Disease of the tendon

Summary

Disease of the tendon (MONDO:0100010) is a disease with 1 cohort gene (6 GWAS associations across 4 studies) and 114 clinical trials. Top therapeutic interventions include hyaluronate sodium, amino acids, and mecasermin.

At a glance

• Cohort genes: 1
• GWAS associations: 6
• Clinical trials: 114

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	disease of the tendon
Mondo ID	MONDO:0100010
EFO	EFO:1001434
MeSH	D052256
SNOMED CT	68172002
UMLS	C0151936
MedGen	508839
Anatomy (UBERON)	UBERON:0000043
Is cancer (heuristic)	no

Also known as: disease of tendon · disease or disorder of tendon · disorder of tendon · tendinopathy · tendon disease · tendon disease or disorder

Data availability: 6 GWAS associations (4 studies).

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › disease of the tendon

Related subtypes (21): autoimmune disorder of musculoskeletal system, musculoskeletal system benign neoplasm, musculoskeletal system cancer, Klippel-Feil syndrome, enthesopathy, muscle tissue disorder, fasciitis, skeletal system disorder, synovial chondromatosis, auriculoosteodysplasia, hypertrophic osteoarthropathy, primary, autosomal dominant, Upington disease, Ramon syndrome, osteoporosis-oculocutaneous hypopigmentation syndrome, short stature, Brussels type, wormian bone-multiple fractures-dentinogenesis imperfecta-skeletal dysplasia, CINCA syndrome, chondrodysplasia with joint dislocations, gPAPP type, ligament disorder, synovium disorder, Short stature, Dauber-Argente type

Subtypes (3): tendinitis, tendon sheath disorder, tendinosis

Genetics & variants

GWAS landscape

6 GWAS associations across 4 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
rs1937810	2e-07	MPP7	C	1.16
rs57104447	3e-07	CACNA1E	C	1.28
rs57224706	6e-07	SMARCD1	G	1.36
rs60713544	7e-07	LINC02434 - RPL7AP27	C	1.43
rs11154027	1e-06	RNU4-35P - RNU4-76P	A	2.11
rs10263021	5e-06	CNTNAP2	?	2.38

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90018787	Sakaue S	2021	7,746	349,912	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST004263	Kim SK	2017	4,258	79,006	Genome-wide association screens for Achilles tendon and ACL tears and tendinopathy.
GCST90018567	Sakaue S	2021	312	175,979	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST009002	Rodas G	2019	181	0	Genomic Prediction of Tendinopathy Risk in Elite Team Sports.

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	0
Tier 4: intronic/intergenic	6

MAF distribution

Bucket	Variants
common (>=0.05)	6
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	4
intergenic_variant	2

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs1937810	10	28175021	T>C	0.05	intron_variant	MPP7	2e-07	Tier 4: intronic/intergenic
rs57104447	1	181810543	T>C	0.05	intron_variant	CACNA1E	3e-07	Tier 4: intronic/intergenic
rs57224706	12	50086502	A>C,G,T	0.05	intron_variant	SMARCD1	6e-07	Tier 4: intronic/intergenic
rs60713544	4	188193554	G>A,C	0.05	intergenic_variant	LINC02434 - RPL7AP27	7e-07	Tier 4: intronic/intergenic
rs11154027	6	121460244	T>A,C,G	0.05	intergenic_variant	RNU4-35P - RNU4-76P	1e-06	Tier 4: intronic/intergenic
rs10263021	7	148228400	T>C	0.05	intron_variant	CNTNAP2	5e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GJA1	Orphanet:1010	Autosomal dominant palmoplantar keratoderma and congenital alopecia
GJA1	Orphanet:1522	Craniometaphyseal dysplasia
GJA1	Orphanet:2248	Hypoplastic left heart syndrome
GJA1	Orphanet:2710	Oculodentodigital dysplasia
GJA1	Orphanet:317	Erythrokeratodermia variabilis
GJA1	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
GJA1	Orphanet:93404	Syndactyly type 3

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GJA1	HGNC:4274	ENSG00000152661	P17302	Gap junction alpha-1 protein	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GJA1	Gap junction alpha-1 protein	Structural component of the gap junction, a specialized intercellular structure consisting of a cluster of closely packed pairs of transmembrane channels, the connexons, that allow passage of small molecules and electrical signals between…

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GJA1	Other/Unknown	no		Connexin, Connexin43, Connexin_N

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
dorsal motor nucleus of vagus nerve	1
hair follicle	1
lateral globus pallidus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GJA1	292	ubiquitous	marker	lateral globus pallidus, dorsal motor nucleus of vagus nerve, hair follicle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GJA1	4,942

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GJA1	P17302	19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Oligomerization of connexins into connexons	1	3806.7×	1e-03	GJA1
Transport of connexins along the secretory pathway	1	3806.7×	1e-03	GJA1
Regulation of gap junction activity	1	3806.7×	1e-03	GJA1
SARS-CoV-2 targets PDZ proteins in cell-cell junction	1	2284.0×	0.001	GJA1
Formation of annular gap junctions	1	1038.2×	0.002	GJA1
Gap junction degradation	1	951.7×	0.002	GJA1
Mechanical load activates signaling by PIEZO1 and integrins in osteocytes	1	671.8×	0.002	GJA1
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	1	543.8×	0.003	GJA1
Gap junction assembly	1	292.8×	0.004	GJA1
RHOJ GTPase cycle	1	200.3×	0.005	GJA1
RHOQ GTPase cycle	1	181.3×	0.006	GJA1

GO biological processes by enrichment

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

GO term	Cohort genes	Fold	FDR	Sample cohort genes
microtubule-based transport	1	16852.0×	9e-04	GJA1
positive regulation of mesodermal cell differentiation	1	16852.0×	9e-04	GJA1
negative regulation of gonadotropin secretion	1	8426.0×	0.001	GJA1
positive regulation of morphogenesis of an epithelium	1	5617.3×	0.001	GJA1
cell communication by electrical coupling	1	4213.0×	0.001	GJA1
negative regulation of trophoblast cell migration	1	2407.4×	0.002	GJA1
gap junction assembly	1	2106.5×	0.002	GJA1
glutamate secretion	1	1685.2×	0.002	GJA1
atrial cardiac muscle cell action potential	1	1685.2×	0.002	GJA1
export across plasma membrane	1	1685.2×	0.002	GJA1
cell communication by electrical coupling involved in cardiac conduction	1	1404.3×	0.002	GJA1
cardiac conduction system development	1	1053.2×	0.002	GJA1
bone remodeling	1	936.2×	0.002	GJA1
xenobiotic transport	1	842.6×	0.003	GJA1
positive regulation of stem cell proliferation	1	526.6×	0.004	GJA1
establishment of mitotic spindle orientation	1	481.5×	0.004	GJA1
maintenance of blood-brain barrier	1	481.5×	0.004	GJA1
positive regulation of vascular associated smooth muscle cell proliferation	1	432.1×	0.004	GJA1
cellular response to amyloid-beta	1	391.9×	0.004	GJA1
bone development	1	276.3×	0.005	GJA1
monoatomic ion transmembrane transport	1	208.1×	0.007	GJA1
positive regulation of cold-induced thermogenesis	1	163.6×	0.008	GJA1
negative regulation of cell growth	1	144.0×	0.009	GJA1
intracellular protein localization	1	104.7×	0.012	GJA1
heart development	1	78.8×	0.015	GJA1
positive regulation of canonical NF-kappaB signal transduction	1	72.6×	0.016	GJA1
cell-cell signaling	1	69.6×	0.016	GJA1
positive regulation of gene expression	1	38.7×	0.028	GJA1
spermatogenesis	1	35.2×	0.029	GJA1
signal transduction	1	16.1×	0.062	GJA1

Therapeutics

Drugs indicated for this disease

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

Drug	Development status
Capsaicin	Approved (phase 4)
Lidocaine	Approved (phase 4)
Menthol	Approved (phase 4)
Methyl Salicylate	Approved (phase 4)
Naproxen	Approved (phase 4)
Betamethasone Acetate	Phase 3 (in late-stage trials)
Genipin	Phase 3 (in late-stage trials)
Hyaluronic Acid	Phase 3 (in late-stage trials)
Ketoprofen	Phase 3 (in late-stage trials)
Secukinumab	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Triamcinolone Acetonide	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Dextrose, Nitroglycerin, Onabotulinumtoxina, Polidocanol, Somatropin, Tetracaine.

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
GJA1	KANAMYCIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GJA1	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
KANAMYCIN	4	GJA1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
GJA1	4	Binding:4

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

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)
KANAMYCIN	4	GJA1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GJA1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 114.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	89
PHASE4	7
PHASE2	6
PHASE3	4
PHASE1	4
PHASE2/PHASE3	2
PHASE1/PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05292339	PHASE4	RECRUITING	Ketorolac in Upper Extremity Tendinopathy and Arthropathy
NCT05603468	PHASE4	ACTIVE_NOT_RECRUITING	Effect of PRP vs Corticosteroid in Rotator Cuff Tendinopathy Subtypes in Arthroscopic Repair
NCT06160427	PHASE4	ACTIVE_NOT_RECRUITING	Connective Tissue Matrix for Rotator Cuff Tendinopathy
NCT01652495	PHASE4	COMPLETED	Evaluation of Efficacy and Hypothalamus-pituitary-adrenal Axis Suppression Due to Corticosteroids Intrabursal Injection
NCT02978833	PHASE4	TERMINATED	Platelet-rich Plasma vs. Whole Blood for Gluteus Medius Tendinopathy
NCT02996409	PHASE4	COMPLETED	High-Volume Image-Guided Injection in Chronic Midportion Achilles Tendinopathy
NCT04278833	PHASE4	TERMINATED	Comparative Effectiveness of Particulate Versus Nonparticulate Steroid Injections for Musculoskeletal Conditions
NCT01269879	PHASE3	UNKNOWN	VIBration Training in EpicondylitiS
NCT01273688	PHASE3	UNKNOWN	Eccentric Training With or Without Elbow Brace for Epicondylitis
NCT01343836	PHASE2/PHASE3	COMPLETED	Autologous Tenocyte Implantation in Patients With Chronic Achilles Tendinopathy
NCT03986372	PHASE2/PHASE3	UNKNOWN	The Effect of Multiple Injection of Platlet-rich Plasma in Chronic Patellar Tendinopathy
NCT04231357	PHASE3	COMPLETED	Greater Trochanteric Pain Syndrome: Efficacy of Ultrasound Guided Platelet-rich Plasma vs Needle Tenotomy.
NCT05569174	PHASE3	COMPLETED	Study of Efficacy and Safety of AIN457/Secukinumab in Patients With Rotator Cuff Tendinopathy
NCT01185951	PHASE2	UNKNOWN	TENDOSHOCK-2010 Combination Therapy for Athletic Tendinopathies
NCT02064062	PHASE2	UNKNOWN	Autologous Stem Cells in Achilles Tendinopathy
NCT02330146	PHASE1/PHASE2	TERMINATED	Safety and Efficacy of RCT-01 in Men and Women With Unilateral, Chronic Achilles Tendinosis
NCT02597660	PHASE2	WITHDRAWN	A Study to Evaluate the Efficacy of Somatropin in the Treatment of Patellar Tendinopathy
NCT03344640	PHASE2	COMPLETED	Study of Efficacy, Safety and Tolerability of AIN457 in Patients With Active Overuse Tendinopathy
NCT03496649	PHASE2	UNKNOWN	Pubalgia and Adductor Tendinopathies Refractory to Medical Treatment
NCT04136743	PHASE2	UNKNOWN	Ultrasound-Guided Treatments for Shoulder Pain in Wheelchair Users With Spinal Cord Injury
NCT06100822	PHASE1	RECRUITING	Managing Chronic Tendon Pain by Metformin
NCT00279630	PHASE1	COMPLETED	Exercise and Shoe Orthoses in Treatment of Posterior Tibial Tendon Dysfunction
NCT03229291	PHASE1	COMPLETED	A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of SM04755 Following Topical Administration to Healthy Subjects
NCT03502434	PHASE1	COMPLETED	A Repeat Insult Patch Test (RIPT) Study Evaluating the Sensitization Potential of Topical SM04755 Solution in Healthy Volunteers
NCT01834989	EARLY_PHASE1	UNKNOWN	Patellar Tendinopathy - Effect of Training and Enhancement of the Collagen Synthesis by Insulin-like Growth Factor-I
NCT02600910	Not specified	ACTIVE_NOT_RECRUITING	Natural History of Shoulder Pathology in Manual Wheelchair Users
NCT03456778	Not specified	RECRUITING	Assessing the Tendons With Shear Wave Elastography
NCT04578418	Not specified	ACTIVE_NOT_RECRUITING	Effect of Collagen Supplementation on Tendinopathy
NCT05352139	Not specified	ENROLLING_BY_INVITATION	Treatment of Tendinosis Using the TenJet Hydroresection System
NCT05464498	Not specified	RECRUITING	Evaluation of Collagen-based Medical Device Treatment Combined With Physiotherapy in Subjects With Achilles Tendinopathy.
NCT05950022	Not specified	RECRUITING	Clinical Improvement Obtained by Endoscopic Ilio-Psoas Tenotomy (Lesser Trochanter Versus Acetabular Notch)
NCT06095050	Not specified	RECRUITING	Embolization Treatment of Chronic Refractory Shoulder Tendinopathy
NCT06142747	Not specified	RECRUITING	Tracking of Red Blood Cells Using Super Resolution Ultrasound in Persons With Healthy or Overuse Injured Tendons
NCT06583707	Not specified	NOT_YET_RECRUITING	Real Dry Needling and Placebo Dry Needling Applied With and Without Ultrasound Guidance on the Infraspinatus Muscle
NCT06639308	Not specified	ACTIVE_NOT_RECRUITING	Eendoscopic Versus Open Flexor Hallucis Longus Transfer in Managing Various Tendon Achilles Disorders
NCT06681051	Not specified	RECRUITING	Effectiveness and Safety of OSTENIL® TENDON in the Treatment of Pain and Restricted Mobility in Tendon Disorders
NCT07025668	Not specified	RECRUITING	The Effectiveness of Different Exercise Approaches in Biceps Brachii Long Head Tendinopathy
NCT07231471	Not specified	RECRUITING	Platelet Rich Plasma for Musculoskeletal Conditions
NCT07247825	Not specified	RECRUITING	Efficacy of Therapeutic Percutaneous Electrolysis vs Laser Therapy in Supraspinatus Tendinopathy.
NCT07540806	Not specified	NOT_YET_RECRUITING	Ultrasound-Guided Percutaneous Needle Tenotomy (PNT) vs Percutaneous Ultrasonic Needle Tenotomy (PUT) for Gluteal Tendinosis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
HYALURONATE SODIUM	4	2
AMINO ACIDS	4	1
MECASERMIN	4	1
METHYLPREDNISOLONE ACETATE	4	1
NITROGLYCERIN	4	1
PETROLATUM, WHITE	4	1
POLIDOCANOL	4	1
TRIAMCINOLONE ACETONIDE	4	1
BLOOD, WHOLE	3	1
SODIUM LAURYL SULFATE	3	1
CHEMBL1200844	0	1
CHEMBL1231723	0	1
CHEMBL1204779	0	1
CHEMBL3527065	0	1