TMOD4
protein-codingtropomodulin 4, the group of Tropomodulins
Gene summary
Predicted to enable tropomyosin binding activity. Predicted to be involved in actin filament organization; muscle contraction; and myofibril assembly. Located in striated muscle thin filament. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TMOD4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_013353.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 56 | 56 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 57 | 0 | 0 | 57 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_037485.2 | 9 | MANE Select | |
| Ensembl | ENSP00000295314.4 | 9 | MANE Select | |
| Ensembl | ENSP00000406333.1 | 4 | Standard | |
| Ensembl | ENSP00000468489.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| tmod4 | Danio rerio | Structure: fast muscle cell Quality: increased width abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Striated Muscle Contraction
- Muscle contraction
Biological Process
- muscle contraction
- myofibril assembly
- pointed-end actin filament capping
Molecular Function
- tropomyosin binding
- actin filament binding
Cellular Component
- striated muscle thin filament
- myofibril
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000295314
- Coding exons
- 9
- Length
- 6299
- Individuals with no LoFs
- 125602
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 144
- Defined
- 125747
- p
- 0.000577
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.715 | 177 | 206 | 0.860 | 0.0000115 | 2284 |
| Missense (PolyPhen) | 63 | 71.729 | 0.87831 | 834 | ||
| Synonymous | 1.05 | 61 | 72.4 | 0.842 | 0.00000378 | 642 |
| Loss of Function | 1.25 | 15 | 21.2 | 0.708 | 0.00000127 | 218 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0014 | 0.0014 | notable |
| Latino/Admixed American | 0.00046 | 0.00046 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00049 | 0.00049 | rare |
| Finnish | 0.0033 | 0.0033 | notable |
| European (Non-Finnish) | 0.00016 | 0.00016 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00065 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Blocks the elongation and depolymerization of the actin filaments at the pointed end. The Tmod/TM complex contributes to the formation of the short actin protofilament, which in turn defines the geometry of the membrane skeleton.;
Recessive Scores
- pRec
- 0.129
Intolerance Scores
- LoFtool
- 0.458
- RVIS EVS
- 0.33
- RVIS percentile EVS
- 73.41
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.903
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |