Scoliosis

Summary

Scoliosis (MONDO:0005392) is a disease caused by POC5 (GenCC Strong), with 36 cohort genes (11 GWAS associations across 25 studies) and 205 clinical trials. Top therapeutic interventions include clonidine, methadone, and sodium chloride.

At a glance

• Causal gene: POC5 (GenCC Strong)
• Cohort genes: 36
• GWAS associations: 11
• ClinVar variants: 66
• Clinical trials: 205

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	scoliosis
Mondo ID	MONDO:0005392
EFO	EFO:0004273
MeSH	D012600
DOID	DOID:0060249
ICD-10-CM	M41
ICD-11	1925604007
NCIT	C78603
SNOMED CT	298382003
UMLS	C0036439
MedGen	11348
Is cancer (heuristic)	no

Data availability: 66 ClinVar variants · 11 GWAS associations (25 studies) · 1 GenCC gene-disease record · 1 HPO phenotype.

Disease family

An umbrella term covering 1 Mondo subtype.

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

Related subtypes (4): spondylosis, spondylolysis, spinal stenosis, spondylolisthesis

Subtypes (1): idiopathic scoliosis

Genetics & variants

GWAS landscape

11 GWAS associations across 25 studies. Top hits map to 4 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs11190870	1e-19	LINC01514 - LBX1-AS1	?	1.56
rs6570507	1e-14	ADGRG6	?	1.27
rs182476445	8e-12	TMTC2	G	4.32
rs867264618	2e-11	MAGI1 - SLC25A26	G	3.06
rs7269692	9e-10	RPL41P1 - LINC01432	T	0.04
rs62471379	2e-08	SEM1	A	0.04
rs6442966	2e-08	RN7SL553P - MTARC2P1	G	0.03
rs78434143	3e-07	KRT8P23 - PSTPIP1	?
rs10510181	8e-07	CHL1-AS2	A	1.37
rs10908366	3e-06	RSPO1 - AIRIM	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90479001	Verma A	2024	4,945	436,975	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90474059	UK Biobank Whole-Genome Sequencing Consortium	2025	4,539	453,901	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90479003	Verma A	2024	3,554	441,035	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90080472	Backman JD	2021	1,582	385,435	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084458	Backman JD	2021	1,582	385,435	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90080471	Backman JD	2021	1,360	386,551	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084457	Backman JD	2021	1,360	386,551	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90436714	Zhou W	2018	1,134	394,914	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90479000	Verma A	2024	1,070	118,377	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481016	Verma A	2024	1,070	118,377	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	1
Tier 4: intronic/intergenic	9

MAF distribution

Bucket	Variants
common (>=0.05)	8
low_freq (0.01-0.05)	0
rare (<0.01)	2
unknown	0

Functional consequences

Consequence	Count
intergenic_variant	5
intron_variant	4
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs11190870	10	101219450	T>A,C	0.43	intergenic_variant	LINC01514 - LBX1-AS1	1e-19	Tier 4: intronic/intergenic
rs6570507	6	142358435	G>A	0.43	intron_variant	ADGRG6	1e-14	Tier 4: intronic/intergenic
rs182476445	12	82729110	G>A,C	0	intron_variant	TMTC2	8e-12	Tier 4: intronic/intergenic
rs867264618	3	66119234	G>A	0	intron_variant	MAGI1 - SLC25A26	2e-11	Tier 4: intronic/intergenic
rs7269692	20	21839429	T>A,C	0.4	intergenic_variant	RPL41P1 - LINC01432	9e-10	Tier 4: intronic/intergenic
rs62471379	7	96552527	A>C,G,T	0.191	intergenic_variant	SEM1	2e-08	Tier 4: intronic/intergenic
rs6442966	3	5626364	G>A,C,T	0.361	intergenic_variant	RN7SL553P - MTARC2P1	2e-08	Tier 4: intronic/intergenic
rs78434143	15	76988771	C>A	0.05	regulatory_region_variant	KRT8P23 - PSTPIP1	3e-07	Tier 3: regulatory
rs10510181	3	149364	G>A,T	0.33	intron_variant	CHL1-AS2	8e-07	Tier 4: intronic/intergenic
rs10908366	1	37656262	T>C,G	0.05	intergenic_variant	RSPO1 - AIRIM	3e-06	Tier 4: intronic/intergenic

ClinVar germline variants

66 retrieved; paginated sample, class counts are floors:

22 pathogenic, 22 uncertain significance, 9 likely pathogenic, 8 conflicting classifications of pathogenicity, 5 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
267840	46;XY;t(15;17)(q24;q21.3)dn		Pathogenic	criteria provided, single submitter
1697211	NM_001659.3(ARF3):c.200A>T (p.Asp67Val)	ARF3	Pathogenic	criteria provided, single submitter
1697213	NM_001659.3(ARF3):c.379A>G (p.Lys127Glu)	ARF3	Pathogenic	criteria provided, single submitter
1047887	GRCh37/hg19 17p12(chr17:14100118-15455297)	CDRT15	Pathogenic	criteria provided, single submitter
374090	NM_017780.4(CHD7):c.6892C>T (p.Gln2298Ter)	CHD7	Pathogenic	criteria provided, single submitter
548021	NM_005199.5(CHRNG):c.202C>T (p.Arg68Ter)	CHRNG	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
373943	NM_004380.3(CREBBP):c.6244C>T (p.Gln2082Ter)	CREBBP	Pathogenic	criteria provided, single submitter
684727	NM_000396.4(CTSK):c.905G>A (p.Trp302Ter)	CTSK	Pathogenic	criteria provided, multiple submitters, no conflicts
691884	NM_001039348.3(EFEMP1):c.320_324del (p.Met107fs)	EFEMP1	Pathogenic	criteria provided, single submitter
691885	NM_001039348.3(EFEMP1):c.615T>A (p.Tyr205Ter)	EFEMP1	Pathogenic	criteria provided, single submitter
523271	GRCh37/hg19 1q41(chr1:215829463-219225857)	ESRRG	Pathogenic	criteria provided, single submitter
163462	NM_000138.5(FBN1):c.7754T>C (p.Ile2585Thr)	FBN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
373981	NM_000138.5(FBN1):c.6800A>T (p.Asn2267Ile)	FBN1	Pathogenic	no assertion criteria provided
978559	NM_000138.5(FBN1):c.3757_3760del (p.Gln1253fs)	FBN1	Pathogenic	criteria provided, single submitter
804287	NM_002109.6(HARS1):c.910_912dup (p.Leu305dup)	HARS1	Pathogenic	criteria provided, single submitter
1684631	Single allele	LOC126862799	Pathogenic	criteria provided, single submitter
996015	NM_018840.5(RAB5IF):c.75G>A (p.Trp25Ter)	LOC130065793	Pathogenic/Likely pathogenic	no assertion criteria provided
218934	t(12;19)(q24.21;q12)	MED13L	Pathogenic	criteria provided, single submitter
523662	NM_005593.3(MYF5):c.283C>T (p.Arg95Cys)	MYF5	Pathogenic	no assertion criteria provided
523663	NM_005593.3(MYF5):c.23_32del (p.Gln8fs)	MYF5	Pathogenic	no assertion criteria provided
159398	NM_022455.5(NSD1):c.6050G>A (p.Arg2017Gln)	NSD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
40554	NM_002834.5(PTPN11):c.1493G>T (p.Arg498Leu)	PTPN11	Pathogenic	criteria provided, multiple submitters, no conflicts
684430	NM_005045.4(RELN):c.7456A>G (p.Ser2486Gly)	RELN	Pathogenic	no assertion criteria provided
418996	NM_001379110.1(SLC9A6):c.1143_1144del (p.Phe382fs)	SLC9A6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
694406	NM_004608.4(TBX6):c.473_475dup (p.Trp158_Glu159insGly)	TBX6	Pathogenic	criteria provided, single submitter
694414	NM_004608.4(TBX6):c.418C>T (p.Leu140Phe)	TBX6	Pathogenic	criteria provided, single submitter
1684630	NC_000017.11:g.8117792_8126946del	TRG-GCC2-6	Pathogenic	criteria provided, single submitter
1697208	NM_001659.3(ARF3):c.34C>G (p.Leu12Val)	ARF3	Likely pathogenic	criteria provided, single submitter
18336	NM_005199.5(CHRNG):c.13C>T (p.Gln5Ter)	CHRNG	Likely pathogenic	criteria provided, single submitter
374114	NM_001844.5(COL2A1):c.1916G>A (p.Gly639Asp)	COL2A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 104 · 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
POC5	Strong	Autosomal dominant	scoliosis	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RYR1	Orphanet:169186	Autosomal recessive centronuclear myopathy
RYR1	Orphanet:169189	Autosomal dominant centronuclear myopathy
RYR1	Orphanet:178145	Moderate multiminicore disease with hand involvement
RYR1	Orphanet:324581	Benign Samaritan congenital myopathy
RYR1	Orphanet:33108	Lethal multiple pterygium syndrome
RYR1	Orphanet:423	Malignant hyperthermia of anesthesia
RYR1	Orphanet:424107	Congenital myopathy with myasthenic-like onset
RYR1	Orphanet:466650	Exercise-induced malignant hyperthermia
RYR1	Orphanet:597	Central core disease
RYR1	Orphanet:700188	Calf-predominant weakness-gastrocnemius medialis atrophy-distal myopathy
RYR1	Orphanet:98905	Congenital multicore myopathy with external ophthalmoplegia
RYR1	Orphanet:99741	King-Denborough syndrome
SLC9A6	Orphanet:85278	Christianson syndrome
TBX6	Orphanet:1797	Autosomal dominant spondylocostal dysostosis
TBX6	Orphanet:2311	Autosomal recessive spondylocostal dysostosis
NSDHL	Orphanet:139	CHILD syndrome
NSDHL	Orphanet:251383	CK syndrome
NSD1	Orphanet:1627	Deletion 5q35 syndrome
NSD1	Orphanet:228415	5q35 microduplication syndrome
NSD1	Orphanet:3447	Weaver syndrome
NSD1	Orphanet:821	Sotos syndrome
KIF1B	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
KIF1B	Orphanet:99946	Autosomal dominant Charcot-Marie-Tooth disease type 2A1
LBX1	Orphanet:661	Congenital central hypoventilation syndrome
CHRNG	Orphanet:2990	Autosomal recessive multiple pterygium syndrome
CHRNG	Orphanet:33108	Lethal multiple pterygium syndrome
CHD7	Orphanet:138	CHARGE syndrome
CHD7	Orphanet:39041	Omenn syndrome
CHD7	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
CHD7	Orphanet:478	Kallmann syndrome
COL2A1	Orphanet:137678	Spondyloepiphyseal dysplasia with metatarsal shortening
COL2A1	Orphanet:166100	Autosomal dominant otospondylomegaepiphyseal dysplasia
COL2A1	Orphanet:1856	Spondyloperipheral dysplasia-short ulna syndrome
COL2A1	Orphanet:209867	Autosomal dominant rhegmatogenous retinal detachment
COL2A1	Orphanet:2380	Legg-Calvé-Perthes disease
COL2A1	Orphanet:459051	Spondyloepiphyseal dysplasia, Stanescu type
COL2A1	Orphanet:485	Kniest dysplasia
COL2A1	Orphanet:85166	Platyspondylic dysplasia, Torrance type
COL2A1	Orphanet:85198	Dysspondyloenchondromatosis
COL2A1	Orphanet:86820	Familial avascular necrosis of femoral head
COL2A1	Orphanet:90653	Stickler syndrome type 1
COL2A1	Orphanet:93279	Mild spondyloepiphyseal dysplasia due to COL2A1 mutation with early-onset osteoarthritis
COL2A1	Orphanet:93296	Achondrogenesis type 2
COL2A1	Orphanet:93297	Hypochondrogenesis
COL2A1	Orphanet:93315	Spondylometaphyseal dysplasia, ‘corner fracture’ type
COL2A1	Orphanet:93316	Spondylometaphyseal dysplasia, Schmidt type
COL2A1	Orphanet:93346	Spondyloepimetaphyseal dysplasia congenita, Strudwick type
COL2A1	Orphanet:94068	Spondyloepiphyseal dysplasia congenita
MED13L	Orphanet:216718	Isolated congenitally uncorrected transposition of the great arteries
MED13L	Orphanet:369891	Developmental delay-facial dysmorphism syndrome due to MED13L deficiency

Cohort genes → proteins

36 cohort genes, 35 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	3
multi_evidence	33

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
POC5	HGNC:26658	ENSG00000152359	Q8NA72	Centrosomal protein POC5	gencc,clinvar
RYR1	HGNC:10483	ENSG00000196218	P21817	Ryanodine receptor 1	clinvar
SLC9A6	HGNC:11079	ENSG00000198689	Q92581	Sodium/hydrogen exchanger 6	clinvar
TBX6	HGNC:11605	ENSG00000149922	O95947	T-box transcription factor TBX6	clinvar
TRG-GCC2-6	HGNC:12273			tRNA-Gly (anticodon GCC) 2-6	clinvar
NSDHL	HGNC:13398	ENSG00000147383	Q15738	Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating	clinvar
ADGRG6	HGNC:13841	ENSG00000112414	Q86SQ4	Adhesion G-protein coupled receptor G6	gwas
NSD1	HGNC:14234	ENSG00000165671	Q96L73	Histone-lysine N-methyltransferase, H3 lysine-36 specific	clinvar
CDRT15	HGNC:14395	ENSG00000223510	Q96T59	CMT1A duplicated region transcript 15 protein	clinvar
KIF1B	HGNC:16636	ENSG00000054523	O60333	Kinesin-like protein KIF1B	clinvar
LBX1	HGNC:16960	ENSG00000138136	P52954	Transcription factor LBX1	gwas
CHRNG	HGNC:1967	ENSG00000196811	P07510	Acetylcholine receptor subunit gamma	clinvar
CHD7	HGNC:20626	ENSG00000171316	Q9P2D1	ATP-dependent chromatin remodeler CHD7	clinvar
COL2A1	HGNC:2200	ENSG00000139219	P02458	Collagen alpha-1(II) chain	clinvar
MED13L	HGNC:22962	ENSG00000123066	Q71F56	Mediator of RNA polymerase II transcription subunit 13-like	clinvar
FAM120AOS	HGNC:23389	ENSG00000188938	Q5T036	Uncharacterized protein FAM120AOS	clinvar
CREBBP	HGNC:2348	ENSG00000005339	Q92793	CREB-binding protein	clinvar
CTSK	HGNC:2536	ENSG00000143387	P43235	Cathepsin K	clinvar
PIEZO2	HGNC:26270	ENSG00000154864	Q9H5I5	Piezo-type mechanosensitive ion channel component 2	clinvar
TAPT1	HGNC:26887	ENSG00000169762	Q6NXT6	Transmembrane anterior posterior transformation protein 1 homolog	clinvar
DDX11	HGNC:2736	ENSG00000013573	Q96FC9	ATP-dependent DNA helicase DDX11	gwas
SH3TC2	HGNC:29427	ENSG00000169247	Q8TF17	SH3 domain and tetratricopeptide repeat-containing protein 2	clinvar
EFEMP1	HGNC:3218	ENSG00000115380	Q12805	EGF-containing fibulin-like extracellular matrix protein 1	clinvar
ESRRG	HGNC:3474	ENSG00000196482	P62508	Estrogen-related receptor gamma	clinvar
FBN1	HGNC:3603	ENSG00000166147	P35555	Fibrillin-1	clinvar
FLNA	HGNC:3754	ENSG00000196924	P21333	Filamin-A	clinvar
FXR1	HGNC:4023	ENSG00000114416	P51114	RNA-binding protein FXR1	clinvar
GDF3	HGNC:4218	ENSG00000184344	Q9NR23	Growth/differentiation factor 3	clinvar
GFAP	HGNC:4235	ENSG00000131095	P14136	Glial fibrillary acidic protein	clinvar
GRIN2B	HGNC:4586	ENSG00000273079	Q13224	Glutamate receptor ionotropic, NMDA 2B	clinvar
HARS1	HGNC:4816	ENSG00000170445	P12081	Histidine–tRNA ligase, cytoplasmic	clinvar
JAG1	HGNC:6188	ENSG00000101384	P78504	Protein jagged-1	clinvar
ARF3	HGNC:654	ENSG00000134287	P61204	ADP-ribosylation factor 3	clinvar
MYF5	HGNC:7565	ENSG00000111049	P13349	Myogenic factor 5	clinvar
PTPN11	HGNC:9644	ENSG00000179295	Q06124	Tyrosine-protein phosphatase non-receptor type 11	clinvar
RELN	HGNC:9957	ENSG00000189056	P78509	Reelin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
POC5	Centrosomal protein POC5	Essential for the assembly of the distal half of centrioles, required for centriole elongation.
RYR1	Ryanodine receptor 1	Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules.
SLC9A6	Sodium/hydrogen exchanger 6	Endosomal Na(+), K(+)/H(+) antiporter.
TBX6	T-box transcription factor TBX6	T-box transcription factor that plays an essential role in the determination of the fate of axial stem cells: neural vs mesodermal.
NSDHL	Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating	Catalyzes the NAD(P)(+)-dependent oxidative decarboxylation of the C4 methyl groups of 4-alpha-carboxysterols in post-squalene cholesterol biosynthesis.
ADGRG6	Adhesion G-protein coupled receptor G6	Adhesion G-protein coupled receptor (aGPCR) for steroid hormones, such as progesterone and 17alpha-hydroxyprogesterone (17OHP).
NSD1	Histone-lysine N-methyltransferase, H3 lysine-36 specific	Histone methyltransferase that dimethylates Lys-36 of histone H3 (H3K36me2).
KIF1B	Kinesin-like protein KIF1B	Has a plus-end-directed microtubule motor activity and functions as a motor for transport of vesicles and organelles along microtubules.
LBX1	Transcription factor LBX1	Transcription factor required for the development of GABAergic interneurons in the dorsal horn of the spinal cord and migration and further development of hypaxial muscle precursor cells for limb muscles, diaphragm and hypoglossal cord.
CHRNG	Acetylcholine receptor subunit gamma	After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
CHD7	ATP-dependent chromatin remodeler CHD7	ATP-dependent chromatin-remodeling factor, slides nucleosomes along DNA; nucleosome sliding requires ATP.
COL2A1	Collagen alpha-1(II) chain	Type II collagen is specific for cartilaginous tissues.
MED13L	Mediator of RNA polymerase II transcription subunit 13-like	Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.
CREBBP	CREB-binding protein	Acetylates histones, giving a specific tag for transcriptional activation.
CTSK	Cathepsin K	Thiol protease involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling.
PIEZO2	Piezo-type mechanosensitive ion channel component 2	Pore-forming subunit of the mechanosensitive non-specific cation Piezo channel required for rapidly adapting mechanically activated (MA) currents and has a key role in sensing touch and tactile pain.
TAPT1	Transmembrane anterior posterior transformation protein 1 homolog	Plays a role in primary cilia formation.
DDX11	ATP-dependent DNA helicase DDX11	DNA-dependent ATPase and ATP-dependent DNA helicase that participates in various functions in genomic stability, including DNA replication, DNA repair and heterochromatin organization as well as in ribosomal RNA synthesis.
SH3TC2	SH3 domain and tetratricopeptide repeat-containing protein 2	Is involved in nerve myelination and is required for the integrity of nodes of Ranvier.
EFEMP1	EGF-containing fibulin-like extracellular matrix protein 1	Binds EGFR, the EGF receptor, inducing EGFR autophosphorylation and the activation of downstream signaling pathways.
ESRRG	Estrogen-related receptor gamma	Orphan receptor that acts as a transcription activator in the absence of bound ligand.
FBN1	Fibrillin-1	Structural component of the 10-12 nm diameter microfibrils of the extracellular matrix, which conveys both structural and regulatory properties to load-bearing connective tissues.
FLNA	Filamin-A	Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins.
FXR1	RNA-binding protein FXR1	mRNA-binding protein that acts as a regulator of mRNAs translation and/or stability, and which is required for various processes, such as neurogenesis, muscle development and spermatogenesis.
GDF3	Growth/differentiation factor 3	Growth factor involved in early embryonic development and adipose-tissue homeostasis.
GFAP	Glial fibrillary acidic protein	GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells.
GRIN2B	Glutamate receptor ionotropic, NMDA 2B	Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+).
HARS1	Histidine–tRNA ligase, cytoplasmic	Catalyzes the ATP-dependent ligation of histidine to the 3’-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (His-AMP).
JAG1	Protein jagged-1	Ligand for multiple Notch receptors and involved in the mediation of Notch signaling.
ARF3	ADP-ribosylation factor 3	GTP-binding protein that functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase.
MYF5	Myogenic factor 5	Transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation.
PTPN11	Tyrosine-protein phosphatase non-receptor type 11	Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus.
RELN	Reelin	Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment.

Protein-family classification

Druggable: 10 · Difficult: 7 · Unknown: 19 · Druggable fraction: 0.28

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
Nuclear receptor	1	10.7×	0.693
Complement	1	7.4×	0.693
Ion channel	1	3.1×	0.785
Phosphatase	1	2.3×	0.785
Transcription factor	5	1.1×	0.785
Protease	1	1.0×	0.785
Enzyme (other)	3	1.0×	0.785
Scaffold/PPI	2	1.0×	0.785
Other/Unknown	19	0.9×	0.785
Antibody/Immunoglobulin	1	0.8×	0.785
GPCR	1	0.7×	0.785

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
POC5	Other/Unknown	no		POC5
RYR1	Ion channel	yes		RIH_dom, B30.2/SPRY, Ryanodine_rcpt
SLC9A6	Other/Unknown	no		NHE-6/7/9, NaH_exchanger, Cation/H_exchanger_TM
TBX6	Transcription factor	no		TF_T-box, TF_Brachyury, p53-like_TF_DNA-bd_sf
TRG-GCC2-6	Other/Unknown	no
NSDHL	Enzyme (other)	yes	1.1.1.170	3Beta_OHSteriod_DH/Estase, NAD(P)-bd_dom_sf, Lipid_A_modif_metabolic_enz
ADGRG6	GPCR	yes		GPS, GPCR_2_secretin-like, CUB_dom
NSD1	Transcription factor	no	2.1.1.357	PWWP_dom, SET_dom, Znf_PHD
CDRT15	Other/Unknown	no
KIF1B	Scaffold/PPI	no		FHA_dom, Kinesin_motor_dom, PH_domain
LBX1	Transcription factor	no		HTH_motif, HD, Homeodomain-like_sf
CHRNG	Other/Unknown	no		Nicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel
CHD7	Other/Unknown	no		SNF2_N, Chromo/chromo_shadow_dom, Helicase_C-like
COL2A1	Other/Unknown	no		Fib_collagen_C, VWF_dom, Collagen
MED13L	Other/Unknown	no		Med13_C, Mediator_Med13_N, MID_MedPIWI
FAM120AOS	Other/Unknown	no
CREBBP	Transcription factor	no	2.3.1.48	Znf_TAZ, Znf_ZZ, Bromodomain
CTSK	Protease	yes	3.4.22.38	Pept_cys_AS, Peptidase_C1A_C, Peptidase_C1A
PIEZO2	Other/Unknown	no		Piezo, Piezo_cap_dom, Piezo_TM25-28
TAPT1	Other/Unknown	no		Tatp1
DDX11	Enzyme (other)	yes	3.6.4.12	Helicase-like_DEXD_c2, ATP-dep_Helicase_C, RAD3-like_helicase_DEAD
SH3TC2	Scaffold/PPI	no		SH3_domain, TPR-like_helical_dom_sf, TPR_rpt
EFEMP1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
ESRRG	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
FBN1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
FLNA	Antibody/Immunoglobulin	yes		Filamin/ABP280_rpt, Actinin_actin-bd_CS, CH_dom
FXR1	Complement	yes		KH_dom, KH_dom_type_1, Agenet-like_dom
GDF3	Other/Unknown	no		TGF-b_C, TGF-beta-like, TGFb_CS
GFAP	Other/Unknown	no		Intermed_filament_DNA-bd, IF_conserved, IF_rod_dom
GRIN2B	Other/Unknown	no		Iontro_rcpt_C, Iono_Glu_rcpt_met, ANF_lig-bd_rcpt
HARS1	Enzyme (other)	yes	6.1.1.21	WHEP-TRS_dom, Anticodon-bd, HisRS/HisZ
JAG1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, VWF_dom
ARF3	Other/Unknown	no		Small_GTP-bd, Small_GTPase_ARF/SAR, Small_GTPase_ARF
MYF5	Transcription factor	no		MyoD_N, bHLH_dom, Myf5
PTPN11	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, SH2
RELN	Other/Unknown	no		EGF, Reeler_dom, EGF_extracell

Expression context

Cohort genes with no expression data: 1.

31 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)	35
unknown	1

Top tissues across cohort

Tissue	Cohort genes
gastrocnemius	5
sural nerve	5
hindlimb stylopod muscle	4
secondary oocyte	3
skin of hip	3
oocyte	2
primordial germ cell in gonad	2
lateral nuclear group of thalamus	2
pons	2
buccal mucosa cell	2
lower esophagus mucosa	2
amniotic fluid	2
calcaneal tendon	2
colonic epithelium	2
male germ line stem cell (sensu Vertebrata) in testis	2
biceps brachii	2
medial globus pallidus	2
muscle of leg	2
cerebellar vermis	2
tibia	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
POC5	224	ubiquitous	yes	secondary oocyte, oocyte, primordial germ cell in gonad
RYR1	214	broad	marker	gluteal muscle, gastrocnemius, hindlimb stylopod muscle
SLC9A6	286	ubiquitous	yes	lateral nuclear group of thalamus, middle temporal gyrus, pons
TBX6	166	tissue_specific	marker	lower esophagus mucosa, buccal mucosa cell, diaphragm
TRG-GCC2-6
NSDHL	271	ubiquitous	marker	cervix squamous epithelium, adrenal tissue, esophagus mucosa
ADGRG6	247	ubiquitous	marker	endometrium epithelium, amniotic fluid, placenta
NSD1	235	ubiquitous	marker	sural nerve, colonic epithelium, calcaneal tendon
CDRT15	127		yes	right testis, male germ line stem cell (sensu Vertebrata) in testis, left testis
KIF1B	287	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, biceps brachii, medial globus pallidus
LBX1	28		yes	gastrocnemius, muscle of leg, hindlimb stylopod muscle
CHRNG	54	tissue_specific	marker	pancreatic ductal cell, gastrocnemius, muscle of leg
CHD7	269	ubiquitous	marker	secondary oocyte, cerebellar vermis, sural nerve
COL2A1	145	broad	marker	tibia, cartilage tissue, corpus epididymis
MED13L	297	ubiquitous	marker	calcaneal tendon, colonic epithelium, tendon
FAM120AOS	256	ubiquitous	marker	cardiac muscle of right atrium, adenohypophysis, ileal mucosa
CREBBP	297	ubiquitous	marker	sural nerve, tibia, amniotic fluid
CTSK	254	ubiquitous	marker	periodontal ligament, stromal cell of endometrium, skin of hip
PIEZO2	237	broad	marker	sural nerve, corpus callosum, dorsal root ganglion
TAPT1	266	ubiquitous	marker	secondary oocyte, endothelial cell, oocyte
DDX11	201	ubiquitous	marker	lower esophagus mucosa, mucosa of transverse colon, body of pancreas
SH3TC2	168	broad	marker	corpus callosum, sural nerve, C1 segment of cervical spinal cord
EFEMP1	286	ubiquitous	marker	right coronary artery, thoracic aorta, descending thoracic aorta
ESRRG	250	broad	marker	pons, nephron tubule, endothelial cell
FBN1	275	ubiquitous	marker	synovial joint, skin of hip, decidua
FLNA	285	ubiquitous	marker	right coronary artery, popliteal artery, tibial artery
FXR1	299	ubiquitous	marker	sperm, hindlimb stylopod muscle, gastrocnemius
GDF3	82	tissue_specific	marker	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, type B pancreatic cell
GFAP	210	broad	marker	medulla oblongata, inferior olivary complex, dorsal motor nucleus of vagus nerve
GRIN2B	138	broad	marker	buccal mucosa cell, cortical plate, Brodmann (1909) area 23

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GFAP	6,997
CREBBP	6,959
PTPN11	6,009
FLNA	5,321
CHD7	4,819
JAG1	4,405
FXR1	4,128
FBN1	3,640
GRIN2B	3,611
NSDHL	3,566

Intra-cohort edges

A	B	Sources
ADGRG6	LBX1	string_interaction
FLNA	FXR1	intact

Structural data

PDB: 22 · AlphaFold-only: 13 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CREBBP	Q92793	144
PTPN11	Q06124	115
CTSK	P43235	70
ESRRG	P62508	43
GRIN2B	Q13224	36
FLNA	P21333	26
COL2A1	P02458	11
FBN1	P35555	11
HARS1	P12081	10
JAG1	P78504	7
NSD1	Q96L73	4
CHD7	Q9P2D1	3
FXR1	P51114	3
RYR1	P21817	2
NSDHL	Q15738	2
PIEZO2	Q9H5I5	2
ARF3	P61204	2
MYF5	P13349	2
ADGRG6	Q86SQ4	1
KIF1B	O60333	1
GFAP	P14136	1
RELN	P78509	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GDF3	Q9NR23	82.72
CHRNG	P07510	81.91
SH3TC2	Q8TF17	78.63
EFEMP1	Q12805	77.67
TAPT1	Q6NXT6	71.98
DDX11	Q96FC9	71.77
SLC9A6	Q92581	70.61
LBX1	P52954	68.61
TBX6	O95947	66.18
POC5	Q8NA72	65.76
MED13L	Q71F56	56.79
FAM120AOS	Q5T036	55.38
CDRT15	Q96T59	52.21

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 286. Enrichment computed across 36 evidence-associated genes (27 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 27 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RUNX3 regulates NOTCH signaling	2	60.4×	0.080	CREBBP, JAG1
Signaling by NOTCH3	2	38.5×	0.080	CREBBP, JAG1
Signaling by NOTCH4	2	36.8×	0.080	CREBBP, JAG1
Signaling by NOTCH1 PEST Domain Mutants in Cancer	2	30.2×	0.080	CREBBP, JAG1
Signaling by NOTCH1 in Cancer	2	30.2×	0.080	CREBBP, JAG1
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	2	30.2×	0.080	CREBBP, JAG1
Formation of paraxial mesoderm	2	30.2×	0.080	TBX6, CREBBP
Defective SLC9A6 causes X-linked, syndromic mental retardation,, Christianson type (MRXSCH)	1	423.0×	0.081	SLC9A6
Signaling by NOTCH1	2	26.4×	0.081	CREBBP, JAG1
Molecules associated with elastic fibres	2	22.9×	0.097	EFEMP1, FBN1
Transcriptional regulation by RUNX3	2	20.1×	0.114	CREBBP, JAG1
Gastrulation	2	19.2×	0.114	TBX6, CREBBP
Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	1	105.7×	0.121	JAG1
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production	1	84.6×	0.121	CREBBP
MET activates PTPN11	1	84.6×	0.121	PTPN11
NFE2L2 regulating inflammation associated genes	1	84.6×	0.121	CREBBP
NFE2L2 regulating ER-stress associated genes	1	84.6×	0.121	CREBBP
Co-inhibition by BTLA	1	84.6×	0.121	PTPN11
Reelin signalling pathway	1	70.5×	0.121	RELN
Activated NTRK2 signals through FYN	1	70.5×	0.121	GRIN2B
Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	1	60.4×	0.121	JAG1
Highly sodium permeable postsynaptic acetylcholine nicotinic receptors	1	60.4×	0.121	CHRNG
STAT5 Activation	1	60.4×	0.121	PTPN11
RUNX1 regulates transcription of genes involved in differentiation of myeloid cells	1	52.9×	0.121	CREBBP
NFE2L2 regulates pentose phosphate pathway genes	1	52.9×	0.121	CREBBP
NFE2L2 regulating MDR associated enzymes	1	52.9×	0.121	CREBBP
Regulation of NFE2L2 gene expression	1	52.9×	0.121	CREBBP
Signaling by NOTCH1 HD Domain Mutants in Cancer	1	47.0×	0.121	JAG1
Netrin mediated repulsion signals	1	47.0×	0.121	PTPN11
Sodium/Proton exchangers	1	47.0×	0.121	SLC9A6

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 33 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
post-embryonic eye morphogenesis	2	340.4×	0.005	EFEMP1, FBN1
negative regulation of transcription by RNA polymerase I	2	145.9×	0.009	CREBBP, FLNA
notochord development	2	102.1×	0.009	COL2A1, GDF3
genitalia development	2	102.1×	0.009	CHD7, PTPN11
somite rostral/caudal axis specification	2	92.8×	0.009	TBX6, GDF3
atrioventricular canal development	2	92.8×	0.009	CHD7, PTPN11
embryonic eye morphogenesis	2	92.8×	0.009	EFEMP1, FBN1
Bergmann glial cell differentiation	2	92.8×	0.009	GFAP, PTPN11
camera-type eye development	3	32.6×	0.009	EFEMP1, FBN1, MYF5
long-term synaptic potentiation	3	25.5×	0.009	GFAP, GRIN2B, RELN
skeletal system development	4	15.2×	0.009	CHD7, COL2A1, FBN1, GDF3
cartilage development	3	22.9×	0.011	ADGRG6, COL2A1, TAPT1
cardiac septum morphogenesis	2	73.0×	0.012	CHD7, JAG1
aorta morphogenesis	2	53.8×	0.020	CHD7, JAG1
right ventricular compact myocardium morphogenesis	1	510.7×	0.024	CHD7
positive regulation of Schwann cell proliferation	1	510.7×	0.024	GFAP
spinal cord patterning	1	510.7×	0.024	RELN
spinal cord association neuron specification	1	510.7×	0.024	LBX1
regulation of peptidyl-serine phosphorylation	1	510.7×	0.024	NSD1
negative regulation of cortisol secretion	1	510.7×	0.024	PTPN11
negative regulation of growth hormone secretion	1	510.7×	0.024	PTPN11
endocardial cushion cell development	1	510.7×	0.024	JAG1
negative regulation of glutamatergic neuron differentiation	1	510.7×	0.024	LBX1
regulation of ERBB signaling pathway	1	510.7×	0.024	SH3TC2
positive regulation of lateral motor column neuron migration	1	510.7×	0.024	RELN
regulation of RNA polymerase II regulatory region sequence-specific DNA binding	1	510.7×	0.024	NSD1
regulation of membrane repolarization during atrial cardiac muscle cell action potential	1	510.7×	0.024	FLNA
regulation of membrane repolarization during cardiac muscle cell action potential	1	510.7×	0.024	FLNA
glutamatergic neuron differentiation	1	510.7×	0.024	LBX1
cartilage condensation	2	46.4×	0.024	COL2A1, MYF5

Therapeutics

Drugs indicated for this disease

0 approved, 9 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Acetaminophen	Phase 3 (in late-stage trials)
Clonidine	Phase 3 (in late-stage trials)
Epoetin Beta	Phase 3 (in late-stage trials)
Gabapentin	Phase 3 (in late-stage trials)
Lidocaine	Phase 3 (in late-stage trials)
Methadone	Phase 3 (in late-stage trials)
Morphine	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Tranexamic Acid	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Alfacalcidol, Clevidipine, Fentanyl, Ketorolac, Meperidine, Onabotulinumtoxina.

Drug target analysis

Approved (phase 4): 7 · Phase ≥3: 7 · Phased (≥1): 8 · Undrugged: 28

Druggability breadth: 15 of 36 evidence-associated genes (42%) 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
NSD1	VENETOCLAX
CHRNG	VARENICLINE
CREBBP	COLCHICINE
CTSK	BOCEPREVIR
ESRRG	DIETHYLSTILBESTROL
GRIN2B	HALOPERIDOL
PTPN11	ESTRAMUSTINE PHOSPHATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GRIN2B	35	4
CREBBP	13	4
CHRNG	10	4
CTSK	8	4
PTPN11	8	4
NSD1	7	4
ESRRG	2	4
FLNA	1	2
POC5	0	0
RYR1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VENETOCLAX	4	NSD1
PRIMAQUINE	4	NSD1
CHLOROQUINE PHOSPHATE	4	NSD1
VARENICLINE	4	CHRNG
NICOTINE	4	CHRNG
TROPISETRON	4	CHRNG
BUPROPION	4	CHRNG
MECAMYLAMINE	4	CHRNG
COLCHICINE	4	CREBBP
ALTRETAMINE	4	CREBBP
BOCEPREVIR	4	CTSK
TELAPREVIR	4	CTSK
NIRMATRELVIR	4	CTSK
DIETHYLSTILBESTROL	4	ESRRG
TAMOXIFEN	4	ESRRG
HALOPERIDOL	4	GRIN2B
DEXTROMETHORPHAN	4	GRIN2B
KETAMINE	4	GRIN2B
CYCLOSERINE	4	GRIN2B
MEMANTINE	4	GRIN2B
TACRINE	4	GRIN2B
LEVORPHANOL	4	GRIN2B
AMANTADINE	4	GRIN2B
CHLORPROMAZINE	4	GRIN2B
PROCYCLIDINE	4	GRIN2B
ORPHENADRINE	4	GRIN2B
ESTRAMUSTINE PHOSPHATE	4	PTPN11
SURAMIN	3	NSD1
DEXMECAMYLAMINE	3	CHRNG
CYTISINICLINE	3	CHRNG

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

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

Symbol	Assays	Type breakdown
CREBBP	687	Binding:644, Functional:43
PTPN11	588	Binding:585, Functional:2, ADMET:1
GRIN2B	471	Binding:429, Functional:36, ADMET:5, Toxicity:1
CTSK	376	Binding:365, ADMET:5, Toxicity:5, Functional:1
ESRRG	135	Binding:121, Functional:13, ADMET:1
NSD1	90	Binding:90
CHRNG	67	Binding:36, Functional:31
RYR1	16	Binding:13, Functional:3
FLNA	7	Binding:7
FXR1	6	Binding:6
HARS1	5	Binding:5
ADGRG6	2	Binding:2
COL2A1	2	Binding:2
KIF1B	1	Binding:1
JAG1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
NSDHL	1.1.1.170	3beta-hydroxysteroid-4alpha-carboxylate 3-dehydrogenase (decarboxylating)
NSD1	2.1.1.357, 2.1.1.362	[histone H3]-lysine36 N-dimethyltransferase, [histone H4]-N-methyl-L-lysine20 N-methyltransferase
CREBBP	2.3.1.48	histone acetyltransferase
CTSK	3.4.22.38	cathepsin K
DDX11	3.6.4.12, 3.6.4.13	DNA helicase, RNA helicase
HARS1	6.1.1.21	histidine-tRNA ligase
PTPN11	3.1.3.48	protein-tyrosine-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CREBBP	687
CTSK	376
ESRRG	135
GRIN2B	471
PTPN11	588

Pharmacogenomics

Cohort genes with a PharmGKB record: 35; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
RYR1	1

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)
VENETOCLAX	4	NSD1
PRIMAQUINE	4	NSD1
CHLOROQUINE PHOSPHATE	4	NSD1
VARENICLINE	4	CHRNG
NICOTINE	4	CHRNG
TROPISETRON	4	CHRNG
BUPROPION	4	CHRNG
MECAMYLAMINE	4	CHRNG
COLCHICINE	4	CREBBP
ALTRETAMINE	4	CREBBP
BOCEPREVIR	4	CTSK
TELAPREVIR	4	CTSK
NIRMATRELVIR	4	CTSK
DIETHYLSTILBESTROL	4	ESRRG
TAMOXIFEN	4	ESRRG
HALOPERIDOL	4	GRIN2B
DEXTROMETHORPHAN	4	GRIN2B
KETAMINE	4	GRIN2B
CYCLOSERINE	4	GRIN2B
MEMANTINE	4	GRIN2B
TACRINE	4	GRIN2B
LEVORPHANOL	4	GRIN2B
AMANTADINE	4	GRIN2B
CHLORPROMAZINE	4	GRIN2B
PROCYCLIDINE	4	GRIN2B
ORPHENADRINE	4	GRIN2B
ESTRAMUSTINE PHOSPHATE	4	PTPN11
SURAMIN	3	NSD1
DEXMECAMYLAMINE	3	CHRNG
CYTISINICLINE	3	CHRNG

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	7	NSD1, CHRNG, CREBBP, CTSK, ESRRG, GRIN2B, PTPN11
B	Phased (≥1) drug, not yet approved	1	FLNA
C	Druggable family + PDB, no drug	5	RYR1, NSDHL, ADGRG6, FXR1, HARS1
D	Druggable family + AlphaFold only, no drug	1	DDX11
E	Difficult family or no structure, no drug	22	POC5, SLC9A6, TBX6, TRG-GCC2-6, CDRT15, KIF1B, LBX1, CHD7, COL2A1, MED13L (+12 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
POC5	0	—
RYR1	16	—
SLC9A6	0	—
TBX6	0	—
TRG-GCC2-6	0	—
NSDHL	0	—
ADGRG6	2	—
CDRT15	0	—
KIF1B	1	—
LBX1	0	—
CHD7	0	—
COL2A1	2	—
MED13L	0	—
FAM120AOS	0	—
PIEZO2	0	—
TAPT1	0	—
DDX11	0	—
SH3TC2	0	—
EFEMP1	0	—
FBN1	0	—
FXR1	6	—
GDF3	0	—
GFAP	0	—
HARS1	5	—
JAG1	1	—
ARF3	0	—
MYF5	0	—
RELN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 205.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	180
PHASE4	11
PHASE3	8
PHASE1	4
PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06540885	PHASE4	RECRUITING	A Comparison Between Palonosetron Versus Granisetron as PONV Prophylaxis in Scoliotic Patients Undergoing Spine Surgery
NCT00508066	PHASE4	COMPLETED	Continuous Local Infusion of Anesthetic at the Incisional Site for Scoliosis Surgery
NCT00510575	PHASE4	COMPLETED	Surgical Outcomes Using Variable Rod Diameters in the Treatment of Idiopathic Scoliosis
NCT00768313	PHASE4	WITHDRAWN	Phase IV Comparing Rods of Yield Strengths to Correct Adolescent Idiopathic Scoliosis.
NCT00880607	PHASE4	COMPLETED	Intrathecal Morphine Versus Epidural Extended Release Morphine for Pediatric Patients Undergoing Spinal Fusion
NCT00958581	PHASE4	COMPLETED	Tranexamic Acid (TXA) Versus Epsilon Aminocaproic Acid (EACA) Versus Placebo for Spine Surgery
NCT01852747	PHASE4	TERMINATED	Comparison of Actifuse ABX and Local Bone in Spinal Surgery
NCT02464813	PHASE4	COMPLETED	Effect of Pregabalin on Immediate Post-operative and Longterm Pain
NCT02465099	PHASE4	TERMINATED	Posterior Spinal Fusion With Two Energy Dissection Techniques
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
NCT00323752	PHASE3	COMPLETED	Recombinant Human Erythropoietin Compared to Autologous Pre-Donation Prior to Scoliosis Surgery in Children.
NCT00684112	PHASE3	COMPLETED	Analgesic Effects of Gabapentin After Scoliosis Surgery in Children
NCT00737997	PHASE3	COMPLETED	Effect of Early Morphine Administration on the Development of Acute Opioid Tolerance During Pediatric Scoliosis Surgery
NCT01103115	PHASE3	COMPLETED	Calcium + Vitamin D Supplementation for Low Bone Mass in Adolescent Idiopathic Scoliosis (AIS)
NCT01108211	PHASE3	COMPLETED	Improving Low Bone Mass With Vibration Therapy in Adolescent Idiopathic Scoliosis (AIS)
NCT01205256	PHASE3	COMPLETED	IRB-HSR# 14145 R,S Methadone: Analgesia and Pharmacokinetics in Adolescents Undergoing Scoliosis Correction
NCT02558010	PHASE3	COMPLETED	Perioperative Methadone Use to Decrease Opioid Requirement in Pediatric Spinal Fusion Patients
NCT03537612	PHASE3	TERMINATED	Sensorial and Physiological Mechanism-based Assessments of Perioperative Pain
NCT00273598	PHASE2	COMPLETED	Comparing Two Instrumentation Systems for the Treatment of Adolescent Scoliosis
NCT01148888	PHASE2	COMPLETED	The Effect of Magnesium Sulfate on Motor and Somatosensory Evoked Potentials in Children Undergoing Scoliosis Surgery
NCT00154505	PHASE1	COMPLETED	Effects of Lateral Trunk Support on Spinal Alignment in Spinal Cord Injured Persons
NCT00155545	PHASE1	COMPLETED	Influence of Leg Length Discrepancy on the Spinal Shape and Biomechanics in Functional and Idiopathic Scoliosis Patients
NCT00671931	PHASE1	COMPLETED	Susceptibility of Motor-Evoked Potentials to Varying Targeted Blood Levels of Dexmedetomidine
NCT01677650	PHASE1	WITHDRAWN	Pharmacogenomics of Methadone in Spine Fusion Surgery
NCT00411060	Not specified	RECRUITING	Clinical Orthopaedic Data Bank (Acute and Chronic)
NCT02434003	Not specified	RECRUITING	Prospective Multicenter Evaluation of a New Predictive Model for the Progression of Adolescent Idiopathic Scoliosis
NCT02589106	Not specified	RECRUITING	Anisotropic Textile Braces for Adolescent Idiopathic Scoliosis
NCT02610855	Not specified	ENROLLING_BY_INVITATION	Effect of Treatment on Activity and Muscle Function in Pediatric Patients With Scoliosis
NCT02998138	Not specified	ACTIVE_NOT_RECRUITING	Postoperative and Chronic Pain Genetic Spine Surgery Study
NCT03107533	Not specified	RECRUITING	Scoliosis Shared Decision Making
NCT03330158	Not specified	ACTIVE_NOT_RECRUITING	Clinical Assessment of a Motorized Spinal Distraction Rod in the Severe to Early Scoliosis Child
NCT03332251	Not specified	RECRUITING	Trial of Posture Correction Girdle for Adolescents With Early Scoliosis
NCT03506334	Not specified	ENROLLING_BY_INVITATION	Anterior Vertebral Body Tethering (AVBT) Using Zimmer Biomet Tether System or Dynesys System Components to Treat Pediatric Scoliosis
NCT04081896	Not specified	RECRUITING	Evaluation of the Effects of a Rehabilitation Program in Individuals with Spine Pain
NCT04116723	Not specified	RECRUITING	Trial of Flexible Bracing Treatment of Adolescents Idiopathic Scoliosis
NCT04194138	Not specified	RECRUITING	Complex Adult Deformity Surgery (CADS)
NCT04885244	Not specified	RECRUITING	Prospective Evaluation of Complex Adult Spinal Deformity (CAD) Treated With Minimally Invasive Surgery
NCT04888104	Not specified	RECRUITING	Prospective, Multicenter, Case-Control Analysis of the VersaTie Posterior Fixation System to Prevent Proximal Junctional Failure in Long Posterior Spinal Fusion Constructs for Adult Patients
NCT04904627	Not specified	RECRUITING	Constructive Variations of Classic Orthopedic Braces for Spinal Deformity During Growth

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CLONIDINE	4	2
METHADONE	4	2
SODIUM CHLORIDE	4	2
BUPIVACAINE	4	1
HYDROXYETHYL STARCH 130/0.4	4	1
MORPHINE	4	1
OXYCODONE	4	1
PREGABALIN	4	1
TRANEXAMIC ACID	4	1
MAGNESIUM	3	1
CHEMBL4589226	0	1