TARDBP

Summary

TARDBP (TAR DNA binding protein, HGNC:11571) is a protein-coding gene on chromosome 1p36.22, encoding TAR DNA-binding protein 43 (Q13148). RNA-binding protein that is involved in various steps of RNA biogenesis and processing. It is a common-essential gene (DepMap: required in 97.5% of cancer cell lines).

HIV-1, the causative agent of acquired immunodeficiency syndrome (AIDS), contains an RNA genome that produces a chromosomally integrated DNA during the replicative cycle. Activation of HIV-1 gene expression by the transactivator Tat is dependent on an RNA regulatory element (TAR) located downstream of the transcription initiation site. The protein encoded by this gene is a transcriptional repressor that binds to chromosomally integrated TAR DNA and represses HIV-1 transcription. In addition, this protein regulates alternate splicing of the CFTR gene. A similar pseudogene is present on chromosome 20.

Source: NCBI Gene 23435 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amyotrophic lateral sclerosis type 10 (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 311 total — 9 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 81
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 97.5% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_007375

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11571
Approved symbol	TARDBP
Name	TAR DNA binding protein
Location	1p36.22
Locus type	gene with protein product
Status	Approved
Aliases	TDP-43, ALS10
Ensembl gene	ENSG00000120948
Ensembl biotype	protein_coding
OMIM	605078
Entrez	23435

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 21 protein_coding, 15 nonsense_mediated_decay, 8 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000240185, ENST00000315091, ENST00000439080, ENST00000472476, ENST00000473118, ENST00000473869, ENST00000476201, ENST00000477447, ENST00000480464, ENST00000496840, ENST00000607145, ENST00000610369, ENST00000611008, ENST00000611136, ENST00000611963, ENST00000612387, ENST00000612542, ENST00000613177, ENST00000613864, ENST00000614494, ENST00000614757, ENST00000616545, ENST00000617172, ENST00000617757, ENST00000618606, ENST00000619555, ENST00000620028, ENST00000620505, ENST00000620632, ENST00000621573, ENST00000621715, ENST00000621790, ENST00000622057, ENST00000622108, ENST00000629725, ENST00000639083, ENST00000639599, ENST00000649624, ENST00000881691, ENST00000913574, ENST00000913575, ENST00000913576, ENST00000913577, ENST00000958690, ENST00000958691

RefSeq mRNA: 1 — MANE Select: NM_007375 NM_007375

CCDS: CCDS122

Canonical transcript exons

ENST00000240185 — 6 exons

Exon	Start	End
ENSE00001145815	11022124	11025492
ENSE00003900994	11012654	11012743
ENSE00003910367	11016844	11017007
ENSE00003910947	11013716	11013965
ENSE00003911074	11018733	11018873
ENSE00003914377	11020429	11020599

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 63.1355 / max 1779.8482, expressed in 1820 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
608	60.5269	1820
609	1.3739	849
610	1.2347	549

Top tissues by expression

301 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.12	gold quality
ventricular zone	UBERON:0003053	98.99	gold quality
ganglionic eminence	UBERON:0004023	98.85	gold quality
tibia	UBERON:0000979	98.45	gold quality
embryo	UBERON:0000922	98.41	gold quality
esophagus squamous epithelium	UBERON:0006920	98.36	gold quality
cortical plate	UBERON:0005343	98.26	gold quality
rectum	UBERON:0001052	98.02	gold quality
epithelium of nasopharynx	UBERON:0001951	98.01	gold quality
nasopharynx	UBERON:0001728	97.99	gold quality
left lobe of thyroid gland	UBERON:0001120	97.87	gold quality
left ovary	UBERON:0002119	97.87	gold quality
tibial nerve	UBERON:0001323	97.86	gold quality
visceral pleura	UBERON:0002401	97.85	gold quality
body of uterus	UBERON:0009853	97.85	gold quality
adenohypophysis	UBERON:0002196	97.81	gold quality
tendon of biceps brachii	UBERON:0008188	97.80	gold quality
right ovary	UBERON:0002118	97.77	gold quality
right lobe of thyroid gland	UBERON:0001119	97.76	gold quality
islet of Langerhans	UBERON:0000006	97.75	gold quality
ovary	UBERON:0000992	97.75	gold quality
thyroid gland	UBERON:0002046	97.73	gold quality
colonic epithelium	UBERON:0000397	97.72	gold quality
mucosa of transverse colon	UBERON:0004991	97.72	gold quality
endocervix	UBERON:0000458	97.71	gold quality
body of pancreas	UBERON:0001150	97.68	gold quality
skin of abdomen	UBERON:0001416	97.68	gold quality
vagina	UBERON:0000996	97.67	gold quality
ectocervix	UBERON:0012249	97.64	gold quality
esophagus mucosa	UBERON:0002469	97.62	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.92

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

191 targeting TARDBP, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-607	99.97	73.62	5593

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 97.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• The dissection of the RNA binding properties of TDP-43 and their functional implications in relationship with the splicing process is reported (PMID:11470789)
• Through the analysis of TDP, a protein functional in both transcriptional repression and alternative splicing, we have identified a new category of nuclear bodies within which the TDP molecules reside. (PMID:12361981)
• the C-terminal region of TDP-43 is capable of binding directly to several proteins of the heterogeneous nuclear ribonucleoprotein (hnRNP) family with well known splicing inhibitory activity, in particular, hnRNP A2/B1 and hnRNP A1 (PMID:16157593)
• findings showed that TDP-43 is the major disease protein in frontotemporal lobar degeneration and amyotrophic lateral sclerosis; it was recovered only from affected central nervous system regions (PMID:17023659)
• familial aggregation & clinical presentation of frontotemporal dementia + motor neuron disease; TDP-43 antibody stained neuronal inclusions similar in distribution & morphology to neuronal cytoplasmatic inclusions & neuronal intranuclear inclusions (PMID:17360763)
• TDP-43 proteinopathy is the common pathologic substrate linking frontotemporal lobar degeneration and amyotrophic lateral sclerosis. (PMID:17492294)
• TDP-43 immunoreactivity was detected in the hypoglossal nucleus in all cases of amyotrophic lateral sclerosis, all cases of frontotemporal lobar degeneration and some of cases of primary lateral sclerosis (PLS). (PMID:17569066)
• There is no evidence, that common variants in TDP-43 confer a strong risk to the development of sporadic FTD. (PMID:17614162)
• TDP-43 has a role in transcription and splicing regulation and may be involved in other cellular processes such as microRNA biogenesis, apoptosis, and cell division [review] (PMID:17981595)
• Our data implicate that TDP-43 has no primary genetic role in the pathophysiological mechanisms underlying central nervous system neurodegeneration in frontotemporal dementia and amyotrophic lateral sclerosis (PMID:18068872)
• TDP-43 inclusions seen in frontotemporal dementias and motor neuron diseases are specific to a neurodegenerative process. (PMID:18087705)
• TDP-43 is a neuronal activity-responsive factor functioning in the regulation of neuronal plasticity, the impairment of which leads to frontotemporal lobar degeneration. (PMID:18088371)
• These results suggest that neurons with abnormal TDP-43 immunoreactivities are associated with dysfunction of the secretory pathway in motor neurons. (PMID:18206910)
• Sequencing of the TDP-43 gene led to the identification of a novel missense mutation, Ala-315-Thr, which segregates with all affected members of an autosomal dominant motor neuron disease family. (PMID:18288693)
• The discovery of a missense mutation Ala-315-Thr in a family with dominantly inherited motor neuron disease provides a direct link between altered TDP-43 function and neurodegeneration. (PMID:18288693)
• 2E2-D3 monoclonal antibody reacted with human TDP-43, but not mouse or rat TDP-43, and recognized amino acids 205-222 of human TDP-43 (PMID:18304732)
• ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis pathogenesis may be linked mechanistically to deleterious perturbations of nuclear trafficking and solubility of TDP-43 (PMID:18305110)
• Cdk6 up-regulation in TDP-43-depleted cells is accompanied by an increase in phosphorylation of two of its major targets, the retinoblastoma protein pRb and pRb-related protein pRb2/p130. (PMID:18305152)
• study identified neighboring mutations in a highly conserved region of TARDBP in sporadic and familial amyotrophic lateral sclerosis (ALS) cases; evidence suggests a pathophysiological link between TDP-43 and ALS (PMID:18309045)
• These findings further corroborate that TDP-43 is involved in amyotrophic lateral sclerosis pathogenesis. (PMID:18372902)
• TAR DNA-binding protein 43 immunohistochemistry reveals extensive neuritic pathology in frontotemporal lobar degeneration with ubiquitinated inclusions. (PMID:18379440)
• This study identified two variants in TARDBP, which would encode Gly290Ala and Gly298Ser forms of TDP-43, in two kindreds with familial ALS. (PMID:18396105)
• In three affected individuals in two generations of one family with amyotrophic lateral sclerosis (ALS), a single base-pair change from A to G is found at position 1028 in TDP-43. providing a new insight into the molecular pathogenesis of ALS. (PMID:18438952)
• Mutant variant A90V may be a genetic risk factor for FTLD/ALS because it predisposes nuclear TDP-43 to redistribute to the cytoplasm and form pathological aggregates. (PMID:18505686)
• As a predictive test, plasma TDP-43 level may have great practical value (PMID:18506455)
• These findings provide further insight into the burden and clinical significance of TDP-43 pathology in disorders other than FTLD-U and amyotrophic lateral sclerosis. (PMID:18520774)
• pathogenic structural variants were not observed in the cases and there was no genetic or haplotype association with disease status across the TARDBP locus (PMID:18545701)
• Phosphorylated TDP-43 is a major component of the inclusions, and that abnormal phosphorylation of TDP-43 is a critical step in the pathogenesis of FTLD-U and ALS. (PMID:18546284)
• analysis of mutations in TDP-43 that may have roles in neurodegenerative disorders [review] (PMID:18549326)
• There are many precedents in neurodegenerative disease in which rare single-gene mutations have given great insight into understanding disease processes, which is why the TDP-43 mutations are potentially very important. (PMID:18592312)
• Data show that Caspase-cleaved TDP-43 presents in Hirano bodies, tangles, reactive astrocytes and neuritic plaques of the AD brain and co-localized with ubiquitin labeled neurons as well as dystrophic neurites within plaque regions. (PMID:18634762)
• These results suggest that the phosphorylation of Ser409/410 is an abnormal event in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. (PMID:18656473)
• Data do not support a role for TDP-43 in prion disease pathogenesis and argue that TDP-43 inclusions define a distinct group of neurodegenerative disorders. (PMID:18657254)
• TDP-43 overexpression enhances exon 7 inclusion during the survival of motor neuron pre-mRNA splicing (PMID:18703504)
• Perry syndrome displays unique TDP-43 pathology that is selective for the extrapyramidal system and spares the neocortex and motor neurons. (PMID:18723384)
• Genetic variability in a miR-659 binding-site of GNR increased the risk for TDP-43 positive frontotemporal dementia. (PMID:18723524)
• Neuropathological examination reveals cytoplasmic deposition of the TDP-43 protein in affected pedigree members with frontotemporal lobar degeneration–motor neuron disease. (PMID:18755042)
• Mutations in TARDBP are a rare cause of familial non-superoxide dismutase-1 amyotrophic lateral sclerosis in two German pedigrees. (PMID:18779421)
• Three missense mutations in exon 6 of TARDBP were identified in the analysis of 92 familial amyotrophic lateral sclerosis patients, while no mutations were detected in 24 patients with sporadic amyotrophic lateral sclerosis . (PMID:18802454)
• Data show that the pathological deposits with antibodies against TDP-43 has involved in the neuropathogenesis of the amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam. (PMID:18843496)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	tardbpa	ENSDARG00000004452
danio_rerio	tardbpb	ENSDARG00000040031
mus_musculus	Tardbp	ENSMUSG00000041459
rattus_norvegicus	Tardbp	ENSRNOG00000012455
drosophila_melanogaster	TBPH	FBGN0025790
drosophila_melanogaster	cocoon	FBGN0036496
caenorhabditis_elegans		WBGENE00006514

Paralogs (24): ELAVL1 (ENSG00000066044), PABPC1 (ENSG00000070756), RBMS2 (ENSG00000076067), PABPC4 (ENSG00000090621), PABPC1L (ENSG00000101104), ELAVL2 (ENSG00000107105), RBM24 (ENSG00000112183), HNRNPR (ENSG00000125944), RBM38 (ENSG00000132819), SYNCRIP (ENSG00000135316), SF3B4 (ENSG00000143368), RBMS3 (ENSG00000144642), PABPC3 (ENSG00000151846), RBMS1 (ENSG00000153250), RBM45 (ENSG00000155636), ELAVL4 (ENSG00000162374), PABPC5 (ENSG00000174740), PUF60 (ENSG00000179950), PABPC1L2B (ENSG00000184388), PABPC1L2A (ENSG00000186288), RBM34 (ENSG00000188739), ELAVL3 (ENSG00000196361), RBM14 (ENSG00000239306), PABPC4L (ENSG00000254535)

Protein

Protein identifiers

TAR DNA-binding protein 43 — Q13148 (reviewed: Q13148)

All UniProt accessions (24): A0A087WTG4, A0A087WTZ4, A0A087WV68, A0A087WVX6, A0A087WW61, A0A087WX29, A0A087WX67, A0A087WXQ5, A0A087WXV3, A0A087WYE7, A0A087WYY0, A0A087WZC9, A0A087WZM1, A0A087X260, A0A0A0MSV7, Q13148, A0A0A0N0M3, B1AKP7, G3V162, K7EJ99, K7EJM5, K7EL26, K7EN94, K7ENM9

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein that is involved in various steps of RNA biogenesis and processing. Preferentially binds, via its two RNA recognition motifs RRM1 and RRM2, to GU-repeats on RNA molecules predominantly localized within long introns and in the 3’UTR of mRNAs. In turn, regulates the splicing of many non-coding and protein-coding RNAs including proteins involved in neuronal survival, as well as mRNAs that encode proteins relevant for neurodegenerative diseases. Plays a role in maintaining mitochondrial homeostasis by regulating the processing of mitochondrial transcripts. Also regulates mRNA stability by recruiting CNOT7/CAF1 deadenylase on mRNA 3’UTR leading to poly(A) tail deadenylation and thus shortening. In response to oxidative insult, associates with stalled ribosomes localized to stress granules (SGs) and contributes to cell survival. Also participates in the normal skeletal muscle formation and regeneration, forming cytoplasmic myo-granules and binding mRNAs that encode sarcomeric proteins. Plays a role in the maintenance of the circadian clock periodicity via stabilization of the CRY1 and CRY2 proteins in a FBXL3-dependent manner. Negatively regulates the expression of CDK6. Regulates the expression of HDAC6, ATG7 and VCP in a PPIA/CYPA-dependent manner.

Subunit / interactions. Homodimer. Homooligomer (via its N-terminal domain). Interacts with BRDT. Binds specifically to pyrimidine-rich motifs of TAR DNA and to single stranded TG repeated sequences. Binds to RNA, specifically to UG repeated sequences with a minimum of six contiguous repeats. Interacts with ATXN2; the interaction is RNA-dependent. Interacts with MATR3. Interacts with UBQLN2. Interacts with HNRNPA2B1. Interacts with ZNF106. Interacts with CNOT7/CAF1. Interacts with CRY2. Interacts with PPIA/CYPA; the interaction is dependent on RNA-binding activity of TARDBP and PPIase activity of PPIA/CYPA and acetylation of PPIA/CYPA at ‘Lys-125’ favors the interaction.

Subcellular location. Nucleus. Cytoplasm. Stress granule. Mitochondrion.

Tissue specificity. Ubiquitously expressed. In particular, expression is high in pancreas, placenta, lung, genital tract and spleen.

Post-translational modifications. Hyperphosphorylated in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU. Phosphorylated upon cellular stress. Ubiquitinated in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU. Cleaved to generate C-terminal fragments in hippocampus, neocortex, and spinal cord from individuals affected with ALS and FTLDU.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry. Neurodegeneration is caused by activation of the cGAS-STING pathway: defects in TARDBP trigger mitochondrial DNA release into the cytosol via the permeability transition pore. Released mitochondrial DNA is then detected by CGAS, leading to activation of the cGAS-STING pathway, triggering type-I interferon production and autoinflammation.

Domain organisation. Consists of an N-terminal domain (NTD) and two tandem RNA recognition motifs, RRM1 and RRM2, followed by a C-terminal glycine-rich region. Contains a nuclear localization sequence and is mostly nuclear; however, its nuclear export sequence permits it to transport mRNAs to the cytoplasm and even to synapses as part of neuronal granules.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13148-1	1	yes
Q13148-4	2

RefSeq proteins (1): NP_031401* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR041105	TDP-43_N	Domain
IPR049124	TDP-43_C	Domain

Pfam: PF00076, PF18694, PF20910

UniProt features (111 total): strand 41, sequence variant 28, mutagenesis site 7, cross-link 6, turn 6, helix 5, compositionally biased region 3, modified residue 3, region of interest 3, domain 2, splice variant 2, sequence conflict 2, short sequence motif 2, chain 1

Structure

Experimental structures (PDB)

44 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6CF4	ELECTRON CRYSTALLOGRAPHY	0.75
5WHP	X-RAY DIFFRACTION	1
5WKB	ELECTRON CRYSTALLOGRAPHY	1
5WIA	X-RAY DIFFRACTION	1
5WHN	X-RAY DIFFRACTION	1.1
5WIQ	X-RAY DIFFRACTION	1.25
5W50	X-RAY DIFFRACTION	1.4
5W52	ELECTRON CRYSTALLOGRAPHY	1.4
6CFH	ELECTRON CRYSTALLOGRAPHY	1.5
5WKD	X-RAY DIFFRACTION	1.8
5MDI	X-RAY DIFFRACTION	2.1
7N9H	X-RAY DIFFRACTION	2.2
8CG3	ELECTRON MICROSCOPY	2.39
8CGG	ELECTRON MICROSCOPY	2.5
6T4B	X-RAY DIFFRACTION	2.55
7PY2	ELECTRON MICROSCOPY	2.59
4Y0F	X-RAY DIFFRACTION	2.65
8CGH	ELECTRON MICROSCOPY	2.68
9FOR	ELECTRON MICROSCOPY	2.75
4IUF	X-RAY DIFFRACTION	2.75
9FOF	ELECTRON MICROSCOPY	2.9
4Y00	X-RAY DIFFRACTION	3
7KWZ	ELECTRON MICROSCOPY	3.2
6N3A	ELECTRON MICROSCOPY	3.3
6N3C	ELECTRON MICROSCOPY	3.3
7Q3U	ELECTRON MICROSCOPY	3.7
8QX9	ELECTRON MICROSCOPY	3.76
5W7V	ELECTRON MICROSCOPY	3.8
6N37	ELECTRON MICROSCOPY	3.8
6N3B	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13148-F1	66.49	0.01

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (9): 183, 292, 293, 79, 84, 95, 102, 181, 263

Mutagenesis-validated functional residues (7):

Position	Phenotype
48	complete loss of self-oligomerization.
103–183	loss of rna-binding and reduced interaction with ppia/cypa.
106–175	completely abolishes rna binding.
106–111	completely abolishes rna binding.
147–149	highly reduces binding to rna and dna.
193–257	alters but does not abolish rna binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 548 (showing top): GOBP_CIRCADIAN_RHYTHM, GCACCTT_MIR18A_MIR18B, MORF_DNMT1, AAGCAAT_MIR137, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GGTGTGT_MIR329, MORF_ESPL1, MORF_SMC1L1, GCM_GSPT1, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, PAL_PRMT5_TARGETS_UP, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_INSULIN_SECRETION

GO Biological Process (19): negative regulation of protein phosphorylation (GO:0001933), mRNA processing (GO:0006397), RNA splicing (GO:0008380), regulation of gene expression (GO:0010468), negative regulation of gene expression (GO:0010629), regulation of protein stability (GO:0031647), positive regulation of insulin secretion (GO:0032024), response to endoplasmic reticulum stress (GO:0034976), positive regulation of protein import into nucleus (GO:0042307), regulation of circadian rhythm (GO:0042752), regulation of apoptotic process (GO:0042981), host-mediated suppression of viral transcription (GO:0043922), rhythmic process (GO:0048511), regulation of cell cycle (GO:0051726), 3’-UTR-mediated mRNA destabilization (GO:0061158), 3’-UTR-mediated mRNA stabilization (GO:0070935), nuclear inner membrane organization (GO:0071765), amyloid fibril formation (GO:1990000), gene expression (GO:0010467)

GO Molecular Function (11): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA binding (GO:0003677), double-stranded DNA binding (GO:0003690), RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), lipid binding (GO:0008289), identical protein binding (GO:0042802), pre-mRNA intronic binding (GO:0097157), molecular condensate scaffold activity (GO:0140693), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (9): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), perichromatin fibrils (GO:0005726), mitochondrion (GO:0005739), cytoplasmic stress granule (GO:0010494), nuclear speck (GO:0016607), interchromatin granule (GO:0035061), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
binding	3
RNA processing	2
gene expression	2
nucleic acid binding	2
intracellular membrane-bounded organelle	2
regulation of protein phosphorylation	1
protein phosphorylation	1
negative regulation of protein modification process	1
negative regulation of phosphorylation	1
mRNA metabolic process	1
regulation of macromolecule biosynthetic process	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
regulation of biological quality	1
insulin secretion	1
positive regulation of protein secretion	1
regulation of insulin secretion	1
positive regulation of peptide hormone secretion	1
cellular response to stress	1
protein import into nucleus	1
regulation of protein import into nucleus	1
positive regulation of nucleocytoplasmic transport	1
positive regulation of intracellular protein transport	1
positive regulation of protein localization to nucleus	1
circadian rhythm	1
regulation of biological process	1
apoptotic process	1
regulation of programmed cell death	1
host-mediated perturbation of viral transcription	1
host-mediated suppression of viral proces	1
biological_process	1
cell cycle	1
regulation of cellular process	1
mRNA destabilization	1
mRNA stabilization	1
nuclear membrane organization	1
protein metabolic process	1
supramolecular fiber organization	1
macromolecule biosynthetic process	1

Protein interactions and networks

STRING

5318 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TARDBP	FUS	P35637	999
TARDBP	SNCA	P37840	995
TARDBP	MATR3	P43243	990
TARDBP	DROSHA	Q9NRR4	990
TARDBP	SOD1	P00441	989
TARDBP	ATXN2	Q99700	984
TARDBP	HNRNPA2B1	P22626	980
TARDBP	HNRNPA1	P09651	978
TARDBP	DICER1	Q9UPY3	977
TARDBP	MAPT	P10636	970
TARDBP	GRN	P23781	959
TARDBP	OPTN	Q96CV9	952
TARDBP	FMR1	Q06787	950
TARDBP	G3BP1	Q13283	949
TARDBP	C9orf72	Q96LT7	944

IntAct

1195 interactions, top by confidence:

A	B	Type	Score
TARDBP	TARDBP	psi-mi:“MI:0915”(physical association)	0.970
TARDBP	TARDBP	psi-mi:“MI:0407”(direct interaction)	0.970
FUS	TARDBP	psi-mi:“MI:0914”(association)	0.750
FUS	TARDBP	psi-mi:“MI:0403”(colocalization)	0.750
FUS	TARDBP	psi-mi:“MI:0915”(physical association)	0.750
TOB1	TARDBP	psi-mi:“MI:0914”(association)	0.670
HNRNPH1	TARDBP	psi-mi:“MI:0915”(physical association)	0.670
TOB1	TARDBP	psi-mi:“MI:0915”(physical association)	0.670
GNB2	TARDBP	psi-mi:“MI:0915”(physical association)	0.670
TARDBP	KLHL22	psi-mi:“MI:0915”(physical association)	0.670
TARDBP	ELAVL1	psi-mi:“MI:0915”(physical association)	0.610
PPP1R15A	TARDBP	psi-mi:“MI:0915”(physical association)	0.600
CHEK2	PPM1G	psi-mi:“MI:0914”(association)	0.560
	TARDBP	psi-mi:“MI:0915”(physical association)	0.560
MED19	TARDBP	psi-mi:“MI:0915”(physical association)	0.560
MKL1	TARDBP	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (732): TARDBP (Reconstituted Complex), TARDBP (Affinity Capture-Western), TARDBP (Co-fractionation), ZFAND2B (Two-hybrid), TARDBP (Affinity Capture-MS), TARDBP (Affinity Capture-MS), TARDBP (Affinity Capture-MS), FLD1 (Dosage Growth Defect), MRPL39 (Dosage Growth Defect), MSN2 (Dosage Growth Defect), NHX1 (Dosage Growth Defect), RPL16B (Dosage Growth Defect), TIF4631 (Dosage Growth Defect), CCE1 (Dosage Rescue), DBR1 (Dosage Rescue)

ESM2 similar proteins: A5D7P8, A6QLK2, F1LQ48, O55047, O95628, P25916, P35226, P59326, P97855, Q08CW1, Q0VCY1, Q0VCZ3, Q12906, Q13148, Q13283, Q1ECX4, Q32KX7, Q32LC7, Q3SWT1, Q3ZBD9, Q4R5D9, Q5FVP2, Q5PRC7, Q5R601, Q5R8L2, Q5RB87, Q5SDR3, Q5U2U0, Q5ZLN5, Q64213, Q66K94, Q6DE02, Q6NRF9, Q86UE8, Q8BGW5, Q8BT14, Q8C0V0, Q8R2Y9, Q90ZY6, Q91YT7

Diamond homologs: A0A0D1C8Z4, A0A2R8Y4L2, A5A6H4, A5A6M3, A7VJC2, D0VWM8, G5EFS2, O14979, O43347, O88569, O89086, O93235, O94432, P04256, P07909, P08199, P09405, P09651, P09867, P13383, P17130, P19338, P19682, P19683, P19684, P20397, P21522, P22626, P28644, P38159, P41891, P48809, P48810, P49312, P49313, P49314, P51968, P51989, P51990, P51991

SIGNOR signaling

14 interactions.

A	Effect	B	Mechanism
UBQLN2	“down-regulates quantity by destabilization”	TARDBP	binding
TARDBP	“down-regulates quantity by repression”	GSK3B	“post transcriptional regulation”
TARDBP	“up-regulates quantity”	Protein_aggregates
D-glucitol	“down-regulates activity”	TARDBP	relocalization
Osmotic_stress	“down-regulates activity”	TARDBP	relocalization
TARDBP	up-regulates	HNRNPA1	“post transcriptional regulation”
IKBKB	“down-regulates quantity by destabilization”	TARDBP	phosphorylation
CDC7	“up-regulates activity”	TARDBP	phosphorylation
ABL1	“up-regulates quantity”	TARDBP	phosphorylation
TNKS	“up-regulates quantity by stabilization”	TARDBP	binding
TNKS2	“up-regulates quantity by stabilization”	TARDBP	binding
TARDBP	“up-regulates quantity”	DICER1	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 176 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Processing of Capped Intron-Containing Pre-mRNA	16	11.4×	4e-10
mRNA Polyadenylation	14	10.7×	1e-08
Toll Like Receptor 10 (TLR10) Cascade	5	9.4×	9e-03
Toll Like Receptor 5 (TLR5) Cascade	5	9.4×	9e-03
Interleukin-1 signaling	8	8.6×	4e-04
mRNA Splicing - Major Pathway	17	8.1×	1e-08
Cellular Senescence	6	7.2×	9e-03
Regulation of PD-L1(CD274) transcription	7	6.6×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
amyloid fibril formation	5	19.4×	9e-04
mRNA stabilization	6	14.2×	9e-04
mRNA splicing, via spliceosome	17	10.1×	1e-09
regulation of RNA splicing	7	9.9×	1e-03
RNA processing	6	8.5×	6e-03
RNA splicing	9	5.1×	6e-03
mRNA processing	10	5.1×	3e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	13	4.4×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

311 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	7
Uncertain significance	143
Likely benign	87
Benign	24

Top pathogenic / likely-pathogenic (16)

Variant ID	HGVS	Classification
21467	NM_007375.4(TARDBP):c.1035C>A (p.Asn345Lys)	Pathogenic
21485	NM_007375.4(TARDBP):c.883G>A (p.Gly295Ser)	Pathogenic
2202699	NM_007375.4(TARDBP):c.1123A>G (p.Ser375Gly)	Pathogenic
266064	NM_007375.4(TARDBP):c.1043G>T (p.Gly348Val)	Pathogenic
5229	NM_007375.4(TARDBP):c.991C>A (p.Gln331Lys)	Pathogenic
5233	NM_007375.4(TARDBP):c.506A>G (p.Asp169Gly)	Pathogenic
5235	NM_007375.4(TARDBP):c.1028A>G (p.Gln343Arg)	Pathogenic
5236	NM_007375.4(TARDBP):c.943G>A (p.Ala315Thr)	Pathogenic
5238	NM_007375.4(TARDBP):c.787A>G (p.Lys263Glu)	Pathogenic
21487	NM_007375.4(TARDBP):c.931A>G (p.Met311Val)	Likely pathogenic
2501300	NM_007375.4(TARDBP):c.1133A>G (p.Asn378Ser)	Likely pathogenic
4783510	NM_007375.4(TARDBP):c.962C>G (p.Ala321Gly)	Likely pathogenic
801435	NM_007375.4(TARDBP):c.1129T>C (p.Ser377Pro)	Likely pathogenic
873228	NM_007375.4(TARDBP):c.1060C>G (p.Gln354Glu)	Likely pathogenic
938527	NM_007375.4(TARDBP):c.962C>A (p.Ala321Asp)	Likely pathogenic
939152	NM_007375.4(TARDBP):c.1132A>G (p.Asn378Asp)	Likely pathogenic

SpliceAI

1658 predictions. Top by Δscore:

Variant	Effect	Δscore
1:11013838:G:T	donor_gain	1.0000
1:11013874:GT:G	donor_gain	1.0000
1:11013941:GT:G	donor_gain	1.0000
1:11013963:AAGGT:A	donor_loss	1.0000
1:11013964:AGGTT:A	donor_loss	1.0000
1:11013965:GGT:G	donor_loss	1.0000
1:11013966:G:C	donor_loss	1.0000
1:11016839:TTTA:T	acceptor_loss	1.0000
1:11016840:TTA:T	acceptor_loss	1.0000
1:11016841:TA:T	acceptor_loss	1.0000
1:11016842:A:AG	acceptor_gain	1.0000
1:11016843:G:GA	acceptor_gain	1.0000
1:11016843:GAT:G	acceptor_gain	1.0000
1:11017008:G:A	donor_loss	1.0000
1:11018727:TTCTA:T	acceptor_loss	1.0000
1:11018728:TCTAG:T	acceptor_loss	1.0000
1:11018729:CTAG:C	acceptor_loss	1.0000
1:11018730:TA:T	acceptor_loss	1.0000
1:11018731:A:AG	acceptor_gain	1.0000
1:11018731:A:G	acceptor_loss	1.0000
1:11018732:G:GG	acceptor_gain	1.0000
1:11018869:CTAAG:C	donor_loss	1.0000
1:11018870:TAAG:T	donor_loss	1.0000
1:11018871:AAGGT:A	donor_loss	1.0000
1:11018874:G:GA	donor_loss	1.0000
1:11018875:T:G	donor_loss	1.0000
1:11020417:T:A	acceptor_gain	1.0000
1:11020422:T:A	acceptor_gain	1.0000
1:11020425:TCA:T	acceptor_loss	1.0000
1:11020426:CA:C	acceptor_loss	1.0000

AlphaMissense

2760 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:11013776:G:A	E17K	1.000
1:11013780:T:A	I18K	1.000
1:11013780:T:G	I18R	1.000
1:11013804:T:A	V26E	1.000
1:11013819:T:A	V31D	1.000
1:11013824:G:C	A33P	1.000
1:11013825:C:A	A33D	1.000
1:11013830:T:C	F35L	1.000
1:11013831:T:C	F35S	1.000
1:11013832:T:A	F35L	1.000
1:11013832:T:G	F35L	1.000
1:11013840:C:A	A38E	1.000
1:11013845:G:A	G40R	1.000
1:11013845:G:C	G40R	1.000
1:11013845:G:T	G40W	1.000
1:11013846:G:A	G40E	1.000
1:11013846:G:T	G40V	1.000
1:11013849:T:A	L41H	1.000
1:11013849:T:C	L41P	1.000
1:11013882:G:C	R52T	1.000
1:11013882:G:T	R52I	1.000
1:11013883:A:C	R52S	1.000
1:11013883:A:T	R52S	1.000
1:11013884:G:C	G53R	1.000
1:11013885:G:A	G53D	1.000
1:11013888:T:A	V54D	1.000
1:11013894:T:C	L56P	1.000
1:11013909:T:C	L61P	1.000
1:11013929:T:A	W68R	1.000
1:11013929:T:C	W68R	1.000

dbSNP variants (sampled 300 via entrez): RS1000121889 (1:11012239 C>T), RS1000269574 (1:11021666 T>G), RS1000357083 (1:11030029 G>A), RS1000440594 (1:11028865 C>G,T), RS1000683371 (1:11023599 A>G), RS1000782499 (1:11021700 G>C), RS1000853521 (1:11025003 T>A,C), RS1000866233 (1:11017188 A>G), RS1000978912 (1:11017480 T>C,G), RS1001098576 (1:11012768 A>G), RS1001211713 (1:11029964 A>G), RS1001257419 (1:11021217 C>T), RS1001286221 (1:11025337 C>A,G,T), RS1001355282 (1:11023975 C>T), RS1001427816 (1:11015509 A>C)

Disease associations

OMIM: gene MIM:605078 | disease phenotypes: MIM:612069, MIM:613791, MIM:147421

GenCC curated gene-disease

Disease	Classification	Inheritance
amyotrophic lateral sclerosis type 10	Definitive	Autosomal dominant
frontotemporal dementia with motor neuron disease	Supportive	Autosomal dominant
amyotrophic lateral sclerosis	Supportive	Autosomal dominant
inclusion body myositis	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
amyotrophic lateral sclerosis type 10	Definitive	AD

Mondo (8): amyotrophic lateral sclerosis type 10 (MONDO:0012790), parkinsonian disorder (MONDO:0021095), motor neuron disorder (MONDO:0020128), immunodeficiency due to MASP-2 deficiency (MONDO:0013423), inclusion body myositis (MONDO:0007827), frontotemporal dementia (MONDO:0017276), frontotemporal dementia with motor neuron disease (MONDO:0017161), amyotrophic lateral sclerosis (MONDO:0004976)

Orphanet (6): Frontotemporal dementia with motor neuron disease (Orphanet:275872), Amyotrophic lateral sclerosis (Orphanet:803), Motor neuron disease (Orphanet:98503), Immunodeficiency due to MASP-2 deficiency (Orphanet:331187), Inclusion body myositis (Orphanet:611), Frontotemporal dementia (Orphanet:282)

HPO phenotypes

81 total (30 of 81 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000217	Xerostomia
HP:0000508	Ptosis
HP:0000605	Supranuclear gaze palsy
HP:0000708	Atypical behavior
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000733	Motor stereotypy
HP:0000734	Disinhibition
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000741	Apathy
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001265	Hyporeflexia
HP:0001283	Bulbar palsy
HP:0001300	Parkinsonism
HP:0001308	Tongue fasciculations
HP:0001324	Muscle weakness
HP:0001347	Hyperreflexia
HP:0001618	Dysphonia
HP:0001824	Weight loss
HP:0002015	Dysphagia
HP:0002071	Abnormality of extrapyramidal motor function
HP:0002073	Progressive cerebellar ataxia
HP:0002094	Dyspnea
HP:0002127	Abnormal upper motor neuron morphology
HP:0002145	Frontotemporal dementia
HP:0002171	Gliosis
HP:0002180	Neurodegeneration

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001407_1	Ewing sarcoma	1.000000e-20
GCST001548_3	Male-pattern baldness	9.000000e-11
GCST003475_1	Beard thickness	4.000000e-07
GCST006661_190	Male-pattern baldness	1.000000e-08
GCST006661_235	Male-pattern baldness	6.000000e-55

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D000690	Amyotrophic Lateral Sclerosis	C10.228.854.139; C10.574.562.250; C10.574.950.050; C10.668.467.250; C18.452.845.800.050
D057180	Frontotemporal Dementia	C10.228.140.380.266.299; C10.574.950.300.299; C18.452.845.800.300.299; F03.615.400.380.299
D016472	Motor Neuron Disease	C10.574.562; C10.668.467
D018979	Myositis, Inclusion Body	C05.651.594.600; C10.668.491.562.500
D020734	Parkinsonian Disorders	C10.228.140.079.862; C10.228.662.600
C567429	Amyotrophic Lateral Sclerosis 10 (supp.)
C566288	Frontotemporal Dementia With Motor Neuron Disease (supp.)
C565360	MASP2 Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2362981 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 166,878 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL58	MITOXANTRONE	4	166,878

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

6 potent at pChembl≥5 of 9 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.00	IC50	100	nM	CHEMBL4635203
6.75	Kd	176	nM	CHEMBL5653589
6.75	ED50	176	nM	CHEMBL5653589
6.09	Kd	813.5	nM	CHEMBL3752910
6.09	ED50	813.5	nM	CHEMBL3752910
5.00	IC50	1e+04	nM	MITOXANTRONE

PubChem BioAssay actives

4 with measured affinity, of 20 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-(3,5-dimethoxyphenyl)-3-[1-[(4-fluoro-3-methoxyphenyl)methyl]piperidin-3-yl]propanamide	1666489: Inhibition of TDP-43 (unknown origin) binding to RNA	ic50	0.1000	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149547: Binding affinity to human TARDBP incubated for 45 mins by Kinobead based pull down assay	kd	0.1760	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149547: Binding affinity to human TARDBP incubated for 45 mins by Kinobead based pull down assay	kd	0.8135	uM
Mitoxantrone	1666489: Inhibition of TDP-43 (unknown origin) binding to RNA	ic50	10.0000	uM

CTD chemical–gene interactions

99 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects binding, increases reaction, increases phosphorylation, affects reaction (+4 more)	6
methylmercuric chloride	decreases expression, increases activity, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, decreases expression, affects cotreatment	2
Paraquat	affects binding, affects localization, decreases reaction, increases expression, increases reaction	2
Valproic Acid	decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
triptolide	decreases reaction, affects binding	1
2,4,6-tribromophenol	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
geraniol	decreases expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	affects cotreatment, decreases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	decreases reaction, increases reaction, affects localization, increases phosphorylation, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
lanatoside C	affects binding, decreases reaction	1
tetrabromobisphenol A	decreases expression	1
bufalin	decreases expression	1
nickel chloride	decreases expression	1
ochratoxin A	decreases expression	1
cupric chloride	affects localization, decreases reaction	1
hydroquinone	affects expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
cyclic 3’,5’-uridine monophosphate	affects binding	1

ChEMBL screening assays

8 unique, capped per target: 7 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2354287	Functional	PubChem BioAssay. qHTS of TDP-43 Inhibitors. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL4627527	Binding	Inhibition of TDP-43 (unknown origin) binding to RNA	Emerging small-molecule therapeutic approaches for amyotrophic lateral sclerosis and frontotemporal dementia. — Bioorg Med Chem Lett

Cellosaurus cell lines

39 cell lines: 33 induced pluripotent stem cell, 2 finite cell line, 2 transformed cell line, 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A8KQ	CSSi012-A	Induced pluripotent stem cell	Male
CVCL_A9S0	NH50305	Induced pluripotent stem cell	Female
CVCL_A9S1	NH50306	Induced pluripotent stem cell	Female
CVCL_B7SG	CSSi013-A	Induced pluripotent stem cell	Female
CVCL_C0JS	UCSCi002-A	Induced pluripotent stem cell	Female
CVCL_D0P9	UQi001-A-1	Induced pluripotent stem cell	Male
CVCL_E4SE	KOLF2.1J TARDBP M337V SNV/SNV	Induced pluripotent stem cell	Male
CVCL_E4SF	KOLF2.1J TARDBP M337V SNV/WT	Induced pluripotent stem cell	Male
CVCL_E4SH	KOLF2.1J TARDBP Q331K SNV/SNV	Induced pluripotent stem cell	Male
CVCL_E4SI	KOLF2.1J TARDBP Q331K SNV/WT	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

423 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00542412	PHASE4	COMPLETED	CARE Canadian ALS Riluzole Evaluation
NCT00560287	PHASE4	UNKNOWN	Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis
NCT00613899	PHASE4	COMPLETED	Feasibility of Telesurveillance and Home Cough Assistance for Amyotrophic Lateral Patients (ALS)
NCT04997954	PHASE4	UNKNOWN	EMERALD TRIAL Open Label Extension Study
NCT06849115	PHASE4	COMPLETED	Effects of L-Carnitine in Amyotrophic Lateral Sclerosis Patients With CHCHD10 Mutations
NCT07223723	PHASE4	RECRUITING	A Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Chinese Participants With SOD-1 Amyotrophic Lateral Sclerosis (ALS)
NCT01662414	PHASE4	COMPLETED	Effect of Undenatured Cysteine-Rich Whey Protein Isolate (HMS 90®) in Patients With Parkinson’s Disease
NCT04871464	PHASE4	UNKNOWN	Role and Mechanism of Probiotics in Improving Motor Symptoms in Mild to Moderate Parkinson’s Disease
NCT00021697	PHASE3	COMPLETED	Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS
NCT00035815	PHASE3	COMPLETED	Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
NCT00047723	PHASE3	COMPLETED	Minocycline to Treat Amyotrophic Lateral Sclerosis
NCT00069186	PHASE3	UNKNOWN	Study of Creatine Monohydrate in Patients With Amyotrophic Lateral Sclerosis
NCT00136110	PHASE3	COMPLETED	Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis
NCT00330681	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS)
NCT00349622	PHASE3	COMPLETED	Clinical Trial Ceftriaxone in Subjects With ALS
NCT00372879	PHASE3	COMPLETED	Clinical Trial of Vitamin E to Treat Muscular Cramps in Patients With ALS
NCT00415519	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS) Who Met Severity Classification III
NCT00424463	PHASE3	COMPLETED	Expanded Controlled Study of Safety and Efficacy of MCI-186 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT00839033	PHASE3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00868166	PHASE3	COMPLETED	Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS
NCT00965497	PHASE3	COMPLETED	Escitalopram (Lexapro) for Depression MS or ALS
NCT01016522	PHASE3	TERMINATED	Safety and Tolerability of the Ketogenic Diet in Amyotrophic Lateral Sclerosis (ALS)
NCT01160263	PHASE3	COMPLETED	Study of Dopamine and Serotonin Transporters in Patients With Amyotrophic Lateral Sclerosis and Controls
NCT01281189	PHASE3	COMPLETED	Phase 3 Study of Dexpramipexole in ALS
NCT01492686	PHASE3	COMPLETED	Phase 3 Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis
NCT01583088	PHASE3	TERMINATED	Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation
NCT01622088	PHASE3	TERMINATED	Phase 3 Extension Study of Dexpramipexole in ALS
NCT02496767	PHASE3	COMPLETED	Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year
NCT02623699	PHASE3	COMPLETED	An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)
NCT02936635	PHASE3	COMPLETED	A Study for Patients Who Completed VITALITY-ALS (CY 4031)
NCT03127267	PHASE3	RECRUITING	Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
NCT03280056	PHASE3	COMPLETED	Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients
NCT03491462	PHASE3	COMPLETED	Arimoclomol in Amyotropic Lateral Sclerosis
NCT03505021	PHASE3	COMPLETED	Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS
NCT03548311	PHASE3	COMPLETED	Clinical Trial of Ultra-high Dose Methylcobalamin for ALS
NCT03690791	PHASE3	UNKNOWN	Efficacy of Cannabinoids in Amyotrophic Lateral Sclerosis or Motor Neurone Disease
NCT03800524	PHASE3	UNKNOWN	Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS
NCT03836716	PHASE3	TERMINATED	Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
NCT03948178	PHASE3	TERMINATED	Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension
NCT04165824	PHASE3	COMPLETED	Safety Study of Oral Edaravone Administered in Subjects With ALS