Motor neuron disorder
diseaseOn this page
Also known as anterior horn cell diseasedisease of motor neurondisease or disorder of motor neurondisorder of motor neuronmotor neuron diseasemotor neuron disease or disorder
Summary
Motor neuron disorder (MONDO:0020128) is a disease with 9 cohort genes and 104 clinical trials. Top therapeutic interventions include acamprosate, trimetazidine, and pegcetacoplan.
At a glance
- Cohort genes: 9
- ClinVar variants: 41
- Clinical trials: 104
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | motor neuron disorder |
| Mondo ID | MONDO:0020128 |
| EFO | EFO:0003782 |
| MeSH | D016472 |
| Orphanet | 98503 |
| DOID | DOID:231 |
| ICD-10-CM | G12.2 |
| ICD-11 | 661720689 |
| SNOMED CT | 37340000 |
| UMLS | C0085084 |
| MedGen | 38785 |
| GARD | 0019477 |
| MedDRA | 10028003 |
| Is cancer (heuristic) | no |
Also known as: anterior horn cell disease · disease of motor neuron · disease or disorder of motor neuron · disorder of motor neuron · motor neuron disease · motor neuron disease or disorder
Data availability: 41 ClinVar variants · 1 GenCC gene-disease record.
Disease family
An umbrella term covering 4 Mondo subtypes.
Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › neurodegenerative disease › motor neuron disorder
Related subtypes (21): synucleinopathy, eyelid degenerative disorder, senile degeneration of brain, olivopontocerebellar atrophy, neuroaxonal dystrophy, demyelinating disease, choroidal sclerosis, tauopathy, secondary Parkinson disease, infantile bilateral striatal necrosis, Marchiafava-Bignami disease, superficial siderosis, primary progressive apraxia of speech, human prion disease, primary progressive freezing gait, primary progressive aphasia, brachial amyotrophic diplegia, cerebellar degeneration, inherited neurodegenerative disorder, cerebral degeneration, hypertrophic olivary degeneration
Subtypes (4): amyotrophic lateral sclerosis, Madras motor neuron disease, acquired motor neuron disease, hereditary motor neuron disease
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
41 retrieved; paginated sample, class counts are floors:
17 conflicting classifications of pathogenicity, 8 uncertain significance, 4 pathogenic, 3 likely pathogenic, 3 other, 3 pathogenic; other, 2 pathogenic/likely pathogenic, 1 likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 266055 | NM_001199397.3(NEK1):c.214+1G>A | NEK1 | Pathogenic; other | criteria provided, multiple submitters, no conflicts |
| 266058 | NM_001199397.3(NEK1):c.481C>T (p.Arg161Ter) | NEK1 | Pathogenic; other | criteria provided, multiple submitters, no conflicts |
| 14752 | NM_000454.5(SOD1):c.112G>A (p.Gly38Arg) | SOD1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 14761 | NM_000454.5(SOD1):c.302A>G (p.Glu101Gly) | SOD1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 14784 | NM_000454.5(SOD1):c.280G>C (p.Gly94Arg) | SOD1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 197145 | NM_000454.5(SOD1):c.341T>C (p.Ile114Thr) | SOD1 | 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 |
| 266064 | NM_007375.4(TARDBP):c.1043G>T (p.Gly348Val) | TARDBP | Pathogenic | criteria provided, single submitter |
| 266072 | NM_013254.4(TBK1):c.1330C>T (p.Arg444Ter) | TBK1 | Pathogenic; other | criteria provided, multiple submitters, no conflicts |
| 1328480 | NM_000530.8(MPZ):c.130T>C (p.Ser44Pro) | MPZ | Likely pathogenic | criteria provided, single submitter |
| 266043 | NM_001199397.3(NEK1):c.386T>G (p.Ile129Ser) | NEK1 | Likely pathogenic | criteria provided, single submitter |
| 266063 | NM_000454.5(SOD1):c.437C>A (p.Ala146Asp) | SOD1 | Likely pathogenic | criteria provided, single submitter |
| 266059 | NM_001008212.2(OPTN):c.280A>C (p.Lys94Gln) | LOC108903148 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 199125 | NM_001199397.3(NEK1):c.782G>A (p.Arg261His) | NEK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 266044 | NM_001199397.3(NEK1):c.695G>A (p.Arg232His) | NEK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 266046 | NM_001199397.3(NEK1):c.1021G>A (p.Ala341Thr) | NEK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 266047 | NM_001199397.3(NEK1):c.1137T>A (p.Asp379Glu) | NEK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 266048 | NM_001199397.3(NEK1):c.1789T>A (p.Phe597Ile) | NEK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 266049 | NM_001199397.3(NEK1):c.2137G>A (p.Val713Met) | NEK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 266050 | NM_001199397.3(NEK1):c.2306A>G (p.His769Arg) | NEK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 266051 | NM_001199397.3(NEK1):c.2235T>G (p.Asn745Lys) | NEK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 266053 | NM_001199397.3(NEK1):c.2392C>G (p.Leu798Val) | NEK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 266054 | NM_001199397.3(NEK1):c.3140C>T (p.Ser1047Leu) | NEK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 266056 | NM_001199397.3(NEK1):c.1750-5T>C | NEK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 266060 | NM_001008212.2(OPTN):c.941A>T (p.Gln314Leu) | OPTN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 266062 | NM_001008212.2(OPTN):c.1403T>G (p.Met468Arg) | OPTN | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 266065 | NM_007375.4(TARDBP):c.1122T>G (p.Tyr374Ter) | TARDBP | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 266068 | NM_013254.4(TBK1):c.452C>T (p.Ser151Phe) | TBK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 266069 | NM_013254.4(TBK1):c.829C>G (p.Leu277Val) | TBK1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 549699 | NM_002047.4(GARS1):c.123_124insG (p.Pro42fs) | GARS1 | Uncertain significance | no assertion criteria provided |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 4 · Orphanet: 23 · 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 |
|---|---|---|---|---|
| DSCAML1 | Limited | Autosomal recessive | motor neuron disorder | 4 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| SOD1 | 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 |
| PARK7 | Orphanet:2828 | Young-onset Parkinson disease |
| PARK7 | Orphanet:90020 | Parkinson-dementia complex of Guam |
| OPTN | Orphanet:803 | Amyotrophic lateral sclerosis |
| GARS1 | Orphanet:139536 | Distal hereditary motor neuropathy type 5 |
| GARS1 | Orphanet:99938 | Autosomal dominant Charcot-Marie-Tooth disease type 2D |
| MPZ | Orphanet:100046 | Autosomal dominant intermediate Charcot-Marie-Tooth disease type D |
| MPZ | Orphanet:101082 | Charcot-Marie-Tooth disease type 1B |
| MPZ | Orphanet:3115 | Roussy-Lévy syndrome |
| MPZ | Orphanet:324585 | Autosomal dominant intermediate Charcot-Marie-Tooth disease with neuropathic pain |
| MPZ | Orphanet:538574 | Palmoplantar keratoderma-hereditary motor and sensory neuropathy syndrome |
| MPZ | Orphanet:64748 | Dejerine-Sottas syndrome |
| MPZ | Orphanet:99942 | Autosomal dominant Charcot-Marie-Tooth disease type 2I |
| MPZ | Orphanet:99943 | Autosomal dominant Charcot-Marie-Tooth disease type 2J |
| NEK1 | Orphanet:2751 | Orofaciodigital syndrome type 2 |
| NEK1 | Orphanet:803 | Amyotrophic lateral sclerosis |
| NEK1 | Orphanet:93269 | Short rib-polydactyly syndrome, Majewski type |
Cohort genes → proteins
9 cohort genes, 9 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 9 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| DSCAML1 | HGNC:14656 | ENSG00000177103 | Q8TD84 | Cell adhesion molecule DSCAML1 | gencc |
| SOD1 | HGNC:11179 | ENSG00000142168 | P00441 | Superoxide dismutase [Cu-Zn] | clinvar |
| TARDBP | HGNC:11571 | ENSG00000120948 | Q13148 | TAR DNA-binding protein 43 | clinvar |
| TBK1 | HGNC:11584 | ENSG00000183735 | Q9UHD2 | Serine/threonine-protein kinase TBK1 | clinvar |
| PARK7 | HGNC:16369 | ENSG00000116288 | Q99497 | Parkinson disease protein 7 | clinvar |
| OPTN | HGNC:17142 | ENSG00000123240 | Q96CV9 | Optineurin | clinvar |
| GARS1 | HGNC:4162 | ENSG00000106105 | P41250 | Glycine–tRNA ligase | clinvar |
| MPZ | HGNC:7225 | ENSG00000158887 | P25189 | Myelin protein P0 | clinvar |
| NEK1 | HGNC:7744 | ENSG00000137601 | Q96PY6 | Serine/threonine-protein kinase Nek1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| DSCAML1 | Cell adhesion molecule DSCAML1 | Cell adhesion molecule that plays a role in neuronal self-avoidance. |
| SOD1 | Superoxide dismutase [Cu-Zn] | Destroys radicals which are normally produced within the cells and which are toxic to biological systems. |
| 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. |
| PARK7 | Parkinson disease protein 7 | Multifunctional protein with controversial molecular function which plays an important role in cell protection against oxidative stress and cell death acting as oxidative stress sensor and redox-sensitive chaperone and protease. |
| 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. |
| GARS1 | Glycine–tRNA ligase | Catalyzes the ATP-dependent ligation of glycine to the 3’-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (Gly-AMP). |
| MPZ | Myelin protein P0 | Is an adhesion molecule necessary for normal myelination in the peripheral nervous system. |
| NEK1 | Serine/threonine-protein kinase Nek1 | Phosphorylates serines and threonines, but also appears to possess tyrosine kinase activity. |
Protein-family classification
Druggable: 7 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.78
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 |
|---|---|---|---|
| Antibody/Immunoglobulin | 2 | 6.5× | 0.053 |
| Kinase | 2 | 6.2× | 0.053 |
| Enzyme (other) | 3 | 4.0× | 0.053 |
| Other/Unknown | 2 | 0.4× | 0.992 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| DSCAML1 | Antibody/Immunoglobulin | yes | Ig_sub2, Ig_sub, FN3_dom | |
| SOD1 | Enzyme (other) | yes | 1.15.1.1 | SOD_Cu_Zn_dom, SOD_Cu/Zn_BS, SOD_Cu/Zn_/chaperone |
| 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 | |
| PARK7 | Enzyme (other) | yes | 3.5.1.124 | DJ-1/PfpI, DJ-1, Class_I_gatase-like |
| OPTN | Other/Unknown | no | NEMO_N, CC2-LZ_dom, NEMO_ZF | |
| GARS1 | Enzyme (other) | yes | 6.1.1.14 | WHEP-TRS_dom, aa-tRNA-synt_IIb, tRNA-synt_gly |
| MPZ | Antibody/Immunoglobulin | yes | Myelin_P0-rel, Ig_sub, Ig-like_dom | |
| NEK1 | Kinase | yes | Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf |
Expression context
Cohort genes with no expression data: 0.
9 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) | 9 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| secondary oocyte | 3 |
| lateral nuclear group of thalamus | 2 |
| C1 segment of cervical spinal cord | 1 |
| cortical plate | 1 |
| germinal epithelium of ovary | 1 |
| dorsal root ganglion | 1 |
| pons | 1 |
| substantia nigra pars compacta | 1 |
| ganglionic eminence | 1 |
| ventricular zone | 1 |
| calcaneal tendon | 1 |
| colonic epithelium | 1 |
| adult organism | 1 |
| deltoid | 1 |
| tibia | 1 |
| amniotic fluid | 1 |
| gastrocnemius | 1 |
| muscle of leg | 1 |
| cartilage tissue | 1 |
| olfactory bulb | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| DSCAML1 | 187 | broad | marker | cortical plate, germinal epithelium of ovary, C1 segment of cervical spinal cord |
| SOD1 | 304 | ubiquitous | marker | pons, dorsal root ganglion, substantia nigra pars compacta |
| TARDBP | 301 | ubiquitous | marker | secondary oocyte, ventricular zone, ganglionic eminence |
| TBK1 | 284 | ubiquitous | marker | colonic epithelium, calcaneal tendon, lateral nuclear group of thalamus |
| PARK7 | 294 | ubiquitous | marker | adult organism, tibia, deltoid |
| OPTN | 302 | ubiquitous | marker | amniotic fluid, gastrocnemius, muscle of leg |
| GARS1 | 293 | ubiquitous | marker | secondary oocyte, cartilage tissue, lateral nuclear group of thalamus |
| MPZ | 178 | ubiquitous | marker | tibial nerve, sural nerve, olfactory bulb |
| NEK1 | 288 | ubiquitous | marker | secondary oocyte, trigeminal ganglion, oocyte |
Protein interactions among cohort
Intra-cohort edges: 5.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| TARDBP | 7,245 |
| SOD1 | 6,807 |
| PARK7 | 5,722 |
| TBK1 | 5,476 |
| OPTN | 3,505 |
| GARS1 | 2,426 |
| DSCAML1 | 1,929 |
| NEK1 | 1,512 |
| MPZ | 25 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| NEK1 | TARDBP | string_interaction |
| OPTN | SOD1 | biogrid_interaction, string_interaction |
| OPTN | TARDBP | string_interaction |
| OPTN | TBK1 | intact, string_interaction |
| SOD1 | TARDBP | string_interaction |
Structural data
PDB: 9 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| SOD1 | P00441 | 156 |
| PARK7 | Q99497 | 88 |
| TARDBP | Q13148 | 44 |
| TBK1 | Q9UHD2 | 25 |
| OPTN | Q96CV9 | 14 |
| GARS1 | P41250 | 14 |
| MPZ | P25189 | 2 |
| NEK1 | Q96PY6 | 2 |
| DSCAML1 | Q8TD84 | 1 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 75. Enrichment computed across 9 evidence-associated genes (8 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 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation | 2 | 237.9× | 0.001 | TBK1, OPTN |
| TICAM1-dependent activation of IRF3/IRF7 | 2 | 203.9× | 0.001 | TBK1, OPTN |
| Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 | 2 | 190.3× | 0.001 | TBK1, OPTN |
| Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) | 2 | 150.3× | 0.001 | TBK1, OPTN |
| TNFR1-induced proapoptotic signaling | 2 | 109.8× | 0.002 | TBK1, OPTN |
| PINK1-PRKN Mediated Mitophagy | 2 | 89.2× | 0.003 | TBK1, OPTN |
| Regulation of TNFR1 signaling | 2 | 56.0× | 0.006 | TBK1, OPTN |
| STAT6-mediated induction of chemokines | 1 | 475.8× | 0.020 | TBK1 |
| DSCAM interactions | 1 | 285.5× | 0.029 | DSCAML1 |
| IRF3 mediated activation of type 1 IFN | 1 | 237.9× | 0.031 | TBK1 |
| ZBP1(DAI) mediated induction of type I IFNs | 1 | 129.8× | 0.041 | TBK1 |
| STING mediated induction of host immune responses | 1 | 129.8× | 0.041 | TBK1 |
| Mitophagy | 1 | 129.8× | 0.041 | TBK1 |
| Signaling by Interleukins | 2 | 16.0× | 0.041 | SOD1, TBK1 |
| IRF3-mediated induction of type I IFN | 1 | 102.0× | 0.046 | TBK1 |
| Regulation of innate immune responses to cytosolic DNA | 1 | 95.2× | 0.046 | TBK1 |
| TRAF3-dependent IRF activation pathway | 1 | 95.2× | 0.046 | TBK1 |
| Regulation of pyruvate metabolism | 1 | 71.4× | 0.054 | NEK1 |
| Mitochondrial tRNA aminoacylation | 1 | 64.9× | 0.054 | GARS1 |
| Interleukin-37 signaling | 1 | 64.9× | 0.054 | TBK1 |
| Chaperone Mediated Autophagy | 1 | 62.1× | 0.054 | PARK7 |
| Interleukin-12 family signaling | 1 | 59.5× | 0.054 | SOD1 |
| Cytosolic tRNA aminoacylation | 1 | 54.9× | 0.054 | GARS1 |
| TNF signaling | 1 | 52.9× | 0.054 | TBK1 |
| Pyruvate metabolism | 1 | 51.0× | 0.054 | NEK1 |
| Interleukin-12 signaling | 1 | 51.0× | 0.054 | SOD1 |
| Cytokine Signaling in Immune system | 2 | 10.2× | 0.054 | SOD1, TBK1 |
| TRAF6 mediated IRF7 activation | 1 | 47.6× | 0.056 | TBK1 |
| EGR2 and SOX10-mediated initiation of Schwann cell myelination | 1 | 46.0× | 0.056 | MPZ |
| TNFR1-induced NF-kappa-B signaling pathway | 1 | 42.0× | 0.057 | OPTN |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway | 2 | 749.0× | 5e-04 | SOD1, PARK7 |
| positive regulation of xenophagy | 2 | 468.1× | 7e-04 | TBK1, OPTN |
| removal of superoxide radicals | 2 | 234.1× | 0.002 | SOD1, PARK7 |
| positive regulation of acute inflammatory response to antigenic stimulus | 1 | 1872.4× | 0.005 | PARK7 |
| cellular response to glyoxal | 1 | 1872.4× | 0.005 | PARK7 |
| glycolate biosynthetic process | 1 | 1872.4× | 0.005 | PARK7 |
| detoxification of mercury ion | 1 | 1872.4× | 0.005 | PARK7 |
| detoxification of hydrogen peroxide | 1 | 1872.4× | 0.005 | PARK7 |
| obsolete methylglyoxal catabolic process to lactate | 1 | 1872.4× | 0.005 | PARK7 |
| nuclear inner membrane organization | 1 | 1872.4× | 0.005 | TARDBP |
| guanine deglycation | 1 | 1872.4× | 0.005 | PARK7 |
| obsolete guanine deglycation, methylglyoxal removal | 1 | 1872.4× | 0.005 | PARK7 |
| guanine deglycation, glyoxal removal | 1 | 1872.4× | 0.005 | PARK7 |
| cellular detoxification of methylglyoxal | 1 | 1872.4× | 0.005 | PARK7 |
| regulation of supramolecular fiber organization | 1 | 1872.4× | 0.005 | PARK7 |
| negative regulation of death-inducing signaling complex assembly | 1 | 1872.4× | 0.005 | PARK7 |
| negative regulation of TRAIL-activated apoptotic signaling pathway | 1 | 1872.4× | 0.005 | PARK7 |
| glyoxal metabolic process | 1 | 1872.4× | 0.005 | PARK7 |
| obsolete positive regulation of L-dopa biosynthetic process | 1 | 1872.4× | 0.005 | PARK7 |
| regulation of mitochondrial membrane potential | 2 | 120.8× | 0.005 | SOD1, PARK7 |
| negative regulation of gene expression | 3 | 23.0× | 0.005 | TARDBP, TBK1, PARK7 |
| methylglyoxal metabolic process | 1 | 936.2× | 0.007 | PARK7 |
| mitochondrial glycyl-tRNA aminoacylation | 1 | 936.2× | 0.007 | GARS1 |
| detection of oxidative stress | 1 | 936.2× | 0.007 | PARK7 |
| response to antipsychotic drug | 1 | 936.2× | 0.007 | SOD1 |
| cell aggregation | 1 | 936.2× | 0.007 | MPZ |
| negative regulation of protein K48-linked deubiquitination | 1 | 936.2× | 0.007 | PARK7 |
| positive regulation of dopamine biosynthetic process | 1 | 936.2× | 0.007 | PARK7 |
| negative regulation of nitrosative stress-induced intrinsic apoptotic signaling pathway | 1 | 936.2× | 0.007 | PARK7 |
| positive regulation of autophagy | 2 | 46.2× | 0.007 | TBK1, OPTN |
Therapeutics
Drugs indicated for this disease
0 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.
| Drug | Development status |
|---|---|
| Cannabidiol | Phase 3 (in late-stage trials) |
| Human Immunoglobulin G | Phase 3 (in late-stage trials) |
Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Tocilizumab.
Drug target analysis
Approved (phase 4): 3 · Phase ≥3: 4 · Phased (≥1): 5 · Undrugged: 4
Druggability breadth: 6 of 9 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 |
|---|---|
| TARDBP | MITOXANTRONE |
| TBK1 | MOMELOTINIB |
| NEK1 | FEDRATINIB |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| TBK1 | 38 | 4 |
| NEK1 | 12 | 4 |
| TARDBP | 1 | 4 |
| PARK7 | 1 | 2 |
| GARS1 | 1 | 3 |
| DSCAML1 | 0 | 0 |
| SOD1 | 0 | 0 |
| OPTN | 0 | 0 |
| MPZ | 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 | NEK1, 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 |
| DABRAFENIB | 4 | NEK1 |
| ORANTINIB | 3 | TBK1 |
| ALVOCIDIB | 3 | TBK1 |
| DOVITINIB | 3 | TBK1 |
| LESTAURTINIB | 3 | NEK1, TBK1 |
| RUBOXISTAURIN | 3 | TBK1 |
| CRENOLANIB | 3 | GARS1 |
| SILMITASERTIB | 2 | TBK1 |
| FORETINIB | 2 | TBK1 |
| SU-014813 | 2 | TBK1 |
| CENISERTIB | 2 | TBK1 |
| ADAVOSERTIB | 2 | TBK1 |
| CERDULATINIB | 2 | TBK1 |
| R-406 | 2 | NEK1, TBK1 |
| AT-9283 | 2 | TBK1 |
| MILCICLIB | 2 | TBK1 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 3.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| TBK1 | 475 | Binding:473, Functional:2 |
| NEK1 | 288 | Binding:288 |
| PARK7 | 62 | Binding:62 |
| SOD1 | 38 | Binding:32, Functional:5, ADMET:1 |
| TARDBP | 8 | Binding:7, Functional:1 |
| GARS1 | 8 | Binding:8 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| SOD1 | 1.15.1.1 | superoxide dismutase |
| PARK7 | 3.5.1.124, 4.2.1.130 | protein deglycase, D-lactate dehydratase |
| GARS1 | 6.1.1.14 | glycine-tRNA ligase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| TBK1 | 475 |
| NEK1 | 288 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 9; 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 | NEK1, 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 |
| DABRAFENIB | 4 | NEK1 |
| ORANTINIB | 3 | TBK1 |
| ALVOCIDIB | 3 | TBK1 |
| DOVITINIB | 3 | TBK1 |
| LESTAURTINIB | 3 | NEK1, TBK1 |
| RUBOXISTAURIN | 3 | TBK1 |
| CRENOLANIB | 3 | GARS1 |
| SILMITASERTIB | 2 | TBK1 |
| FORETINIB | 2 | TBK1 |
| SU-014813 | 2 | TBK1 |
| CENISERTIB | 2 | TBK1 |
| ADAVOSERTIB | 2 | TBK1 |
| CERDULATINIB | 2 | TBK1 |
| R-406 | 2 | NEK1, TBK1 |
| AT-9283 | 2 | TBK1 |
| MILCICLIB | 2 | TBK1 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 3 | TARDBP, TBK1, NEK1 |
| B | Phased (≥1) drug, not yet approved | 2 | PARK7, GARS1 |
| C | Druggable family + PDB, no drug | 3 | DSCAML1, SOD1, MPZ |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 1 | OPTN |
Undrugged target profiles
4 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 | TBK1 |
| DSCAML1 | 0 | — |
| MPZ | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 104.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 76 |
| PHASE2 | 11 |
| PHASE1 | 9 |
| PHASE1/PHASE2 | 4 |
| PHASE3 | 2 |
| PHASE4 | 1 |
| PHASE2/PHASE3 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT04997954 | PHASE4 | UNKNOWN | EMERALD TRIAL Open Label Extension Study |
| NCT01776970 | PHASE2/PHASE3 | COMPLETED | Safety and Efficacy on Spasticity Symptoms of a Cannabis Sativa Extract in Motor Neuron Disease |
| NCT01951924 | PHASE3 | COMPLETED | LIME Study (LFB IVIg MMN Efficacy Study) |
| NCT03690791 | PHASE3 | UNKNOWN | Efficacy of Cannabinoids in Amyotrophic Lateral Sclerosis or Motor Neurone Disease |
| NCT06315608 | PHASE2 | NOT_YET_RECRUITING | MRG-001 in Patients With Amyotrophic Lateral Sclerosis |
| NCT07396818 | PHASE1/PHASE2 | NOT_YET_RECRUITING | Kamlanoflast In Amyotrophic Lateral Sclerosis |
| NCT00076687 | PHASE2 | COMPLETED | Safety Study of Botulinum Toxin Type A in Post-Upper Limb Stroke Patients With Reduced Lung Function |
| NCT00324454 | PHASE2 | COMPLETED | Levetiracetam for Cramps, Spasticity and Neuroprotection in Motor Neuron Disease |
| NCT00956488 | PHASE1/PHASE2 | COMPLETED | Supported Treadmill Ambulation Training (STAT) for Patients Diagnosed With Amyotrophic Lateral Aclerosis |
| NCT01369901 | PHASE1/PHASE2 | COMPLETED | Effect of Functional Exercise in Patients With Spinal Bulbar Muscular Atrophy |
| NCT02469896 | PHASE2 | COMPLETED | A Trial of Tocilizumab in ALS Subjects |
| NCT03067857 | PHASE1/PHASE2 | UNKNOWN | Autologous Bone Marrow-Derived Stem Cell Therapy for Motor Neuron Disease |
| NCT03114215 | PHASE2 | COMPLETED | Effect of MD1003 in Amyotrophic Lateral Sclerosis |
| NCT03127514 | PHASE2 | COMPLETED | AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS) |
| NCT03196375 | PHASE2 | TERMINATED | A Study to Assess FLX-787 in Subjects With Motor Neuron Disease Experiencing Muscle Cramps. |
| NCT03508453 | PHASE2 | WITHDRAWN | IC14 for Treatment of Amyotrophic Lateral Sclerosis |
| NCT03705390 | PHASE2 | TERMINATED | A Safety and Tolerability Study of ILB® in Patients With Amyotrophic Lateral Sclerosis (ALS) |
| NCT04579666 | PHASE2 | TERMINATED | MERIDIAN: A Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Adults With Amyotrophic Lateral Sclerosis (ALS) |
| NCT04788745 | PHASE2 | COMPLETED | Targeting Metabolic Flexibility in Amyotrophic Lateral Sclerosis (ALS) |
| NCT07093268 | PHASE1 | NOT_YET_RECRUITING | Safety of Intrathecal Riluzole in Patients With Amyotrophic Lateral Sclerosis |
| NCT07204977 | PHASE1 | ACTIVE_NOT_RECRUITING | Acamprosate in C9orf72 Hexanucleotide Repeat Expansion Amyotrophic Lateral Sclerosis (ACALS) |
| NCT01758510 | PHASE1 | COMPLETED | Safety Study of HLA-haplo Matched Allogenic Bone Marrow Derived Stem Cell Treatment in Amyotrophic Lateral Sclerosis |
| NCT02870634 | PHASE1 | COMPLETED | Phase 1 Dose Escalation and PK Study of Cu(II)ATSM in ALS/MND |
| NCT02987413 | PHASE1 | COMPLETED | Escalated Application of Mesenchymal Stem Cells in Amyotrophic Lateral Sclerosis Patients |
| NCT03487263 | PHASE1 | COMPLETED | Dose-Escalation, Safety and Pharmacokinetic Study of IC14 in Motor Neurone Disease |
| NCT03929068 | PHASE1 | COMPLETED | Sinemet for Spasticity and Function in Amyotrophic Lateral Sclerosis and Primary Lateral Sclerosis |
| NCT04894240 | PHASE1 | COMPLETED | A Study of Monepantel in Individuals With Motor Neurone Disease |
| NCT06177431 | PHASE1 | COMPLETED | An Open Label Extension Study of Monepantel in Individuals With Motor Neurone Disease |
| NCT00004568 | Not specified | RECRUITING | Study of Inherited Neurological Disorders |
| NCT01900132 | Not specified | RECRUITING | Electrical Impedance Myography: Natural History Studies inNeuromuscular Disorders and Healthy Volunteers |
| NCT02869048 | Not specified | RECRUITING | Amyotrophic Lateral Sclerosis and the Innate Immune System |
| NCT03362658 | Not specified | ACTIVE_NOT_RECRUITING | Novel MRI Biomarkers for Monitoring Disease Progression in ALS |
| NCT03827187 | Not specified | RECRUITING | Awareness Detection and Communication in Disorders of Consciousness |
| NCT04380649 | Not specified | ACTIVE_NOT_RECRUITING | Development and Test of a Headset for BCI Until Obtaining an Efficient and Comfortable System That Can be Used in Daily Practice by ALS People |
| NCT04695210 | Not specified | RECRUITING | Virtual Peer-to-peer Support Programme for Carers of MND |
| NCT04706234 | Not specified | RECRUITING | Systematic Assessment of Laryngopharyngeal Function in Patients With Neurodegenerative Diseases |
| NCT04944940 | Not specified | RECRUITING | Clinical, Molecular and Imaging Biomarkers in Spinal and Bulbar Muscular Atrophy (SBMA) |
| NCT04961450 | Not specified | ENROLLING_BY_INVITATION | Explore Biomarkers of Motor Neuron Disease/Frontal Dementia Spectrum Disease in China |
| NCT05136222 | Not specified | RECRUITING | Polysomnographic Titration of Non-invasive Ventilation in Motor Neurone Disease |
| NCT05137665 | Not specified | RECRUITING | Target ALS Biomarker Study; Longitudinal Biofluids, Clinical Measures, and At Home Measures |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| ACAMPROSATE | 4 | 2 |
| TRIMETAZIDINE | 4 | 2 |
| PEGCETACOPLAN | 4 | 1 |
| RILUZOLE | 4 | 1 |
| SODIUM CHLORIDE | 4 | 1 |
| IC14 | 2 | 2 |
| ATSM COPPER (II) | 2 | 1 |
| MONEPANTEL | 1 | 2 |
Related Atlas pages
- Cohort genes: DSCAML1, SOD1, TARDBP, TBK1, PARK7, OPTN, GARS1, MPZ, NEK1
- Drugs: Acamprosate, Trimetazidine, Pegcetacoplan, Riluzole, Sodium Chloride