Spondylosis

Summary

Spondylosis (MONDO:0002253) is a disease with 18 cohort genes (53 GWAS associations across 49 studies) and 37 clinical trials. Top therapeutic interventions include dibotermin alfa and sodium chloride.

At a glance

• Cohort genes: 18
• GWAS associations: 53
• Clinical trials: 37

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	spondylosis
Mondo ID	MONDO:0002253
MeSH	D055009
DOID	DOID:2247
ICD-10-CM	M47
SNOMED CT	48210000
UMLS	C0038019
MedGen	21295
Is cancer (heuristic)	no

Data availability: 53 GWAS associations (49 studies).

Disease family

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

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

Genetics & variants

GWAS landscape

53 GWAS associations across 49 studies. Top hits map to 20 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs146683910	3e-228	HLA-B - RNU6-283P	?
chr7:114091844	4e-12		C	0.04
chr12:23936398	6e-12		G	0.06
chr15:67338780	2e-11		C	0.04
rs10808583	4e-11	CCDC26	G	0.05
rs2054564	2e-10	ADAMTS17	C	1.71
rs12190551	9e-09	BMP6	C	1.03
chr5:112929796	9e-09		G	0.05
chr20:58891038	9e-09		T	0.14
chr6:34687698	1e-08		CA	0.05
chr5:53594872	1e-08		TTGTTTG	2.13
chr7:54391636	2e-08		A	2.55
chr1:38950098	2e-08		A	0.13
chr14:54779976	2e-08		T	0.36
rs290680	3e-08	LINC02852 - LETR1	G	1.18
chr3:54316430	3e-08		T	0.51
chr4:101975434	3e-08		G	0.08
chr16:30303532	3e-08		G	2.29
chr18:23527589	3e-08		CT	0.04
chr7:114399396	4e-08		C	0.04
rs151021536	5e-08	DEPDC1-AS1 - LINC01707	T	1.94
chr3:59478321	5e-08		A	2.17
chr3:50132282	5e-08		T	0.04
rs7131902	9e-08	CNTN1	?
rs74730948	3e-07	PTPRD	?
rs12499841	4e-07	CNGA1, NIPAL1	G	1.03
rs72649149	9e-07	RPS4XP4 - FAM43B	T	0.97
rs77092580	1e-06	ATXN7L3B - KCNC2	G	0.92
rs116974427	2e-06	RFC5P1 - VPS13A-AS1	A	1.1
rs4492265	2e-06	RBMX2P4 - ETV1	A	0.97

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90476235	Verma A	2024	62,366	345,762	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90476236	Verma A	2024	57,675	351,353	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90474069	UK Biobank Whole-Genome Sequencing Consortium	2025	34,707	423,733	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90667804	UK Biobank Whole-Genome Sequencing Consortium	2025	34,707	423,733	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90478891	Verma A	2024	19,864	89,239	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480509	Verma A	2024	19,864	89,239	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90478894	Verma A	2024	18,090	91,172	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481009	Verma A	2024	18,090	91,172	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90080486	Backman JD	2021	13,192	364,110	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084472	Backman JD	2021	13,192	364,110	Exome sequencing and analysis of 454,787 UK Biobank participants.

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	49

MAF distribution

Bucket	Variants
common (>=0.05)	34
low_freq (0.01-0.05)	1
rare (<0.01)	0
unknown	15

Functional consequences

Consequence	Count
intron_variant	22
unknown	18
intergenic_variant	9
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs146683910	6	31368220	C>T	0.05	intron_variant	HLA-B - RNU6-283P	3e-228	Tier 4: intronic/intergenic
chr7:114091844				0.439			4e-12	Tier 4: intronic/intergenic
chr12:23936398				0.149			6e-12	Tier 4: intronic/intergenic
chr15:67338780				0.48			2e-11	Tier 4: intronic/intergenic
rs10808583	8	129705774	G>A	0.324	intergenic_variant	CCDC26	4e-11	Tier 4: intronic/intergenic
rs2054564	15	100209085	C>A,T	0.323	intron_variant	ADAMTS17	2e-10	Tier 4: intronic/intergenic
rs12190551	6	7805683	G>A,C	0.05	intron_variant	BMP6	9e-09	Tier 4: intronic/intergenic
chr5:112929796							9e-09	Tier 4: intronic/intergenic
chr20:58891038							9e-09	Tier 4: intronic/intergenic
chr6:34687698							1e-08	Tier 4: intronic/intergenic
chr5:53594872							1e-08	Tier 4: intronic/intergenic
chr7:54391636							2e-08	Tier 4: intronic/intergenic
chr1:38950098							2e-08	Tier 4: intronic/intergenic
chr14:54779976							2e-08	Tier 4: intronic/intergenic
rs290680	15	95152580	A>G	0.465	intergenic_variant	LINC02852 - LETR1	3e-08	Tier 4: intronic/intergenic
chr3:54316430							3e-08	Tier 4: intronic/intergenic
chr4:101975434							3e-08	Tier 4: intronic/intergenic
chr16:30303532							3e-08	Tier 4: intronic/intergenic
chr18:23527589							3e-08	Tier 4: intronic/intergenic
chr7:114399396							4e-08	Tier 4: intronic/intergenic
rs151021536	1	68772152	C>T	0.02	intron_variant	DEPDC1-AS1 - LINC01707	5e-08	Tier 4: intronic/intergenic
chr3:59478321							5e-08	Tier 4: intronic/intergenic
chr3:50132282							5e-08	Tier 4: intronic/intergenic
rs7131902	12	40752848	C>T	0.05	intron_variant	CNTN1	9e-08	Tier 4: intronic/intergenic
rs74730948	9	9271338	T>C	0.05	intron_variant	PTPRD	3e-07	Tier 4: intronic/intergenic
rs12499841	4	47961721	G>A,C	0.05	intron_variant	CNGA1, NIPAL1	4e-07	Tier 4: intronic/intergenic
rs72649149	1	20548689	C>A,T	0.05	intergenic_variant	RPS4XP4 - FAM43B	9e-07	Tier 4: intronic/intergenic
rs77092580	12	74871649	A>G	0.05	intergenic_variant	ATXN7L3B - KCNC2	1e-06	Tier 4: intronic/intergenic
rs116974427	9	77167719	G>A,T	0.05	regulatory_region_variant	RFC5P1 - VPS13A-AS1	2e-06	Tier 3: regulatory
rs4492265	7	13484058	A>G	0.05	intron_variant	RBMX2P4 - ETV1	2e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 10 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BMP6	Orphanet:465508	Symptomatic form of HFE-related hemochromatosis
XYLT1	Orphanet:1425	Desbuquois syndrome
XYLT1	Orphanet:370930	XYLT1-CDG
SUMF1	Orphanet:585	Multiple sulfatase deficiency
CNGA1	Orphanet:791	Retinitis pigmentosa
DOK7	Orphanet:98913	Postsynaptic congenital myasthenic syndrome
DOK7	Orphanet:994	Fetal akinesia deformation sequence
IQSEC1	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability
AP2S1	Orphanet:101050	Familial hypocalciuric hypercalcemia type 3
IL1RN	Orphanet:210115	Sterile multifocal osteomyelitis with periostitis and pustulosis

Cohort genes → proteins

18 cohort genes, 16 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	18

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BMP6	HGNC:1073	ENSG00000153162	P22004	Bone morphogenetic protein 6	gwas
SETMAR	HGNC:10762	ENSG00000170364	Q53H47	Histone-lysine N-methyltransferase SETMAR	gwas
XYLT1	HGNC:15516	ENSG00000103489	Q86Y38	Xylosyltransferase 1	gwas
SUMF1	HGNC:20376	ENSG00000144455	Q8NBK3	Formylglycine-generating enzyme	gwas
CNGA1	HGNC:2148	ENSG00000198515	P29973	Cyclic nucleotide-gated channel alpha-1	gwas
UNC13C	HGNC:23149	ENSG00000137766	Q8NB66	Protein unc-13 homolog C	gwas
DYTN	HGNC:23279	ENSG00000232125	A2CJ06	Dystrotelin	gwas
PHF21B	HGNC:25161	ENSG00000056487	Q96EK2	PHD finger protein 21B	gwas
DOK7	HGNC:26594	ENSG00000175920	Q18PE1	Protein Dok-7	gwas
DACH1	HGNC:2663	ENSG00000276644	Q9UI36	Dachshund homolog 1	gwas
NIPAL1	HGNC:27194	ENSG00000163293	Q6NVV3	Magnesium transporter NIPA3	gwas
IQSEC1	HGNC:29112	ENSG00000144711	Q6DN90	IQ motif and SEC7 domain-containing protein 1	gwas
FAM43B	HGNC:31791	ENSG00000183114	Q6ZT52	Protein FAM43B	gwas
MIR920	HGNC:33670	ENSG00000216192		microRNA 920	gwas
NALF1	HGNC:33877	ENSG00000204442	B1AL88	NALCN channel auxiliary factor 1	gwas
VPS13A-AS1	HGNC:44167	ENSG00000232998		VPS13A antisense RNA 1	gwas
AP2S1	HGNC:565	ENSG00000042753	P53680	AP-2 complex subunit sigma	gwas
IL1RN	HGNC:6000	ENSG00000136689	P18510	Interleukin-1 receptor antagonist protein	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BMP6	Bone morphogenetic protein 6	Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes including cartilage and bone formation.
SETMAR	Histone-lysine N-methyltransferase SETMAR	Protein derived from the fusion of a methylase with the transposase of an Hsmar1 transposon that plays a role in DNA double-strand break repair, stalled replication fork restart and DNA integration.
XYLT1	Xylosyltransferase 1	Catalyzes the first step in the biosynthesis of chondroitin sulfate and dermatan sulfate proteoglycans, such as DCN.
SUMF1	Formylglycine-generating enzyme	Oxidase that catalyzes the conversion of cysteine to 3-oxoalanine on target proteins, using molecular oxygen and an unidentified reducing agent. 3-oxoalanine modification, which is also named formylglycine (fGly), occurs in the maturation…
CNGA1	Cyclic nucleotide-gated channel alpha-1	Pore-forming subunit of the rod cyclic nucleotide-gated channel.
UNC13C	Protein unc-13 homolog C	May play a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway.
DOK7	Protein Dok-7	Probable muscle-intrinsic activator of MUSK that plays an essential role in neuromuscular synaptogenesis.
DACH1	Dachshund homolog 1	Transcription factor that is involved in regulation of organogenesis.
NIPAL1	Magnesium transporter NIPA3	Acts as a Mg(2+) transporter.
IQSEC1	IQ motif and SEC7 domain-containing protein 1	Guanine nucleotide exchange factor for ARF1 and ARF6.
NALF1	NALCN channel auxiliary factor 1	Auxillary component of the NALCN sodium channel complex, a channel that regulates the resting membrane potential and controls neuronal excitability.
AP2S1	AP-2 complex subunit sigma	Component of the adaptor protein complex 2 (AP-2).
IL1RN	Interleukin-1 receptor antagonist protein	Anti-inflammatory antagonist of interleukin-1 family of proinflammatory cytokines such as interleukin-1beta/IL1B and interleukin-1alpha/IL1A.

Protein-family classification

Druggable: 4 · Difficult: 4 · Unknown: 10 · Druggable fraction: 0.22

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
Ion channel	1	6.2×	0.659
Scaffold/PPI	2	1.9×	0.659
Kinase	1	1.5×	0.659
Enzyme (other)	2	1.3×	0.659
Other/Unknown	10	1.0×	0.659
Transcription factor	2	0.9×	0.659

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BMP6	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGF-beta-like
SETMAR	Enzyme (other)	yes	2.1.1.357	SET_dom, Transposase_1, Post-SET_dom
XYLT1	Enzyme (other)	yes	2.4.2.26	Glyco_trans_14, XylT_C, XYLT
SUMF1	Kinase	yes	1.8.3.7	SUMF_dom, CTDL_fold, SUMF_sf
CNGA1	Ion channel	yes		cNMP-bd_dom, Ion_trans_dom, RmlC-like_jellyroll
UNC13C	Other/Unknown	no		C2_dom, PKC_DAG/PE, MUN_dom
DYTN	Transcription factor	no		Znf_ZZ, EF-hand-dom_pair, EF-hand_dom_typ1
PHF21B	Transcription factor	no		Znf_PHD, Znf_FYVE_PHD, Znf_RING/FYVE/PHD
DOK7	Scaffold/PPI	no		PH_domain, IRS_PTB, PH-like_dom_sf
DACH1	Other/Unknown	no		SKI/SNO/DAC, DNA-bd_dom_put_sf, Ski_DNA-bd_sf
NIPAL1	Other/Unknown	no		Mg_trans_NIPA, EmrE-like
IQSEC1	Scaffold/PPI	no		Sec7_dom, PH_domain, PH-like_dom_sf
FAM43B	Other/Unknown	no		PTB/PI_dom, PH-like_dom_sf, FAM43A/B_PTB
MIR920	Other/Unknown	no
NALF1	Other/Unknown	no		NALCN_aux_factor_1/2
VPS13A-AS1	Other/Unknown	no
AP2S1	Other/Unknown	no		Clathrin_sm-chain_CS, Longin-like_dom_sf, AP_complex_ssu
IL1RN	Other/Unknown	no		IL-1_fam, IL-1RA/IL-36, IL1/FGF

Expression context

Cohort genes with no expression data: 0.

14 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)	1
broad (>20)	17
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lower esophagus mucosa	3
endothelial cell	3
buccal mucosa cell	3
cartilage tissue	2
oocyte	2
secondary oocyte	2
upper arm skin	2
ganglionic eminence	2
right adrenal gland	2
body of uterus	1
popliteal artery	1
tibial artery	1
hair follicle	1
tibia	1
kidney epithelium	1
renal medulla	1
amniotic fluid	1
right lobe of liver	1
leukocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BMP6	197	ubiquitous	marker	secondary oocyte, cartilage tissue, oocyte
SETMAR	250	ubiquitous	marker	body of uterus, popliteal artery, tibial artery
XYLT1	272	broad	marker	tibia, cartilage tissue, hair follicle
SUMF1	258	ubiquitous	marker	kidney epithelium, renal medulla, upper arm skin
CNGA1	182	broad	marker	lower esophagus mucosa, amniotic fluid, right lobe of liver
UNC13C	174	broad	marker	secondary oocyte, oocyte, endothelial cell
DYTN	15		marker	primordial germ cell in gonad, monocyte, leukocyte
PHF21B	152	broad	marker	ganglionic eminence, adenohypophysis, pituitary gland
DOK7	180	broad	yes	apex of heart, tibialis anterior, right atrium auricular region
DACH1	235	broad	marker	ventricular zone, endothelial cell, ganglionic eminence
NIPAL1	192	broad	marker	buccal mucosa cell, upper arm skin, rectum
IQSEC1	286	ubiquitous	marker	Brodmann (1909) area 46, postcentral gyrus, parietal lobe
FAM43B	154	broad	yes	right adrenal gland cortex, right adrenal gland, left adrenal gland cortex
MIR920	77		yes	calcaneal tendon, muscle of leg, adult mammalian kidney
NALF1	187	broad	marker	endothelial cell, Brodmann (1909) area 23, buccal mucosa cell
VPS13A-AS1	61	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, tendon of biceps brachii, left testis
AP2S1	299	ubiquitous	marker	lower esophagus mucosa, stromal cell of endometrium, right adrenal gland
IL1RN	220	broad	marker	lower esophagus mucosa, buccal mucosa cell, palpebral conjunctiva

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IL1RN	2,550
AP2S1	2,185
SETMAR	1,942
BMP6	1,739
SUMF1	1,541
DACH1	1,366
PHF21B	1,272
UNC13C	1,239
CNGA1	1,181
IQSEC1	1,117

Intra-cohort edges

A	B	Sources
SETMAR	SUMF1	string_interaction

Structural data

PDB: 10 · AlphaFold-only: 6 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CNGA1	P29973	19
SUMF1	Q8NBK3	18
XYLT1	Q86Y38	9
IQSEC1	Q6DN90	6
BMP6	P22004	5
SETMAR	Q53H47	5
NALF1	B1AL88	5
IL1RN	P18510	5
DACH1	Q9UI36	1
AP2S1	P53680	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NIPAL1	Q6NVV3	80.98
FAM43B	Q6ZT52	69.91
DYTN	A2CJ06	69.89
DOK7	Q18PE1	65.61
UNC13C	Q8NB66	61.64
PHF21B	Q96EK2	60.69

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 57. Enrichment computed across 18 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Nef Mediated CD8 Down-regulation	1	271.9×	0.049	AP2S1
Nef Mediated CD4 Down-regulation	1	211.5×	0.049	AP2S1
Activation of the phototransduction cascade	1	158.6×	0.049	CNGA1
The activation of arylsulfatases	1	146.4×	0.049	SUMF1
WNT5A-dependent internalization of FZD2, FZD5 and ROR2	1	146.4×	0.049	AP2S1
Retrograde neurotrophin signalling	1	135.9×	0.049	AP2S1
WNT5A-dependent internalization of FZD4	1	126.9×	0.049	AP2S1
VLDLR internalisation and degradation	1	119.0×	0.049	AP2S1
Trafficking of GluR2-containing AMPA receptors	1	112.0×	0.049	AP2S1
Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters	1	105.7×	0.049	AP2S1
The role of Nef in HIV-1 replication and disease pathogenesis	1	105.7×	0.049	AP2S1
LDL clearance	1	90.6×	0.052	AP2S1
Plasma lipoprotein clearance	1	79.3×	0.053	AP2S1
Miscellaneous transport and binding events	1	73.2×	0.053	NIPAL1
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	1	70.5×	0.053	SUMF1
Glycosaminoglycan-protein linkage region biosynthesis	1	65.6×	0.053	XYLT1
Host Interactions of HIV factors	1	56.0×	0.053	AP2S1
Inactivation, recovery and regulation of the phototransduction cascade	1	52.9×	0.053	CNGA1
Glycosphingolipid metabolism	1	50.1×	0.053	SUMF1
PCP/CE pathway	1	50.1×	0.053	AP2S1
Beta-catenin independent WNT signaling	1	48.8×	0.053	AP2S1
Glycosphingolipid catabolism	1	48.8×	0.053	SUMF1
Dengue Virus Attachment and Entry	1	43.3×	0.057	AP2S1
Interleukin-10 signaling	1	38.8×	0.057	IL1RN
Plasma lipoprotein assembly, remodeling, and clearance	1	38.1×	0.057	AP2S1
Recycling pathway of L1	1	37.3×	0.057	AP2S1
EPH-ephrin mediated repulsion of cells	1	36.6×	0.057	AP2S1
Signaling by NTRK1 (TRKA)	1	32.8×	0.061	AP2S1
Signaling by NTRKs	1	30.2×	0.064	AP2S1
Sphingolipid metabolism	1	28.0×	0.066	SUMF1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 14 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mitotic DNA integrity checkpoint signaling	1	1203.7×	0.032	SETMAR
negative regulation of chromosome organization	1	1203.7×	0.032	SETMAR
negative regulation of adherens junction organization	1	601.9×	0.032	BMP6
protein oxidation	1	401.2×	0.032	SUMF1
positive regulation of aldosterone biosynthetic process	1	401.2×	0.032	BMP6
dense core granule priming	1	401.2×	0.032	UNC13C
positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity	1	401.2×	0.032	SETMAR
development of primary female sexual characteristics	1	300.9×	0.032	DACH1
negative regulation of cell proliferation involved in contact inhibition	1	300.9×	0.032	DACH1
glycosaminoglycan-protein linkage region biosynthetic process	1	300.9×	0.032	XYLT1
positive regulation of aldosterone secretion	1	300.9×	0.032	BMP6
negative regulation of synaptic plasticity	1	240.7×	0.032	UNC13C
regulation of nuclear cell cycle DNA replication	1	240.7×	0.032	DACH1
nucleic acid metabolic process	1	200.6×	0.032	SETMAR
cellular response to iron ion	1	172.0×	0.032	BMP6
DNA integration	1	150.5×	0.032	SETMAR
positive regulation of protein tyrosine kinase activity	1	150.5×	0.032	DOK7
postsynaptic neurotransmitter receptor internalization	1	150.5×	0.032	AP2S1
negative regulation of heterotypic cell-cell adhesion	1	133.8×	0.032	IL1RN
positive regulation of focal adhesion disassembly	1	133.8×	0.032	IQSEC1
positive regulation of skeletal muscle acetylcholine-gated channel clustering	1	133.8×	0.032	DOK7
negative regulation of DNA biosynthetic process	1	133.8×	0.032	DACH1
suckling behavior	1	120.4×	0.032	DACH1
negative regulation of interleukin-1-mediated signaling pathway	1	120.4×	0.032	IL1RN
DNA double-strand break processing	1	109.4×	0.032	SETMAR
positive regulation of lipopolysaccharide-mediated signaling pathway	1	109.4×	0.032	BMP6
positive regulation of endothelial cell differentiation	1	109.4×	0.032	BMP6
glycosphingolipid catabolic process	1	109.4×	0.032	SUMF1
synaptic signaling	1	109.4×	0.032	DYTN
negative regulation of cell-cell adhesion mediated by cadherin	1	109.4×	0.032	BMP6

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 17

Druggability breadth: 5 of 18 evidence-associated genes (28%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DACH1	1	2
BMP6	0	0
SETMAR	0	0
XYLT1	0	0
SUMF1	0	0
CNGA1	0	0
UNC13C	0	0
DYTN	0	0
PHF21B	0	0
DOK7	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	DACH1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
IL1RN	26	Binding:26
DACH1	7	Binding:7
BMP6	1	Binding:1
SETMAR	1	Binding:1
AP2S1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SETMAR	2.1.1.357, 2.7.7.B22	[histone H3]-lysine36 N-dimethyltransferase,
XYLT1	2.4.2.26	protein xylosyltransferase
SUMF1	1.8.3.7	formylglycine-generating enzyme

Pharmacogenomics

Cohort genes with a PharmGKB record: 17; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 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)
MOLIBRESIB	2	DACH1

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	1	DACH1
C	Druggable family + PDB, no drug	4	SETMAR, XYLT1, SUMF1, CNGA1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	13	BMP6, UNC13C, DYTN, PHF21B, DOK7, NIPAL1, IQSEC1, FAM43B, MIR920, NALF1 (+3 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BMP6	1	—
SETMAR	1	—
XYLT1	0	—
SUMF1	0	—
CNGA1	0	—
UNC13C	0	—
DYTN	0	—
PHF21B	0	—
DOK7	0	—
NIPAL1	0	—
IQSEC1	0	—
FAM43B	0	—
MIR920	0	—
NALF1	0	—
VPS13A-AS1	0	—
AP2S1	1	—
IL1RN	26	—

Clinical trials & evidence

Clinical trials

Clinical trials: 37.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	35
PHASE3	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03327272	PHASE3	WITHDRAWN	Impact of Local Steroid Application in Extreme Lateral Lumbar Interbody Fusion
NCT06438471	PHASE1	RECRUITING	Novel Soluble Epoxide Hydrolase Inhibitor for Neuropathic Pain in Patients With Spinal Cord Injury
NCT04883411	Not specified	RECRUITING	CEM-Plate and CEM-Cage First-In-Human Use Efficacy Study
NCT05110833	Not specified	ENROLLING_BY_INVITATION	Dose Responsiveness as a Measure of Clinical Effectiveness During Neuromonitored Spine Surgery
NCT05238740	Not specified	RECRUITING	Comparison of Radiographic Fusion Rate and Clinical Outcome of ALIF and XLIF Performed With Either Recombinant Human Bone Morphogenetic Protein-2 or ViviGen®
NCT05306665	Not specified	RECRUITING	PREventing Pain After Surgery
NCT05356286	Not specified	RECRUITING	Recording of Intraoperative Spinal Cord Stimulation and Monitoring
NCT00555659	Not specified	COMPLETED	Prospective Clinical Evaluation of the New Aegis Plate for Anterior Interbody Fusions
NCT01430299	Not specified	COMPLETED	Efficacy and Safety of Accell Evo3 Demineralized Bone Matrix (DBM) in Instrumented Posterolateral Lumbar Spine Fusion
NCT01714804	Not specified	COMPLETED	Efficacy and Safety of Integra Accell Evo3 DBM in Instrumented Lumbar Spine Fusion
NCT01873586	Not specified	COMPLETED	OsteoStrux™ Collagen Ceramic Scaffold in Instrumented Lumbar Spine Fusion
NCT01918943	Not specified	UNKNOWN	Evaluation of Aspen Spinous Process Fixation System and PLIF Technique for the Treatment of Low Back Pain
NCT02018445	Not specified	COMPLETED	Accell Evo3™ Demineralized Bone Matrix in Instrumented Lumbar Spine Fusion
NCT02023372	Not specified	COMPLETED	Efficacy Study of NuCel® in Patients Undergoing Fusion of the Lumbar Spine
NCT02057744	Not specified	UNKNOWN	MIS ReFRESH: Robotic vs. Freehand Minimally Invasive Spinal Surgeries
NCT02058238	Not specified	WITHDRAWN	ADDRESS - Adult Deformity Robotic vs. Freehand Surgery to Correct Spinal Deformity
NCT02070484	Not specified	TERMINATED	Human Amniotic Tissue-derived Allograft, NuCel, in Posteriolateral Lumbar Fusions for Degenerative Disc Disease
NCT02381067	Not specified	TERMINATED	A Prospective Study of NuCel® in Cervical Spine Fusion
NCT02403453	Not specified	TERMINATED	RHINE™ Cervical Disc Clinical Study: A Prospective Observational Study for Patients Requiring 1-2 Level C-spine Surgery
NCT02558621	Not specified	COMPLETED	New Robotic Assistance System for Spinal Fusion Surgery
NCT02628210	Not specified	COMPLETED	Interbody Spacers With map3® Cellular Allogeneic Bone Graft in Anterior or Lateral Lumbar Interbody Fusion
NCT02700451	Not specified	COMPLETED	Post-op Acetaminophen vs NSAID Use on Lumbar Spinal Fusion Outcomes
NCT02808234	Not specified	UNKNOWN	Study of Nucel for One and Two Level Lumbar Interbody Fusion
NCT02873182	Not specified	UNKNOWN	Protection of Autonomic Nervous System During Lower Spine Surgical Procedures: A Safety and Feasibility Study
NCT02926391	Not specified	COMPLETED	UNiD 3D VBR Register
NCT03237104	Not specified	COMPLETED	Back in the Game: An Immediate Functional Progression Program in Athletes With a Spondylolysis.
NCT03321357	Not specified	COMPLETED	Retest-reliability and At-home-assessment Feasibility of the 5R-STS
NCT03425682	Not specified	COMPLETED	ViBone in Cervical and Lumbar Spine Fusion
NCT03744260	Not specified	COMPLETED	Medial Branch Radiofrequency Ablation and Lumbar Multifidi
NCT03826056	Not specified	COMPLETED	Neurology Inpatient Clinical Education Trial
NCT03945461	Not specified	COMPLETED	Return of Bowel Function After One or Two Level Anterior Lumbar Interbody Fusion With Chewing Gum
NCT04007094	Not specified	TERMINATED	Single-Armed Use of ViviGen Cellular Bone Matrix in Patients Undergoing Posterolateral Lumbar Surgery
NCT04591249	Not specified	COMPLETED	Physical Activity Intervention for Patients Following Lumbar Spine Surgery
NCT05098431	Not specified	WITHDRAWN	Comparison of Three Approaches of Electrode Placement to Detect Changes in Motor Evoked Potentials During Spine Surgery
NCT05768438	Not specified	UNKNOWN	Mulligan Mobilizations and McKenzie Exercises Along With Neural Mobilizations in Cervical Spondylosis
NCT06750874	Not specified	COMPLETED	Perioperative ACT for Preventing CPSP
NCT07023393	Not specified	WITHDRAWN	Proprio Spine Measurement Tool

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DIBOTERMIN ALFA	4	1
SODIUM CHLORIDE	4	1