secretion	1	356.9×	0.012	VCP
ZBP1(DAI) mediated induction of type I IFNs	1	259.6×	0.013	TBK1
STING mediated induction of host immune responses	1	259.6×	0.013	TBK1
Early SARS-CoV-2 Infection Events	1	259.6×	0.013	VCP
Josephin domain DUBs	1	237.9×	0.013	VCP
Pexophagy	1	237.9×	0.013	SQSTM1
Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation	1	237.9×	0.013	TBK1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
macroautophagy	3	144.4×	9e-05	SQSTM1, TBK1, VCP
nuclear inner membrane organization	1	3370.4×	0.008	TARDBP
flavin adenine dinucleotide catabolic process	1	3370.4×	0.008	VCP
endoplasmic reticulum stress-induced pre-emptive quality control	1	1685.2×	0.008	VCP
positive regulation of protein K63-linked deubiquitination	1	1685.2×	0.008	VCP
dendritic cell proliferation	1	1123.5×	0.008	TBK1
mitotic spindle disassembly	1	1123.5×	0.008	VCP
brown fat cell proliferation	1	1123.5×	0.008	SQSTM1
protein targeting to vacuole involved in autophagy	1	1123.5×	0.008	SQSTM1
cytoplasm protein quality control	1	1123.5×	0.008	VCP
cellular response to arsenite ion	1	1123.5×	0.008	VCP
positive regulation of oxidative phosphorylation	1	1123.5×	0.008	VCP
regulation of protein localization to chromatin	1	1123.5×	0.008	VCP
positive regulation of autophagy	2	83.2×	0.008	SQSTM1, TBK1
autophagy	2	44.1×	0.008	SQSTM1, VCP
cGAS/STING signaling pathway	1	674.1×	0.011	TBK1
endosome to lysosome transport via multivesicular body sorting pathway	1	561.7×	0.011	VCP
aggresome assembly	1	561.7×	0.011	VCP
response to mitochondrial depolarisation	1	561.7×	0.011	SQSTM1
mitochondrial membrane organization	1	481.5×	0.011	CHCHD10
stress granule disassembly	1	481.5×	0.011	VCP
positive regulation of mitochondrial membrane potential	1	421.3×	0.011	VCP
regulation of aerobic respiration	1	421.3×	0.011	VCP
positive regulation of xenophagy	1	421.3×	0.011	TBK1
positive regulation of TORC2 signaling	1	421.3×	0.011	TBK1
regulation of apoptotic process	2	33.4×	0.011	TARDBP, VCP
ubiquitin-dependent protein catabolic process	2	29.7×	0.011	SQSTM1, VCP
negative regulation of gene expression	2	27.6×	0.011	TARDBP, TBK1
NAD+ metabolic process	1	374.5×	0.012	VCP
regulation of Ras protein signal transduction	1	374.5×	0.012	SQSTM1

Therapeutics

Drug target analysis

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

Druggability breadth: 4 of 5 evidence-associated genes (80%) 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
TARDBP	MITOXANTRONE
TBK1	MOMELOTINIB
VCP	CLOTRIMAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TBK1	38	4
VCP	4	4
TARDBP	1	4
SQSTM1	0	0
CHCHD10	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MITOXANTRONE	4	TARDBP
MOMELOTINIB	4	TBK1
AMLEXANOX	4	TBK1
FEDRATINIB	4	TBK1
RUXOLITINIB	4	TBK1
ENTRECTINIB	4	TBK1
PACRITINIB	4	TBK1
BOSUTINIB	4	TBK1
FILGOTINIB	4	TBK1
NINTEDANIB	4	TBK1
SUNITINIB	4	TBK1
ERLOTINIB	4	TBK1
CRIZOTINIB	4	TBK1
MIDOSTAURIN	4	TBK1
CLOTRIMAZOLE	4	VCP
GANCICLOVIR	4	VCP
HEXACHLOROPHENE	4	VCP
ORANTINIB	3	TBK1
ALVOCIDIB	3	TBK1
DOVITINIB	3	TBK1
LESTAURTINIB	3	TBK1
RUBOXISTAURIN	3	TBK1
SILMITASERTIB	2	TBK1
FORETINIB	2	TBK1
SU-014813	2	TBK1
CENISERTIB	2	TBK1
ADAVOSERTIB	2	TBK1
CERDULATINIB	2	TBK1
R-406	2	TBK1
AT-9283	2	TBK1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
TBK1	475	Binding:473, Functional:2
VCP	120	Binding:120
SQSTM1	20	Binding:20
TARDBP	8	Binding:7, Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
VCP	3.6.4.6	vesicle-fusing ATPase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TBK1	475
VCP	120

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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)
MITOXANTRONE	4	TARDBP
MOMELOTINIB	4	TBK1
AMLEXANOX	4	TBK1
FEDRATINIB	4	TBK1
RUXOLITINIB	4	TBK1
ENTRECTINIB	4	TBK1
PACRITINIB	4	TBK1
BOSUTINIB	4	TBK1
FILGOTINIB	4	TBK1
NINTEDANIB	4	TBK1
SUNITINIB	4	TBK1
ERLOTINIB	4	TBK1
CRIZOTINIB	4	TBK1
MIDOSTAURIN	4	TBK1
CLOTRIMAZOLE	4	VCP
GANCICLOVIR	4	VCP
HEXACHLOROPHENE	4	VCP
ORANTINIB	3	TBK1
ALVOCIDIB	3	TBK1
DOVITINIB	3	TBK1
LESTAURTINIB	3	TBK1
RUBOXISTAURIN	3	TBK1
SILMITASERTIB	2	TBK1
FORETINIB	2	TBK1
SU-014813	2	TBK1
CENISERTIB	2	TBK1
ADAVOSERTIB	2	TBK1
CERDULATINIB	2	TBK1
R-406	2	TBK1
AT-9283	2	TBK1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	TARDBP, TBK1, VCP
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	SQSTM1, CHCHD10

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)
SQSTM1	20	—
CHCHD10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.