TARDBP
TAR DNA binding protein, the group of RNA binding motif containing
Basic information
Region (hg38): 1:11012344-11030528
Links
Phenotypes
GenCC
Source:
- amyotrophic lateral sclerosis type 10 (Strong), mode of inheritance: AD
- amyotrophic lateral sclerosis type 10 (Definitive), mode of inheritance: AD
- amyotrophic lateral sclerosis type 10 (Strong), mode of inheritance: AD
- amyotrophic lateral sclerosis (Supportive), mode of inheritance: AD
- frontotemporal dementia with motor neuron disease (Supportive), mode of inheritance: AD
- amyotrophic lateral sclerosis type 10 (Definitive), mode of inheritance: AD
- inclusion body myositis (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Amyotrophic lateral sclerosis 10, with or without frontotemporal dementia | AD | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Neurologic | 17036243; 18288693; 18309045; 18372902; 18396105; 18438952; 18779421; 19224587; 19350673; 19609911; 20697052; 21220647; 21956716; 22292843; 22398199; 22456481; 22539580; 22722621; 24300238 |
ClinVar
This is a list of variants' phenotypes submitted to
- Amyotrophic_lateral_sclerosis_type_10 (147 variants)
- FRONTOTEMPORAL_LOBAR_DEGENERATION_WITH_TDP43_INCLUSIONS,_TARDBP-RELATED (133 variants)
- not_provided (54 variants)
- Inborn_genetic_diseases (52 variants)
- TARDBP-related_disorder (22 variants)
- not_specified (4 variants)
- Frontotemporal_dementia (3 variants)
- Motor_neuron_disease (3 variants)
- FRONTOTEMPORAL_DEMENTIA_WITH_TDP43_INCLUSIONS,_TARDBP-RELATED (2 variants)
- Amyotrophic_Lateral_Sclerosis,_Dominant (2 variants)
- Parkinsonian_disorder (1 variants)
- See_cases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TARDBP gene is commonly pathogenic or not. These statistics are base on transcript: NM_000007375.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 54 | 57 | ||||
| missense | 11 | 18 | 69 | 99 | ||
| nonsense | 6 | |||||
| start loss | 0 | |||||
| frameshift | 4 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 11 | 18 | 81 | 55 | 1 |
Highest pathogenic variant AF is 0.0000625772
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TARDBP | protein_coding | protein_coding | ENST00000240185 | 5 | 13383 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.985 | 0.0146 | 125746 | 0 | 2 | 125748 | 0.00000795 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.71 | 74 | 234 | 0.317 | 0.0000129 | 2753 |
| Missense in Polyphen | 3 | 39.151 | 0.076627 | 553 | ||
| Synonymous | -0.752 | 97 | 88.0 | 1.10 | 0.00000561 | 790 |
| Loss of Function | 3.62 | 1 | 17.2 | 0.0581 | 9.23e-7 | 194 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000879 | 0.00000879 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: DNA and RNA-binding protein which regulates transcription and splicing. Involved in the regulation of CFTR splicing. It promotes CFTR exon 9 skipping by binding to the UG repeated motifs in the polymorphic region near the 3'-splice site of this exon. The resulting aberrant splicing is associated with pathological features typical of cystic fibrosis. May also be involved in microRNA biogenesis, apoptosis and cell division. Can repress HIV-1 transcription by binding to the HIV-1 long terminal repeat. Stabilizes the low molecular weight neurofilament (NFL) mRNA through a direct interaction with the 3' UTR. {ECO:0000269|PubMed:11285240, ECO:0000269|PubMed:17481916}.;
- Disease
- DISEASE: Amyotrophic lateral sclerosis 10 (ALS10) [MIM:612069]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5- 10% of the cases. {ECO:0000269|PubMed:18288693, ECO:0000269|PubMed:18309045, ECO:0000269|PubMed:18372902, ECO:0000269|PubMed:18396105, ECO:0000269|PubMed:18438952, ECO:0000269|PubMed:19224587, ECO:0000269|PubMed:19350673, ECO:0000269|PubMed:19655382, ECO:0000269|PubMed:19695877, ECO:0000269|PubMed:20740007, ECO:0000269|PubMed:21220647, ECO:0000269|PubMed:21418058, ECO:0000269|PubMed:22456481}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- HDAC6 interactions
(Consensus)
Recessive Scores
- pRec
- 0.254
Intolerance Scores
- loftool
- rvis_EVS
- -0.38
- rvis_percentile_EVS
- 27.42
Haploinsufficiency Scores
- pHI
- 0.194
- hipred
- Y
- hipred_score
- 0.783
- ghis
- 0.686
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.895
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Low | Low | Low |
Mouse Genome Informatics
- Gene name
- Tardbp
- Phenotype
- muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype; hematopoietic system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype;
Zebrafish Information Network
- Gene name
- tardbp
- Affected structure
- CaP motoneuron
- Phenotype tag
- abnormal
- Phenotype quality
- decreased length
Gene ontology
- Biological process
- negative regulation of protein phosphorylation;transcription by RNA polymerase II;mRNA processing;RNA splicing;negative regulation of gene expression;positive regulation of insulin secretion;response to endoplasmic reticulum stress;positive regulation of protein import into nucleus;regulation of apoptotic process;negative regulation by host of viral transcription;positive regulation of transcription by RNA polymerase II;regulation of cell cycle;3'-UTR-mediated mRNA stabilization;nuclear inner membrane organization
- Cellular component
- nucleus;nucleoplasm;perichromatin fibrils;cytoplasm;nuclear speck;interchromatin granule;ribonucleoprotein complex
- Molecular function
- double-stranded DNA binding;DNA-binding transcription factor activity;RNA binding;single-stranded RNA binding;mRNA 3'-UTR binding;protein binding;identical protein binding;sequence-specific double-stranded DNA binding