Carpal tunnel syndrome

Summary

Carpal tunnel syndrome (MONDO:0007275) is a disease with 14 cohort genes (83 GWAS associations across 12 studies) and 521 clinical trials. The dominant Reactome pathway is Molecules associated with elastic fibres (4 cohort genes). Top therapeutic interventions include lidocaine, dexmedetomidine, and ibuprofen.

At a glance

• Cohort genes: 14
• GWAS associations: 83
• ClinVar variants: 2
• Clinical trials: 521

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	carpal tunnel syndrome
Mondo ID	MONDO:0007275
EFO	EFO:0004143
MeSH	D002349
OMIM	115430
Orphanet	50838
DOID	DOID:12169
ICD-10-CM	G56.0
ICD-11	1275186848
NCIT	C34450
SNOMED CT	57406009
UMLS	C0007286
MedGen	2856
GARD	0027775
Is cancer (heuristic)	no

Also known as: carpal tunnel syndrome · CTS

Data availability: 2 ClinVar variants · 83 GWAS associations (12 studies) · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › peripheral nervous system disorder › peripheral neuropathy › nerve compression syndrome › carpal tunnel syndrome

Related subtypes (2): meralgia paresthetica, piriformis syndrome

Subtypes (2): carpal tunnel syndrome 1, carpal tunnel syndrome 2

Genetics & variants

GWAS landscape

83 GWAS associations across 12 studies. Top hits map to 31 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs28929474	3e-24	SERPINA1	T	0.76
rs12694411	3e-24	TESHL	T	0.92
rs11205303	7e-21	MTMR11	C	0.93
rs62621197	7e-20	ADAMTS10	T	1.2
rs66525731	9e-20	U6 - HSP90AB2P	T	1.1
rs72755233	3e-19	ADAMTS17	A	1.1
rs3791679	4e-19	EFEMP1	G	1.08
rs1474313	4e-18	LINC02517 - ACOX3	G	1.07
rs1325494	7e-18	R3HCC1L	G	0.94
rs9722048	2e-16	ADAMTSL2	A	1.06
rs150512726	2e-15	ITGB5	T	0.92
rs9923544	5e-15	FTO	T	1.06
rs10221933	2e-14	TESHL	C	0.11
rs2871960	3e-14	ZBTB38	C	0.95
rs6977081	4e-14	AOC1	T	0.95
rs2815536	4e-14	LINC02680 - MKX	A	0.95
rs79101546	6e-14	ZBTB34 - RALGPS1	T	0.94
rs12762780	6e-14	ADAMTS14	C	1.05
rs7251031	3e-13	SPC24 - KANK2	G	1.06
rs4655025	4e-13	WNT4	A	0.95
rs1863190	5e-13	TESHL	T	1.12
rs1866745	5e-13	SMAD6	A	1.05
rs10916207	6e-13	SNAP47	G	0.95
rs17214004	2e-12	SEMA3A	T	1.08
rs6712473	2e-12	LTBP1	G	1.05
rs72725608	4e-12	TTLL5	C	1.13
rs12539945	5e-12	LINC02587 - CRPPA	A	1.05
rs6843953	6e-12	U6 - HSP90AB2P	T	1.14
rs5758007	6e-12	MRTFA	T	1.05
rs1394094	7e-12	STAG1	A	0.95

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90104786	Skuladottir AT	2022	48,843	1,190,837	A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome.
GCST90018813	Sakaue S	2021	18,855	461,346	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90043763	Jiang L	2021	12,887	443,461	A generalized linear mixed model association tool for biobank-scale data.
GCST007581	Wiberg A	2019	12,312	389,344	A genome-wide association analysis identifies 16 novel susceptibility loci for carpal tunnel syndrome.
GCST90129434	Zorina-Lichtenwalter K	2023	11,912	424,059	Genetic risk shared across 24 chronic pain conditions: identification and characterization with genomic structural equation modeling.
GCST90079844	Backman JD	2021	11,271	376,659	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083830	Backman JD	2021	11,271	376,659	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90077929	Backman JD	2021	928	330,826	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90081915	Backman JD	2021	928	330,826	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90077930	Backman JD	2021	830	328,222	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	9
Tier 2: splice/UTR	5
Tier 3: regulatory	1
Tier 4: intronic/intergenic	35

MAF distribution

Bucket	Variants
common (>=0.05)	45
low_freq (0.01-0.05)	5
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	21
intergenic_variant	14
missense_variant	8
splice_region_variant	2
inframe_insertion	1
5_prime_UTR_variant	1
regulatory_region_variant	1
splice_polypyrimidine_tract_variant	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs28929474	14	94378610	C>A,G,T	0.018	missense_variant	SERPINA1	3e-24	Tier 1: coding
rs12694411	2	217281820	T>A,C,G	0.264	intron_variant	TESHL	3e-24	Tier 4: intronic/intergenic
rs11205303	1	149934520	T>C	0.388	missense_variant	MTMR11	7e-21	Tier 1: coding
rs62621197	19	8605262	C>A,T	0.028	missense_variant	ADAMTS10	7e-20	Tier 1: coding
rs66525731	4	13221803	C>T	0.11	intergenic_variant	U6 - HSP90AB2P	9e-20	Tier 4: intronic/intergenic
rs72755233	15	100152748	G>A,T	0.121	missense_variant	ADAMTS17	3e-19	Tier 1: coding
rs3791679	2	55869757	A>C,G,T	0.218	intron_variant	EFEMP1	4e-19	Tier 4: intronic/intergenic
rs1474313	4	8327339	G>A,C,T	0.274	intergenic_variant	LINC02517 - ACOX3	4e-18	Tier 4: intronic/intergenic
rs1325494	10	98186463	C>G,T	0.429	splice_region_variant	R3HCC1L	7e-18	Tier 2: splice/UTR
rs9722048	9	133563561	A>G	0.44	intron_variant	ADAMTSL2	2e-16	Tier 4: intronic/intergenic
rs150512726	3	124763648	TTTGTTGAAC>T,TTTGTTGAACTTGTTGAAC	0.112	inframe_insertion	ITGB5	2e-15	Tier 1: coding
rs9923544	16	53768073	C>T	0.43	intron_variant	FTO	5e-15	Tier 4: intronic/intergenic
rs10221933	2	217281385	G>A,C	0.05	intron_variant	TESHL	2e-14	Tier 4: intronic/intergenic
rs2871960	3	141402972	A>C	0.462	intron_variant	ZBTB38	3e-14	Tier 4: intronic/intergenic
rs6977081	7	150845427	G>A,C,T	0.327	intron_variant	AOC1	4e-14	Tier 4: intronic/intergenic
rs2815536	10	27644947	G>A,T	0.421	intergenic_variant	LINC02680 - MKX	4e-14	Tier 4: intronic/intergenic
rs79101546	9	126910488	T>A,G	0.261	intergenic_variant	ZBTB34 - RALGPS1	6e-14	Tier 4: intronic/intergenic
rs12762780	10	70672742	C>A,G,T	0.479	5_prime_UTR_variant	ADAMTS14	6e-14	Tier 2: splice/UTR
rs7251031	19	11156017	T>A,G	0.289	regulatory_region_variant	SPC24 - KANK2	3e-13	Tier 3: regulatory
rs4655025	1	22133261	A>G	0.445	intron_variant	WNT4	4e-13	Tier 4: intronic/intergenic
rs1863190	2	217263429	A>T	0.24	intron_variant	TESHL	5e-13	Tier 4: intronic/intergenic
rs1866745	15	66742474	G>A	0.354	intron_variant	SMAD6	5e-13	Tier 4: intronic/intergenic
rs10916207	1	227780237	G>A,T	0.495	intron_variant	SNAP47	6e-13	Tier 4: intronic/intergenic
rs17214004	7	84370484	C>A,T	0.103	intron_variant	SEMA3A	2e-12	Tier 4: intronic/intergenic
rs6712473	2	33188573	G>A,C,T	0.462	splice_region_variant	LTBP1	2e-12	Tier 2: splice/UTR
rs72725608	14	75779563	T>C	0.041	splice_polypyrimidine_tract_variant	TTLL5	4e-12	Tier 2: splice/UTR
rs12539945	7	16082848	G>A	0.443	intergenic_variant	LINC02587 - CRPPA	5e-12	Tier 4: intronic/intergenic
rs6843953	4	13220123	C>T	0.138	intergenic_variant	U6 - HSP90AB2P	6e-12	Tier 4: intronic/intergenic
rs5758007	22	40559560	A>C,G,T	0.487	intron_variant	MRTFA	6e-12	Tier 4: intronic/intergenic
rs1394094	3	136476946	A>C,T	0.31	intron_variant	STAG1	7e-12	Tier 4: intronic/intergenic

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
13453	NM_000371.4(TTR):c.250T>C (p.Phe84Leu)	TTR	Pathogenic	criteria provided, multiple submitters, no conflicts
246463	NM_000371.4(TTR):c.122G>A (p.Arg41Gln)	TTR	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 21 · 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
FBN2	Limited	Autosomal dominant	carpal tunnel syndrome	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FBN2	Orphanet:115	Congenital contractural arachnodactyly
TTR	Orphanet:597939	Euthyroid dysprealbuminemic hyperthyroxinemia
TTR	Orphanet:85447	ATTRV30M amyloidosis
TTR	Orphanet:85451	ATTRV122I amyloidosis
ADAMTS10	Orphanet:3449	Weill-Marchesani syndrome
ADAMTS17	Orphanet:3449	Weill-Marchesani syndrome
ADAMTS17	Orphanet:363992	Ichthyosis-short stature-brachydactyly-microspherophakia syndrome
DIRC3	Orphanet:146	Differentiated thyroid carcinoma
DIRC3	Orphanet:422526	Hereditary clear cell renal cell carcinoma
COL11A1	Orphanet:2021	Fibrochondrogenesis
COL11A1	Orphanet:440354	Autosomal dominant myopia-midfacial retrusion-sensorineural hearing loss-rhizomelic dysplasia syndrome
COL11A1	Orphanet:560	Marshall syndrome
COL11A1	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
COL11A1	Orphanet:90654	Stickler syndrome type 2
IFT43	Orphanet:1515	Cranioectodermal dysplasia
IFT43	Orphanet:791	Retinitis pigmentosa
AEBP1	Orphanet:536532	Classical-like Ehlers-Danlos syndrome type 2
EFEMP1	Orphanet:75376	Familial drusen
EFEMP1	Orphanet:98977	Juvenile glaucoma
LTBP1	Orphanet:90349	Autosomal recessive cutis laxa type 1
SMAD6	Orphanet:402075	Familial bicuspid aortic valve

Cohort genes → proteins

14 cohort genes, 13 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	12
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FBN2	HGNC:3604	ENSG00000138829	P35556	Fibrillin-2	gencc
TTR	HGNC:12405	ENSG00000118271	P02766	Transthyretin	clinvar
ADAMTS10	HGNC:13201	ENSG00000142303	Q9H324	A disintegrin and metalloproteinase with thrombospondin motifs 10	gwas
ADAMTS17	HGNC:17109	ENSG00000140470	Q8TE56	A disintegrin and metalloproteinase with thrombospondin motifs 17	gwas
DIRC3	HGNC:17805	ENSG00000231672		disrupted in renal carcinoma 3	gwas
LNPK	HGNC:21610	ENSG00000144320	Q9C0E8	Endoplasmic reticulum junction formation protein lunapark	gwas
COL11A1	HGNC:2186	ENSG00000060718	P12107	Collagen alpha-1(XI) chain	gwas
IFT43	HGNC:29669	ENSG00000119650	Q96FT9	Intraflagellar transport protein 43 homolog	gwas
AEBP1	HGNC:303	ENSG00000106624	Q8IUX7	Adipocyte enhancer-binding protein 1	gwas
EFEMP1	HGNC:3218	ENSG00000115380	Q12805	EGF-containing fibulin-like extracellular matrix protein 1	gwas
ITGB5	HGNC:6160	ENSG00000082781	P18084	Integrin beta-5	gwas
LTBP1	HGNC:6714	ENSG00000049323	Q14766	Latent-transforming growth factor beta-binding protein 1	gwas
SMAD6	HGNC:6772	ENSG00000137834	O43541	SMAD family member 6	gwas
AOC1	HGNC:80	ENSG00000002726	P19801	Diamine oxidase [copper-containing]	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FBN2	Fibrillin-2	Fibrillins are structural components of 10-12 nm extracellular calcium-binding microfibrils, which occur either in association with elastin or in elastin-free bundles.
TTR	Transthyretin	Thyroid hormone-binding protein.
ADAMTS10	A disintegrin and metalloproteinase with thrombospondin motifs 10	Metalloprotease that participate in microfibrils assembly.
LNPK	Endoplasmic reticulum junction formation protein lunapark	Endoplasmic reticulum (ER)-shaping membrane protein that plays a role in determining ER morphology.
COL11A1	Collagen alpha-1(XI) chain	May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.
IFT43	Intraflagellar transport protein 43 homolog	As a component of IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is involved in ciliogenesis.
AEBP1	Adipocyte enhancer-binding protein 1	As a positive regulator of collagen fibrillogenesis, it is probably involved in the organization and remodeling of the extracellular matrix.
EFEMP1	EGF-containing fibulin-like extracellular matrix protein 1	Binds EGFR, the EGF receptor, inducing EGFR autophosphorylation and the activation of downstream signaling pathways.
ITGB5	Integrin beta-5	Integrin alpha-V/beta-5 (ITGAV:ITGB5) is a receptor for fibronectin.
LTBP1	Latent-transforming growth factor beta-binding protein 1	Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space.
SMAD6	SMAD family member 6	Transforming growth factor-beta superfamily receptors signaling occurs through the Smad family of intracellular mediators.
AOC1	Diamine oxidase [copper-containing]	Catalyzes the oxidative deamination of primary amines to the corresponding aldehydes with the concomitant production of hydrogen peroxide and ammonia.

Protein-family classification

Druggable: 4 · Difficult: 1 · Unknown: 9 · Druggable fraction: 0.29

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
Protease	3	7.8×	0.024
Other/Unknown	9	1.1×	0.721
Enzyme (other)	1	0.9×	0.836
Transcription factor	1	0.6×	0.836

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FBN2	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
TTR	Other/Unknown	no		Transthyretin/HIU_hydrolase, Transthyretin/HIU_hydrolase_d, Thyroxine_BS
ADAMTS10	Protease	yes		TSP1_rpt, Peptidase_M12B, Peptidase_M12B_N
ADAMTS17	Protease	yes		TSP1_rpt, Peptidase_M12B, Peptidase_M12B_N
DIRC3	Other/Unknown	no
LNPK	Transcription factor	no		Lunapark_Znf, Lnp
COL11A1	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen
IFT43	Other/Unknown	no		IFT43
AEBP1	Protease	yes		FA58C, Peptidase_M14, CarboxyPept-like_regulatory
EFEMP1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
ITGB5	Other/Unknown	no		VWF_A, Integrin_bsu_VWA, Integrin_bsu_tail
LTBP1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
SMAD6	Other/Unknown	no		SMAD_dom, MAD_homology1_Dwarfin-type, SMAD_FHA_dom_sf
AOC1	Enzyme (other)	yes	1.4.3.22	Cu_amine_oxidase, Cu_amine_oxidase_C, Cu_amine_oxidase_N2

Expression context

Cohort genes with no expression data: 0.

12 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)	14
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right coronary artery	4
descending thoracic aorta	3
cartilage tissue	2
right lobe of liver	2
ascending aorta	2
thoracic aorta	2
adrenal tissue	1
placenta	1
choroid plexus epithelium	1
type B pancreatic cell	1
kidney epithelium	1
primordial germ cell in gonad	1
thymus	1
layer of synovial tissue	1
male germ line stem cell (sensu Vertebrata) in testis	1
synovial joint	1
calcaneal tendon	1
colonic epithelium	1
tibialis anterior	1
periodontal ligament	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FBN2	194	ubiquitous	marker	cartilage tissue, placenta, adrenal tissue
TTR	185	broad	marker	choroid plexus epithelium, type B pancreatic cell, right lobe of liver
ADAMTS10	254	ubiquitous	yes	descending thoracic aorta, right coronary artery, kidney epithelium
ADAMTS17	177	broad	marker	thymus, primordial germ cell in gonad, right lobe of liver
DIRC3	161	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, layer of synovial tissue, synovial joint
LNPK	253	ubiquitous	marker	calcaneal tendon, tibialis anterior, colonic epithelium
COL11A1	209	broad	marker	tibia, cartilage tissue, periodontal ligament
IFT43	252	ubiquitous	marker	right uterine tube, bronchial epithelial cell, bronchus
AEBP1	273	ubiquitous	marker	tendon of biceps brachii, thoracic aorta, ascending aorta
EFEMP1	286	ubiquitous	marker	right coronary artery, thoracic aorta, descending thoracic aorta
ITGB5	293	ubiquitous	marker	stromal cell of endometrium, ascending aorta, right coronary artery
LTBP1	291	ubiquitous	marker	blood vessel layer, right coronary artery, descending thoracic aorta
SMAD6	277	ubiquitous	marker	right lung, renal glomerulus, metanephric glomerulus
AOC1	145	tissue_specific	marker	ileal mucosa, decidua, mucosa of transverse colon

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TTR	4,528
EFEMP1	2,988
FBN2	2,570
COL11A1	2,433
ITGB5	2,194
SMAD6	2,006
AOC1	1,364
LNPK	1,301
AEBP1	1,060
ADAMTS17	817

Intra-cohort edges

A	B	Sources
ADAMTS10	FBN2	string_interaction
ADAMTS17	FBN2	string_interaction

Structural data

PDB: 5 · AlphaFold-only: 8 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TTR	P02766	462
AOC1	P19801	5
IFT43	Q96FT9	3
ITGB5	P18084	3
LTBP1	Q14766	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
EFEMP1	Q12805	77.67
ADAMTS10	Q9H324	73.88
SMAD6	O43541	72.34
ADAMTS17	Q8TE56	70.06
LNPK	Q9C0E8	68.98
AEBP1	Q8IUX7	67.99
COL11A1	P12107	53.06
FBN2	P35556

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 53. Enrichment computed across 14 evidence-associated genes (11 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 11 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Molecules associated with elastic fibres	4	112.2×	2e-06	EFEMP1, FBN2, ITGB5, LTBP1
Elastic fibre formation	3	91.6×	1e-04	FBN2, ITGB5, LTBP1
Non-integrin membrane-ECM interactions	3	42.1×	7e-04	TTR, COL11A1, ITGB5
Signaling by TGFB family members	3	31.5×	0.001	ITGB5, LTBP1, SMAD6
TGF-beta receptor signaling activates SMADs	2	59.3×	0.004	ITGB5, LTBP1
Defective B3GALTL causes PpS	2	56.1×	0.004	ADAMTS10, ADAMTS17
O-glycosylation of TSR domain-containing proteins	2	54.6×	0.004	ADAMTS10, ADAMTS17
Diseases associated with O-glycosylation of proteins	2	39.2×	0.007	ADAMTS10, ADAMTS17
Signaling by TGF-beta Receptor Complex	2	36.4×	0.008	ITGB5, LTBP1
O-linked glycosylation	2	26.3×	0.013	ADAMTS10, ADAMTS17
Defective visual phototransduction due to STRA6 loss of function	1	346.1×	0.013	TTR
Diseases of glycosylation	2	23.9×	0.013	ADAMTS10, ADAMTS17
Cross-presentation of particulate exogenous antigens (phagosomes)	1	129.8×	0.030	ITGB5
Diseases of metabolism	2	14.6×	0.030	ADAMTS10, ADAMTS17
Histidine catabolism	1	103.8×	0.034	AOC1
Extracellular matrix organization	2	11.5×	0.041	ITGB5, LTBP1
RUNX2 regulates bone development	1	74.2×	0.042	SMAD6
Post-translational protein modification	3	5.2×	0.050	ADAMTS10, ADAMTS17, LTBP1
The canonical retinoid cycle in rods (twilight vision)	1	47.2×	0.059	TTR
Syndecan interactions	1	38.5×	0.068	ITGB5
MET activates PTK2 signaling	1	34.6×	0.072	COL11A1
Signaling by BMP	1	32.4×	0.073	SMAD6
Antigen processing-Cross presentation	1	28.8×	0.079	ITGB5
Smooth Muscle Contraction	1	24.1×	0.085	ITGB5
Collagen chain trimerization	1	23.6×	0.085	COL11A1
Transcriptional regulation by RUNX2	1	23.1×	0.085	SMAD6
Retinoid metabolism and transport	1	22.6×	0.085	TTR
Developmental Lineage of Pancreatic Ductal Cells	1	20.8×	0.089	COL11A1
Phase I - Functionalization of compounds	1	20.0×	0.089	AOC1
Assembly of collagen fibrils and other multimeric structures	1	18.2×	0.089	COL11A1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 13 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
obsolete sequestering of TGFbeta in extracellular matrix	2	648.1×	3e-04	FBN2, LTBP1
embryonic eye morphogenesis	2	235.7×	0.001	EFEMP1, FBN2
endodermal cell differentiation	2	76.2×	0.009	COL11A1, ITGB5
camera-type eye development	2	55.2×	0.012	EFEMP1, FBN2
putrescine metabolic process	1	648.1×	0.019	AOC1
establishment of protein localization to extracellular region	1	648.1×	0.019	LTBP1
endoplasmic reticulum tubular network maintenance	1	648.1×	0.019	LNPK
zygotic specification of dorsal/ventral axis	1	432.1×	0.019	SMAD6
post-embryonic eye morphogenesis	1	432.1×	0.019	EFEMP1
regulation of collagen fibril organization	1	432.1×	0.019	AEBP1
negative regulation of glomerular filtration	1	324.1×	0.019	TTR
response to laminar fluid shear stress	1	324.1×	0.019	SMAD6
tendon development	1	324.1×	0.019	COL11A1
positive regulation of endoplasmic reticulum tubular network organization	1	324.1×	0.019	LNPK
extracellular matrix organization	2	18.8×	0.028	ADAMTS10, ADAMTS17
purine nucleobase metabolic process	1	185.2×	0.028	TTR
proteolysis	3	7.9×	0.028	ADAMTS10, ADAMTS17, AEBP1
bone trabecula formation	1	162.0×	0.029	FBN2
proteoglycan metabolic process	1	144.0×	0.031	COL11A1
mitral valve morphogenesis	1	129.6×	0.033	SMAD6
regulation of chondrocyte differentiation	1	108.0×	0.036	LNPK
negative regulation of activin receptor signaling pathway	1	108.0×	0.036	SMAD6
phototransduction, visible light	1	99.7×	0.036	TTR
epithelial cell-cell adhesion	1	92.6×	0.036	ITGB5
intraciliary retrograde transport	1	86.4×	0.036	IFT43
endoplasmic reticulum tubular network organization	1	86.4×	0.036	LNPK
visual perception	2	12.2×	0.036	COL11A1, EFEMP1
wound healing, spreading of epidermal cells	1	81.0×	0.037	ITGB5
chondrocyte development	1	72.0×	0.038	COL11A1
pulmonary valve morphogenesis	1	72.0×	0.038	SMAD6

Therapeutics

Drugs indicated for this disease

0 approved, 7 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Betamethasone	Phase 3 (in late-stage trials)
Dextrose	Phase 3 (in late-stage trials)
Gabapentin	Phase 3 (in late-stage trials)
Lidocaine	Phase 3 (in late-stage trials)
Methylprednisolone	Phase 3 (in late-stage trials)
Methylprednisolone Acetate	Phase 3 (in late-stage trials)
Prednisolone Acetate	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Cannabidiol, Dalfampridine, Lipoic Acid, Alpha, Onabotulinumtoxina, Rimabotulinumtoxinb, Sodium Chloride, Tetracaine.

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 11

Druggability breadth: 5 of 14 evidence-associated genes (36%) 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
TTR	TRICLABENDAZOLE
AOC1	PENTAMIDINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TTR	29	4
ITGB5	4	3
AOC1	3	4
FBN2	0	0
ADAMTS10	0	0
ADAMTS17	0	0
DIRC3	0	0
LNPK	0	0
COL11A1	0	0
IFT43	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TRICLABENDAZOLE	4	TTR
AMLEXANOX	4	TTR
TOLCAPONE	4	TTR
DICLOFENAC	4	TTR
LEVOTHYROXINE	4	TTR
TAFAMIDIS	4	TTR
BENZIODARONE	4	TTR
BITHIONOL	4	TTR
BENZBROMARONE	4	TTR
ACORAMIDIS	4	TTR
GEMFIBROZIL	4	TTR
MECLOFENAMIC ACID	4	TTR
DASATINIB	4	TTR
DEXTROTHYROXINE	4	TTR
TRICLOSAN	4	TTR
DIFLUNISAL	4	TTR
PENTAMIDINE	4	AOC1
CAFFEIC ACID	3	TTR
RESVERATROL	3	TTR
EPIGALOCATECHIN GALLATE	3	TTR
DIACEREIN	3	TTR
CILENGITIDE	3	ITGB5
TOLFENAMIC ACID	2	TTR
LUTEOLIN	2	TTR
FLUFENAMIC ACID	2	TTR
XANTHOHUMOL	2	TTR
GENISTEIN	2	TTR
NIFLUMIC ACID	2	TTR
DAIDZEIN	2	TTR
PTEROSTILBENE	2	TTR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
TTR	423	Binding:391, Functional:32
ITGB5	78	Binding:76, Functional:2
AOC1	12	Binding:11, Functional:1
LNPK	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
AOC1	1.4.3.22	diamine oxidase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TTR	423

Pharmacogenomics

Cohort genes with a PharmGKB record: 14; with CPIC/DPWG dosing guidelines: 0.

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

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)
TRICLABENDAZOLE	4	TTR
AMLEXANOX	4	TTR
TOLCAPONE	4	TTR
DICLOFENAC	4	TTR
LEVOTHYROXINE	4	TTR
TAFAMIDIS	4	TTR
BENZIODARONE	4	TTR
BITHIONOL	4	TTR
BENZBROMARONE	4	TTR
ACORAMIDIS	4	TTR
GEMFIBROZIL	4	TTR
MECLOFENAMIC ACID	4	TTR
DASATINIB	4	TTR
DEXTROTHYROXINE	4	TTR
TRICLOSAN	4	TTR
DIFLUNISAL	4	TTR
PENTAMIDINE	4	AOC1
CAFFEIC ACID	3	TTR
RESVERATROL	3	TTR
EPIGALOCATECHIN GALLATE	3	TTR
DIACEREIN	3	TTR
CILENGITIDE	3	ITGB5
TOLFENAMIC ACID	2	TTR
LUTEOLIN	2	TTR
FLUFENAMIC ACID	2	TTR
XANTHOHUMOL	2	TTR
GENISTEIN	2	TTR
NIFLUMIC ACID	2	TTR
DAIDZEIN	2	TTR
PTEROSTILBENE	2	TTR

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	TTR, AOC1
B	Phased (≥1) drug, not yet approved	1	ITGB5
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	3	ADAMTS10, ADAMTS17, AEBP1
E	Difficult family or no structure, no drug	8	FBN2, DIRC3, LNPK, COL11A1, IFT43, EFEMP1, LTBP1, SMAD6

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FBN2	0	—
ADAMTS10	0	—
ADAMTS17	0	—
DIRC3	0	—
LNPK	1	—
COL11A1	0	—
IFT43	0	—
AEBP1	0	—
EFEMP1	0	—
LTBP1	0	—
SMAD6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 521.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	438
PHASE4	37
PHASE2	19
PHASE3	10
PHASE2/PHASE3	5
PHASE1/PHASE2	4
EARLY_PHASE1	4
PHASE1	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03867539	PHASE4	RECRUITING	Exparel and Education to Avoid Opioids After Carpal Tunnel Release
NCT04460521	PHASE4	RECRUITING	The ACTS Trial: N-acetylcysteine (NAC) and Night-splinting as a Non-operative Treatment for Carpal Tunnel Syndrome
NCT05306548	PHASE4	ACTIVE_NOT_RECRUITING	A Norwegian Trial Comparing Treatment Strategies for Carpal Tunnel Syndrome
NCT05475808	PHASE4	ACTIVE_NOT_RECRUITING	Comparison of the Efficacy of Different Treatment Methods in Patients With Carpal Tunnel Syndrome
NCT07283874	PHASE4	NOT_YET_RECRUITING	Does it Matter the Volume of Injectate on the Outcome of Ultrasound-guided Perineural Injection for Carpal Tunnel Syndrome
NCT00277563	PHASE4	COMPLETED	Short and Long Term Exposure to Unique, Time-Varying Pulsed Electro-Magnetic Fields in Refractory Carpal Tunnel Syndrome
NCT00678314	PHASE4	COMPLETED	Patient Controlled Regional Analgesia Following Carpal Tunnel Release: A Double-Blind Study Using Distal Perineural Catheters
NCT00904202	PHASE4	COMPLETED	A Study Of Lidocaine Patch 5% Alone, Gabapentin Alone, And Lidocaine Patch 5% And Gabapentin In Combination For The Relief Of Pain In Patients With Diverse Peripheral Neuropathic Pain Conditions
NCT01310218	PHASE4	COMPLETED	Length of Post Operative Dressing After Carpal Tunnel Release
NCT01588158	PHASE4	TERMINATED	Patient Satisfaction With Pain Relief After Ambulatory Hand Surgery
NCT01751347	PHASE4	COMPLETED	Bupivacaine Versus Lidocaine Local Anesthesia
NCT02038452	PHASE4	COMPLETED	Injection Versus Splinting in Carpal Tunnel Syndrome
NCT02140632	PHASE4	COMPLETED	Efficacy Study of Local Steroid Injection and Wrist Splinting for Carpal Tunnel Syndrome
NCT02652390	PHASE4	COMPLETED	Local Steroid Injection vs Placebo in Carpal Tunnel Syndrome
NCT03196817	PHASE4	UNKNOWN	Non-surgical Treatment of Carpal Tunnel Syndrome: Night Splint Versus Local Corticosteroid Infiltration
NCT03432858	PHASE4	COMPLETED	Preoperative Antibiotics for Carpal Tunnel Release Surgery
NCT03649763	PHASE4	COMPLETED	Onset and Duration of Forearm Nerve Blockade
NCT03792945	PHASE4	COMPLETED	Comparison of the Efficacy of Corticosteroid Injection and ESWT in Patients With CTS
NCT03802448	PHASE4	COMPLETED	Myofascial Release on Electrophysiological Measures of Pregnant Women With CTS
NCT04017390	PHASE4	WITHDRAWN	The Effect of Theraworx Foam in Carpal Tunnel Syndrome
NCT04025203	PHASE4	COMPLETED	Pain Reduction and Changes in Upper Limb Function Produced by Different Treatments in Carpal Tunnel Syndrome
NCT04119739	PHASE4	COMPLETED	Pain Reduction Produced by Different Treatments in Carpal Tunnel Syndrome
NCT04245371	PHASE4	COMPLETED	Lidocaine Patch 1.8% for Moderate to Severe Pain From Carpal Tunnel Syndrome
NCT04285281	PHASE4	COMPLETED	Oral Gabapentin and Median Nerve Mobilization in the Treatment of Carpal Tunnel Syndrome
NCT04328805	PHASE4	COMPLETED	Ibuprofen and Neural Mobilization Treatment in Carpal Tunnel Syndrome.
NCT04515966	PHASE4	UNKNOWN	A Comparison of Ultrasound-guided Steroid Injection With Wrist Splint in Carpal Tunnel Syndrome
NCT04767724	PHASE4	COMPLETED	Extracorporeal Shock Wave Versus Local Corticosteroid Injection for Carpal Tunnel Syndrome
NCT05496764	PHASE4	UNKNOWN	Local Injection of Steroid VS.Glucose 5% in Carpal Tunnel Syndrome
NCT06209957	PHASE4	COMPLETED	Study of Single Platelet-Rich Plasma Local Injection Vs. Single Corticosteroid Local Injection in Carpal Tunnel Syndrome
NCT06249503	PHASE4	COMPLETED	Ultrasound Guided Activated and Non Activated Platelet Rich Plasma Injection Versus Hydro Dissection by Steroids.
NCT06282640	PHASE4	COMPLETED	Comparıson Of Electromyography Results Before And After Vıtamın D Treatment In Patıents Wıth Carpal Tunnel Syndrome
NCT06349265	PHASE4	COMPLETED	Ultrasound-Guided 5% Dextrose Injection for Carpal Tunnel Syndrome
NCT06349824	PHASE4	COMPLETED	Dextrose, Steroid, PRP: Choosing the Right Injection for CRS Relief; a RCT
NCT06778759	PHASE4	COMPLETED	Ibuprofen Arginine and Neural Mobilization Versus Ibuprofen Arginine in the Treatment of Carpal Tunnel Syndrome
NCT06778798	PHASE4	COMPLETED	Gabapentin and Neural Mobilization Pain Reduction Effect Compared to Only Gabapentine
NCT06781489	PHASE4	COMPLETED	Pain Reduction Caused by the Combined Treatment of Physiotherapy, Oral Gabapentin and Oral Ibuprofen Arginine.
NCT07105540	PHASE4	COMPLETED	Comparison of Injection Techniques in Carpal Tunnel Syndrome
NCT06045013	PHASE3	RECRUITING	Ultrasound-guided Dextrose Injection Versus Dextrose With Methylprednisolone in Carpal Tunnel Syndrome
NCT07474714	PHASE3	NOT_YET_RECRUITING	Hyaluronic Acid Injection in Idiopathic Carpal Tunnel Syndrome; is it Effective as Local Corticosteroids
NCT00137735	PHASE3	COMPLETED	Gabapentin for Carpal Tunnel Syndrome

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LIDOCAINE	4	7
DEXMEDETOMIDINE	4	6
IBUPROFEN	4	4
AMITRIPTYLINE	4	3
GABAPENTIN	4	3
HYALURONIDASE	4	3
DEXTROSE	4	2
HYALURONATE SODIUM	4	2
METHYLPREDNISOLONE	4	2
METHYLPREDNISOLONE ACETATE	4	2
ROPIVACAINE	4	2
ACETAMINOPHEN	4	1
ACETYLCYSTEINE	4	1
BUPIVACAINE	4	1
CARBAMAZEPINE	4	1
CEFAZOLIN	4	1
CYANOCOBALAMIN	4	1
DALFAMPRIDINE	4	1
MENTHOL	4	1
MEPIVACAINE	4	1
ONABOTULINUMTOXINA	4	1
SODIUM CHLORIDE	4	1
TRIAMCINOLONE ACETONIDE	4	1
TRIAMCINOLONE HEXACETONIDE	4	1
VANCOMYCIN	4	1
OZONE	3	4
PARAFFIN	3	3
ACETYLCARNITINE	3	1
LEVOMENTHOL	3	1
LIPOIC ACID, ALPHA	3	1