TARDBP (TAR DNA-binding protein 43) variants and mutations
TARDBP (also known as TAR DNA-binding protein 43) is a human protein-coding gene encoding a TAR DNA-binding protein 43 protein. TDP-43 is an RNA-binding protein that regulates RNA processing, splicing, stability, and transport. Its normal activity supports neuronal and muscle cells, while abnormal TDP-43 accumulation is closely associated with amyotrophic lateral sclerosis and frontotemporal degeneration. This analysis covers 132 TARDBP variants and mutations. Of these, 91% have computational variant effect predictions. Disease context includes amyotrophic lateral sclerosis, familial amyotrophic lateral sclerosis, and frontotemporal dementia with motor neuron disease. Example TARDBP variants include S2A, S2T, and S2Y.
Variant analysis overview
- Gene: TARDBP
- Protein: TAR DNA-binding protein 43
- UniProt accession: Q13148
- Organism: Homo sapiens
- Variants analyzed: 132
- Variant scope: all variants
- Completed: 2026-06-10
Variant and mutation evidence
- Variant composition: 28 natural variant; 54 missense variants; 39 synonymous variants; 1 stop-gained variants; 10 substitution
- Prediction scores: 120 variants have prediction scores (91% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: amyotrophic lateral sclerosis, familial amyotrophic lateral sclerosis, frontotemporal dementia with motor neuron disease, frontotemporal dementia, neurodegenerative disease, motor neuron disease, amyotrophic lateral sclerosis, dominant, genetic disorder, immunodeficiency due to MASP-2 deficiency, Parkinson disease, Pick disease, Alzheimer disease.
Protein structure and variant hotspots
- Protein features: 2 domains; 3 post-translational modification sites.
- Structural context: 1 variants have structural context.
- Experimental data: 72 protein positions have experimental scores. Source: binding assays.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, PharmGKB, MaveDB, LitVar.
Notable TARDBP variants
Examples include S2A, S2T, S2Y, S2F, S2C, Y4C, Y4Y, R6R. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- S2A (p.Ser2Ala), gnomAD 1-11013731-T-G, REVEL 0.04, MetaLR 0.43
- S2T (p.Ser2Thr), gnomAD 1-11013731-T-A, REVEL 0.07, MetaLR 0.41
- S2Y (p.Ser2Tyr), gnomAD 1-11013732-C-A, REVEL 0.31, MetaLR 0.50
- S2F (p.Ser2Phe), gnomAD 1-11013732-C-T, REVEL 0.27, MetaLR 0.47
- S2C (p.Ser2Cys), gnomAD 1-11013732-C-G, REVEL 0.29, MetaLR 0.62
- Y4C (p.Tyr4Cys), gnomAD 1-11013738-A-G, REVEL 0.76, MetaLR 0.78
- Y4Y (p.Tyr4Tyr), rs1179641429, gnomAD 1-11013739-T-C, CADD 11.90
- R6R (p.Arg6Arg), rs1570711928, gnomAD 1-11013743-C-A, CADD 15.90
- V7V (p.Val7Val), gnomAD 1-11013748-A-G, CADD 12.80
- T8S (p.Thr8Ser), gnomAD 1-11013750-C-G, REVEL 0.14, MetaLR 0.25
- T8T (p.Thr8Thr), gnomAD 1-11013751-C-A, CADD 4.03
- E9K (p.Glu9Lys), rs1643462638, gnomAD 1-11013752-G-A, REVEL 0.50, MetaLR 0.64
- D10Y (p.Asp10Tyr), gnomAD 1-11013755-G-T, REVEL 0.56, MetaLR 0.75
- D10N (p.Asp10Asn), gnomAD 1-11013755-G-A, REVEL 0.30, MetaLR 0.62
- D10G (p.Asp10Gly), gnomAD 1-11013756-A-G, REVEL 0.41, MetaLR 0.57
- D10E (p.Asp10Glu), gnomAD 1-11013757-T-G, REVEL 0.27, MetaLR 0.35
- E11G (p.Glu11Gly), gnomAD 1-11013759-A-G, REVEL 0.52, MetaLR 0.76
- E11E (p.Glu11Glu), rs1164685852, gnomAD 1-11013760-G-A, CADD 13.70
- N12N (p.Asn12Asn), rs565091566, gnomAD 1-11013763-C-T, CADD 5.83
- N12K (p.Asn12Lys), gnomAD 1-11013763-C-G, REVEL 0.24, MetaLR 0.59
- D13N (p.Asp13Asn), gnomAD 1-11013764-G-A, REVEL 0.20, MetaLR 0.47
- D13H (p.Asp13His), rs1643462850, gnomAD 1-11013764-G-C, REVEL 0.43, MetaLR 0.73
- D13E (p.Asp13Glu), gnomAD 1-11013766-T-G, REVEL 0.09, MetaLR 0.20
- D13D (p.Asp13Asp), gnomAD 1-11013766-T-C, CADD 8.57
- E14E (p.Glu14Glu), rs748698993, gnomAD 1-11013769-G-A, CADD 9.64
- P15S (p.Pro15Ser), gnomAD 1-11013770-C-T, REVEL 0.49, MetaLR 0.66
- E17D (p.Glu17Asp), gnomAD 1-11013778-A-C, REVEL 0.53, MetaLR 0.71
- E17E (p.Glu17Glu), gnomAD 1-11013778-A-G, CADD 12.80
- P19A (p.Pro19Ala), gnomAD 1-11013782-C-G, REVEL 0.68, MetaLR 0.77
- P19P (p.Pro19Pro), rs532319219, gnomAD 1-11013784-A-G, CADD 8.20
- S20A (p.Ser20Ala), rs1643463035, gnomAD 1-11013785-T-G, REVEL 0.26, MetaLR 0.31
- S20L (p.Ser20Leu), gnomAD 1-11013786-C-T, REVEL 0.41, MetaLR 0.37
- S20S (p.Ser20Ser), rs1643463090, gnomAD 1-11013787-G-A, CADD 5.39
- D22D (p.Asp22Asp), rs773358415, gnomAD 1-11013793-C-T, CADD 9.18
- D23N (p.Asp23Asn), rs375089732, gnomAD 1-11013794-G-A, REVEL 0.48, MetaLR 0.53
- D23D (p.Asp23Asp), gnomAD 1-11013796-T-C, CADD 11.30
- G24G (p.Gly24Gly), rs766620483, gnomAD 1-11013799-G-A, CADD 9.24
- T25M (p.Thr25Met), gnomAD 1-11013801-C-T, REVEL 0.75, MetaLR 0.78
- T25T (p.Thr25Thr), rs1338531479, gnomAD 1-11013802-G-A, CADD 2.46
- V26V (p.Val26Val), rs1643463343, gnomAD 1-11013805-G-A, CADD 13.20
- L27L (p.Leu27Leu), gnomAD 1-11013806-C-T, CADD 13.30
- L28L (p.Leu28Leu), rs369718876, gnomAD 1-11013811-C-T, CADD 13.00
- S29S (p.Ser29Ser), rs201693535, gnomAD 1-11013814-C-T, CADD 14.60
- T30T (p.Thr30Thr), rs111671110, gnomAD 1-11013817-G-A, CADD 3.90
- V31V (p.Val31Val), rs1256306320, gnomAD 1-11013820-T-G, CADD 7.20
- T32T (p.Thr32Thr), rs1196927496, gnomAD 1-11013823-A-G, CADD 8.77
- P36P (p.Pro36Pro), gnomAD 1-11013835-A-G, CADD 12.20
- A38S (p.Ala38Ser), gnomAD 1-11013839-G-T, REVEL 0.60, MetaLR 0.56
- A38A (p.Ala38Ala), rs535276506, gnomAD 1-11013841-G-C, CADD 1.81
- G40G (p.Gly40Gly), rs758344713, gnomAD 1-11013847-G-C, CADD 10.60
- L41I (p.Leu41Ile), gnomAD 1-11013848-C-A, REVEL 0.65, MetaLR 0.80
- R42R (p.Arg42Arg), gnomAD 1-11013853-C-T, CADD 15.50
- Y43C (p.Tyr43Cys), rs1239871361, gnomAD 1-11013855-A-G, REVEL 0.90, MetaLR 0.78
- R44K (p.Arg44Lys), gnomAD 1-11013858-G-A, REVEL 0.53, MetaLR 0.46
- N45Y (p.Asn45Tyr), gnomAD 1-11013860-A-T, REVEL 0.77, MetaLR 0.71
- N45S (p.Asn45Ser), rs1643464086, gnomAD 1-11013861-A-G, REVEL 0.36, MetaLR 0.46
- V47A (p.Val47Ala), rs1643464134, gnomAD 1-11013867-T-C, REVEL 0.24, MetaLR 0.38
- S48F (p.Ser48Phe), gnomAD 1-11013870-C-T, REVEL 0.66, MetaLR 0.61
- S48C (p.Ser48Cys), gnomAD 1-11013870-C-G, REVEL 0.64, MetaLR 0.68
- S48S (p.Ser48Ser), rs1237709070, gnomAD 1-11013871-T-G, CADD 8.61
- C50S (p.Cys50Ser), rs953145872, gnomAD 1-11013876-G-C, REVEL 0.33, MetaLR 0.36
- C50F (p.Cys50Phe), gnomAD 1-11013876-G-T, REVEL 0.75, MetaLR 0.57
- C50Y (p.Cys50Tyr), gnomAD 1-11013876-G-A, REVEL 0.77, MetaLR 0.59
- M51R (p.Met51Arg), gnomAD 1-11013879-T-G, REVEL 0.58, MetaLR 0.41
- G53V (p.Gly53Val), gnomAD 1-11013885-G-T, REVEL 0.87, MetaLR 0.78
- V54V (p.Val54Val), gnomAD 1-11013889-C-A, CADD 8.70
- R55W (p.Arg55Trp), gnomAD 1-11013890-C-T, REVEL 0.86, MetaLR 0.78
- R55R (p.Arg55Arg), rs756772204, gnomAD 1-11013892-G-A, CADD 6.18
- L56L (p.Leu56Leu), rs780873066, gnomAD 1-11013893-C-T, CADD 14.30
- V57A (p.Val57Ala), gnomAD 1-11013897-T-C, REVEL 0.27, MetaLR 0.40
- V57V (p.Val57Val), gnomAD 1-11013898-A-G, CADD 5.62
- E58K (p.Glu58Lys), gnomAD 1-11013899-G-A, REVEL 0.55, MetaLR 0.58
- E58G (p.Glu58Gly), gnomAD 1-11013900-A-G, REVEL 0.77, MetaLR 0.57
- I60V (p.Ile60Val), rs866353277, gnomAD 1-11013905-A-G, REVEL 0.08, MetaLR 0.24
- I60T (p.Ile60Thr), rs1643464740, gnomAD 1-11013906-T-C, REVEL 0.16, MetaLR 0.50
- L61L (p.Leu61Leu), rs1643464848, gnomAD 1-11013910-G-A, CADD 12.70
- H62R (p.His62Arg), gnomAD 1-11013912-A-G, REVEL 0.38, MetaLR 0.82
- H62H (p.His62His), gnomAD 1-11013913-T-C, CADD 7.71
- A63A (p.Ala63Ala), rs1399738284, gnomAD 1-11013916-C-T, CADD 11.60
- P64P (p.Pro64Pro), rs2100838504, gnomAD 1-11013919-A-C, CADD 4.67
- D65V (p.Asp65Val), gnomAD 1-11013921-A-T, REVEL 0.49, MetaLR 0.81
- D65E (p.Asp65Glu), rs80356716, gnomAD 1-11013922-T-G, REVEL 0.11, MetaLR 0.56
- A66S (p.Ala66Ser), gnomAD 1-11013923-G-T, REVEL 0.07, MetaLR 0.70
- A66T (p.Ala66Thr), gnomAD 1-11013923-G-A, REVEL 0.06, MetaLR 0.73
- A66A (p.Ala66Ala), rs61730366, gnomAD 1-11013925-T-A, CADD 7.79
- G67G (p.Gly67Gly), rs755357622, gnomAD 1-11013928-C-T, CADD 13.60
- W68* (p.Trp68Ter), rs1356327142, gnomAD 1-11013931-G-A, CADD 41.00
- N70S (p.Asn70Ser), gnomAD 1-11013936-A-G, REVEL 0.12, MetaLR 0.51
- N70T (p.Asn70Thr), rs1276353622, gnomAD 1-11013936-A-C, REVEL 0.15, MetaLR 0.51
- L71M (p.Leu71Met), rs748612906, gnomAD 1-11013938-C-A, REVEL 0.10, MetaLR 0.41
- L71L (p.Leu71Leu), gnomAD 1-11013940-G-C, CADD 14.10
- V72A (p.Val72Ala), rs1228733743, gnomAD 1-11013942-T-C, REVEL 0.27, MetaLR 0.57
- V75V (p.Val75Val), gnomAD 1-11013952-C-G, CADD 13.50
- N76S (p.Asn76Ser), rs142913423, gnomAD 1-11013954-A-G, REVEL 0.21, MetaLR 0.81
- A90V (p.Ala90Val), rs80356715, REVEL 0.17, MetaLR 0.52, Conflicting interpretations, not provided; Amyotrophic lateral sclerosis type 10; Inborn genetic diseases
- D169G (p.Asp169Gly), rs80356717, AlphaMissense 0.90, MetaLR 0.73, Pathogenic, Amyotrophic lateral sclerosis type 10
- N267S (p.Asn267Ser), rs80356718, REVEL 0.18, MetaLR 0.35, Conflicting interpretations, Amyotrophic lateral sclerosis type 10; FRONTOTEMPORAL LOBAR DEGENERATION WITH TD
- E271K (p.Glu271Lys), rs962749418, []
- G287S (p.Gly287Ser), rs80356719, REVEL 0.42, MetaLR 0.49, Pathogenic/Likely pathogenic, not provided; Amyotrophic lateral sclerosis type 10; Motor neuron disease
- G290A (p.Gly290Ala), rs121908395, REVEL 0.54, MetaLR 0.53, Uncertain significance, FRONTOTEMPORAL LOBAR DEGENERATION WITH TDP43 INCLUSIONS, TARDBP-RELATED; Amyotro
- G294A (p.Gly294Ala), rs80356721, REVEL 0.51, MetaLR 0.57, Pathogenic/Likely pathogenic, FRONTOTEMPORAL LOBAR DEGENERATION WITH TDP43 INCLUSIONS, TARDBP-RELATED; Amyotro
- G294V (p.Gly294Val), rs80356721, REVEL 0.53, MetaLR 0.63, Pathogenic/Likely pathogenic, FRONTOTEMPORAL LOBAR DEGENERATION WITH TDP43 INCLUSIONS, TARDBP-RELATED; Amyotro
- G295R (p.Gly295Arg), rs80356723, AlphaMissense 0.81, MetaLR 0.64, Conflicting interpretations, not provided; FRONTOTEMPORAL LOBAR DEGENERATION WITH TDP43 INCLUSIONS, TARDBP-RE
- G295S (p.Gly295Ser), rs80356723, REVEL 0.50, AlphaMissense 0.81, Pathogenic, Amyotrophic lateral sclerosis type 10; FRONTOTEMPORAL LOBAR DEGENERATION WITH TD
- G298S (p.Gly298Ser), rs4884357, AlphaMissense 0.07, MetaLR 0.76, Pathogenic/Likely pathogenic, Amyotrophic lateral sclerosis type 10; FRONTOTEMPORAL LOBAR DEGENERATION WITH TD
- A315T (p.Ala315Thr), rs80356726, REVEL 0.51, MetaLR 0.41, Pathogenic, Amyotrophic lateral sclerosis type 10; FRONTOTEMPORAL LOBAR DEGENERATION WITH TD
- Q331K (p.Gln331Lys), rs80356727, AlphaMissense 0.97, MetaLR 0.80, Pathogenic, Amyotrophic lateral sclerosis type 10
- S332N (p.Ser332Asn), rs80356728, AlphaMissense 0.74, MetaLR 0.80, Uncertain significance, Amyotrophic lateral sclerosis type 10; FRONTOTEMPORAL LOBAR DEGENERATION WITH TD
- G335D (p.Gly335Asp), rs80356729, AlphaMissense 0.99, MetaLR 0.93
- M337V (p.Met337Val), rs80356730, AlphaMissense 0.56, MetaLR 0.81, Pathogenic/Likely pathogenic, Amyotrophic lateral sclerosis type 10; FRONTOTEMPORAL LOBAR DEGENERATION WITH TD
- Q343R (p.Gln343Arg), rs80356731, AlphaMissense 0.78, MetaLR 0.70, Pathogenic, Amyotrophic lateral sclerosis type 10
- G348C (p.Gly348Cys), rs80356733, AlphaMissense 0.19, MetaLR 0.75, Pathogenic/Likely pathogenic, not provided; Amyotrophic lateral sclerosis type 10; FRONTOTEMPORAL LOBAR DEGENE
- G348V (p.Gly348Val), REVEL 0.55, MetaLR 0.62, Pathogenic, Motor neuron disease
- N352S (p.Asn352Ser), rs80356734, Pathogenic
- G357R (p.Gly357Arg), Conflicting interpretations, Amyotrophic lateral sclerosis type 10; FRONTOTEMPORAL LOBAR DEGENERATION WITH TD
- R361S (p.Arg361Ser), rs80356735, AlphaMissense 0.75, MetaLR 0.72
- S379C (p.Ser379Cys), rs80356739, AlphaMissense 0.29, MetaLR 0.69
- S379P (p.Ser379Pro), rs80356738, AlphaMissense 0.12, MetaLR 0.57
- A382T (p.Ala382Thr), rs367543041, REVEL 0.52, MetaLR 0.76, Pathogenic/Likely pathogenic, Amyotrophic lateral sclerosis type 10; FRONTOTEMPORAL LOBAR DEGENERATION WITH TD
- I383V (p.Ile383Val), rs80356740, pathogenic-likely-pathogenic
- N390D (p.Asn390Asp), rs80356741, REVEL 0.49, MetaLR 0.68, Conflicting interpretations, FRONTOTEMPORAL LOBAR DEGENERATION WITH TDP43 INCLUSIONS, TARDBP-RELATED; Amyotro
- N390S (p.Asn390Ser), rs80356742, REVEL 0.37, MetaLR 0.62, Conflicting interpretations, Inborn genetic diseases; not provided; Amyotrophic lateral sclerosis type 10
- S393L (p.Ser393Leu), rs80356743, REVEL 0.68, MetaLR 0.74, Uncertain significance, Amyotrophic lateral sclerosis type 10; FRONTOTEMPORAL LOBAR DEGENERATION WITH TD
- A321V (p.Ala321Val), REVEL 0.48, MetaLR 0.73
- R361T (p.Arg361Thr)
Public TARDBP analysis runs
- TARDBP analysis run — TARDBP (132 variants) — completed 2026-06-10