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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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TNMD
tenomodulin
Chromosome X · Xq22.1
NCBI Gene: 64102Ensembl: ENSG00000000005.6HGNC: HGNC:17757UniProt: Q9H2S6
31PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingnegative regulation of endothelial cell proliferationnegative regulation of angiogenesisnuclear envelopeArthrogryposis - hyperkeratosis, lethal formarthrogryposis-hyperkeratosis syndrome, lethal formcarpal tunnel syndrome 1carpal tunnel syndrome
✦AI Summary

TNMD (tenomodulin) is a type II transmembrane glycoprotein encoded on the X chromosome X functions as a key regulator of tendon development and homeostasis 1. The protein is predominantly expressed in dense connective tissues including tendons, ligaments, and skeletal muscle epimysium, where it serves as an efficient marker of tenocyte differentiation 1. TNMD inhibits angiogenesis and regulates tenocyte proliferation 1. During tendon repair, TNMD plays crucial roles in tendon maturation, differentiation, and extracellular matrix remodeling across multiple stages of the recovery process 2. In pathological conditions, TNMD expression is significantly downregulated in tendinopathy when macrophage-derived inflammatory signals are elevated, with reduced TNMD correlating with impaired tendon stem/progenitor cell differentiation and increased inflammatory infiltration 3. TNMD expression is also modulated by systemic factors; weight loss decreases TNMD mRNA in adipose tissue, and expression correlates with body mass index 4. TNMD polymorphisms (rs4828038) show genetic associations with late-onset preeclampsia susceptibility 5. Additionally, TNMD functions as a molecular marker for layer 6b neuronal differentiation in the developing cerebral cortex 6. These findings suggest TNMD has therapeutic potential in tendon tissue engineering, recovery promotion, and treatment of tendinopathy-related disorders.

Sources cited
1
TNMD is a type II transmembrane glycoprotein on X chromosome, expressed in tendons/ligaments, serves as tenocyte differentiation marker, inhibits angiogenesis, and regulates tenocyte proliferation
PMID: 27383874
2
TNMD is a key regulator of tendon maturation, differentiation, and remodeling in the tendon repair process
PMID: 40803747
3
TNMD expression is downregulated in tendinopathy with elevated macrophage inflammation, and CCL4L2+ M1 macrophages suppress TNMD and other tendon differentiation markers
PMID: 39696421
4
TNMD expression in adipose tissue is decreased by weight loss, correlates with body mass index, and inhibits angiogenesis
PMID: 20429799
5
TNMD rs4828038 polymorphism is associated with decreased susceptibility to late-onset preeclampsia
PMID: 34996340
6
TNMD is expressed as a layer 6b-specific gene required for normal differentiation of layer 6b cortical neurons
PMID: 40164579
7
TNMD+ fibroblasts are enriched in the right ventricle of arrhythmogenic right ventricular cardiomyopathy patients
PMID: 38185631
Disease Associationsⓘ20
Arthrogryposis - hyperkeratosis, lethal formOpen Targets
0.07Suggestive
arthrogryposis-hyperkeratosis syndrome, lethal formOpen Targets
0.07Suggestive
carpal tunnel syndromeOpen Targets
0.05Suggestive
carpal tunnel syndrome 1Open Targets
0.05Suggestive
atrial fibrillationOpen Targets
0.03Suggestive
obesityOpen Targets
0.02Suggestive
diabetes mellitusOpen Targets
0.02Suggestive
psoriasisOpen Targets
0.02Suggestive
age-related macular degenerationOpen Targets
0.01Suggestive
cryopyrin-associated periodic syndromeOpen Targets
0.01Suggestive
oral squamous cell carcinomaOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
neoplasmOpen Targets
0.01Suggestive
breast carcinomaOpen Targets
0.01Suggestive
chronic obstructive pulmonary diseaseOpen Targets
0.01Suggestive
infectionOpen Targets
0.01Suggestive
invasive breast ductal carcinomaOpen Targets
0.01Suggestive
Insulin resistanceOpen Targets
0.01Suggestive
triple-negative breast cancerOpen Targets
0.01Suggestive
breast ductal carcinoma in situOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SCXProtein interaction95%COL1A1Protein interaction92%MKXProtein interaction86%FMODProtein interaction79%THBS4Protein interaction74%GDF7Protein interaction72%
Tissue Expression6 tissues
Ovary
100%
Heart
74%
Brain
6%
Lung
2%
Bone Marrow
0%
Liver
0%
Gene Interaction Network
Click a node to explore
TNMDSCXCOL1A1MKXFMODTHBS4GDF7
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9H2S6
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.86LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.56 [0.37–0.86]
RankingsWhere TNMD stands among ~20K protein-coding genes
  • #11,815of 20,598
    Most Researched31
  • #7,495of 17,882
    Most Constrained (LOEUF)0.86
Genes detectedTNMD
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Single-cell RNA sequencing in donor and end-stage heart failure patients identifies NLRP3 as a therapeutic target for arrhythmogenic right ventricular cardiomyopathy.
PMID: 38185631
BMC Med · 2024
1.00
2
Pristimerin suppresses AIM2 inflammasome by modulating AIM2-PYCARD/ASC stability via selective autophagy to alleviate tendinopathy.
PMID: 37647255
Autophagy · 2024
0.90
3
Associations between the TNMD rs4828038 and ACE2 rs879922 polymorphisms and preeclampsia susceptibility: a case-control study.
PMID: 34996340
J Obstet Gynaecol · 2022
0.80
4
A Prospectus of Tenomodulin.
PMID: 27383874
Folia Med (Plovdiv) · 2016
0.70
5
CCL4L2 participates in tendinopathy progression by promoting macrophage inflammatory responses: a single-cell analysis.
PMID: 39696421
J Orthop Surg Res · 2024
0.60