TAF6L

Summary

TAF6L (TATA-box binding protein associated factor 6 like, HGNC:17305) is a protein-coding gene on chromosome 11q12.3, encoding TAF6-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 6L (Q9Y6J9). Functions as a component of the PCAF complex. It is a selective cancer dependency (DepMap: 34.7% of cell lines).

Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (TFIID), which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes a protein that is a component of the PCAF histone acetylase complex and structurally similar to one of the histone-like TAFs, TAF6. The PCAF histone acetylase complex, which is composed of more than 20 polypeptides some of which are TAFs, is required for myogenic transcription and differentiation.

Source: NCBI Gene 10629 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 84 total
• Cancer dependency (DepMap): dependent in 34.7% of screened cell lines
• MANE Select transcript: NM_006473

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17305
Approved symbol	TAF6L
Name	TATA-box binding protein associated factor 6 like
Location	11q12.3
Locus type	gene with protein product
Status	Approved
Aliases	PAF65A
Ensembl gene	ENSG00000162227
Ensembl biotype	protein_coding
OMIM	602946
Entrez	10629

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 20 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000294168, ENST00000524976, ENST00000525405, ENST00000526261, ENST00000529509, ENST00000531265, ENST00000532915, ENST00000533823, ENST00000853523, ENST00000853524, ENST00000853525, ENST00000853526, ENST00000853527, ENST00000936988, ENST00000936989, ENST00000936990, ENST00000936991, ENST00000936992, ENST00000936993, ENST00000936994, ENST00000936995, ENST00000936996, ENST00000936997, ENST00000936998, ENST00000958840

RefSeq mRNA: 1 — MANE Select: NM_006473 NM_006473

CCDS: CCDS8035

Canonical transcript exons

ENST00000294168 — 11 exons

Exon	Start	End
ENSE00001063530	62782693	62782825
ENSE00001063531	62786260	62786388
ENSE00001142061	62786517	62787342
ENSE00002163640	62771396	62771490
ENSE00003474027	62782113	62782333
ENSE00003474933	62776384	62776470
ENSE00003506332	62777978	62778128
ENSE00003543465	62778869	62778963
ENSE00003600722	62781894	62781968
ENSE00003623860	62775771	62775930
ENSE00003786315	62778285	62778335

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 91.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.2203 / max 98.5822, expressed in 1716 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114746	2.8122	1469
114745	2.4082	1397

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
metanephros cortex	UBERON:0010533	91.35	gold quality
right lobe of thyroid gland	UBERON:0001119	91.00	gold quality
right lobe of liver	UBERON:0001114	90.99	gold quality
apex of heart	UBERON:0002098	90.98	gold quality
left lobe of thyroid gland	UBERON:0001120	90.05	gold quality
adenohypophysis	UBERON:0002196	89.79	gold quality
left uterine tube	UBERON:0001303	89.77	gold quality
right ovary	UBERON:0002118	89.74	gold quality
body of pancreas	UBERON:0001150	89.22	gold quality
gastrocnemius	UBERON:0001388	89.14	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.07	gold quality
right adrenal gland cortex	UBERON:0035827	89.06	gold quality
right adrenal gland	UBERON:0001233	89.01	gold quality
muscle of leg	UBERON:0001383	88.44	gold quality
pituitary gland	UBERON:0000007	88.34	gold quality
body of uterus	UBERON:0009853	88.34	gold quality
left adrenal gland cortex	UBERON:0035825	88.29	gold quality
left ovary	UBERON:0002119	88.22	gold quality
left adrenal gland	UBERON:0001234	88.17	gold quality
thyroid gland	UBERON:0002046	88.16	gold quality
endocervix	UBERON:0000458	88.05	gold quality
granulocyte	CL:0000094	87.83	gold quality
stromal cell of endometrium	CL:0002255	87.75	gold quality
skin of leg	UBERON:0001511	87.66	gold quality
ectocervix	UBERON:0012249	87.57	gold quality
skin of abdomen	UBERON:0001416	87.41	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.35	gold quality
body of stomach	UBERON:0001161	87.21	gold quality
mucosa of stomach	UBERON:0001199	87.05	gold quality
lower esophagus mucosa	UBERON:0035834	86.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.33

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 34.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• immunohistochemical studies suggest that CBP, depending on the balance of nuclear proteins, is a component of AIRE nuclear bodies (PMID:15964547)
• protein kinase C betaII augments NF-kappaB-mediated TNF-alpha-induced transcription of the target gene CCL11, promoting p65 association with the CCL11 promoter, in human airway smooth muscle cells by phosphorylating p300/CBP-associated factor (PMID:18714023)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	taf6l	ENSDARG00000079684
mus_musculus	Taf6l	ENSMUSG00000003680
rattus_norvegicus	Taf6l	ENSRNOG00000019419
drosophila_melanogaster	mia	FBGN0014342
caenorhabditis_elegans		WBGENE00006387
caenorhabditis_elegans		WBGENE00021363

Paralogs (1): TAF6 (ENSG00000106290)

Protein

Protein identifiers

TAF6-like RNA polymerase II p300/CBP-associated factor-associated factor 65 kDa subunit 6L — Q9Y6J9 (reviewed: Q9Y6J9)

Alternative names: PCAF-associated factor 65-alpha

All UniProt accessions (4): E9PK90, E9PLV8, E9PP94, Q9Y6J9

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a component of the PCAF complex. The PCAF complex is capable of efficiently acetylating histones in a nucleosomal context. The PCAF complex could be considered as the human version of the yeast SAGA complex. With TAF5L, acts as an epigenetic regulator essential for somatic reprogramming. Regulates target genes through H3K9ac deposition and MYC recruitment which trigger MYC regulatory network to orchestrate gene expression programs to control embryonic stem cell state. Functions with MYC to activate target gene expression through RNA polymerase II pause release.

Subunit / interactions. The PCAF complex is composed of a number of TBP-associated factors (TAFS), such as TAF5, TAF5L, TAF6, TAF6L, TAF9, TAF10 and TAF12, PCAF, and also PCAF-associated factors (PAFs), such as TADA2L/ADA2, TADA3L/ADA3 and SPT3. Component of the STAGA transcription coactivator-HAT complex, at least composed of SUPT3H, GCN5L2, TAF5L, TAF6L, SUPT7L, TADA3L, TAD1L, TAF10, TAF12, TRRAP and TAF9.

Subcellular location. Nucleus.

Similarity. Belongs to the TAF6 family.

RefSeq proteins (1): NP_006464* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004823	TAF_TATA-bd_Histone-like_dom	Domain
IPR009072	Histone-fold	Homologous_superfamily
IPR011442	TAF6_C	Domain
IPR037796	TAF6	Family
IPR046344	TAF6_C_sf	Homologous_superfamily

Pfam: PF02969, PF07571

UniProt features (20 total): strand 6, modified residue 5, helix 4, region of interest 2, chain 1, turn 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9RDK	ELECTRON MICROSCOPY	2.41
7KTR	ELECTRON MICROSCOPY	2.93
8H7G	ELECTRON MICROSCOPY	3.7
7KTS	ELECTRON MICROSCOPY	19.09

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6J9-F1	68.81	0.45

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 (5): 495, 501, 555, 561, 593

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-3214847	HATs acetylate histones
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization

MSigDB gene sets: 134 (showing top): GOBP_SOMATIC_STEM_CELL_POPULATION_MAINTENANCE, NAGY_STAGA_COMPONENTS_HUMAN, GOBP_REGULATION_OF_DNA_REPAIR, USF_01, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_RNA_SPLICING, GOBP_DNA_DAMAGE_RESPONSE, GOBP_MAINTENANCE_OF_CELL_NUMBER, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, GOBP_REGULATION_OF_STEM_CELL_POPULATION_MAINTENANCE, TANAKA_METHYLATED_IN_ESOPHAGEAL_CARCINOMA, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOCC_RNA_POLYMERASE_COMPLEX, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_STRESS

GO Biological Process (9): regulation of DNA repair (GO:0006282), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), regulation of RNA splicing (GO:0043484), positive regulation of DNA-templated transcription (GO:0045893), RNA polymerase II preinitiation complex assembly (GO:0051123), regulation of somatic stem cell population maintenance (GO:1904672), transcription initiation at RNA polymerase II promoter (GO:0006367)

GO Molecular Function (5): DNA binding (GO:0003677), transcription coactivator activity (GO:0003713), RNA polymerase II general transcription initiation factor activity (GO:0016251), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515)

GO Cellular Component (7): histone deacetylase complex (GO:0000118), SAGA complex (GO:0000124), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription factor TFIID complex (GO:0005669), SLIK (SAGA-like) complex (GO:0046695), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Chromatin organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	3
DNA-templated transcription	2
regulation of gene expression	2
regulation of DNA-templated transcription	2
SAGA-type complex	2
DUBm complex	2
DNA repair	1
regulation of DNA metabolic process	1
regulation of cellular response to stress	1
chromatin organization	1
regulation of RNA biosynthetic process	1
RNA splicing	1
regulation of primary metabolic process	1
positive regulation of RNA biosynthetic process	1
transcription initiation at RNA polymerase II promoter	1
transcription preinitiation complex assembly	1
somatic stem cell population maintenance	1
regulation of stem cell population maintenance	1
DNA-templated transcription initiation	1
nucleic acid binding	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
general transcription initiation factor activity	1
protein dimerization activity	1
binding	1
nucleoplasm	1
nuclear protein-containing complex	1
catalytic complex	1
peptidase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
RNA polymerase II, holoenzyme	1
RNA polymerase II transcription regulator complex	1
extracellular vesicle	1

Protein interactions and networks

STRING

1628 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAF6L	TAF5L	O75529	958
TAF6L	SUPT20H	Q8NEM7	857
TAF6L	TAF10	Q12962	832
TAF6L	TADA3	O75528	792
TAF6L	TAF12	Q16514	788
TAF6L	TAF9	Q16594	783
TAF6L	SUPT7L	O94864	781
TAF6L	SGF29	Q96ES7	764
TAF6L	TRRAP	Q9Y4A5	753
TAF6L	TADA2B	Q86TJ2	739
TAF6L	TAF9B	Q9HBM6	684
TAF6L	KAT2B	Q92831	679
TAF6L	SUPT3H	O75486	675
TAF6L	ATXN7L3	Q14CW9	665
TAF6L	TAF8	Q7Z7C8	616

IntAct

138 interactions, top by confidence:

A	B	Type	Score
TAF6L	TAF9	psi-mi:“MI:0915”(physical association)	0.880
TAF9	TAF6L	psi-mi:“MI:0915”(physical association)	0.880
TAF6L	TAF9	psi-mi:“MI:0407”(direct interaction)	0.880
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
SGF29	NDC80	psi-mi:“MI:0914”(association)	0.840
TAF9B	TAF6L	psi-mi:“MI:0915”(physical association)	0.830
MED23	MED19	psi-mi:“MI:2364”(proximity)	0.770
TAF12	TAF4	psi-mi:“MI:0914”(association)	0.760
TRRAP	ATXN7	psi-mi:“MI:0914”(association)	0.740
TADA3	TADA2A	psi-mi:“MI:0914”(association)	0.740
KAT2B	TADA2A	psi-mi:“MI:0914”(association)	0.640
TADA1	TAF5L	psi-mi:“MI:0914”(association)	0.640
ATXN7L3	USP27X	psi-mi:“MI:0914”(association)	0.640
TADA1	TADA3	psi-mi:“MI:0914”(association)	0.640
PFDN5	TAF6L	psi-mi:“MI:0915”(physical association)	0.560
SPINT2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
TADA2B	SUPT3H	psi-mi:“MI:0914”(association)	0.530
HLA-DPA1	TYW5	psi-mi:“MI:0914”(association)	0.530

BioGRID (205): TAF6L (Two-hybrid), TAF9B (Two-hybrid), TAF6L (Protein-peptide), TAF6L (Affinity Capture-MS), TAF6L (Affinity Capture-MS), TAF6L (Affinity Capture-MS), TAF6L (Affinity Capture-MS), TAF6L (Affinity Capture-MS), TAF6L (Affinity Capture-MS), TAF6L (Two-hybrid), TAF6L (Affinity Capture-MS), TAF6L (Proximity Label-MS), TAF6L (Affinity Capture-MS), TAF6L (Affinity Capture-MS), TAF6L (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RR11, A0A0U1RRI6, A6NCS6, A6NJG2, B0BN44, D3YXK1, E9PY61, E9Q0B3, F5H4A9, O00220, O00221, P09038, P0DPI3, P22083, P98077, Q08AU9, Q2M2W7, Q2M3V2, Q2TBI2, Q5F267, Q5FW56, Q5IS69, Q5R866, Q5T4W7, Q5TM52, Q5U4P2, Q5VTJ3, Q659K9, Q673H1, Q69ZB3, Q6AYE8, Q6IPT2, Q6PJ61, Q7RTU4, Q7TSX9, Q7YR31, Q80SU3, Q86SH2, Q86Y97, Q8NBR0

Diamond homologs: F4HVA6, O74462, P49847, P49848, P53040, Q9MAU3, Q9Y6J9, Q8R2K4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TAF6L	“form complex”	“SAGA complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 156 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
HATs acetylate histones	17	13.8×	2e-12
Formation of WDR5-containing histone-modifying complexes	5	13.6×	3e-03
Chromatin organization	14	11.7×	2e-09
Chromatin modifying enzymes	15	11.1×	1e-09
Epigenetic regulation by WDR5-containing histone modifying complexes	7	11.0×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
regulation of DNA repair	18	37.1×	4e-21
regulation of RNA splicing	17	27.8×	9e-18
RNA polymerase II preinitiation complex assembly	6	12.2×	1e-03
positive regulation of transcription initiation by RNA polymerase II	6	12.2×	1e-03
chromatin remodeling	11	6.0×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1794 predictions. Top by Δscore:

Variant	Effect	Δscore
11:62771487:TCAGG:T	donor_loss	1.0000
11:62771488:CAGG:C	donor_loss	1.0000
11:62771489:AGGTG:A	donor_loss	1.0000
11:62771490:GGTG:G	donor_loss	1.0000
11:62771491:G:C	donor_loss	1.0000
11:62775769:A:AG	acceptor_gain	1.0000
11:62775770:G:GC	acceptor_gain	1.0000
11:62775770:GCTCC:G	acceptor_gain	1.0000
11:62775898:G:GT	donor_gain	1.0000
11:62775926:CGCAG:C	donor_loss	1.0000
11:62775927:GCAG:G	donor_gain	1.0000
11:62775928:C:T	donor_gain	1.0000
11:62775928:CAGGT:C	donor_loss	1.0000
11:62775932:T:A	donor_loss	1.0000
11:62776378:TCCCA:T	acceptor_loss	1.0000
11:62776379:CCCA:C	acceptor_loss	1.0000
11:62776380:CCAGA:C	acceptor_loss	1.0000
11:62776381:CAGAA:C	acceptor_loss	1.0000
11:62776382:A:AG	acceptor_gain	1.0000
11:62776382:A:AT	acceptor_loss	1.0000
11:62776383:G:GT	acceptor_gain	1.0000
11:62776383:GA:G	acceptor_gain	1.0000
11:62776383:GAA:G	acceptor_gain	1.0000
11:62776383:GAAT:G	acceptor_gain	1.0000
11:62776383:GAATA:G	acceptor_gain	1.0000
11:62776469:AGGTG:A	donor_loss	1.0000
11:62776471:G:GG	donor_gain	1.0000
11:62776472:T:G	donor_loss	1.0000
11:62778105:G:GT	donor_gain	1.0000
11:62778119:GCT:G	donor_gain	1.0000

AlphaMissense

3963 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:62775914:T:C	L44P	1.000
11:62776387:A:C	S51R	1.000
11:62776389:C:A	S51R	1.000
11:62776389:C:G	S51R	1.000
11:62782287:T:A	W261R	1.000
11:62782287:T:C	W261R	1.000
11:62782289:G:C	W261C	1.000
11:62782289:G:T	W261C	1.000
11:62786773:G:T	G449V	1.000
11:62775833:T:A	V17D	0.999
11:62775844:G:C	A21P	0.999
11:62775890:T:A	L36H	0.999
11:62775898:G:C	D39H	0.999
11:62775907:T:G	Y42D	0.999
11:62775911:G:C	R43P	0.999
11:62775917:G:C	R45T	0.999
11:62775917:G:T	R45I	0.999
11:62775918:A:C	R45S	0.999
11:62775918:A:T	R45S	0.999
11:62775922:G:C	A47P	0.999
11:62776435:G:C	D67H	0.999
11:62776436:A:C	D67A	0.999
11:62776436:A:G	D67G	0.999
11:62776436:A:T	D67V	0.999
11:62776447:G:C	A71P	0.999
11:62776448:C:A	A71D	0.999
11:62776451:T:C	L72P	0.999
11:62778913:T:G	Y161D	0.999
11:62781910:T:C	L183S	0.999
11:62781920:C:A	N186K	0.999

dbSNP variants (sampled 300 via entrez): RS1000009827 (11:62780240 C>T), RS1000011074 (11:62780484 C>A,G,T), RS1000067794 (11:62786746 T>C,G), RS1000081793 (11:62786984 T>C), RS1000506168 (11:62775232 A>G), RS1000571143 (11:62777086 G>A), RS1000579824 (11:62784424 C>T), RS1000632081 (11:62784190 A>G,T), RS1000921235 (11:62777438 A>G), RS1001085217 (11:62787648 G>A,C,T), RS1001205308 (11:62771775 G>A), RS1001272030 (11:62787085 C>T), RS1001360268 (11:62778545 T>G), RS1001400844 (11:62781567 G>A,C), RS1001428514 (11:62781273 A>C,G)

Disease associations

OMIM: gene MIM:602946 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005956_2	Waist-to-hip ratio adjusted for BMI	1.000000e-08
GCST005962_51	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	3
bisphenol A	affects cotreatment, increases methylation, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
methylmercuric chloride	increases expression	1
sodium arsenite	decreases expression	1
vanadyl sulfate	decreases expression	1
jinfukang	increases 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
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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