TAF15

Summary

TAF15 (TATA-box binding protein associated factor 15, HGNC:11547) is a protein-coding gene on chromosome 17q12, encoding TATA-binding protein-associated factor 2N (Q92804). RNA and ssDNA-binding protein that may play specific roles during transcription initiation at distinct promoters.

This gene encodes a member of the TET family of RNA-binding proteins. The encoded protein plays a role in RNA polymerase II gene transcription as a component of a distinct subset of multi-subunit transcription initiation factor TFIID complexes. Translocations involving this gene play a role in acute leukemia and extraskeletal myxoid chondrosarcoma, and mutations in this gene may play a role in amyotrophic lateral sclerosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 8148 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amyotrophic lateral sclerosis (Limited, ClinGen)
• GWAS associations: 2
• Clinical variants (ClinVar): 228 total
• Phenotypes (HPO): 47
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types
• MANE Select transcript: NM_139215

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11547
Approved symbol	TAF15
Name	TATA-box binding protein associated factor 15
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	hTAFII68, RBP56, Npl3
Ensembl gene	ENSG00000270647
Ensembl biotype	protein_coding
OMIM	601574
Entrez	8148

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 13 protein_coding, 7 retained_intron, 6 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000603067, ENST00000603346, ENST00000603393, ENST00000603427, ENST00000603777, ENST00000603967, ENST00000604360, ENST00000604434, ENST00000604694, ENST00000604841, ENST00000604879, ENST00000605197, ENST00000605649, ENST00000605844, ENST00000685897, ENST00000687618, ENST00000689923, ENST00000691608, ENST00000852321, ENST00000852322, ENST00000852323, ENST00000852324, ENST00000852325, ENST00000852326, ENST00000919937, ENST00000919938, ENST00000919939, ENST00000947553

RefSeq mRNA: 2 — MANE Select: NM_139215 NM_003487, NM_139215

CCDS: CCDS32623, CCDS59279

Canonical transcript exons

ENST00000605844 — 16 exons

Exon	Start	End
ENSE00003468722	35820332	35820437
ENSE00003484588	35820024	35820075
ENSE00003489903	35834566	35834598
ENSE00003504314	35844077	35844158
ENSE00003506414	35809484	35809576
ENSE00003528591	35833907	35833941
ENSE00003536677	35820164	35820248
ENSE00003572275	35846906	35847242
ENSE00003574405	35842367	35842459
ENSE00003590400	35838424	35838553
ENSE00003594153	35817716	35817755
ENSE00003636803	35822640	35822833
ENSE00003641314	35844477	35845038
ENSE00003657247	35824078	35824198
ENSE00003657743	35844280	35844368
ENSE00003687995	35836132	35836241

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 105.7709 / max 1607.6048, expressed in 1822 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160380	102.6929	1822
160386	1.6634	857
160387	0.9915	590
160385	0.4231	228

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endometrium	UBERON:0001295	98.84	gold quality
ganglionic eminence	UBERON:0004023	98.83	gold quality
right testis	UBERON:0004534	98.81	gold quality
left testis	UBERON:0004533	98.73	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.51	gold quality
lower esophagus	UBERON:0013473	98.50	gold quality
monocyte	CL:0000576	98.41	gold quality
leukocyte	CL:0000738	98.38	gold quality
zone of skin	UBERON:0000014	98.37	gold quality
lymph node	UBERON:0000029	98.37	gold quality
skin of abdomen	UBERON:0001416	98.37	gold quality
mucosa of stomach	UBERON:0001199	98.36	gold quality
skin of leg	UBERON:0001511	98.36	gold quality
colonic epithelium	UBERON:0000397	98.33	gold quality
adenohypophysis	UBERON:0002196	98.33	gold quality
ventricular zone	UBERON:0003053	98.33	gold quality
esophagus	UBERON:0001043	98.32	gold quality
right uterine tube	UBERON:0001302	98.30	gold quality
pituitary gland	UBERON:0000007	98.28	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.28	gold quality
vermiform appendix	UBERON:0001154	98.23	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.20	gold quality
body of pancreas	UBERON:0001150	98.19	gold quality
esophagus mucosa	UBERON:0002469	98.17	gold quality
cortical plate	UBERON:0005343	98.10	gold quality
cerebellum	UBERON:0002037	98.09	gold quality
cerebellar cortex	UBERON:0002129	98.09	gold quality
cerebellar hemisphere	UBERON:0002245	98.09	gold quality
uterine cervix	UBERON:0000002	98.05	gold quality
body of uterus	UBERON:0009853	98.04	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting TAF15, 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-4668-3P	100.00	68.74	2635
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-4999-3P	99.11	65.55	424
HSA-MIR-6516-5P	98.42	70.19	1551
HSA-MIR-92A-1-5P	98.28	64.51	631
HSA-MIR-4717-5P	98.19	67.97	894
HSA-MIR-12120	98.05	68.44	1768

Literature-anchored findings (GeneRIF, showing 40)

• The transcription factor gene CIZ/NMP4 is recurrently involved in acute leukemia through fusion with either EWSR1 or TAF15. (PMID:12359745)
• hTAF(II)68-mediated transactivation is linked to the cytoplasmic Src signal transduction pathway. The hTAF(II)68 protein can associate with the SH3 domains of several cell signaling proteins, including v-Src. (PMID:15094065)
• The oncogenic effect of the t(9;17) translocation may be due to the hTAF(II)68-TEC chimeric protein and that fusion of the hTAF(II)68 NTD to the TEC protein produces a gain of function chimeric product. (PMID:18330902)
• FUS, EWS and TAF15 proto-oncoproteins were targeted to stress granules induced by heat shock and oxidative stress (PMID:18620564)
• Data demonstrate that arginine methylation of TAF15 by PRMT1 is a crucial event determining its proper localization and gene regulatory function. (PMID:19124016)
• Data show that a fraction of human U1 snRNA specifically associates with the nuclear RNA-binding protein TBP-associated factor 15 (TAF15). (PMID:19282884)
• These results suggest that caspase-mediated degradation may represent a novel regulatory mechanism that controls TAF15 and TAF15-CIZ/NMP4 activities. (PMID:19426707)
• Our findings define a role for a tumor-specific TAF15 antigen in malignant processes. (PMID:20048082)
• Elevated TAF15 mRNA levels did not translate to strongly elevated protein levels, consistent with its infrequent occurrence as translocation partner in tumors. (PMID:21344536)
• These results suggest that additional studies are needed to determine whether mutations in the TAF15 gene represent a cause of familial amyotrophic lateral sclerosis. (PMID:21438137)
• Rare translocation t(12;17)(p13;q12), this translocation has been reported in 25 cases and its putative molecular consequence, the formation of a TAF15-ZNF384 fusion gene, in only six cases. (PMID:21504714)
• REsults suggest the possibility that alterations of TAF15 and EWS might also be involved in the pathogenesis of FUS proteinopathies such as ALS and FTLD. (PMID:21856723)
• The existence of a functionally discrete subset of U1 snRNP in association with TAF15 was suggested and provided further support for the involvement of U1 snRNP components in early steps of coordinated gene expression. (PMID:22019700)
• Missense mutations of TAF-15, an RNA-binding protein, were found in patients with amyotrophic lateral sclerosis, and gene conferred neurodegeneration when expressend in Drosophila. (PMID:22065782)
• TAF15 plays a role in RNA transport and/or local RNA translation (PMID:22771914)
• Data show that FUS and TAF15 locate to cellular stress granules to a larger extend than EWS. FET-protein stress granule association most likely is a downstream response to cellular stress. (PMID:23049996)
• TAF15 depletion inhibits growth & increases apoptosis. Its knockdown affects many genes involved in cell cycle & cell death. Among these, targets of microRNAs generated from the onco-miR-17 locus were overrepresented. (PMID:23128393)
• Data indicate that distinct differences in proteins becoming Poly(ADP-ribose) PARylated upon various genotoxic insults are observed, exemplified by the PARylation of RNA-processing factors THRAP3 and TAF15 under oxidative stress. (PMID:24055347)
• our data suggest that TAF15 and TLS/FUS operate within similar but not identical hnRNP M-TET protein complexes to influence the transcriptional or post-transcriptional output of a particular cell type. (PMID:24474660)
• RNA binding by TAF-15 is dependent upon structural elements in the RNA rather than sequence. (PMID:26612539)
• Aggregation of FET proteins FUS, EWSR1, and TAF15 mediate a pathological change in amyotrophic lateral sclerosis. (Review) (PMID:27311318)
• In human stem cell-derived motor neurons, the RNA profile associated with concomitant loss of both TAF15 and FUS resembles that observed in the presence of the amyotrophic lateral sclerosis (ALS)-associated mutation FUS R521G, but contrasts with late-stage sporadic ALS patients. (PMID:27378374)
• Studies provide evidence that FUS/TLS, EWS and TAF15 proteins play a major role in neurodegenerative disorders. (review). (PMID:27415968)
• O-GlcNAc glycosylation stoichiometry of TAF15 (PMID:27903134)
• In a cohort of youth at risk for bipolar disorder, pathway analysis showed an enrichment of the glucocorticoid receptor (GR) pathway with the genes MED1, HSPA1L, GTF2A1 and TAF15, which might underlie the previously reported role of stress response in the risk for bipolar disorder in vulnerable populations. (PMID:28291257)
• weak, multivalent interactions between TAF15 fibrils and heptads throughout RNA pol II CTD collectively mediate complex formation. (PMID:28945358)
• Results find that the Asp residue in TAF15 YGGDR(S/G)G repeats confers poor binding to PRMT1 indicating that YGGDR(S/G)G repeats may contribute to TAF15 specialization by enabling differential interactions with PRMT1 and reduced overall levels of TAF15 methylation compared with other FET proteins. (PMID:29193371)
• FUS, EWSR1, TAF15 and MATR3 within the RNAP II/U1 snRNP machinery play distinct roles in the development of amyotrophic lateral sclerosis and spinal muscular atrophy that are more intimately tied to one another than previously thought. (PMID:30398641)
• NR4A3 fusion proteins trigger an axon guidance switch that marks the difference between EWSR1 and TAF15 translocated extraskeletal myxoid chondrosarcomas cells. (PMID:31020999)
• TRPM2-AS promotes cancer cell proliferation through control of TAF15. (PMID:31887411)
• LncRNA PITPNA-AS1 boosts the proliferation and migration of lung squamous cell carcinoma cells by recruiting TAF15 to stabilize HMGB3 mRNA. (PMID:32871048)
• SCF-Slimb is critical for Glycogen synthase kinase-3beta-mediated suppression of TAF15-induced neurotoxicity in Drosophila. (PMID:32915460)
• Loci-specific phase separation of FET fusion oncoproteins promotes gene transcription. (PMID:33674598)
• LncRNA GAS5 activates the HIF1A/VEGF pathway by binding to TAF15 to promote wound healing in diabetic foot ulcers. (PMID:33875793)
• LncRNA LINC00649 recruits TAF15 and enhances MAPK6 expression to promote the development of lung squamous cell carcinoma via activating MAPK signaling pathway. (PMID:35228660)
• The SGYS motif of TAF15 prion-like domain is critical to amyloid fibril formation. (PMID:35643629)
• CircDNAJC11 interacts with TAF15 to promote breast cancer progression via enhancing MAPK6 expression and activating the MAPK signaling pathway. (PMID:36895010)
• TAF15 promotes cell proliferation, migration and invasion of gastric cancer via activation of the RAF1/MEK/ERK signalling pathway. (PMID:37037864)
• m6A-enriched lncRNA LINC00839 promotes tumor progression by enhancing TAF15-mediated transcription of amine oxidase AOC1 in nasopharyngeal carcinoma. (PMID:37257820)
• TAF15 amyloid filaments in frontotemporal lobar degeneration. (PMID:38057661)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	taf15	ENSDARG00000070019
mus_musculus	Taf15	ENSMUSG00000020680
rattus_norvegicus	Taf15	ENSRNOG00000058393
drosophila_melanogaster	caz	FBGN0285954
caenorhabditis_elegans		WBGENE00016173

Paralogs (2): FUS (ENSG00000089280), EWSR1 (ENSG00000182944)

Protein

Protein identifiers

TATA-binding protein-associated factor 2N — Q92804 (reviewed: Q92804)

Alternative names: 68 kDa TATA-binding protein-associated factor, RNA-binding protein 56

All UniProt accessions (7): A0A075B7C1, A0A075B7D6, A0A075B7D9, A0A075B7E4, A0A075B7F2, A0A8I5KR73, Q92804

UniProt curated annotations — full annotation on UniProt →

Function. RNA and ssDNA-binding protein that may play specific roles during transcription initiation at distinct promoters. Binds to ssRNA containing the consensus sequence 5’-AGGUAA-3’. Can enter the preinitiation complex together with the RNA polymerase II (Pol II).

Subunit / interactions. Belongs to the RNA polymerase II (Pol II) transcriptional multiprotein complex, together with the TATA-binding protein (TBP) and other TBP-associated factors (TAF(II)s). Binds SF1.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Ubiquitous. Observed in all fetal and adult tissues.

Post-translational modifications. Dimethylated by PRMT1 at Arg-206 to asymmetric dimethylarginine. The methylation may favor nuclear localization and positive regulation of TAF15 transcriptional activity. ADP-ribosylated during genotoxic stress.

Disease relevance. A chromosomal aberration involving TAF15/TAF2N is found in a form of extraskeletal myxoid chondrosarcomas (EMC). Translocation t(9;17)(q22;q11) with NR4A3.

Similarity. Belongs to the RRM TET family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q92804-1	Long	yes
Q92804-2	Short

RefSeq proteins (2): NP_003478, NP_631961* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR001876	Znf_RanBP2	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034870	TET_fam	Family
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036443	Znf_RanBP2_sf	Homologous_superfamily

Pfam: PF00076

UniProt features (81 total): repeat 21, modified residue 21, strand 15, compositionally biased region 10, region of interest 4, cross-link 2, helix 2, turn 2, chain 1, domain 1, zinc finger region 1, splice variant 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
9THM	ELECTRON MICROSCOPY	1.64
8ONS	ELECTRON MICROSCOPY	1.97
9THN	ELECTRON MICROSCOPY	1.97
9THP	ELECTRON MICROSCOPY	1.98
9TKH	ELECTRON MICROSCOPY	2.05
9TKG	ELECTRON MICROSCOPY	2.08
9TKJ	ELECTRON MICROSCOPY	2.21
9TKK	ELECTRON MICROSCOPY	2.38
9TKI	ELECTRON MICROSCOPY	2.39
9TKF	ELECTRON MICROSCOPY	2.55
9TKL	ELECTRON MICROSCOPY	2.6
9TKE	ELECTRON MICROSCOPY	2.74
9TL2	ELECTRON MICROSCOPY	2.82
9TKZ	ELECTRON MICROSCOPY	3.59
2MMY	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92804-F1	50.61	0.06

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 (23): 206, 206, 226, 231, 268, 375, 423, 431, 433, 438, 442, 451, 459, 475, 483, 528, 535, 554, 562, 570 …

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-167161	HIV Transcription Initiation
R-HSA-167162	RNA Polymerase II HIV Promoter Escape
R-HSA-167172	Transcription of the HIV genome
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-73776	RNA Polymerase II Promoter Escape
R-HSA-73779	RNA Polymerase II Transcription Pre-Initiation And Promoter Opening
R-HSA-75953	RNA Polymerase II Transcription Initiation
R-HSA-76042	RNA Polymerase II Transcription Initiation And Promoter Clearance

MSigDB gene sets: 266 (showing top): GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, FISCHER_G1_S_CELL_CYCLE, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, CDP_01, AP1_Q4_01, REACTOME_HIV_INFECTION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_UP, BACH2_01, GOBP_RNA_SPLICING, TGANTCA_AP1_C, FUJII_YBX1_TARGETS_DN

GO Biological Process (5): RNA splicing (GO:0008380), positive regulation of DNA-templated transcription (GO:0045893), mRNA stabilization (GO:0048255), regulation of DNA-templated transcription (GO:0006355), gene expression (GO:0010467)

GO Molecular Function (8): DNA binding (GO:0003677), transcription coregulator activity (GO:0003712), RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), zinc ion binding (GO:0008270), nucleic acid binding (GO:0003676), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
RNA Polymerase II Transcription	3
Transcription of the HIV genome	2
RNA Polymerase II Transcription Initiation And Promoter Clearance	2
Late Phase of HIV Life Cycle	1
Regulation of TP53 Activity	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	2
nucleic acid binding	2
binding	2
cellular anatomical structure	2
RNA processing	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
regulation of mRNA stability	1
RNA stabilization	1
negative regulation of mRNA catabolic process	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
macromolecule biosynthetic process	1
transcription regulator activity	1
mRNA binding	1
transition metal ion binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1570 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAF15	NR4A3	Q92570	866
TAF15	TCF12	Q99081	835
TAF15	SNRPC	P09234	727
TAF15	NR4A2	P43354	638
TAF15	TARDBP	Q13148	632
TAF15	TBP	P20226	579
TAF15	A0A087WTZ4	A0A087WTZ4	575
TAF15	MATR3	P43243	565
TAF15	PATZ1	Q9HBE1	539
TAF15	TIA1	P31483	513
TAF15	NR4A1	P22736	503
TAF15	ETV4	P43268	501
TAF15	ETV1	P50549	499
TAF15	RTRAF	Q9Y224	495
TAF15	C9orf72	Q96LT7	495

IntAct

143 interactions, top by confidence:

A	B	Type	Score
HDAC2	KDM1A	psi-mi:“MI:0914”(association)	0.890
FUS	FUS	psi-mi:“MI:0914”(association)	0.830
TAF15	FUS	psi-mi:“MI:0915”(physical association)	0.740
TAF15	FUS	psi-mi:“MI:0914”(association)	0.740
TBP	TAF7	psi-mi:“MI:0914”(association)	0.640
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
EWSR1	FUS	psi-mi:“MI:0914”(association)	0.550
TAF15	HNRNPU	psi-mi:“MI:0915”(physical association)	0.540
SUPT5H	POLR2D	psi-mi:“MI:0914”(association)	0.530
KAT5	TAF15	psi-mi:“MI:0915”(physical association)	0.520
TAF15	KAT5	psi-mi:“MI:0915”(physical association)	0.520
	FUS	psi-mi:“MI:0914”(association)	0.510
TAF15		psi-mi:“MI:0403”(colocalization)	0.510
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
FUS	DDX3X	psi-mi:“MI:0914”(association)	0.430
TAF15	Crebbp	psi-mi:“MI:0915”(physical association)	0.400
EP300	TAF15	psi-mi:“MI:0915”(physical association)	0.400
Taf15	TAF15	psi-mi:“MI:0915”(physical association)	0.400
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
PLEC	TAF15	psi-mi:“MI:0915”(physical association)	0.400
TAF15		psi-mi:“MI:0915”(physical association)	0.370

BioGRID (528): TAF15 (Protein-peptide), TAF15 (Affinity Capture-MS), TAF15 (Affinity Capture-MS), TAF15 (Affinity Capture-MS), TAF15 (Affinity Capture-MS), TAF15 (Affinity Capture-MS), TAF15 (Affinity Capture-MS), TAF15 (Affinity Capture-MS), TAF15 (Affinity Capture-MS), HSP104 (Synthetic Rescue), ACAA2 (Co-fractionation), TAF15 (Affinity Capture-MS), TAF15 (Affinity Capture-MS), TAF15 (Affinity Capture-MS), TAF15 (Affinity Capture-MS)

ESM2 similar proteins: A5A6M3, D4AE41, O22703, O75526, P30352, P35637, P38159, P56959, P60824, P60825, P60826, P62995, P62996, P62997, P78814, P84586, P92965, P92966, Q01560, Q01844, Q14011, Q24491, Q27294, Q28009, Q29RT0, Q3ZBT6, Q4P2Q5, Q4R7F0, Q4R813, Q4V898, Q54Y98, Q55FQ0, Q5RF83, Q61545, Q6IRQ4, Q7ZWA3, Q8L3X8, Q8RWN5, Q8VYA5, Q91VM5

Diamond homologs: A0A0R4IEW8, A4FV72, A4RHN3, A5A6M3, A5E1Z4, A6NDE4, A6NEQ0, A7SKE9, D4AE41, F4JCU0, O02008, O15226, O75526, O89086, O93235, P0C7P1, P0C8Z4, P0CB38, P0DJD3, P0DJD4, P10979, P19018, P31209, P38159, P39697, P41891, P60824, P60825, P60826, P62995, P62996, P62997, P84586, P98179, Q03251, Q03878, Q05196, Q09511, Q0U1G2, Q10422

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRMT1	up-regulates	TAF15	methylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 133 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
mRNA Polyadenylation	13	12.3×	2e-08
Formation of TC-NER Pre-Incision Complex	5	11.4×	3e-03
Transcription of the HIV genome	6	11.2×	9e-04
Late Phase of HIV Life Cycle	6	10.8×	1e-03
Processing of Capped Intron-Containing Pre-mRNA	12	10.6×	3e-07
HIV Life Cycle	6	10.4×	1e-03
ESR-mediated signaling	7	9.7×	5e-04
mRNA Splicing	8	9.4×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
intrinsic apoptotic signaling pathway	6	18.9×	2e-04
autophagosome maturation	5	15.4×	3e-03
mitophagy	5	13.9×	3e-03
cellular response to UV	5	13.0×	3e-03
G1/S transition of mitotic cell cycle	6	10.6×	3e-03
autophagosome assembly	5	9.8×	8e-03
mRNA splicing, via spliceosome	10	8.0×	2e-04
RNA splicing	8	6.2×	3e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 2 cancer types — BLCA, PLMESO.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	107
Likely benign	60
Benign	33

Top pathogenic / likely-pathogenic (0)

SpliceAI

3479 predictions. Top by Δscore:

Variant	Effect	Δscore
17:35820022:A:AG	acceptor_gain	1.0000
17:35820023:G:GA	acceptor_gain	1.0000
17:35820075:AG:A	donor_loss	1.0000
17:35820076:G:GA	donor_loss	1.0000
17:35820076:G:GG	donor_gain	1.0000
17:35820077:TAG:T	donor_loss	1.0000
17:35820240:G:GG	donor_gain	1.0000
17:35820433:GGAAG:G	donor_gain	1.0000
17:35820434:GAAGG:G	donor_gain	1.0000
17:35820435:A:T	donor_gain	1.0000
17:35820435:AAGG:A	donor_loss	1.0000
17:35820436:AGGT:A	donor_loss	1.0000
17:35820437:GGTA:G	donor_loss	1.0000
17:35820438:G:T	donor_loss	1.0000
17:35820439:T:G	donor_loss	1.0000
17:35822638:A:AG	acceptor_gain	1.0000
17:35822639:G:GA	acceptor_gain	1.0000
17:35822639:G:T	acceptor_loss	1.0000
17:35822639:GC:G	acceptor_gain	1.0000
17:35822639:GCC:G	acceptor_gain	1.0000
17:35822639:GCCA:G	acceptor_gain	1.0000
17:35822639:GCCAA:G	acceptor_gain	1.0000
17:35822830:CAAGG:C	donor_loss	1.0000
17:35822831:AAGGT:A	donor_loss	1.0000
17:35822832:AGGTA:A	donor_loss	1.0000
17:35822833:GGTA:G	donor_loss	1.0000
17:35822834:G:GG	donor_gain	1.0000
17:35822835:T:A	donor_loss	1.0000
17:35833905:A:AG	acceptor_gain	1.0000
17:35833906:G:GG	acceptor_gain	1.0000

AlphaMissense

3769 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:35836157:C:A	N233K	1.000
17:35836157:C:G	N233K	1.000
17:35836160:C:A	N234K	1.000
17:35836160:C:G	N234K	1.000
17:35836161:A:C	T235P	1.000
17:35836162:C:T	T235I	1.000
17:35836164:A:T	I236F	1.000
17:35836165:T:A	I236N	1.000
17:35836165:T:C	I236T	1.000
17:35836165:T:G	I236S	1.000
17:35836167:T:A	F237I	1.000
17:35836167:T:C	F237L	1.000
17:35836167:T:G	F237V	1.000
17:35836168:T:C	F237S	1.000
17:35836168:T:G	F237C	1.000
17:35836169:T:A	F237L	1.000
17:35836169:T:G	F237L	1.000
17:35836171:T:A	V238E	1.000
17:35836174:A:C	Q239P	1.000
17:35836180:T:A	L241H	1.000
17:35836180:T:C	L241P	1.000
17:35836207:T:A	V250D	1.000
17:35836218:T:A	F254I	1.000
17:35836218:T:C	F254L	1.000
17:35836219:T:C	F254S	1.000
17:35836220:T:A	F254L	1.000
17:35836220:T:G	F254L	1.000
17:35836228:T:A	I257K	1.000
17:35836230:G:A	G258R	1.000
17:35836230:G:C	G258R	1.000

dbSNP variants (sampled 300 via entrez): RS1000034907 (17:35814669 A>G), RS1000047034 (17:35837344 G>A,T), RS1000086895 (17:35814444 A>C,G), RS1000114699 (17:35831763 CT>C,CTT), RS1000177813 (17:35830907 A>G,T), RS1000185108 (17:35840918 C>T), RS1000216034 (17:35826695 C>G,T), RS1000260048 (17:35815692 G>C), RS1000288556 (17:35836846 C>T), RS1000448399 (17:35830665 T>C), RS1000600625 (17:35825639 G>A), RS1000632746 (17:35830671 C>A,T), RS1000649641 (17:35835994 G>A), RS1000670564 (17:35826760 G>C), RS1000695135 (17:35845834 C>G)

Disease associations

OMIM: gene MIM:601574 | disease phenotypes: MIM:612237

GenCC curated gene-disease

Disease	Classification	Inheritance
amyotrophic lateral sclerosis	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
amyotrophic lateral sclerosis	Limited	AD

Mondo (2): amyotrophic lateral sclerosis (MONDO:0004976), extraskeletal myxoid chondrosarcoma (MONDO:0012825)

Orphanet (2): Amyotrophic lateral sclerosis (Orphanet:803), Extraskeletal myxoid chondrosarcoma (Orphanet:209916)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000217	Xerostomia
HP:0000708	Atypical behavior
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000739	Anxiety
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001308	Tongue fasciculations
HP:0001347	Hyperreflexia
HP:0001618	Dysphonia
HP:0001824	Weight loss
HP:0002015	Dysphagia
HP:0002094	Dyspnea
HP:0002145	Frontotemporal dementia
HP:0002180	Neurodegeneration
HP:0002307	Drooling
HP:0002313	Spastic paraparesis
HP:0002360	Sleep disturbance
HP:0002380	Fasciculations
HP:0002463	Language impairment
HP:0002878	Respiratory failure
HP:0003202	Skeletal muscle atrophy
HP:0003324	Generalized muscle weakness
HP:0003376	Steppage gait
HP:0003394	Muscle spasm
HP:0003470	Paralysis
HP:0003484	Upper limb muscle weakness
HP:0003487	Babinski sign
HP:0003693	Distal amyotrophy
HP:0004326	Cachexia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004619_113	Reticulocyte fraction of red cells	6.000000e-13
GCST004622_52	Reticulocyte count	7.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count

MeSH disease descriptors (2)

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
C563195	Chondrosarcoma, Extraskeletal Myxoid (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067122 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.56	Kd	27.48	nM	CHEMBL5653589
7.56	ED50	27.48	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149537: Binding affinity to human TAF15 incubated for 45 mins by Kinobead based pull down assay	kd	0.0275	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	3
sodium arsenite	affects binding, affects reaction, increases reaction, increases expression, affects cotreatment (+2 more)	3
methylmercuric chloride	decreases expression, increases expression	2
methylparaben	increases expression	2
Acetaminophen	decreases expression, increases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
graphene oxide	decreases expression	1
dicrotophos	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, increases expression, decreases expression, affects localization	1
kojic acid	decreases expression	1
beta-lapachone	increases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
coumarin	increases phosphorylation	1
tamibarotene	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
bisphenol S	affects expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Leflunomide	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Caffeine	decreases phosphorylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652579	Binding	Binding affinity to human TAF15 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C6MY	USZ22-EMC2	Cancer cell line	Male
CVCL_D8FE	Ubigene Caco-2 TAF15 KO	Cancer cell line	Male
CVCL_TR46	HAP1 TAF15 (-) 1	Cancer cell line	Male
CVCL_TR47	HAP1 TAF15 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

300 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)
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
NCT04248465	PHASE3	TERMINATED	An Efficacy and Safety Study of Ravulizumab in ALS Participants
NCT04569084	PHASE3	TERMINATED	Efficacy and Safety Study of Oral Edaravone Administered in Subjects With ALS