Idiopathic scoliosis

Summary

Idiopathic scoliosis (MONDO:0000726) is a disease with 1 cohort gene and 168 clinical trials. Top therapeutic interventions include ondansetron, desflurane, and ketamine.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 168

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	idiopathic scoliosis
Mondo ID	MONDO:0000726
DOID	DOID:0060250
ICD-11	712180005
SNOMED CT	203639008
UMLS	C0595995
MedGen	671079
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › disease of bone structure › scoliosis › idiopathic scoliosis

Subtypes (2): adolescent idiopathic scoliosis, juvenile idiopathic scoliosis

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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
397652	NM_001408.3(CELSR2):c.6859G>A (p.Val2287Ile)	CELSR2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CELSR2	HGNC:3231	ENSG00000143126	Q9HCU4	Cadherin EGF LAG seven-pass G-type receptor 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CELSR2	Cadherin EGF LAG seven-pass G-type receptor 2	Receptor that may have an important role in cell/cell signaling during nervous system formation.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
GPCR	1	23.9×	0.042

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CELSR2	GPCR	yes		EGF-type_Asp/Asn_hydroxyl_site, GPS, EGF

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ganglionic eminence	1
right frontal lobe	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CELSR2	248	ubiquitous	marker	ganglionic eminence, ventricular zone, right frontal lobe

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CELSR2	1,539

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CELSR2	Q9HCU4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
neural plate anterior/posterior regionalization	1	5617.3×	0.002	CELSR2
cerebrospinal fluid secretion	1	4213.0×	0.002	CELSR2
motor neuron migration	1	1685.2×	0.003	CELSR2
regulation of cell-cell adhesion	1	1203.7×	0.003	CELSR2
ventricular system development	1	842.6×	0.004	CELSR2
Wnt signaling pathway, planar cell polarity pathway	1	455.5×	0.005	CELSR2
dendrite morphogenesis	1	432.1×	0.005	CELSR2
cell-cell adhesion mediated by cadherin	1	411.0×	0.005	CELSR2
cilium movement	1	391.9×	0.005	CELSR2
regulation of protein localization	1	205.5×	0.008	CELSR2
axonogenesis	1	160.5×	0.009	CELSR2
homophilic cell-cell adhesion	1	140.4×	0.009	CELSR2
Wnt signaling pathway	1	99.7×	0.012	CELSR2
cilium assembly	1	73.6×	0.016	CELSR2
G protein-coupled receptor signaling pathway	1	36.2×	0.029	CELSR2
regulation of DNA-templated transcription	1	31.6×	0.032	CELSR2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CELSR2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	1	CELSR2
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CELSR2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 168.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	152
PHASE4	9
PHASE3	3
PHASE2	3
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01325493	PHASE4	COMPLETED	Low Dose Ketamine Study on Opioid Tolerance and Hyperalgesia
NCT01932424	PHASE4	COMPLETED	Blood Propofol Concentrations in Children During Spinal Surgery
NCT02651324	PHASE4	COMPLETED	Efficacy of Ketamine for Improvement in Postoperative Pain Control After Spinal Fusion for Idiopathic Scoliosis
NCT03190668	PHASE4	COMPLETED	Skeletal Muscle and Adipose Tissue Study
NCT05938959	PHASE4	UNKNOWN	Erector Spinae Plane Block for Pediatric Idiopathic Scoliosis Surgery
NCT05956899	PHASE4	COMPLETED	Palonosetron vs Ondansetron In PONV Prophylaxis Among Idiopathic Scoliosis Patients
NCT06086431	PHASE4	COMPLETED	Dexamethasone Vs. Dexmedetomidine for ESPB in Pain Management After Pediatric Idiopathic Scoliosis Surgery
NCT06616220	PHASE4	COMPLETED	Dexamethasone for ESPB in Pain Management After Pediatric Idiopathic Scoliosis Surgery
NCT06789016	PHASE4	COMPLETED	Dexmedetomidine for ESPB in Pain Management After Pediatric Idiopathic Scoliosis Surgery
NCT06626503	PHASE3	RECRUITING	Evaluation of Analgesia for Spine Fusion Elective Surgery in Children
NCT06774898	PHASE3	NOT_YET_RECRUITING	Spinal Bracing in Adults With Painful Degenerative Scoliosis: a Randomized Controlled Open Trial
NCT03867240	PHASE3	WITHDRAWN	Gabapentin and Chronic Post Surgical Pain
NCT06822374	PHASE2/PHASE3	WITHDRAWN	Hypertonic Saline in Posterior Spinal Fusion
NCT01795495	PHASE2	COMPLETED	Methadone vs Magnesium in Spinal Fusion
NCT03968146	PHASE2	COMPLETED	Erector Spinae Plane Block in Scoliotic Adolescents
NCT04922983	PHASE2	UNKNOWN	Incobotulinumtoxin A and Yoga-like Isometric Exercise in Adolescent Idiopathic Lumbar Scoliosis
NCT01761305	Not specified	ACTIVE_NOT_RECRUITING	Trial on Three Treatments for Scoliosis
NCT03858244	Not specified	ACTIVE_NOT_RECRUITING	Idiopathic Scoliosis Progression and Sleep-disordered Breathing in Children
NCT04031716	Not specified	ACTIVE_NOT_RECRUITING	Comprehensive Study of Post-surgical Pain After Pectus or Spine Surgery
NCT04500041	Not specified	ACTIVE_NOT_RECRUITING	Casting vs Bracing for Idiopathic Early-Onset Scoliosis
NCT04505579	Not specified	RECRUITING	The Tether™ - Vertebral Body Tethering System Post Approval Study
NCT04805437	Not specified	RECRUITING	Brace Treatment for Idiopathic Scoliosis; PReventing Idiopathic SCOliosis PROgression
NCT04914507	Not specified	RECRUITING	A Prospective Analysis of Long-Term Clinical Outcomes and 3D Spine Growth in Anterior Vertebral Body Tethering
NCT05071144	Not specified	RECRUITING	Advanced SPinal Innovations With Robotics and Enabling Technology Registry
NCT05138393	Not specified	RECRUITING	Scoliosis-specific Exercises for Mild Idiopathic Scoliosis
NCT05281757	Not specified	RECRUITING	Post-Market Clinical Follow-Up Study on the Safety and Performance of Ennovate® Complex
NCT05830825	Not specified	RECRUITING	PMCF (Post-Market Clinical Follow-up) Study on The Tether™ in UK (United Kingdom)
NCT06093477	Not specified	RECRUITING	Studying Melatonin and Recovery in Teens
NCT06161038	Not specified	RECRUITING	Precision Medicine for Nociception, Sngception and Proprioception.
NCT06242821	Not specified	RECRUITING	Yoga for Back Pain in Adolescent Scoliosis
NCT06298812	Not specified	RECRUITING	REFLECT Scoliosis System Post Approval Study
NCT06408896	Not specified	ACTIVE_NOT_RECRUITING	Development and Internal Validation of Predicting Models of Idiopathic Scoliosis Natural History and Treatment Outcomes Through the Use of Artificial Intelligence in a Large Clinical Database
NCT06433167	Not specified	NOT_YET_RECRUITING	Investigation of Gait Pattern in Idiopathic Scoliosis
NCT06502613	Not specified	RECRUITING	Idiopathic Scoliosis New Onset and Melatonin Phase Delay in Children
NCT06512038	Not specified	ACTIVE_NOT_RECRUITING	The Use of DXA in Scoliosis
NCT06563141	Not specified	RECRUITING	A Suggested Rehabilitation Protocol for the Treatment of C-shape Scoliosis
NCT06728046	Not specified	NOT_YET_RECRUITING	Erector Spinae Plane Block v.s Patient Controlled Analgesia in Correction Surgery for Idiopathic Scoliosis
NCT06777992	Not specified	NOT_YET_RECRUITING	Implementation of Momentum SpineTM: a New 3D Imaging Software for Idiopathic Scoliosis
NCT06779240	Not specified	ACTIVE_NOT_RECRUITING	Distinguishing Non-Specific Low Back Pain from Scoliosis-Related Pain Via Quality of Life Questionnaires
NCT06820190	Not specified	RECRUITING	Analgesic Efficacy of Multiple Mid-Transverse Process to Pleura (MTP) Block and PCA in Idiopathic Scoliosis Patients Undergoing Posterior Spinal Fusion

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ONDANSETRON	4	3
DESFLURANE	4	2
KETAMINE	4	2
CYANOCOBALAMIN	4	1
DESMOPRESSIN	4	1
FERRIC CARBOXYMALTOSE	4	1
MEPERIDINE	4	1
METHADONE HYDROCHLORIDE	4	1
PALONOSETRON	4	1
PROPOFOL	4	1
RETINOL	4	1
SODIUM CHLORIDE	4	1
BIFIDOBACTERIUM SPP.	3	1
ESMETHADONE	3	1
CHEMBL4303681	0	1
VITAMIN B12	0	1