Spastic cerebral palsy

Summary

Spastic cerebral palsy (MONDO:0000396) is a disease (an umbrella term covering 5 Mondo subtypes) with 3 cohort genes and 67 clinical trials. Top therapeutic interventions include incobotulinumtoxina.

At a glance

• Umbrella term: 5 Mondo subtypes
• Cohort genes: 3
• ClinVar variants: 2
• Clinical trials: 67

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spastic cerebral palsy
Mondo ID	MONDO:0000396
DOID	DOID:0050669
ICD-11	1426032265
NCIT	C116903
SNOMED CT	230773005
UMLS	C0338596
MedGen	137905
Is cancer (heuristic)	no

Also known as: hypertonic cerebral palsy

Data availability: 2 ClinVar variants.

Disease family

An umbrella term covering 5 Mondo subtypes.

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

Related subtypes (4): ataxic cerebral palsy, mixed cerebral palsy, hypotonic cerebral palsy, athetoid cerebral palsy

Subtypes (5): spastic diplegia, spastic hemiplegia, spastic monoplegia, spastic quadriplegic cerebral palsy, spastic triplegia

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:

1 pathogenic/likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1344806	NM_024735.5(FBXO31):c.1000G>A (p.Asp334Asn)	FBXO31	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3383294	NM_020649.3(CBX8):c.20G>A (p.Gly7Glu)	CBX8	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FBXO31	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability

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
FBXO5	HGNC:13584	ENSG00000112029	Q9UKT4	F-box only protein 5	clinvar
CBX8	HGNC:15962	ENSG00000141570	Q9HC52	Chromobox protein homolog 8	clinvar
FBXO31	HGNC:16510	ENSG00000103264	Q5XUX0	F-box only protein 31	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FBXO5	F-box only protein 5	Regulator of APC activity during mitotic and meiotic cell cycle.
CBX8	Chromobox protein homolog 8	Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development.
FBXO31	F-box only protein 31	Substrate-recognition component of the SCF(FBXO31) protein ligase complex, which specifically mediates the ubiquitination of proteins amidated at their C-terminus in response to oxidative stress, leading to their degradation by the proteas…

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · 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
Other/Unknown	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FBXO5	Other/Unknown	no		F-box_dom, ZF_ZBR, FBX5_43
CBX8	Other/Unknown	no		Chromo/chromo_shadow_dom, Chromo-like_dom_sf, Chromodomain_CS
FBXO31	Other/Unknown	no		F-box_dom, F-box-like_dom_sf, FBXO31/39

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
ganglionic eminence	1
secondary oocyte	1
ventricular zone	1
primordial germ cell in gonad	1
right uterine tube	1
stromal cell of endometrium	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FBXO5	225	ubiquitous	marker	ventricular zone, ganglionic eminence, secondary oocyte
CBX8	169	ubiquitous	yes	right uterine tube, primordial germ cell in gonad, stromal cell of endometrium
FBXO31	261	ubiquitous	marker	cerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FBXO5	2,844
CBX8	2,259
FBXO31	634

Intra-cohort edges

A	B	Sources
FBXO31	FBXO5	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FBXO5	Q9UKT4	3
CBX8	Q9HC52	3
FBXO31	Q5XUX0	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 31. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Mitotic Metaphase/Anaphase Transition	1	1268.9×	0.024	FBXO5
Phosphorylation of Emi1	1	475.8×	0.033	FBXO5
SUMOylation of DNA methylation proteins	1	223.9×	0.037	CBX8
G1/S-Specific Transcription	1	119.0×	0.037	FBXO5
Regulation of APC/C activators between G1/S and early anaphase	1	102.9×	0.037	FBXO5
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	100.2×	0.037	CBX8
SUMOylation of transcription cofactors	1	81.0×	0.037	CBX8
SCF-beta-TrCP mediated degradation of Emi1	1	79.3×	0.037	FBXO5
SUMOylation of RNA binding proteins	1	79.3×	0.037	CBX8
PTEN Regulation	1	76.1×	0.037	CBX8
SUMO E3 ligases SUMOylate target proteins	1	59.5×	0.037	CBX8
Regulation of PTEN gene transcription	1	59.5×	0.037	CBX8
SUMOylation	1	54.4×	0.037	CBX8
SUMOylation of chromatin organization proteins	1	52.9×	0.037	CBX8
SUMOylation of DNA damage response and repair proteins	1	48.8×	0.037	CBX8
Transcriptional regulation by RUNX1	1	48.8×	0.037	CBX8
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	48.8×	0.037	CBX8
Cellular Senescence	1	45.9×	0.037	CBX8
Intracellular signaling by second messengers	1	30.4×	0.051	CBX8
Oxidative Stress Induced Senescence	1	30.2×	0.051	CBX8
PIP3 activates AKT signaling	1	22.3×	0.065	CBX8
Neddylation	1	15.8×	0.087	FBXO31
Antigen processing: Ubiquitination & Proteasome degradation	1	12.4×	0.102	FBXO31
Cellular responses to stress	1	12.3×	0.102	CBX8
Cellular responses to stimuli	1	10.5×	0.115	CBX8
RNA Polymerase II Transcription	1	7.5×	0.152	CBX8
Post-translational protein modification	1	6.4×	0.170	CBX8
Gene expression (Transcription)	1	6.0×	0.176	CBX8
Generic Transcription Pathway	1	5.0×	0.199	CBX8
Metabolism of proteins	1	4.1×	0.231	CBX8

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
negative regulation of DNA endoreduplication	1	2808.7×	0.004	FBXO5
negative regulation of mitotic metaphase/anaphase transition	1	1404.3×	0.004	FBXO5
negative regulation of ubiquitin-protein transferase activity	1	1404.3×	0.004	FBXO5
positive regulation of mesenchymal stem cell migration	1	1404.3×	0.004	FBXO5
spindle assembly involved in female meiosis I	1	1123.5×	0.004	FBXO5
negative regulation of ubiquitin protein ligase activity	1	1123.5×	0.004	FBXO5
positive regulation of biomineral tissue development	1	936.2×	0.004	FBXO5
DNA damage response	2	35.7×	0.004	FBXO5, FBXO31
negative regulation of meiotic nuclear division	1	702.2×	0.005	FBXO5
protein ubiquitination	2	27.6×	0.005	FBXO5, FBXO31
vesicle organization	1	374.5×	0.007	FBXO5
mitotic G1 DNA damage checkpoint signaling	1	351.1×	0.007	FBXO31
positive regulation of cell population proliferation	2	22.4×	0.007	FBXO5, CBX8
microtubule polymerization	1	295.6×	0.007	FBXO5
signal transduction in response to DNA damage	1	267.5×	0.007	FBXO31
anaphase-promoting complex-dependent catabolic process	1	234.1×	0.007	FBXO31
positive regulation of collagen biosynthetic process	1	216.1×	0.007	CBX8
negative regulation of cellular senescence	1	216.1×	0.007	FBXO5
regulation of mitotic nuclear division	1	208.1×	0.007	FBXO5
oocyte maturation	1	200.6×	0.007	FBXO5
positive regulation of G2/M transition of mitotic cell cycle	1	200.6×	0.007	FBXO5
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	1	124.8×	0.011	FBXO31
regulation of DNA replication	1	122.1×	0.011	FBXO5
positive regulation of DNA repair	1	119.5×	0.011	CBX8
regulation of mitotic cell cycle	1	80.2×	0.015	FBXO5
cellular response to hydrogen peroxide	1	78.0×	0.015	CBX8
positive regulation of osteoblast differentiation	1	74.9×	0.015	FBXO5
cellular response to oxidative stress	1	51.5×	0.021	FBXO31
proteasome-mediated ubiquitin-dependent protein catabolic process	1	17.4×	0.060	FBXO31
cell division	1	15.4×	0.066	FBXO5

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FBXO5	0	0
CBX8	0	0
FBXO31	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CBX8	15	Binding:14, Functional:1

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	3	FBXO5, CBX8, FBXO31

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FBXO5	0	—
CBX8	15	—
FBXO31	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 67.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	62
PHASE2	3
PHASE2/PHASE3	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03676439	PHASE2/PHASE3	UNKNOWN	Lateral Cord Magnetic Stimulation For Refractory Spastic Cerebral Palsy
NCT00011024	PHASE2	COMPLETED	Prospective Studies of the Use of Self Hypnosis, Acupuncture and Osteopathic Manipulation on Muscle Tension in Children With Spastic Cerebral Palsy
NCT01147653	PHASE2	COMPLETED	A Randomized Study of Autologous Umbilical Cord Blood Reinfusion in Children With Cerebral Palsy
NCT05340439	PHASE2	UNKNOWN	INcobotulinumtoxina in ChIldren Upper and Lower Limb sPasticITy (INCIPIT)
NCT03107975	PHASE1	UNKNOWN	Effect of Human Amniotic Epithelial Cells on Children With Spastic Cerebral Palsy
NCT05197764	Not specified	RECRUITING	Evaluation of Macroscopic Muscle Growth in Infants and Young Children With Spastic Cerebral Palsy
NCT05571033	Not specified	RECRUITING	Operant Conditioning of the Soleus Stretch Reflex in Adults With Cerebral Palsy
NCT06044168	Not specified	RECRUITING	Feasibility Nutritional Supplements for Muscle Growth in CP
NCT06070233	Not specified	RECRUITING	Radiosurgery Treatment for Spasticity Associated With Stroke, SCI & Cerebral Palsy
NCT06532981	Not specified	RECRUITING	The Effect of AFOs on the EMG of Children With CP
NCT06584851	Not specified	RECRUITING	3D-Microscopic Muscle Architecture in Cerebral Palsy
NCT06598657	Not specified	RECRUITING	Talocrural Mobilization With Movement in Spastic Cerebral Palsy
NCT06673849	Not specified	RECRUITING	Rhythmic Stabilization Versus Ball Balancing
NCT06785220	Not specified	NOT_YET_RECRUITING	The Effects of Oral Facial Facilitation and Oral Motor Therapy in Dysphagia
NCT06902168	Not specified	RECRUITING	Effect of Diving and Aquatic Exercises on Muscle Spasticity and Motor Function in Children With Spastic Cerebral Palsy
NCT06925425	Not specified	RECRUITING	Effect of Task Specific Electrical Stimulation on Upper Limb Gross Motor Skills in Children With Spastic Quadriplegia
NCT06991725	Not specified	RECRUITING	Botulinum Neurotoxin for Children With CP: a Delicate Balance Between Clinical Benefits and Muscular Harm
NCT07392398	Not specified	NOT_YET_RECRUITING	Virtual Reality Combined With Bobath Therapy for Spastic Cerebral Palsy
NCT07403162	Not specified	RECRUITING	Cuevas Medek Exercises to Improve Postural Control and Balance in Children With Spastic Cerebral Palsy
NCT07437274	Not specified	RECRUITING	Bimanual Training Versus Unilateral Task Specific Training in Children With Spastic Hemiplegic Cerebral Palsy
NCT07516860	Not specified	ACTIVE_NOT_RECRUITING	Effect of SCS Technique on Oromotor Skills in Children With CP
NCT07573865	Not specified	NOT_YET_RECRUITING	tDCS and Bi-manual Training in Cerebral Palsy
NCT00955877	Not specified	TERMINATED	Extended-release Epidural Morphine for Acute Post-operative Analgesia Following Selective Dorsal Rhizotomy in Children
NCT01049581	Not specified	COMPLETED	Effects of Pediatric Aquatic Therapy in Children With Spastic Cerebral Palsy
NCT01815814	Not specified	COMPLETED	Therapeutic Potential of Myofascial Structural Integration in Children With Cerebral Palsy
NCT02359799	Not specified	COMPLETED	Robotic Rehabilitation of Cerebral Palsy
NCT03486483	Not specified	COMPLETED	Spastic Cerebral Palsy and Slackline
NCT03529682	Not specified	UNKNOWN	Circuit Training in Children With Cerebral Palsy
NCT03708757	Not specified	COMPLETED	Effect of Post Isometric Relaxation Technique & Eccentric Muscle Contraction on Hamstring Spasticity in CP
NCT03901703	Not specified	COMPLETED	The Effects of Functional Strengthening in Spastic Cerebral Palsy
NCT04078321	Not specified	COMPLETED	Evaluation of Multifocal Transcutaneous Electrical Stimulation for Self-treatment Among Children With Cerebral Palsy
NCT04322825	Not specified	COMPLETED	Mollii - Personalized Suit for Treatment of Spasticity, GFMCS 3-5
NCT04634136	Not specified	COMPLETED	Full-spectrum Medical Cannabis for Treatment of Spasticity in Patients With Severe Forms of Cerebral Palsy
NCT04858646	Not specified	COMPLETED	Aerobic Exercises and Gross Motor Function in Spastic Cerebral Palsy
NCT04879199	Not specified	COMPLETED	Stop Tip-toeing Around Toe-walking
NCT04904094	Not specified	COMPLETED	Homebased (6-week) Stretching Intervention in Children With Spastic Cerebral Palsy
NCT04925102	Not specified	UNKNOWN	Prediction of Recovery in Spastic Cerebral Palsy.
NCT05094921	Not specified	COMPLETED	Halliwick Concept on Motor Functions in Spastic CP
NCT05113433	Not specified	UNKNOWN	Effects of Different Time Period of Standing Frame on Spasticity and Gait in Children With Spastic Cerebral Palsy.
NCT05126693	Not specified	COMPLETED	Short Term Follow-up of a Botulinum Toxin Intervention in Children With Spastic Cerebral Palsy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
INCOBOTULINUMTOXINA	4	1
CHEMBL454299	0	1