Amyotrophic lateral sclerosis type 10

Summary

Amyotrophic lateral sclerosis type 10 (MONDO:0012790) is a disease caused by TARDBP (GenCC Definitive), with 8 cohort genes.

At a glance

• Causal gene: TARDBP (GenCC Definitive)
• Cohort genes: 8
• ClinVar variants: 229

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	amyotrophic lateral sclerosis type 10
Mondo ID	MONDO:0012790
MeSH	C567429
OMIM	612069
DOID	DOID:0060201
UMLS	C2677565
MedGen	383137
GARD	0015540
Is cancer (heuristic)	no

Also known as: ALS10 · amyotrophic lateral sclerosis 10 with or without frontotemporal dementia · amyotrophic lateral sclerosis 10, with or without FTD · amyotrophic lateral sclerosis caused by mutation in TARDBP · amyotrophic lateral sclerosis type 10 · frontotemporal lobar degeneration, TARDBP-related · TARDBP amyotrophic lateral sclerosis

Data availability: 229 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › spinal cord disorder › anterior horn disorder › amyotrophic lateral sclerosis › familial amyotrophic lateral sclerosis › amyotrophic lateral sclerosis type 10

Related subtypes (29): amyotrophic lateral sclerosis type 1, frontotemporal dementia and/or amyotrophic lateral sclerosis 1, spinocerebellar ataxia type 2, amyotrophic lateral sclerosis type 15, frontotemporal dementia and/or amyotrophic lateral sclerosis 7, amyotrophic lateral sclerosis type 4, amyotrophic lateral sclerosis type 21, amyotrophic lateral sclerosis type 3, amyotrophic lateral sclerosis type 6, amyotrophic lateral sclerosis type 7, amyotrophic lateral sclerosis type 8, amyotrophic lateral sclerosis type 9, amyotrophic lateral sclerosis type 11, amyotrophic lateral sclerosis type 12, frontotemporal dementia and/or amyotrophic lateral sclerosis 6, amyotrophic lateral sclerosis type 18, amyotrophic lateral sclerosis type 20, amyotrophic lateral sclerosis type 19, frontotemporal dementia and/or amyotrophic lateral sclerosis 2, amyotrophic lateral sclerosis type 22, frontotemporal dementia and/or amyotrophic lateral sclerosis 3, frontotemporal dementia and/or amyotrophic lateral sclerosis 4, juvenile amyotrophic lateral sclerosis, amyotrophic lateral sclerosis type 23, frontotemporal dementia and/or amyotrophic lateral sclerosis 8, frontotemporal dementia and/or amyotrophic lateral sclerosis 5, amyotrophic lateral sclerosis 26 with or without frontotemporal dementia, amyotrophic lateral sclerosis 27, juvenile, amyotrophic lateral sclerosis 28

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

229 retrieved; paginated sample, class counts are floors:

104 uncertain significance, 63 likely benign, 15 conflicting classifications of pathogenicity, 14 benign, 9 pathogenic, 9 pathogenic/likely pathogenic, 7 benign/likely benign, 6 likely pathogenic, 2 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
98177	NM_002087.4(GRN):c.1252C>T (p.Arg418Ter)	GRN	Pathogenic	criteria provided, multiple submitters, no conflicts
21484	NM_007375.4(TARDBP):c.881G>T (p.Gly294Val)	MASP2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1801690	NM_001008212.2(OPTN):c.493C>T (p.Gln165Ter)	OPTN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14756	NM_000454.5(SOD1):c.131A>G (p.His44Arg)	SOD1	Pathogenic	criteria provided, multiple submitters, no conflicts
21467	NM_007375.4(TARDBP):c.1035C>A (p.Asn345Lys)	TARDBP	Pathogenic	criteria provided, single submitter
21468	NM_007375.4(TARDBP):c.1055A>G (p.Asn352Ser)	TARDBP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
21474	NM_007375.4(TARDBP):c.1144G>A (p.Ala382Thr)	TARDBP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
21476	NM_007375.4(TARDBP):c.1147A>G (p.Ile383Val)	TARDBP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
21483	NM_007375.4(TARDBP):c.859G>A (p.Gly287Ser)	TARDBP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
21485	NM_007375.4(TARDBP):c.883G>A (p.Gly295Ser)	TARDBP	Pathogenic	criteria provided, single submitter
2202699	NM_007375.4(TARDBP):c.1123A>G (p.Ser375Gly)	TARDBP	Pathogenic	criteria provided, single submitter
5228	NM_007375.4(TARDBP):c.1009A>G (p.Met337Val)	TARDBP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5229	NM_007375.4(TARDBP):c.991C>A (p.Gln331Lys)	TARDBP	Pathogenic	no assertion criteria provided
5232	NM_007375.4(TARDBP):c.892G>A (p.Gly298Ser)	TARDBP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5233	NM_007375.4(TARDBP):c.506A>G (p.Asp169Gly)	TARDBP	Pathogenic	no assertion criteria provided
5234	NM_007375.4(TARDBP):c.1042G>T (p.Gly348Cys)	TARDBP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5235	NM_007375.4(TARDBP):c.1028A>G (p.Gln343Arg)	TARDBP	Pathogenic	no assertion criteria provided
5236	NM_007375.4(TARDBP):c.943G>A (p.Ala315Thr)	TARDBP	Pathogenic	criteria provided, multiple submitters, no conflicts
21487	NM_007375.4(TARDBP):c.931A>G (p.Met311Val)	TARDBP	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2501300	NM_007375.4(TARDBP):c.1133A>G (p.Asn378Ser)	TARDBP	Likely pathogenic	criteria provided, single submitter
4783510	NM_007375.4(TARDBP):c.962C>G (p.Ala321Gly)	TARDBP	Likely pathogenic	criteria provided, single submitter
873228	NM_007375.4(TARDBP):c.1060C>G (p.Gln354Glu)	TARDBP	Likely pathogenic	criteria provided, single submitter
938527	NM_007375.4(TARDBP):c.962C>A (p.Ala321Asp)	TARDBP	Likely pathogenic	criteria provided, single submitter
939152	NM_007375.4(TARDBP):c.1132A>G (p.Asn378Asp)	TARDBP	Likely pathogenic	criteria provided, single submitter
807060	NM_001097577.3(ANG):c.3G>A (p.Met1Ile)	ANG	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1300489	NM_007375.4(TARDBP):c.1169A>G (p.Asn390Ser)	TARDBP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1446008	NM_007375.4(TARDBP):c.1069G>C (p.Gly357Arg)	TARDBP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1806944	NM_007375.4(TARDBP):c.883G>C (p.Gly295Arg)	TARDBP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
190399	NM_007375.4(TARDBP):c.1150G>C (p.Gly384Arg)	TARDBP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
21477	NM_007375.4(TARDBP):c.1168A>G (p.Asn390Asp)	TARDBP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 13 · 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
TARDBP	Definitive	Autosomal dominant	amyotrophic lateral sclerosis type 10	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
SOD1	Orphanet:803	Amyotrophic lateral sclerosis
OPTN	Orphanet:803	Amyotrophic lateral sclerosis
ERBB4	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
ERBB4	Orphanet:803	Amyotrophic lateral sclerosis
GRN	Orphanet:100069	Semantic dementia
GRN	Orphanet:100070	Progressive non-fluent aphasia
GRN	Orphanet:275864	Behavioral variant of frontotemporal dementia
GRN	Orphanet:314629	CLN11 disease
ANG	Orphanet:803	Amyotrophic lateral sclerosis
MASP2	Orphanet:331187	Immunodeficiency due to MASP-2 deficiency

Cohort genes → proteins

8 cohort genes, 8 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	8

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TARDBP	HGNC:11571	ENSG00000120948	Q13148	TAR DNA-binding protein 43	gencc,clinvar
SOD1	HGNC:11179	ENSG00000142168	P00441	Superoxide dismutase [Cu-Zn]	clinvar
TUBA4A	HGNC:12407	ENSG00000127824	P68366	Tubulin alpha-4A chain	clinvar
OPTN	HGNC:17142	ENSG00000123240	Q96CV9	Optineurin	clinvar
ERBB4	HGNC:3432	ENSG00000178568	Q15303	Receptor tyrosine-protein kinase erbB-4	clinvar
GRN	HGNC:4601	ENSG00000030582	P28799	Progranulin	clinvar
ANG	HGNC:483	ENSG00000214274	P03950	Angiogenin	clinvar
MASP2	HGNC:6902	ENSG00000009724	O00187	Mannan-binding lectin serine protease 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TARDBP	TAR DNA-binding protein 43	RNA-binding protein that is involved in various steps of RNA biogenesis and processing.
SOD1	Superoxide dismutase [Cu-Zn]	Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
TUBA4A	Tubulin alpha-4A chain	Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers.
OPTN	Optineurin	Plays an important role in the maintenance of the Golgi complex, in membrane trafficking, in exocytosis, through its interaction with myosin VI and Rab8.
ERBB4	Receptor tyrosine-protein kinase erbB-4	Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell prolife…
GRN	Progranulin	Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation.
ANG	Angiogenin	Secreted ribonuclease that can either promote or restrict cell proliferation of target cells, depending on the context.
MASP2	Mannan-binding lectin serine protease 2	Precursor of a serum protease that activates the lectin pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 5 · Druggable fraction: 0.38

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
Protease	1	4.6×	0.502
Kinase	1	3.5×	0.502
Enzyme (other)	1	1.5×	0.502
Other/Unknown	5	1.1×	0.502

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TARDBP	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RBD_domain_sf
SOD1	Enzyme (other)	yes	1.15.1.1	SOD_Cu_Zn_dom, SOD_Cu/Zn_BS, SOD_Cu/Zn_/chaperone
TUBA4A	Other/Unknown	no		Tubulin, Alpha_tubulin, Tubulin_FtsZ_GTPase
OPTN	Other/Unknown	no		NEMO_N, CC2-LZ_dom, NEMO_ZF
ERBB4	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
GRN	Other/Unknown	no		Granulin, Granulin_sf, Granulin_fam
ANG	Other/Unknown	no		RNaseA, RNaseA_AS, RNaseA_domain
MASP2	Protease	yes	3.4.21.104	EGF-type_Asp/Asn_hydroxyl_site, Sushi_SCR_CCP_dom, EGF

Expression context

Cohort genes with no expression data: 0.

8 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)	8
unknown	0

Top tissues across cohort

Tissue	Cohort genes
secondary oocyte	2
liver	2
right lobe of liver	2
ganglionic eminence	1
ventricular zone	1
dorsal root ganglion	1
pons	1
substantia nigra pars compacta	1
frontal pole	1
gingiva	1
gingival epithelium	1
amniotic fluid	1
gastrocnemius	1
muscle of leg	1
cranial nerve II	1
endothelial cell	1
granulocyte	1
monocyte	1
stromal cell of endometrium	1
left ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TARDBP	301	ubiquitous	marker	secondary oocyte, ventricular zone, ganglionic eminence
SOD1	304	ubiquitous	marker	pons, dorsal root ganglion, substantia nigra pars compacta
TUBA4A	299	ubiquitous	marker	gingival epithelium, frontal pole, gingiva
OPTN	302	ubiquitous	marker	amniotic fluid, gastrocnemius, muscle of leg
ERBB4	226	broad	marker	endothelial cell, secondary oocyte, cranial nerve II
GRN	301	ubiquitous	marker	monocyte, granulocyte, stromal cell of endometrium
ANG	238	ubiquitous	marker	right lobe of liver, liver, left ovary
MASP2	172	tissue_specific	marker	right lobe of liver, liver, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TARDBP	7,245
SOD1	6,807
ERBB4	4,325
OPTN	3,505
GRN	1,490
MASP2	1,321
TUBA4A	1,118
ANG	852

Intra-cohort edges

A	B	Sources
OPTN	SOD1	biogrid_interaction, string_interaction
OPTN	TARDBP	string_interaction
SOD1	TARDBP	string_interaction

Structural data

PDB: 7 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SOD1	P00441	156
ANG	P03950	56
TARDBP	Q13148	44
OPTN	Q96CV9	14
ERBB4	Q15303	14
MASP2	O00187	10
GRN	P28799	8

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TUBA4A	P68366	92.02

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 143. Enrichment computed across 8 evidence-associated genes (7 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 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
tRNA-derived small RNA (tsRNA or tRNA-related fragment, tRF) biogenesis	1	543.8×	0.062	ANG
Ficolins bind to repetitive carbohydrate structures on the target cell surface	1	326.3×	0.062	MASP2
Lectin pathway of complement activation	1	181.3×	0.062	MASP2
Downregulation of ERBB4 signaling	1	163.1×	0.062	ERBB4
PI3K events in ERBB4 signaling	1	148.3×	0.062	ERBB4
Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation	1	135.9×	0.062	OPTN
ERBB2 Activates PTK6 Signaling	1	116.5×	0.062	ERBB4
TICAM1-dependent activation of IRF3/IRF7	1	116.5×	0.062	OPTN
Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7	1	108.8×	0.062	OPTN
SHC1 events in ERBB4 signaling	1	102.0×	0.062	ERBB4
ERBB2 Regulates Cell Motility	1	102.0×	0.062	ERBB4
PI3K events in ERBB2 signaling	1	96.0×	0.062	ERBB4
GRB2 events in ERBB2 signaling	1	90.6×	0.062	ERBB4
Initial triggering of complement	1	85.9×	0.062	MASP2
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	1	85.9×	0.062	OPTN
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	1	77.7×	0.062	TUBA4A
Transport of connexons to the plasma membrane	1	77.7×	0.062	TUBA4A
SHC1 events in ERBB2 signaling	1	68.0×	0.062	ERBB4
Gap junction trafficking and regulation	1	68.0×	0.062	TUBA4A
Gap junction trafficking	1	68.0×	0.062	TUBA4A
Post-chaperonin tubulin folding pathway	1	68.0×	0.062	TUBA4A
Interleukin-12 family signaling	1	68.0×	0.062	SOD1
Long-term potentiation	1	68.0×	0.062	ERBB4
Signaling by ERBB2 TMD/JMD mutants	1	68.0×	0.062	ERBB4
TNFR1-induced proapoptotic signaling	1	62.8×	0.062	OPTN
Formation of tubulin folding intermediates by CCT/TriC	1	60.4×	0.062	TUBA4A
Signaling by ERBB2 KD Mutants	1	60.4×	0.062	ERBB4
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	1	58.3×	0.062	TUBA4A
Interleukin-12 signaling	1	58.3×	0.062	SOD1
Prefoldin mediated transfer of substrate to CCT/TriC	1	56.3×	0.062	TUBA4A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
placenta development	2	110.9×	0.014	SOD1, ANG
ovarian follicle development	2	98.0×	0.014	SOD1, ANG
embryo implantation	2	87.8×	0.014	SOD1, GRN
nuclear inner membrane organization	1	2106.5×	0.015	TARDBP
positive regulation of aspartic-type peptidase activity	1	2106.5×	0.015	GRN
central nervous system morphogenesis	1	1053.2×	0.015	ERBB4
establishment of planar polarity involved in nephron morphogenesis	1	1053.2×	0.015	ERBB4
response to antipsychotic drug	1	1053.2×	0.015	SOD1
positive regulation of inflammatory response to wounding	1	1053.2×	0.015	GRN
positive regulation of trophectodermal cell proliferation	1	1053.2×	0.015	GRN
negative regulation of translation in response to stress	1	702.2×	0.015	ANG
response to carbon monoxide	1	702.2×	0.015	SOD1
action potential initiation	1	702.2×	0.015	SOD1
positive regulation of protein folding	1	702.2×	0.015	GRN
astrocyte activation involved in immune response	1	526.6×	0.015	GRN
cardiac muscle tissue regeneration	1	526.6×	0.015	ERBB4
positive regulation of lysosome organization	1	526.6×	0.015	GRN
response to superoxide	1	421.3×	0.015	SOD1
trophectodermal cell proliferation	1	421.3×	0.015	GRN
negative regulation of receptor recycling	1	421.3×	0.015	OPTN
microglial cell activation involved in immune response	1	421.3×	0.015	GRN
tRNA decay	1	421.3×	0.015	ANG
olfactory bulb interneuron differentiation	1	421.3×	0.015	ERBB4
positive regulation of axon regeneration	1	421.3×	0.015	GRN
negative regulation of respiratory burst involved in inflammatory response	1	421.3×	0.015	GRN
type 2 mitophagy	1	421.3×	0.015	OPTN
positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	1	421.3×	0.015	SOD1
positive regulation of epithelial cell proliferation	2	61.1×	0.015	ERBB4, GRN
negative regulation of neuron apoptotic process	2	27.7×	0.015	SOD1, GRN
signal transduction	4	8.0×	0.015	OPTN, ERBB4, GRN, ANG

Therapeutics

Drug target analysis

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

Druggability breadth: 7 of 8 evidence-associated genes (88%) 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
TUBA4A	COLCHICINE
ERBB4	MOBOCERTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ERBB4	47	4
TUBA4A	22	4
TARDBP	1	4
SOD1	0	0
OPTN	0	0
GRN	0	0
ANG	0	0
MASP2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MITOXANTRONE	4	TARDBP
COLCHICINE	4	TUBA4A
VINBLASTINE	4	TUBA4A
LEVOFLOXACIN ANHYDROUS	4	TUBA4A
DOCETAXEL	4	TUBA4A
NOSCAPINE	4	TUBA4A
VINBLASTINE SULFATE	4	TUBA4A
PACLITAXEL	4	TUBA4A
LEVOFLOXACIN	4	TUBA4A
VINORELBINE	4	TUBA4A
TIRBANIBULIN	4	TUBA4A
PODOFILOX	4	TUBA4A
VINCRISTINE	4	TUBA4A
DOCETAXEL ANHYDROUS	4	TUBA4A
MOBOCERTINIB	4	ERBB4
AFATINIB	4	ERBB4
FEDRATINIB	4	ERBB4
NERATINIB	4	ERBB4
IBRUTINIB	4	ERBB4
AFATINIB DIMALEATE	4	ERBB4
DACOMITINIB	4	ERBB4
DACOMITINIB ANHYDROUS	4	ERBB4
VANDETANIB	4	ERBB4
BOSUTINIB	4	ERBB4
BRIGATINIB	4	ERBB4
ACALABRUTINIB	4	ERBB4
ZANUBRUTINIB	4	ERBB4
TIRABRUTINIB	4	ERBB4
RITLECITINIB	4	ERBB4
DASATINIB	4	ERBB4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
TUBA4A	1,695	Binding:1654, Functional:35, ADMET:6
ERBB4	591	Binding:579, ADMET:8, Functional:4
SOD1	38	Binding:32, Functional:5, ADMET:1
MASP2	9	Binding:9
TARDBP	8	Binding:7, Functional:1
GRN	2	Binding:2
ANG	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SOD1	1.15.1.1	superoxide dismutase
ERBB4	2.7.10.1	receptor protein-tyrosine kinase
MASP2	3.4.21.104	mannan-binding lectin-associated serine protease-2

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TUBA4A	1,695
ERBB4	591

Pharmacogenomics

Cohort genes with a PharmGKB record: 8; 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
COLCHICINE	4	TUBA4A
VINBLASTINE	4	TUBA4A
LEVOFLOXACIN ANHYDROUS	4	TUBA4A
DOCETAXEL	4	TUBA4A
NOSCAPINE	4	TUBA4A
VINBLASTINE SULFATE	4	TUBA4A
PACLITAXEL	4	TUBA4A
LEVOFLOXACIN	4	TUBA4A
VINORELBINE	4	TUBA4A
TIRBANIBULIN	4	TUBA4A
PODOFILOX	4	TUBA4A
VINCRISTINE	4	TUBA4A
DOCETAXEL ANHYDROUS	4	TUBA4A
MOBOCERTINIB	4	ERBB4
AFATINIB	4	ERBB4
FEDRATINIB	4	ERBB4
NERATINIB	4	ERBB4
IBRUTINIB	4	ERBB4
AFATINIB DIMALEATE	4	ERBB4
DACOMITINIB	4	ERBB4
DACOMITINIB ANHYDROUS	4	ERBB4
VANDETANIB	4	ERBB4
BOSUTINIB	4	ERBB4
BRIGATINIB	4	ERBB4
ACALABRUTINIB	4	ERBB4
ZANUBRUTINIB	4	ERBB4
TIRABRUTINIB	4	ERBB4
RITLECITINIB	4	ERBB4
DASATINIB	4	ERBB4

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	TARDBP, TUBA4A, ERBB4
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	SOD1, MASP2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	OPTN, GRN, ANG

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SOD1	38	TARDBP
OPTN	0	—
GRN	2	—
ANG	2	—
MASP2	9	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.