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Atlas / Disease / Spastic hemiplegia

Spastic hemiplegia

disease
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Also known as hemiplegic infantile cerebral palsy

Summary

Spastic hemiplegia (MONDO:0001168) is a disease with 2 cohort genes and 19 clinical trials. Top therapeutic interventions include baclofen and onabotulinumtoxina.

At a glance

  • Cohort genes: 2
  • ClinVar variants: 2
  • Clinical trials: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namespastic hemiplegia
Mondo IDMONDO:0001168
DOIDDOID:10967
ICD-10-CMG81.1
ICD-111030700023
NCITC116905
SNOMED CT79633009
UMLSC0154694
MedGen56345
Is cancer (heuristic)no

Also known as: hemiplegic infantile cerebral palsy

Data availability: 2 ClinVar variants.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › palsy › cerebral palsy › spastic cerebral palsy › spastic hemiplegia

Related subtypes (4): spastic diplegia, spastic monoplegia, spastic quadriplegic cerebral palsy, spastic triplegia

Subtypes (1): cerebral palsy spastic hemiplegic

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

2 retrieved; paginated sample, class counts are floors:

2 uncertain significance

ClinVarVariant (HGVS)GeneClassificationReview
1174006NM_025150.5(TARS2):c.968T>G (p.Phe323Cys)TARS2Uncertain significancecriteria provided, single submitter
425012NM_013254.4(TBK1):c.871A>G (p.Lys291Glu)TBK1Uncertain significancecriteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
TBK1Orphanet:1930Herpes simplex virus encephalitis
TBK1Orphanet:275872Frontotemporal dementia with motor neuron disease
TBK1Orphanet:803Amyotrophic lateral sclerosis
TARS2Orphanet:420733Combined oxidative phosphorylation defect type 21

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence2

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
TBK1HGNC:11584ENSG00000183735Q9UHD2Serine/threonine-protein kinase TBK1clinvar
TARS2HGNC:30740ENSG00000143374Q9BW92Threonine–tRNA ligase, mitochondrialclinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
TBK1Serine/threonine-protein kinase TBK1Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents.
TARS2Threonine–tRNA ligase, mitochondrialCatalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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.

FamilyGenesFoldFDR
Kinase113.9×0.142
Other/Unknown10.9×0.805

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
TBK1KinaseyesProt_kinase_dom, Kinase-like_dom_sf, Protein_kinase_ATP_BS
TARS2Other/Unknownnoaa-tRNA-synt_IIb, Thr-tRNA-ligase_IIa, TGS

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)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)2
unknown0

Top tissues across cohort

TissueCohort genes
calcaneal tendon1
colonic epithelium1
lateral nuclear group of thalamus1
apex of heart1
gastrocnemius1
muscle of leg1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
TBK1284ubiquitousmarkercolonic epithelium, calcaneal tendon, lateral nuclear group of thalamus
TARS2254ubiquitousmarkergastrocnemius, apex of heart, muscle of leg

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
TBK15,476
TARS22,608

Structural data

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

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
TBK1Q9UHD225

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
TARS2Q9BW9291.19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 51. Enrichment computed across 2 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.

PathwayCohort genesFoldFDRSample cohort genes
STAT6-mediated induction of chemokines11903.3×0.012TBK1
IRF3 mediated activation of type 1 IFN1951.7×0.012TBK1
ZBP1(DAI) mediated induction of type I IFNs1519.1×0.012TBK1
STING mediated induction of host immune responses1519.1×0.012TBK1
Mitophagy1519.1×0.012TBK1
Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation1475.8×0.012TBK1
IRF3-mediated induction of type I IFN1407.9×0.012TBK1
TICAM1-dependent activation of IRF3/IRF71407.9×0.012TBK1
Regulation of innate immune responses to cytosolic DNA1380.7×0.012TBK1
TRAF3-dependent IRF activation pathway1380.7×0.012TBK1
Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF71380.7×0.012TBK1
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)1300.5×0.014TBK1
Mitochondrial tRNA aminoacylation1259.6×0.014TARS2
Interleukin-37 signaling1259.6×0.014TBK1
TNFR1-induced proapoptotic signaling1219.6×0.015TBK1
TNF signaling1211.5×0.015TBK1
TRAF6 mediated IRF7 activation1190.3×0.016TBK1
PINK1-PRKN Mediated Mitophagy1178.4×0.016TBK1
Negative regulators of DDX58/IFIH1 signaling1163.1×0.016TBK1
Cytosolic sensors of pathogen-associated DNA1142.8×0.016TBK1
tRNA Aminoacylation1142.8×0.016TARS2
Selective autophagy1139.3×0.016TBK1
Interleukin-1 family signaling1135.9×0.016TBK1
SARS-CoV-1 activates/modulates innate immune responses1135.9×0.016TBK1
DDX58/IFIH1-mediated induction of interferon-alpha/beta1126.9×0.016TBK1
Regulation of TNFR1 signaling1112.0×0.017TBK1
Toll Like Receptor 3 (TLR3) Cascade196.8×0.019TBK1
TRIF (TICAM1)-mediated TLR4 signaling195.2×0.019TBK1
MyD88-independent TLR4 cascade192.1×0.019TBK1
SARS-CoV-1-host interactions187.8×0.019TBK1

GO biological processes 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.

GO termCohort genesFoldFDRSample cohort genes
mitochondrial threonyl-tRNA aminoacylation18426.0×0.004TARS2
threonyl-tRNA aminoacylation12808.7×0.004TARS2
dendritic cell proliferation12808.7×0.004TBK1
cGAS/STING signaling pathway11685.2×0.005TBK1
positive regulation of xenophagy11053.2×0.005TBK1
positive regulation of TORC2 signaling11053.2×0.005TBK1
regulation of type I interferon production1842.6×0.006TBK1
T follicular helper cell differentiation1702.2×0.006TBK1
cytoplasmic pattern recognition receptor signaling pathway1443.5×0.007TBK1
peptidyl-threonine phosphorylation1443.5×0.007TBK1
positive regulation of type I interferon-mediated signaling pathway1421.3×0.007TBK1
positive regulation of interferon-alpha production1324.1×0.009TBK1
positive regulation of macroautophagy1263.3×0.009TBK1
toll-like receptor 4 signaling pathway1263.3×0.009TBK1
peptidyl-serine phosphorylation1247.8×0.009TBK1
activation of innate immune response1240.7×0.009TBK1
positive regulation of type I interferon production1210.7×0.009TBK1
positive regulation of interferon-beta production1195.9×0.010TBK1
canonical NF-kappaB signal transduction1183.2×0.010TBK1
type I interferon-mediated signaling pathway1172.0×0.010TBK1
negative regulation of TORC1 signaling1162.0×0.010TBK1
positive regulation of TORC1 signaling1147.8×0.010TBK1
macroautophagy1120.4×0.012TBK1
antiviral innate immune response1113.9×0.012TBK1
positive regulation of autophagy1104.0×0.013TBK1
response to virus172.0×0.018TBK1
defense response to Gram-positive bacterium163.8×0.020TBK1
positive regulation of canonical NF-kappaB signal transduction136.3×0.032TBK1
defense response to virus134.7×0.032TBK1
negative regulation of gene expression134.5×0.032TBK1

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) 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.

SymbolExample approved molecule
TBK1MOMELOTINIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
TBK1384
TARS200

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
MOMELOTINIB4TBK1
AMLEXANOX4TBK1
FEDRATINIB4TBK1
RUXOLITINIB4TBK1
ENTRECTINIB4TBK1
PACRITINIB4TBK1
BOSUTINIB4TBK1
FILGOTINIB4TBK1
NINTEDANIB4TBK1
SUNITINIB4TBK1
ERLOTINIB4TBK1
CRIZOTINIB4TBK1
MIDOSTAURIN4TBK1
ORANTINIB3TBK1
ALVOCIDIB3TBK1
DOVITINIB3TBK1
LESTAURTINIB3TBK1
RUBOXISTAURIN3TBK1
SILMITASERTIB2TBK1
FORETINIB2TBK1
SU-0148132TBK1
CENISERTIB2TBK1
ADAVOSERTIB2TBK1
CERDULATINIB2TBK1
R-4062TBK1
AT-92832TBK1
MILCICLIB2TBK1
TOZASERTIB2TBK1
UCN-012TBK1
PF-005622711TBK1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

SymbolAssaysType breakdown
TBK1475Binding:473, Functional:2
TARS22Binding:2

Cohort genes with high screening signal

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

SymbolChEMBL assays
TBK1475

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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.

CompoundMax phaseCohort target (bioactivity)
MOMELOTINIB4TBK1
AMLEXANOX4TBK1
FEDRATINIB4TBK1
RUXOLITINIB4TBK1
ENTRECTINIB4TBK1
PACRITINIB4TBK1
BOSUTINIB4TBK1
FILGOTINIB4TBK1
NINTEDANIB4TBK1
SUNITINIB4TBK1
ERLOTINIB4TBK1
CRIZOTINIB4TBK1
MIDOSTAURIN4TBK1
ORANTINIB3TBK1
ALVOCIDIB3TBK1
DOVITINIB3TBK1
LESTAURTINIB3TBK1
RUBOXISTAURIN3TBK1
SILMITASERTIB2TBK1
FORETINIB2TBK1
SU-0148132TBK1
CENISERTIB2TBK1
ADAVOSERTIB2TBK1
CERDULATINIB2TBK1
R-4062TBK1
AT-92832TBK1
MILCICLIB2TBK1
TOZASERTIB2TBK1
UCN-012TBK1
PF-005622711TBK1

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1TBK1
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug1TARS2

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
TARS22—

Clinical trials & evidence

Clinical trials

Clinical trials: 19.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified17
PHASE42

Top trials by phase / activity

NCTPhaseStatusTitle
NCT03860662PHASE4COMPLETEDThe Effect of Oral Baclofen and Botulinum Toxin Treatments in Hemiplegic Spasticity on the Nociceptive Flexor Reflex
NCT05615987PHASE4UNKNOWNComparison of Botulinum Toxin Injection Techniques in Spasticity
NCT03402854Not specifiedRECRUITINGtDCS and Bimanual Therapy for Children With Hemiplegic Cerebral Palsy
NCT07119801Not specifiedRECRUITINGClinical and Ultrasonographic Evaluation of the Efficacy of Extracorporeal Shock Wave Therapy (ESWT) in Post-Stroke Spasticity
NCT07135739Not specifiedNOT_YET_RECRUITINGFunctional Electrical Stimulation With Mirror Therapy on Upper Limb Functions and Quality of Life in Hemiplegic Children
NCT07421505Not specifiedNOT_YET_RECRUITINGSpinal Mobility in Children With Cerebral Palsy: NDT-Bobath and Exergaming
NCT07433647Not specifiedRECRUITINGEvaluation of Brain MRI Changes in Cerebral Palsy Patients
NCT07482618Not specifiedACTIVE_NOT_RECRUITINGEvaluation of Spasticity, Neuropathic Pain, and Gait Analysis in Stroke Patients Receiving Tolperison Therapy After Botulinum Toxin Injection
NCT07538297Not specifiedNOT_YET_RECRUITINGBiomechanical Muscle Properties and Balance in Children With Spastic Hemiplegia
NCT07615569Not specifiedRECRUITINGRobot-assisted Versus Conventional Physical Therapy for Hand in Sub-acute Stroke
NCT01329705Not specifiedWITHDRAWNDynamic Splinting for Plantarflexion in Spastic Hemiplegia
NCT04528966Not specifiedCOMPLETEDEffects of WBV in Children With Hemiparetic CP
NCT04775511Not specifiedUNKNOWNClinical and Ultrasonographic Comparison of the Effect of Hot and Cold Therapy on Spasticity
NCT05069480Not specifiedCOMPLETEDModulation of Upper Limb Spasticity Post-Stroke
NCT05449951Not specifiedUNKNOWNEffect of Dry Needling on Spasticity in Stroke Survivors.
NCT05519592Not specifiedUNKNOWNProximal Lower Limb Intramuscular Block : Effects on Hemiparetic Gait
NCT06086314Not specifiedCOMPLETEDThe Effects of Neurorehabilitation Approaches Involving Different Upper Extremity Reactive Trainings in Stroke Patients
NCT06725069Not specifiedCOMPLETEDEffects of Neuromuscular Electrical Stimulation on Flexor Spasticity and Function in Stroke Patients
NCT07331844Not specifiedCOMPLETEDBTX-A and Mirror Therapy for Chronic Stroke Spasticity

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
BACLOFEN41
ONABOTULINUMTOXINA41

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
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Sources 72

This page pulls from 72 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncicd10cmicd11intactinterpromedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot