Intervertebral disk degenerative disorder

Summary

Intervertebral disk degenerative disorder (MONDO:0011385) is a disease with 9 cohort genes (47 GWAS associations across 23 studies) and 70 clinical trials. Top therapeutic interventions include duloxetine, mepivacaine, and pamidronic acid.

At a glance

• Cohort genes: 9
• GWAS associations: 47
• Clinical trials: 70

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intervertebral disk degenerative disorder
Mondo ID	MONDO:0011385
EFO	EFO:0004994
MeSH	D055959
OMIM	603932
DOID	DOID:90
NCIT	C26983
SNOMED CT	77547008
UMLS	C0158266
MedGen	102357
Is cancer (heuristic)	no

Also known as: cervical disc degenerative disease · cervical disk degenerative disease · degenerative disk disease · degenerative disorder of intervertebral disc · degenerative disorder of intervertebral disk · IDD · intervertebral Disc Degeneration · intervertebral disc degeneration · intervertebral Disc degenerative disease · intervertebral Disc degenerative disorder · intervertebral disc disease · intervertebral disk degeneration · intervertebral disk degenerative disorder · intervertebral disk disease · lumbar disc degeneration · lumbar disk degeneration · vertebral Disc degenerative disease · vertebral Disc degenerative disorder · vertebral disk disease

Data availability: 47 GWAS associations (23 studies).

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › vertebral column disorder › intervertebral disk degenerative disorder

Related subtypes (14): spondylocostal dysostosis, sacrum chordoma, epidural spinal canal neoplasm, Baastrup syndrome, lumbosacral lipoma, spinal stenosis, coccygodynia, vertebral joint disorder, sacrococcygeal teratoma, spinal cord injury, tuberculosis, spinal, vertebral disorder, lumbar disk disease, dropped head syndrome

Subtypes (3): lumbar disk degenerative disorder, thoracic disk degenerative disorder, cervical disk degenerative disorder

Genetics & variants

GWAS landscape

47 GWAS associations across 23 studies. Top hits map to 16 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs181008960	3e-14	DDX39AP1 - SNORD36	A	1.19
rs530949226	3e-11	EEF1A1P11 - RN7SL831P	C	1.5
rs371959604	3e-11	FER1L5	G	3.1
rs16932590	3e-11	PTHLH - CCDC91	T	0.4
rs7163797	4e-10	SMAD3	?	0.92
rs17034687	2e-09	CRBN - SUMF1	C	0.23
rs7907616	2e-08	CHST3	?	1.08
rs2187689	3e-08	PPP1R2P1 - HLA-Z	C	0.23
rs926849	3e-08	PRKN	C	0.13
rs4148933	3e-08	CHST3	?	1.08
rs4284332	3e-08	CHST3	?	1.08
rs1245582	4e-08	CHST3 - SPOCK2	?	1.2
rs7744666	6e-08	PPP1R2P1 - HLA-Z	C	0.2
rs11969002	6e-08	PPP1R2P1 - HLA-Z	A	0.2
rs6457690	9e-08	PPP1R2P1 - HLA-Z	A	0.19
rs1029296	9e-08	PPP1R2P1 - HLA-Z	C	0.19
rs6936004	1e-07	PPP1R2P1 - HLA-Z	C	0.19
rs3749982	1e-07	PPP1R2P1 - HLA-Z	A	0.19
rs9469300	1e-07	PPP1R2P1 - HLA-Z	A	0.19
rs17131012	1e-07	RNU6-695P - LINC02787	?
rs149916197	1e-07	MRPS36P3 - SMILR	?
rs10214886	2e-07	PPP1R2P1 - HLA-Z	A	0.19
rs10046257	3e-07	PPP1R2P1 - HLA-Z	A	0.19
rs4875102	4e-07	CSMD1	A	0.12
rs1029295	5e-07	PPP1R2P1 - HLA-Z	C	0.19
rs9301951	9e-07	GPC6	C	0.26
rs7896691	2e-06	PFKP	C	0.17
rs1154053	4e-06	CSMD1	C	0.13
rs2484990	4e-06	LINC02664, ZEB1-AS1	C	0.68
rs1250307	4e-06	LINC02664, ZEB1-AS1	A	0.68

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90281187	Bovonratwet P	2023	11,310	378,103	Identification of Novel Genetic Markers for the Risk of Spinal Pathologies: A Genome-Wide Association Study of 2 Biobanks.
GCST90651846	Liu TY	2025	10,044	206,188	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90080498	Backman JD	2021	10,022	373,202	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084484	Backman JD	2021	10,022	373,202	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90478909	Verma A	2024	3,996	442,077	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90080497	Backman JD	2021	3,288	384,639	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084483	Backman JD	2021	3,288	384,639	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90651900	Liu TY	2025	3,104	206,188	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90246169	Walters RG	2023	3,039	73,642	Genotyping and population characteristics of the China Kadoorie Biobank.
GCST90726934	Kim HI	2026	2,774	41,252	Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	1
Tier 3: regulatory	4
Tier 4: intronic/intergenic	41

MAF distribution

Bucket	Variants
common (>=0.05)	34
low_freq (0.01-0.05)	8
rare (<0.01)	3
unknown	1

Functional consequences

Consequence	Count
intron_variant	25
intergenic_variant	15
regulatory_region_variant	4
splice_region_variant	1
non_coding_transcript_exon_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs181008960	13	22786747	A>T	0.003	intergenic_variant	DDX39AP1 - SNORD36	3e-14	Tier 4: intronic/intergenic
rs530949226	1	96471406	C>T	0.001	intergenic_variant	EEF1A1P11 - RN7SL831P	3e-11	Tier 4: intronic/intergenic
rs371959604	2	96700507	G>C,T	0	intron_variant	FER1L5	3e-11	Tier 4: intronic/intergenic
rs16932590	12	28083714	T>A,C	0.02	intergenic_variant	PTHLH - CCDC91	3e-11	Tier 4: intronic/intergenic
rs7163797	15	67072574	C>A	0.05	intron_variant	SMAD3	4e-10	Tier 4: intronic/intergenic
rs17034687	3	3638168	C>G,T	0.09	intergenic_variant	CRBN - SUMF1	2e-09	Tier 4: intronic/intergenic
rs7907616	10	72000418	A>C,G	0.05	intron_variant	CHST3	2e-08	Tier 4: intronic/intergenic
rs2187689	6	32884870	T>A,C,G	0.08	intergenic_variant	PPP1R2P1 - HLA-Z	3e-08	Tier 4: intronic/intergenic
rs926849	6	161740587	C>A,G,T	0.31	intron_variant	PRKN	3e-08	Tier 4: intronic/intergenic
rs4148933	10	72000132	T>C,G	0.05	intron_variant	CHST3	3e-08	Tier 4: intronic/intergenic
rs4284332	10	71974194	T>A,C	0.05	intron_variant	CHST3	3e-08	Tier 4: intronic/intergenic
rs1245582	10	72018509	C>A,G,T	0.44	intergenic_variant	CHST3 - SPOCK2	4e-08	Tier 4: intronic/intergenic
rs7744666	6	32891935	T>C	0.1	splice_region_variant	PPP1R2P1 - HLA-Z	6e-08	Tier 2: splice/UTR
rs11969002	6	32891971	G>A,T	0.1	intron_variant	PPP1R2P1 - HLA-Z	6e-08	Tier 4: intronic/intergenic
rs6457690	6	32887940	G>A	0.1	intergenic_variant	PPP1R2P1 - HLA-Z	9e-08	Tier 4: intronic/intergenic
rs1029296	6	32888604	T>A,C,G	0.1	intergenic_variant	PPP1R2P1 - HLA-Z	9e-08	Tier 4: intronic/intergenic
rs6936004	6	32889157	T>C,G	0.1	intergenic_variant	PPP1R2P1 - HLA-Z	1e-07	Tier 4: intronic/intergenic
rs3749982	6	32894830	T>A,G	0.1	non_coding_transcript_exon_variant	PPP1R2P1 - HLA-Z	1e-07	Tier 4: intronic/intergenic
rs9469300	6	32892975	G>A	0.1	intron_variant	PPP1R2P1 - HLA-Z	1e-07	Tier 4: intronic/intergenic
rs17131012	1	90360055	C>T	0.05	intergenic_variant	RNU6-695P - LINC02787	1e-07	Tier 4: intronic/intergenic
rs149916197	8	122351561	A>G		intron_variant	MRPS36P3 - SMILR	1e-07	Tier 4: intronic/intergenic
rs10214886	6	32889642	T>A	0.1	intergenic_variant	PPP1R2P1 - HLA-Z	2e-07	Tier 4: intronic/intergenic
rs10046257	6	32886920	G>A	0.1	regulatory_region_variant	PPP1R2P1 - HLA-Z	3e-07	Tier 3: regulatory
rs4875102	8	4427170	G>A,T	0.26	intron_variant	CSMD1	4e-07	Tier 4: intronic/intergenic
rs1029295	6	32888705	T>A,C,G	0.1	intergenic_variant	PPP1R2P1 - HLA-Z	5e-07	Tier 4: intronic/intergenic
rs9301951	13	94300578	T>C,G	0.04	intron_variant	GPC6	9e-07	Tier 4: intronic/intergenic
rs7896691	10	3112981	C>G,T	0.1	intron_variant	PFKP	2e-06	Tier 4: intronic/intergenic
rs1154053	8	4427868	G>A,C	0.17	intron_variant	CSMD1	4e-06	Tier 4: intronic/intergenic
rs2484990	10	31226203	T>A,C,G	0.01	intron_variant	LINC02664, ZEB1-AS1	4e-06	Tier 4: intronic/intergenic
rs1250307	10	31207045	G>A,C,T	0.01	intron_variant	LINC02664, ZEB1-AS1	4e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PIGQ	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
CHST3	Orphanet:263463	CHST3-related skeletal dysplasia
MYH14	Orphanet:397744	MYH14-related peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome
MYH14	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
GPC6	Orphanet:93329	Autosomal recessive omodysplasia
PRKN	Orphanet:2828	Young-onset Parkinson disease

Cohort genes → proteins

9 cohort genes, 9 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	9

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PIGQ	HGNC:14135	ENSG00000007541	Q9BRB3	Phosphatidylinositol N-acetylglucosaminyltransferase subunit Q	gwas
RAB40C	HGNC:18285	ENSG00000197562	Q96S21	Ras-related protein Rab-40C	gwas
CHST3	HGNC:1971	ENSG00000122863	Q7LGC8	Carbohydrate sulfotransferase 3	gwas
MYH14	HGNC:23212	ENSG00000105357	Q7Z406	Myosin-14	gwas
ARL8B	HGNC:25564	ENSG00000134108	Q9NVJ2	ADP-ribosylation factor-like protein 8B	gwas
GPC6	HGNC:4454	ENSG00000183098	Q9Y625	Glypican-6	gwas
PRKN	HGNC:8607	ENSG00000185345	O60260	E3 ubiquitin-protein ligase parkin	gwas
PFKP	HGNC:8878	ENSG00000067057	Q01813	ATP-dependent 6-phosphofructokinase, platelet type	gwas
PSMB9	HGNC:9546	ENSG00000240065	P28065	Proteasome subunit beta type-9	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PIGQ	Phosphatidylinositol N-acetylglucosaminyltransferase subunit Q	Part of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI bi…
RAB40C	Ras-related protein Rab-40C	RAB40C small GTPase acts as substrate-recognition component of the ECS(RAB40C) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
CHST3	Carbohydrate sulfotransferase 3	Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the transfer of sulfate to position 6 of the N-acetylgalactosamine (GalNAc) residue of chondroitin.
MYH14	Myosin-14	Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping.
ARL8B	ADP-ribosylation factor-like protein 8B	Small GTPase which cycles between active GTP-bound and inactive GDP-bound states.
GPC6	Glypican-6	Cell surface proteoglycan that bears heparan sulfate.
PRKN	E3 ubiquitin-protein ligase parkin	Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins.
PFKP	ATP-dependent 6-phosphofructokinase, platelet type	Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.
PSMB9	Proteasome subunit beta type-9	The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH.

Protein-family classification

Druggable: 3 · Difficult: 2 · Unknown: 4 · Druggable fraction: 0.33

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
Kinase	1	3.1×	0.692
Enzyme (other)	2	2.7×	0.692
Scaffold/PPI	1	1.9×	0.692
Transcription factor	1	0.9×	0.847
Other/Unknown	4	0.8×	0.847

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PIGQ	Enzyme (other)	yes	2.4.1.198	PigQ/GPI1
RAB40C	Other/Unknown	no		SOCS_box, Small_GTPase, Small_GTP-bd
CHST3	Enzyme (other)	yes	2.8.2.17	Sulfotransferase_dom, Carbohydrate_sulfotransferase, P-loop_NTPase
MYH14	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_tail
ARL8B	Other/Unknown	no		Small_GTP-bd, Small_GTPase_ARF/SAR, P-loop_NTPase
GPC6	Other/Unknown	no		Glypican, Glypican_CS
PRKN	Transcription factor	no	2.3.2.27	Ubiquitin-like_dom, IBR_dom, Parkin
PFKP	Kinase	yes	2.7.1.11	Phosphofructokinase_dom, 6-Pfructokinase_euk, Phosphofructokinase_CS
PSMB9	Other/Unknown	no		Pept_T1A_subB, Proteasome_sua/b, Proteasome_bsu_CS

Expression context

Cohort genes with no expression data: 0.

9 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)	9
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cartilage tissue	2
tibia	2
left lobe of thyroid gland	1
right lobe of thyroid gland	1
right uterine tube	1
right frontal lobe	1
skin of abdomen	1
skin of leg	1
ventricular zone	1
gastrocnemius	1
ileal mucosa	1
mucosa of transverse colon	1
Brodmann (1909) area 23	1
lateral nuclear group of thalamus	1
middle temporal gyrus	1
vena cava	1
hindlimb stylopod muscle	1
male germ line stem cell (sensu Vertebrata) in testis	1
sural nerve	1
dorsal root ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PIGQ	186	broad	marker	right lobe of thyroid gland, right uterine tube, left lobe of thyroid gland
RAB40C	168	ubiquitous	marker	skin of leg, skin of abdomen, right frontal lobe
CHST3	233	ubiquitous	marker	tibia, cartilage tissue, ventricular zone
MYH14	227	broad	marker	mucosa of transverse colon, ileal mucosa, gastrocnemius
ARL8B	292	ubiquitous	marker	middle temporal gyrus, Brodmann (1909) area 23, lateral nuclear group of thalamus
GPC6	217	ubiquitous	marker	cartilage tissue, tibia, vena cava
PRKN	174	ubiquitous	marker	sural nerve, male germ line stem cell (sensu Vertebrata) in testis, hindlimb stylopod muscle
PFKP	287	ubiquitous	marker	tendon of biceps brachii, saphenous vein, dorsal root ganglion
PSMB9	133	ubiquitous	marker	granulocyte, leukocyte, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRKN	10,281
PFKP	3,665
PSMB9	2,896
ARL8B	2,713
MYH14	1,569
RAB40C	1,440
GPC6	1,237
PIGQ	771
CHST3	579

Structural data

PDB: 5 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PRKN	O60260	21
PFKP	Q01813	7
PSMB9	P28065	7
ARL8B	Q9NVJ2	3
MYH14	Q7Z406	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GPC6	Q9Y625	82.67
CHST3	Q7LGC8	80.58
RAB40C	Q96S21	75.24
PIGQ	Q9BRB3	64.70

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 48. Enrichment computed across 9 evidence-associated genes (8 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 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective CHST3 causes SEDCJD	1	178.4×	0.042	CHST3
Josephin domain DUBs	1	119.0×	0.042	PRKN
Defective EXT2 causes exostoses 2	1	102.0×	0.042	GPC6
Defective EXT1 causes exostoses 1, TRPS2 and CHDS	1	102.0×	0.042	GPC6
Sema4D in semaphorin signaling	1	84.0×	0.042	MYH14
Synthesis of glycosylphosphatidylinositol (GPI)	1	79.3×	0.042	PIGQ
RHO GTPases activate CIT	1	75.1×	0.042	MYH14
RHO GTPases Activate ROCKs	1	75.1×	0.042	MYH14
Attachment and Entry	1	75.1×	0.042	GPC6
Defective B4GALT7 causes EDS, progeroid type	1	71.4×	0.042	GPC6
Defective B3GAT3 causes JDSSDHD	1	71.4×	0.042	GPC6
Sema4D induced cell migration and growth-cone collapse	1	71.4×	0.042	MYH14
Defective B3GALT6 causes EDSP2 and SEMDJL1	1	71.4×	0.042	GPC6
Antigen processing: Ub, ATP-independent proteasomal degradation	1	71.4×	0.042	PSMB9
CS-GAG biosynthesis	1	68.0×	0.042	CHST3
RHO GTPases activate PAKs	1	68.0×	0.042	MYH14
HS-GAG degradation	1	62.1×	0.042	GPC6
Respiratory syncytial virus (RSV) attachment and entry	1	62.1×	0.042	GPC6
Initiation of coagulation cascade	1	59.5×	0.042	GPC6
Regulation of necroptotic cell death	1	54.9×	0.042	PRKN
Glycosaminoglycan-protein linkage region biosynthesis	1	49.2×	0.042	GPC6
Semaphorin interactions	1	49.2×	0.042	MYH14
Keratan sulfate biosynthesis	1	47.6×	0.042	CHST3
EPHA-mediated growth cone collapse	1	47.6×	0.042	MYH14
PINK1-PRKN Mediated Mitophagy	1	44.6×	0.042	PRKN
HS-GAG biosynthesis	1	43.3×	0.042	GPC6
RHO GTPases activate PKNs	1	39.6×	0.044	MYH14
Glycolysis	1	35.7×	0.047	PFKP
Dengue Virus Attachment and Entry	1	32.4×	0.048	GPC6
Cross-presentation of soluble exogenous antigens (endosomes)	1	31.7×	0.048	PSMB9

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
antigen processing and presentation of polysaccharide antigen via MHC class II	1	1872.4×	0.013	ARL8B
antigen processing and presentation following phagocytosis	1	1872.4×	0.013	ARL8B
viral exocytosis	1	1872.4×	0.013	ARL8B
positive regulation of neurotransmitter uptake	1	1872.4×	0.013	PRKN
negative regulation of spontaneous neurotransmitter secretion	1	1872.4×	0.013	PRKN
endosome to lysosome transport of low-density lipoprotein particle	1	936.2×	0.013	ARL8B
positive regulation of protein linear polyubiquitination	1	936.2×	0.013	PRKN
negative regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway	1	936.2×	0.013	PRKN
response to curcumin	1	936.2×	0.013	PRKN
positive regulation of retrograde transport, endosome to Golgi	1	936.2×	0.013	PRKN
negative regulation of intralumenal vesicle formation	1	936.2×	0.013	PRKN
negative regulation of glucokinase activity	1	624.1×	0.013	PRKN
mitochondrion to lysosome vesicle-mediated transport	1	624.1×	0.013	PRKN
regulation protein catabolic process at presynapse	1	624.1×	0.013	PRKN
regulation of synaptic vesicle transport	1	624.1×	0.013	PRKN
protein localization to early endosome	1	624.1×	0.013	ARL8B
cellular response to hydrogen sulfide	1	624.1×	0.013	PRKN
calcium ion regulated lysosome exocytosis	1	624.1×	0.013	ARL8B
mitochondrion organization	2	33.7×	0.013	MYH14, PRKN
proteasome-mediated ubiquitin-dependent protein catabolic process	3	17.4×	0.013	RAB40C, PRKN, PSMB9
regulation of lipid transport	1	468.1×	0.014	PRKN
negative regulation of exosomal secretion	1	468.1×	0.014	PRKN
cellular response to L-glutamine	1	468.1×	0.014	PRKN
carbohydrate metabolic process	2	30.2×	0.014	PIGQ, CHST3
positive regulation of mitochondrial fusion	1	374.5×	0.016	PRKN
type 2 mitophagy	1	374.5×	0.016	PRKN
negative regulation of mitochondrial fission	1	374.5×	0.016	PRKN
negative regulation of actin filament bundle assembly	1	312.1×	0.018	PRKN
aggresome assembly	1	312.1×	0.018	PRKN
free ubiquitin chain polymerization	1	267.5×	0.018	PRKN

Therapeutics

Drugs indicated or in trials for this disease

No drug has an approved disease-direct ChEMBL indication for this disease.

6 drugs in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Buprenorphine	Phase 3
Gabapentin	Phase 3
Pregabalin	Phase 3
Rexlemestrocel-L	Phase 3
Sodium Chloride	Phase 3
Tranexamic Acid	Phase 2

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 3 · Undrugged: 6

Druggability breadth: 4 of 9 evidence-associated genes (44%) 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
MYH14	TUCATINIB
PSMB9	BORTEZOMIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PSMB9	7	4
MYH14	1	4
PFKP	1	2
PIGQ	0	0
RAB40C	0	0
CHST3	0	0
ARL8B	0	0
GPC6	0	0
PRKN	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TUCATINIB	4	MYH14
BORTEZOMIB	4	PSMB9
CARFILZOMIB	4	PSMB9
IXAZOMIB	3	PSMB9
MARIZOMIB	3	PSMB9
VISTUSERTIB	2	PFKP
DELANZOMIB	2	PSMB9
ZETOMIPZOMIB	2	PSMB9
OPROZOMIB	2	PSMB9

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

Symbol	Assays	Type breakdown
PSMB9	220	Binding:210, ADMET:7, Functional:3
ARL8B	2	Binding:2
PFKP	2	Binding:2
MYH14	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PIGQ	2.4.1.198	phosphatidylinositol N-acetylglucosaminyltransferase
CHST3	2.8.2.17	chondroitin 6-sulfotransferase
PRKN	2.3.2.27, 2.3.2.31	RING-type E3 ubiquitin transferase, RBR-type E3 ubiquitin transferase
PFKP	2.7.1.11	6-phosphofructokinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PSMB9	220

Pharmacogenomics

Cohort genes with a PharmGKB record: 9; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

9 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)
TUCATINIB	4	MYH14
BORTEZOMIB	4	PSMB9
CARFILZOMIB	4	PSMB9
IXAZOMIB	3	PSMB9
MARIZOMIB	3	PSMB9
VISTUSERTIB	2	PFKP
DELANZOMIB	2	PSMB9
ZETOMIPZOMIB	2	PSMB9
OPROZOMIB	2	PSMB9

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	MYH14, PSMB9
B	Phased (≥1) drug, not yet approved	1	PFKP
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	2	PIGQ, CHST3
E	Difficult family or no structure, no drug	4	RAB40C, ARL8B, GPC6, PRKN

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PIGQ	0	—
RAB40C	0	—
CHST3	0	—
ARL8B	2	—
GPC6	0	—
PRKN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 70.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	55
PHASE1/PHASE2	6
PHASE4	3
PHASE2	3
PHASE3	2
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01615328	PHASE4	COMPLETED	Evaluation of Fusion Rate of Anterior Cervical Discectomy and Fusion (ACDF) Using Cervios ChronOs™ and Bonion™
NCT02535000	PHASE4	COMPLETED	Duloxetine as an Analgesic Agent in Patients Undergoing Elective Spine Surgery
NCT03514277	PHASE4	TERMINATED	A Prospective Study to Compare Bupivacaine and Exparel Versus Bupivacaine or Exparel Alone for Postoperative Pain Relief
NCT01941563	PHASE3	COMPLETED	A Study of SI-6603 in Patients With Lumbar Disc Herniation
NCT02421601	PHASE3	COMPLETED	A Study of SI-6603 in Patients With Lumbar Disc Herniation
NCT05066334	PHASE2	RECRUITING	Efficacy of Intradiscal Injection of Autologous BM-MSC in Subjects With Chronic LBP Due to Multilevel Lumbar IDD
NCT07168603	PHASE1/PHASE2	RECRUITING	EvaluatIon of Autologous Nucleus Pulposus Cells (aNPC) in Degenerative Disc Disease
NCT01158924	PHASE1/PHASE2	COMPLETED	A Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Effectiveness of Single Administration Intradiscal rhGDF-5 for the Treatment of Early Stage Lumbar Disc Degeneration
NCT01182337	PHASE1/PHASE2	COMPLETED	A Clinical Trial to Evaluate the Safety, Tolerability and Preliminary Effectiveness of Single Administration Intradiscal rhGDF-5 for the Treatment of Early Stage Lumbar Disc Degeneration
NCT01513694	PHASE1/PHASE2	COMPLETED	Clinical Trial Based on the Use of Mesenchymal Stem Cells From Autologous Bone Marrow in Patients With Lumbar Intervertebral Degenerative Disc Disease
NCT01640457	PHASE1/PHASE2	COMPLETED	Safety and Efficacy With NOVOCART® Disc Plus (ADCT) for the Treatment of Degenerative Disc Disease in Lumbar Spine
NCT01799616	PHASE2	UNKNOWN	Efficiency and Safety Study of Pamidronate in Inflammatory Back Pain Due to Degenerative Disk Disease
NCT01860417	PHASE1/PHASE2	COMPLETED	Treatment of Degenerative Disc Disease With Allogenic Mesenchymal Stem Cells (MSV)
NCT04759105	PHASE2	COMPLETED	Efficacy of Intradiscal Injection of Autologous BM-MSC in Worker Patients Affected by Chronic LBP Due to Multilevel IDD
NCT06589271	PHASE1	SUSPENDED	SCLife®-LDD hUC-MSCs Injection Therapy for Patients With Lumbar Intervertebral Disc Degeneration
NCT03076658	Not specified	RECRUITING	Open Access Database of Standing Full Body Radiographs in Asymptomatic Volunteers
NCT03853356	Not specified	ACTIVE_NOT_RECRUITING	Evidence For Fusion In Spine With Orthoss®
NCT05110833	Not specified	ENROLLING_BY_INVITATION	Dose Responsiveness as a Measure of Clinical Effectiveness During Neuromonitored Spine Surgery
NCT05299762	Not specified	RECRUITING	A Post Market Surveillance on INFUSE Bone Graft
NCT05648474	Not specified	RECRUITING	Intraoperative Monitoring for the Lateral Lumbar Interbody Fusion Procedure
NCT05997121	Not specified	RECRUITING	Safety and Performance of the Hexanium TLIF System in the Treatment of Degenerative Disc Disease
NCT06155409	Not specified	ACTIVE_NOT_RECRUITING	Safety and Performance of the SPINEVISION Hexanium ACIF in the Treatment of Cervical Spine Degenerative Disc Disease
NCT06342765	Not specified	RECRUITING	Safety and Performance of the SpineVision Posterior Fixation Systems in Thoracolumbar Spinal Treatment
NCT06989632	Not specified	RECRUITING	Total Lumbar Disc Prosthesis and Subsequent Work Activity at at Least Five Years After Total Lumbar Disc Replacement
NCT07085247	Not specified	RECRUITING	The Role of Cutibacterium Acnes in the Development of Degenerative Lumbar Intervertebral Disc Disease
NCT07127380	Not specified	RECRUITING	Comparison of Clinical Outcomes, Complications Rate and Treatment Costs of Mini-TLIF and MIDLIF in the Treatment of Discogenic Low Back Pain
NCT07338877	Not specified	ENROLLING_BY_INVITATION	RenewDisc Trial: Endoscopic Discectomy and Autologous Stem Cell Therapy for Discogenic Low Back Pain
NCT07489001	Not specified	RECRUITING	Opioid Free and Opioid Based Anesthesia in Elective Lumbar Spine Surgery
NCT00310440	Not specified	COMPLETED	An Assessment of P-15 Bone Putty in Anterior Cervical Fusion With Instrumentation
NCT01045473	Not specified	UNKNOWN	Prospective Study of Minimally Invasive Spine Surgery
NCT01326091	Not specified	TERMINATED	Patient Positioning in Lumbar Fusion Surgery and Its Impact on Spinal Sagittal Balance and Surgeon Satisfaction
NCT01439464	Not specified	UNKNOWN	Study of Bioactive Glass-ceramic Intervertebral Spacer (Bonglass-SS) in Posterior Lumbar Interbody Fusion
NCT01452022	Not specified	COMPLETED	Performance of Inductigraft in Spinal Fusion
NCT01633034	Not specified	UNKNOWN	Tissue Collection for Understanding Intervertebral Disc Degeneration and Back Pain
NCT01944345	Not specified	COMPLETED	Patient Registry to Observe Outcomes Following Implantation of the VariLift Interbody Fusion Device
NCT01989481	Not specified	UNKNOWN	Predicting the Outcome of Total Knee Arthroplasty and Spinal Surgeon
NCT02023372	Not specified	COMPLETED	Efficacy Study of NuCel® in Patients Undergoing Fusion of the Lumbar Spine
NCT02070484	Not specified	TERMINATED	Human Amniotic Tissue-derived Allograft, NuCel, in Posteriolateral Lumbar Fusions for Degenerative Disc Disease
NCT02225444	Not specified	COMPLETED	A Prospective Study of Instrumented, Posterolateral Lumbar Fusions (PLF) With OsteoAMP®
NCT02351206	Not specified	COMPLETED	Lumbar Disc Space Height in Young Disc Herniation and Degeneration Patients

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DULOXETINE	4	1
MEPIVACAINE	4	1
PAMIDRONIC ACID	4	1
CONDOLIASE	3	2
RADOTERMIN	2	2
(R)-DULOXETINE	0	1