HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
TPM3
tropomyosin 3
Chromosome 1 Β· 1q21.3
NCBI Gene: 7170Ensembl: ENSG00000143549.22HGNC: HGNC:12012UniProt: A0A087WWU8
312PubMed Papers
22Diseases
0Drugs
35Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneOncogene
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingstress fibermitochondrionextracellular exosomecongenital fiber-type disproportion myopathycongenital myopathy 4B, autosomal recessivenemaline myopathycap myopathy
✦AI Summary

TPM3 (tropomyosin 3) is a critical regulator of muscle contraction that binds to actin filaments in both skeletal and smooth muscle cells. 1 In skeletal muscle, TPM3 functions as an indispensable regulator of muscle contraction in slow muscle fibers, working in association with the troponin complex to enable calcium-dependent regulation of striated muscle contraction. 1 TPM3 exists in multiple isoforms (TPM3Ξ±, TPM3Ξ½, TPM3ΞΎ, and TPM3ΞΏ) that are differentially expressed across tissues, with stronger expression in fetal heart and adult skeletal muscle compared to adult heart. 2 Beyond muscle contraction, TPM3 plays broader roles in actin filament organization and stabilization of the cytoskeleton in non-muscle cells. Mutations in TPM3 are associated with congenital myopathies 4A (autosomal dominant) and 4B (autosomal recessive), representing a class of genetic muscle diseases affecting actin-myosin interaction and myofibril force production. 3 Recent research has identified disease mechanisms by which TPM3 mutations lead to muscle dysfunction, though the precise mechanisms remain incompletely understood. 1 Additionally, TPM3 fusion proteins (TPM3-ALK, TPM3-NTRK1) have been identified in various malignancies including histiocytic neoplasms and renal cell carcinoma, where they function as oncogenic drivers responsive to targeted ALK inhibition. 456

Sources cited
1
TPM3 is an indispensable regulator of muscle contraction in slow muscle fibers with multiple isoforms and functions in skeletal muscle development and myopathy
PMID: 37936227
2
Multiple TPM3 isoforms are expressed in human heart and skeletal muscle with differential tissue expression patterns
PMID: 32761805
3
TPM3 mutations cause congenital myopathies through effects on actin-myosin interaction and myofibril force production
PMID: 39223631
4
TPM3-NTRK1 fusion identified in lung cancer
PMID: 25384085
5
TPM3-ALK fusion identified in ALK-positive histiocytosis responsive to ALK inhibition
PMID: 34727172
6
TPM3-ALK fusion identified in renal cell carcinoma
PMID: 36370168
Disease Associationsβ“˜22
congenital fiber-type disproportion myopathyOpen Targets
0.82Strong
congenital myopathy 4B, autosomal recessiveOpen Targets
0.73Strong
nemaline myopathyOpen Targets
0.57Moderate
cap myopathyOpen Targets
0.56Moderate
TPM3-related myopathyOpen Targets
0.49Moderate
cancerOpen Targets
0.48Moderate
genetic disorderOpen Targets
0.40Moderate
papillary thyroid carcinomaOpen Targets
0.38Weak
anaplastic large cell lymphomaOpen Targets
0.38Weak
non-small cell lung carcinomaOpen Targets
0.37Weak
inflammatory myofibroblastic tumorOpen Targets
0.37Weak
congenital myopathyOpen Targets
0.37Weak
spitz nevusOpen Targets
0.37Weak
colon adenocarcinomaOpen Targets
0.37Weak
melanocytic neoplasmOpen Targets
0.37Weak
childhood-onset nemaline myopathyOpen Targets
0.37Weak
intermediate nemaline myopathyOpen Targets
0.37Weak
Ovarian Endometrioid Adenocarcinoma with Squamous DifferentiationOpen Targets
0.37Weak
thyroid gland oncocytic adenomaOpen Targets
0.37Weak
Thyroid Gland Oncocytic Follicular CarcinomaOpen Targets
0.37Weak
Congenital myopathy 4A, autosomal dominantUniProt
Congenital myopathy 4B, autosomal recessiveUniProt
Pathogenic Variants35
NM_152263.4(TPM3):c.503G>A (p.Arg168His)Pathogenic
Congenital myopathy 4B, autosomal recessive|not provided|Congenital myopathy 4A, autosomal dominant|Congenital myopathy 4B, autosomal recessive;Congenital myopathy with fiber type disproportion|See cases
β˜…β˜…β˜†β˜†2025β†’ Residue 168
NM_152263.4(TPM3):c.502C>T (p.Arg168Cys)Pathogenic
Congenital myopathy with fiber type disproportion|Congenital myopathy 4A, autosomal dominant|not provided|Congenital myopathy with fiber type disproportion;Congenital myopathy 4B, autosomal recessive|Inborn genetic diseases|Nemaline myopathy
β˜…β˜…β˜†β˜†2025β†’ Residue 168
NM_152263.4(TPM3):c.272G>A (p.Arg91His)Likely pathogenic
Congenital myopathy 4B, autosomal recessive;Congenital myopathy with fiber type disproportion|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 91
NM_152263.4(TPM3):c.271C>T (p.Arg91Cys)Pathogenic
Congenital myopathy with fiber type disproportion;Congenital myopathy 4B, autosomal recessive|Congenital myopathy 4A, autosomal dominant
β˜…β˜…β˜†β˜†2025β†’ Residue 91
NM_152263.4(TPM3):c.118-12G>APathogenic
Congenital myopathy with fiber type disproportion|not provided|Congenital myopathy 4B, autosomal recessive
β˜…β˜…β˜†β˜†2024
NM_152263.4(TPM3):c.502C>G (p.Arg168Gly)Pathogenic
Congenital myopathy with fiber type disproportion|not provided|Congenital myopathy 4B, autosomal recessive|Congenital myopathy with fiber type disproportion;Congenital myopathy 4B, autosomal recessive|Congenital myopathy 4A, autosomal dominant|TPM3-related core myopathy
β˜…β˜…β˜†β˜†2024β†’ Residue 168
NM_152263.4(TPM3):c.94C>T (p.Gln32Ter)Pathogenic
Congenital myopathy 4B, autosomal recessive|not provided|Congenital myopathy 4A, autosomal dominant|Congenital myopathy 4B, autosomal recessive;Congenital myopathy with fiber type disproportion
β˜…β˜…β˜†β˜†2024β†’ Residue 32
NM_152263.4(TPM3):c.455C>T (p.Ala152Val)Pathogenic
not provided|Congenital myopathy 4B, autosomal recessive;Congenital myopathy with fiber type disproportion
β˜…β˜…β˜†β˜†2022β†’ Residue 152
NM_152263.4(TPM3):c.688dup (p.Thr230fs)Pathogenic
Congenital myopathy with fiber type disproportion;Congenital myopathy 4B, autosomal recessive
β˜…β˜†β˜†β˜†2025β†’ Residue 230
NM_152263.4(TPM3):c.857A>C (p.Ter286Ser)Likely pathogenic
Congenital myopathy 4B, autosomal recessive|not provided|Congenital myopathy 4B, autosomal recessive;Congenital myopathy with fiber type disproportion
β˜…β˜†β˜†β˜†2025β†’ Residue 286
NM_152263.4(TPM3):c.272G>C (p.Arg91Pro)Pathogenic
Congenital myopathy with fiber type disproportion|not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 91
NM_152263.4(TPM3):c.298C>G (p.Leu100Val)Likely pathogenic
Congenital myopathy 4B, autosomal recessive;Congenital myopathy with fiber type disproportion
β˜…β˜†β˜†β˜†2024β†’ Residue 100
NM_152263.4(TPM3):c.856T>C (p.Ter286Gln)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 286
NM_152263.4(TPM3):c.41T>G (p.Leu14Ter)Likely pathogenic
Congenital myopathy 4B, autosomal recessive
β˜…β˜†β˜†β˜†2024β†’ Residue 14
NM_152263.4(TPM3):c.138del (p.Met47fs)Pathogenic
Congenital myopathy 4A, autosomal dominant
β˜…β˜†β˜†β˜†2024β†’ Residue 47
NM_152263.4(TPM3):c.87_91del (p.Gln30fs)Pathogenic
Congenital myopathy with fiber type disproportion;Congenital myopathy 4B, autosomal recessive
β˜…β˜†β˜†β˜†2024β†’ Residue 30
NM_152263.4(TPM3):c.243+1G>ALikely pathogenic
Congenital myopathy 4B, autosomal recessive;Congenital myopathy with fiber type disproportion
β˜…β˜†β˜†β˜†2023
NM_152263.4(TPM3):c.452A>C (p.Glu151Ala)Pathogenic
Congenital myopathy 4B, autosomal recessive;Congenital myopathy with fiber type disproportion
β˜…β˜†β˜†β˜†2023β†’ Residue 151
NM_152263.4(TPM3):c.137C>T (p.Ala46Val)Likely pathogenic
Congenital myopathy with fiber type disproportion;Congenital myopathy 4B, autosomal recessive
β˜…β˜†β˜†β˜†2023β†’ Residue 46
NM_152263.4(TPM3):c.271C>G (p.Arg91Gly)Likely pathogenic
Congenital myopathy 4B, autosomal recessive;Congenital myopathy with fiber type disproportion
β˜…β˜†β˜†β˜†2022β†’ Residue 91
View on ClinVar β†—
Related Genes
TSPAN16Protein interaction100%KIF5BProtein interaction98%NTRK1Protein interaction98%TPRProtein interaction92%MYL12BProtein interaction91%KXD1Protein interaction87%
Tissue Expression6 tissues
Lung
100%
Brain
92%
Bone Marrow
81%
Heart
35%
Liver
28%
Ovary
18%
Gene Interaction Network
Click a node to explore
TPM3TSPAN16KIF5BNTRK1TPRMYL12BKXD1
PROTEIN STRUCTURE
Preparing viewer…
PDB6OTN Β· 2.40 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.51Moderately Constrained
pLIβ“˜
0.97Intolerant
Observed/Expected LoF0.32 [0.21–0.51]
RankingsWhere TPM3 stands among ~20K protein-coding genes
  • #1,095of 20,598
    Most Researched312 Β· top 10%
  • #1,665of 5,498
    Most Pathogenic Variants35
  • #3,110of 17,882
    Most Constrained (LOEUF)0.51 Β· top quartile
Genes detectedTPM3
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Anchored multiplex PCR for targeted next-generation sequencing.
PMID: 25384085
Nat Med Β· 2014
1.00
2
A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.
PMID: 34602496
J Neuromuscul Dis Β· 2022
0.90
3
[Congenital myopathies].
PMID: 14593641
Rev Neurol Β· 2003
0.88
4
ALK-positiveΒ histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition.
PMID: 34727172
Blood Β· 2022
0.80
5
Tropomyosin 3 (TPM3) function in skeletal muscle and in myopathy.
PMID: 37936227
Skelet Muscle Β· 2023
0.70