TMOD1
Chr 9tropomodulin 1
Also known as: D9S57E, ETMOD, TMOD
The protein caps the pointed ends of actin filaments by binding to tropomyosin's N-terminus, blocking filament elongation and depolymerization to regulate erythrocyte membrane skeleton structure. Gain-of-function mutations cause congenital myopathy with nemaline rods through disruption of skeletal muscle actin filament organization. The condition follows an autosomal dominant inheritance pattern.
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
92 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 28 | 0 | 28 |
Likely Pathogenic | 0 | 0 | 4 | 0 | 4 |
VUS | 0 | 45 | 4 | 0 | 49 |
Likely Benign | 0 | 0 | 1 | 1 | 2 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 45 | 37 | 1 | 83 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TMOD1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools