TPM3

Chr 1ADAR

tropomyosin 3

Also known as: CAPM1, CFTD, CMYO4A, CMYO4B, CMYP4A, CMYP4B, HEL-189, HEL-S-82p

NCBI Gene: 7170ENSG00000143549UniProt: P06753OMIM: 191030

This gene encodes a member of the tropomyosin family of actin-binding proteins. Tropomyosins are dimers of coiled-coil proteins that provide stability to actin filaments and regulate access of other actin-binding proteins. Mutations in this gene result in autosomal dominant nemaline myopathy and other muscle disorders. This locus is involved in translocations with other loci, including anaplastic lymphoma receptor tyrosine kinase (ALK) and neurotrophic tyrosine kinase receptor type 1 (NTRK1), which result in the formation of fusion proteins that act as oncogenes. There are numerous pseudogenes for this gene on different chromosomes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Congenital myopathy 4A, autosomal dominantMIM #255310
AD
Congenital myopathy 4B, autosomal recessiveMIM #609284
AR

Clinical highlights

Gene-disease validity (ClinGen)
TPM3-related myopathy · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total
1
Active trials
79
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.69
LOEUF
Multiple*
Mechanism· predicted
📖
GeneReview available — TPM3
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.69LOEUF
pLI 0.007
Z-score 2.56
OE 0.37 (0.21–0.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
2.35Z-score
OE missense 0.45 (0.37–0.55)
65 obs / 144.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.37 (0.21–0.69)
0≤0.351.4
Missense OE?0.45 (0.37–0.55)
0≤0.61.4
Synonymous OE?0.96
0≤1.21.6
LoF obs/exp: 7 / 19.0Missense obs/exp: 65 / 144.7Syn Z: 0.24

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TPM3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients