TPM4
tropomyosin 4, the group of Tropomyosins
Basic information
Region (hg38): 19:16067020-16103002
Links
Phenotypes
GenCC
Source:
- autosomal dominant macrothrombocytopenia (Supportive), mode of inheritance: AD
- TPM4-related platelet disorder (Moderate), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Bleeding disorder, platelet-type, 25 | AD | Hematologic | The condition may involve bleeding tendency, and awareness may be beneficial related to prevention and management of bleeding episodes | Hematologic | 27479822; 28134622; 34758189; 35170221 |
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TPM4 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | |||||
| missense | 11 | 11 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 11 | 0 | 1 |
Variants in TPM4
This is a list of pathogenic ClinVar variants found in the TPM4 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 19-16067683-A-T | Hereditary breast ovarian cancer syndrome | Uncertain significance (Aug 01, 2020) | ||
| 19-16067728-A-C | not specified | Uncertain significance (Mar 31, 2023) | ||
| 19-16067730-T-G | not specified | Uncertain significance (Dec 15, 2022) | ||
| 19-16076055-G-A | Benign (Dec 31, 2019) | |||
| 19-16076136-G-C | not specified | Uncertain significance (Oct 25, 2022) | ||
| 19-16076144-T-A | not specified | Uncertain significance (Nov 22, 2022) | ||
| 19-16081925-G-A | not specified | Uncertain significance (Mar 20, 2024) | ||
| 19-16081963-G-C | not specified | Uncertain significance (Dec 28, 2023) | ||
| 19-16081985-C-T | Bleeding disorder, platelet-type, 25 | Pathogenic (Aug 28, 2023) | ||
| 19-16081986-G-A | not specified | Uncertain significance (Sep 20, 2023) | ||
| 19-16086428-T-C | not specified | Uncertain significance (Dec 13, 2022) | ||
| 19-16086446-G-A | not specified | Uncertain significance (Mar 01, 2024) | ||
| 19-16086478-C-T | Bleeding disorder, platelet-type, 25 | Pathogenic (Aug 28, 2023) | ||
| 19-16086526-C-T | not specified | Uncertain significance (May 24, 2023) | ||
| 19-16088078-C-T | Bleeding disorder, platelet-type, 25 | Pathogenic (Aug 28, 2023) | ||
| 19-16088079-G-T | not specified | Uncertain significance (Feb 10, 2023) | ||
| 19-16088082-C-T | Abnormal bleeding;Thrombocytopenia | Uncertain significance (May 01, 2020) | ||
| 19-16089107-C-T | not specified | Uncertain significance (Jun 10, 2024) | ||
| 19-16093694-G-A | not specified | Uncertain significance (Apr 12, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TPM4 | protein_coding | protein_coding | ENST00000538887 | 9 | 35983 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.389 | 0.611 | 125734 | 0 | 12 | 125746 | 0.0000477 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.951 | 127 | 161 | 0.789 | 0.00000932 | 1865 |
| Missense in Polyphen | 41 | 60.834 | 0.67396 | 762 | ||
| Synonymous | 0.888 | 54 | 63.0 | 0.858 | 0.00000378 | 493 |
| Loss of Function | 3.05 | 4 | 18.0 | 0.223 | 9.52e-7 | 227 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000289 | 0.0000289 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.0000800 | 0.0000791 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000370 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Binds to actin filaments in muscle and non-muscle cells. Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction. Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments (By similarity). Binds calcium (PubMed:1836432). {ECO:0000250|UniProtKB:P09495, ECO:0000269|PubMed:1836432}.;
- Pathway
- Cardiac muscle contraction - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Striated Muscle Contraction;Smooth Muscle Contraction;Striated Muscle Contraction;Muscle contraction
(Consensus)
Recessive Scores
- pRec
- 0.204
Intolerance Scores
- loftool
- 0.332
- rvis_EVS
- -0.07
- rvis_percentile_EVS
- 48.12
Haploinsufficiency Scores
- pHI
- 0.207
- hipred
- Y
- hipred_score
- 0.761
- ghis
- 0.540
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.818
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Tpm4
- Phenotype
Zebrafish Information Network
- Gene name
- tpm4a
- Affected structure
- cardiac muscle cell
- Phenotype tag
- abnormal
- Phenotype quality
- absent
Gene ontology
- Biological process
- osteoblast differentiation;muscle contraction;actin filament organization;muscle filament sliding
- Cellular component
- stress fiber;podosome;cytosol;cytoskeleton;muscle thin filament tropomyosin;actin filament;focal adhesion;membrane;cortical cytoskeleton;extracellular exosome
- Molecular function
- calcium ion binding;protein binding;structural constituent of muscle;identical protein binding;protein homodimerization activity;protein heterodimerization activity;actin filament binding