TARDBP

TAR DNA binding protein, the group of RNA binding motif containing

Basic information

Region (hg38): 1:11012343-11030528

Links

ENSG00000120948 ∙ NCBI:23435 ∙ OMIM:605078 ∙ HGNC:11571 ∙ Uniprot:Q13148 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the TARDBP gene.

• Amyotrophic lateral sclerosis type 10 (83 variants)
• Amyotrophic lateral sclerosis type 10;TARDBP-related frontotemporal dementia (71 variants)
• not provided (56 variants)
• Inborn genetic diseases (36 variants)
• TARDBP-related frontotemporal dementia;Amyotrophic lateral sclerosis type 10 (27 variants)
• Frontotemporal dementia (11 variants)
• Amyotrophic Lateral Sclerosis, Dominant (10 variants)
• not specified (4 variants)
• TARDBP-related condition (4 variants)
• Motor neuron disease (3 variants)
• Immunodeficiency due to MASP-2 deficiency (3 variants)
• FRONTOTEMPORAL DEMENTIA WITH TDP43 INCLUSIONS, TARDBP-RELATED (2 variants)
• Frontotemporal lobar degeneration, TARDBP-related (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.

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				36	1	37
missense	7	10	39	1		57
nonsense			4			4
start loss						0
frameshift			1			1
inframe indel			3			3
splice donor/acceptor (+/-2bp)						0
splice region			1	2		3
non coding			40	31	18	89
Total	7	10	87	68	19

Highest pathogenic variant AF is 0.0000131

Variants in TARDBP

This is a list of pathogenic ClinVar variants found in the TARDBP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-11012630-G-T		Amyotrophic lateral sclerosis type 10	Uncertain significance (Jan 13, 2018)
1-11012634-G-A		Amyotrophic lateral sclerosis type 10 • Amyotrophic lateral sclerosis type 10;TARDBP-related frontotemporal dementia	Benign (Oct 25, 2022)
1-11012639-G-A		Amyotrophic lateral sclerosis type 10	Uncertain significance (Jan 13, 2018)
1-11012646-C-T		Amyotrophic lateral sclerosis type 10	Likely benign (Jan 12, 2018)
1-11012679-G-A		Amyotrophic lateral sclerosis type 10	Uncertain significance (Jan 13, 2018)
1-11012714-C-T		Amyotrophic lateral sclerosis type 10	Uncertain significance (Jan 12, 2018)
1-11012838-C-T		TARDBP-related frontotemporal dementia;Amyotrophic lateral sclerosis type 10	Benign (Oct 25, 2022)
1-11013450-TCA-T			Benign (Sep 17, 2018)
1-11013703-CTT-C		Amyotrophic Lateral Sclerosis, Dominant • Frontotemporal dementia	Likely benign (Jun 14, 2016)
1-11013739-T-C		TARDBP-related frontotemporal dementia;Amyotrophic lateral sclerosis type 10	Likely benign (Dec 08, 2022)
1-11013751-C-T		TARDBP-related frontotemporal dementia;Amyotrophic lateral sclerosis type 10 • Inborn genetic diseases	Benign/Likely benign (Jun 22, 2022)
1-11013763-C-T		Amyotrophic lateral sclerosis type 10 • Amyotrophic lateral sclerosis type 10;TARDBP-related frontotemporal dementia • Inborn genetic diseases	Conflicting classifications of pathogenicity (Apr 12, 2022)
1-11013784-A-G		Amyotrophic lateral sclerosis type 10 • Amyotrophic lateral sclerosis type 10;TARDBP-related frontotemporal dementia	Conflicting classifications of pathogenicity (Sep 23, 2022)
1-11013794-G-A		Amyotrophic lateral sclerosis type 10	Uncertain significance (Mar 25, 2024)
1-11013807-TGCTCTCCACGGTTACAG-AT		Inborn genetic diseases	Uncertain significance (Dec 08, 2020)
1-11013814-C-T		Inborn genetic diseases • Amyotrophic lateral sclerosis type 10;TARDBP-related frontotemporal dementia	Conflicting classifications of pathogenicity (Aug 24, 2023)
1-11013822-C-T		Amyotrophic lateral sclerosis type 10;TARDBP-related frontotemporal dementia	Uncertain significance (Sep 12, 2023)
1-11013838-G-A		Amyotrophic lateral sclerosis type 10;TARDBP-related frontotemporal dementia	Likely benign (Nov 15, 2022)
1-11013841-G-A		TARDBP-related frontotemporal dementia;Amyotrophic lateral sclerosis type 10	Likely benign (Apr 09, 2023)
1-11013848-C-T		Inborn genetic diseases	Uncertain significance (Dec 08, 2020)
1-11013876-G-C		Inborn genetic diseases	Likely benign (Oct 30, 2019)
1-11013889-C-T		TARDBP-related frontotemporal dementia;Amyotrophic lateral sclerosis type 10 • Inborn genetic diseases	Likely benign (Apr 09, 2021)
1-11013896-G-A		TARDBP-related frontotemporal dementia;Amyotrophic lateral sclerosis type 10	Uncertain significance (Dec 04, 2023)
1-11013916-C-T		Amyotrophic lateral sclerosis type 10;TARDBP-related frontotemporal dementia	Likely benign (Dec 03, 2021)
1-11013925-T-C		not specified • Amyotrophic lateral sclerosis type 10 • Amyotrophic lateral sclerosis type 10;TARDBP-related frontotemporal dementia • Inborn genetic diseases	Benign/Likely benign (Jan 27, 2024)

GnomAD

Source: gnomAD

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: dbNSFP

• 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

• 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_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