TAF6

Summary

TAF6 (TATA-box binding protein associated factor 6, HGNC:11540) is a protein-coding gene on chromosome 7q22.1, encoding Transcription initiation factor TFIID subunit 6 (P49848). The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription. It is a common-essential gene (DepMap: required in 99.8% of cancer 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 one of the smaller subunits of TFIID that binds weakly to TBP but strongly to TAF1, the largest subunit of TFIID. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 6878 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Alazami-Yuan syndrome (Strong, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 142 total — 2 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 26
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_139315

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11540
Approved symbol	TAF6
Name	TATA-box binding protein associated factor 6
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	TAFII70, TAFII80, MGC:8964, TAFII85
Ensembl gene	ENSG00000106290
Ensembl biotype	protein_coding
OMIM	602955
Entrez	6878

Gene structure

Transcript identifiers

Ensembl transcripts: 123 — 94 protein_coding, 15 retained_intron, 11 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000344095, ENST00000417349, ENST00000421980, ENST00000431404, ENST00000437822, ENST00000440225, ENST00000449571, ENST00000451699, ENST00000452041, ENST00000452438, ENST00000453269, ENST00000460673, ENST00000472509, ENST00000487115, ENST00000487288, ENST00000493322, ENST00000520135, ENST00000523306, ENST00000684938, ENST00000684951, ENST00000685054, ENST00000685258, ENST00000685280, ENST00000685713, ENST00000686096, ENST00000686141, ENST00000686172, ENST00000686580, ENST00000686777, ENST00000687137, ENST00000687151, ENST00000687216, ENST00000687410, ENST00000687447, ENST00000687641, ENST00000687672, ENST00000687768, ENST00000687969, ENST00000688086, ENST00000688091, ENST00000688197, ENST00000688343, ENST00000688498, ENST00000688640, ENST00000688962, ENST00000689052, ENST00000689284, ENST00000689347, ENST00000689536, ENST00000689684, ENST00000689754, ENST00000689866, ENST00000690206, ENST00000690291, ENST00000690335, ENST00000690367, ENST00000690602, ENST00000690962, ENST00000691010, ENST00000691370, ENST00000691413, ENST00000691534, ENST00000691681, ENST00000692029, ENST00000692175, ENST00000692408, ENST00000692466, ENST00000692927, ENST00000693225, ENST00000693256, ENST00000693374, ENST00000907010, ENST00000907011, ENST00000907012, ENST00000907013, ENST00000907014, ENST00000907015, ENST00000907016, ENST00000907017, ENST00000907018, ENST00000907019, ENST00000907020, ENST00000907021, ENST00000907022, ENST00000907023, ENST00000907024, ENST00000907025, ENST00000907026, ENST00000907027, ENST00000907028, ENST00000918699, ENST00000918700, ENST00000918701, ENST00000918702, ENST00000918703, ENST00000918704, ENST00000918705, ENST00000918706, ENST00000918707, ENST00000918708, ENST00000918709, ENST00000918710, ENST00000918711, ENST00000918712, ENST00000918713, ENST00000918714, ENST00000918715, ENST00000918716, ENST00000918717, ENST00000918718, ENST00000918719, ENST00000918720, ENST00000918721, ENST00000918722, ENST00000918723, ENST00000970431, ENST00000970432, ENST00000970433, ENST00000970434, ENST00000970435, ENST00000970436, ENST00000970437, ENST00000970438

RefSeq mRNA: 10 — MANE Select: NM_139315 NM_001190415, NM_001364998, NM_001364999, NM_001365000, NM_001365001, NM_001365002, NM_001365003, NM_001365004, NM_005641, NM_139315

CCDS: CCDS55135, CCDS5686, CCDS94153

Canonical transcript exons

ENST00000453269 — 15 exons

Exon	Start	End
ENSE00000824907	100113616	100113769
ENSE00001929715	100119204	100119358
ENSE00003468521	100112108	100112253
ENSE00003471681	100113868	100113954
ENSE00003482704	100109948	100110073
ENSE00003485342	100107070	100107623
ENSE00003507111	100108367	100108540
ENSE00003520015	100111922	100111999
ENSE00003546321	100111728	100111829
ENSE00003585151	100114054	100114268
ENSE00003600719	100111139	100111321
ENSE00003627676	100107926	100108123
ENSE00003641538	100112798	100112917
ENSE00003680922	100110200	100110274
ENSE00003786915	100113349	100113405

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 95.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.4945 / max 87.7586, expressed in 1739 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85158	7.1473	1721
85156	0.9402	629
85159	0.1833	62
85157	0.1142	24
85155	0.0934	18
85153	0.0136	4
85154	0.0026	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	95.77	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.04	gold quality
right frontal lobe	UBERON:0002810	95.00	gold quality
cerebellar hemisphere	UBERON:0002245	94.50	gold quality
body of uterus	UBERON:0009853	94.43	gold quality
cerebellar cortex	UBERON:0002129	94.39	gold quality
pituitary gland	UBERON:0000007	94.20	gold quality
adenohypophysis	UBERON:0002196	94.20	gold quality
endocervix	UBERON:0000458	94.08	gold quality
right ovary	UBERON:0002118	93.82	gold quality
cingulate cortex	UBERON:0003027	93.78	gold quality
anterior cingulate cortex	UBERON:0009835	93.70	gold quality
left ovary	UBERON:0002119	93.57	gold quality
prefrontal cortex	UBERON:0000451	93.51	gold quality
right adrenal gland	UBERON:0001233	93.47	gold quality
right adrenal gland cortex	UBERON:0035827	93.42	gold quality
cerebellum	UBERON:0002037	93.40	gold quality
right uterine tube	UBERON:0001302	93.29	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.18	gold quality
lower esophagus	UBERON:0013473	93.17	gold quality
islet of Langerhans	UBERON:0000006	93.15	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.09	gold quality
smooth muscle tissue	UBERON:0001135	93.08	gold quality
left testis	UBERON:0004533	93.04	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.01	gold quality
granulocyte	CL:0000094	92.97	gold quality
right lobe of thyroid gland	UBERON:0001119	92.92	gold quality
endometrium epithelium	UBERON:0004811	92.91	gold quality
left adrenal gland	UBERON:0001234	92.90	gold quality
right testis	UBERON:0004534	92.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.30

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TADA2A, TBP

miRNA regulators (miRDB)

18 targeting TAF6, 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-1252-5P	100.00	69.80	2774
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-10226	98.25	66.50	811
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-892B	98.00	67.11	821
HSA-MIR-4778-5P	97.96	68.06	1634
HSA-MIR-4288	97.11	67.23	1636
HSA-MIR-632	96.08	67.17	798

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 8)

• a novel protein-protein interaction was observed between TAFII70 (not TAFII80) and GADD45a (PMID:15328371)
• histone fold domain mediated interaction enhances the DNA binding activity of each of the TAF6-TAF9 and TAF4b-TAF12 pairs and of a histone-like octamer complex composed of the four TAFs (PMID:15601843)
• TAF6delta has a pivotal node in a signaling pathway that controls gene expression programs and apoptosis in the absence of p53 (PMID:18628956)
• The transcriptome data uncovered novel links between TAF6delta expression and the Notch, oxidative stress response, integrin, p53, p53 feedback loop 2, and angiogenesis pathways. (PMID:20096117)
• TFIID TAF6-TAF9 complex formation involves the HEAT repeat-containing C-terminal domain of TAF6 and is modulated by TAF5 protein. (PMID:22696218)
• data point to several new RNA elements that can modulate TAF6delta and also reveal a role for RNA secondary structure in the selection of TAF6delta (PMID:25025302)
• BIM and NOXA contribute to TAF6delta-dependent cell death. (PMID:29358700)
• The third family with TAF6-related phenotype: Alazami-Yuan syndrome. (PMID:32030742)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	taf6	ENSDARG00000102998
mus_musculus	Taf6	ENSMUSG00000036980
rattus_norvegicus	Taf6	ENSRNOG00000001355
drosophila_melanogaster	Taf6	FBGN0010417

Paralogs (1): TAF6L (ENSG00000162227)

Protein

Protein identifiers

Transcription initiation factor TFIID subunit 6 — P49848 (reviewed: P49848)

Alternative names: RNA polymerase II TBP-associated factor subunit E, Transcription initiation factor TFIID 70 kDa subunit, Transcription initiation factor TFIID 80 kDa subunit

All UniProt accessions (16): P49848, A0A1D5RMS5, A0A8I5KQQ6, A0A8I5KR77, A0A8I5KRU1, A0A8I5KSI7, A0A8I5KTW4, A4D299, C9J088, C9JFL8, C9JHQ8, C9JI39, C9JIS2, C9JTY6, F8WEJ7, J3KR72

UniProt curated annotations — full annotation on UniProt →

Function. The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription. TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. The TFIID complex structure can be divided into 3 modules TFIID-A, TFIID-B, and TFIID-C. TAF6 homodimer connects TFIID modules, forming a rigid core. Transcriptional regulator which acts primarily as a positive regulator of transcription. Recruited to the promoters of a number of genes including GADD45A and CDKN1A/p21, leading to transcriptional up-regulation and subsequent induction of apoptosis. Also up-regulates expression of other genes including GCNA/ACRC, HES1 and IFFO1. In contrast, down-regulates transcription of MDM2. Acts as a transcriptional coactivator to enhance transcription of TP53/p53-responsive genes such as DUSP1. Can also activate transcription and apoptosis independently of TP53. Drives apoptosis via the intrinsic apoptotic pathway by up-regulating apoptosis effectors such as BCL2L11/BIM and PMAIP1/NOXA.

Subunit / interactions. Component of the TFIID basal transcription factor complex, composed of TATA-box-binding protein TBP, and a number of TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. Interacts directly with TBP, TAF1/TAFII250, TAF9/TAFII31 and TAF12/TAFII20. The TAF6/TAFII70-TAF9/TAFII31 heterodimer forms an octamer complex with the TAF4B/TFII105-TAF12/TFIID20 heterodimer. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BACC1, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Also interacts with the GTFs, TFIIEalpha/GTF2E1 and TFIIFalpha/GTF2F1. Component of the TBP-free TAFII-histone acetylase complex (TFTC-HAT). Interacts with TP53/p53. Not part of the TBP-free TAFII-histone acetylase complex (TFTC-HAT). Part of a TFIID-like complex which lacks TAF9. Interacts with TP53/p53.

Subcellular location. Nucleus Nucleus.

Post-translational modifications. In cells undergoing apoptosis, cleaved in a caspase-dependent manner to produce a 40 kDa product.

Disease relevance. Alazami-Yuan syndrome (ALYUS) [MIM:617126] An autosomal recessive syndrome reminiscent of Cornelia de Lange syndrome and characterized by delayed psychomotor development with intellectual disability, hypotonia, microcephaly, short stature, poor speech, and dysmorphic features. The disease is caused by variants affecting the gene represented in this entry.

Induction. Induced in cells undergoing apoptosis.

Similarity. Belongs to the TAF6 family.

Isoforms (4)

UniProt ID	Names	Canonical?
P49848-1	1, Alpha	yes
P49848-2	2, Gamma
P49848-3	3
P49848-4	4, Delta

RefSeq proteins (10): NP_001177344, NP_001351927, NP_001351928, NP_001351929, NP_001351930, NP_001351931, NP_001351932, NP_001351933, NP_005632, NP_647476* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004823	TAF_TATA-bd_Histone-like_dom	Domain
IPR009072	Histone-fold	Homologous_superfamily
IPR011442	TAF6_C	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR037796	TAF6	Family
IPR046344	TAF6_C_sf	Homologous_superfamily

Pfam: PF02969, PF07571

UniProt features (58 total): helix 19, modified residue 10, strand 10, region of interest 3, splice variant 3, sequence variant 3, turn 3, compositionally biased region 3, sequence conflict 2, chain 1, cross-link 1

Structure

Experimental structures (PDB)

32 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6F3T	X-RAY DIFFRACTION	2.5
7EGG	ELECTRON MICROSCOPY	2.77
7EGH	ELECTRON MICROSCOPY	3.04
7EGF	ELECTRON MICROSCOPY	3.16
7EGB	ELECTRON MICROSCOPY	3.3
7EG9	ELECTRON MICROSCOPY	3.7
7EGC	ELECTRON MICROSCOPY	3.9
7ENA	ELECTRON MICROSCOPY	4.07
7EGA	ELECTRON MICROSCOPY	4.1
7ENC	ELECTRON MICROSCOPY	4.13
8GXS	ELECTRON MICROSCOPY	4.16
6MZC	ELECTRON MICROSCOPY	4.5
7EDX	ELECTRON MICROSCOPY	4.5
8GXQ	ELECTRON MICROSCOPY	5.04
8WAK	ELECTRON MICROSCOPY	5.47
8WAP	ELECTRON MICROSCOPY	5.85
8WAN	ELECTRON MICROSCOPY	6.07
8WAS	ELECTRON MICROSCOPY	6.13
7EG7	ELECTRON MICROSCOPY	6.2
8WAQ	ELECTRON MICROSCOPY	6.29
8WAO	ELECTRON MICROSCOPY	6.4
7EGD	ELECTRON MICROSCOPY	6.75
8WAR	ELECTRON MICROSCOPY	7.2
7EG8	ELECTRON MICROSCOPY	7.4
6MZM	ELECTRON MICROSCOPY	7.5
5FUR	ELECTRON MICROSCOPY	8.5
8WAL	ELECTRON MICROSCOPY	8.52
7EGJ	ELECTRON MICROSCOPY	8.64
7EGE	ELECTRON MICROSCOPY	9
6MZD	ELECTRON MICROSCOPY	9.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49848-F1	64.81	0.10

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 (11): 264, 524, 626, 634, 636, 653, 660, 196, 120, 248, 253

Function

Pathways and Gene Ontology

Reactome pathways

21 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-6807505	RNA polymerase II transcribes snRNA genes
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
R-HSA-162587	HIV Life Cycle
R-HSA-162599	Late Phase of HIV Life Cycle
R-HSA-162906	HIV Infection
R-HSA-1643685	Disease
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-5663205	Infectious disease
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 250 (showing top): GOBP_POSITIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_REGULATION_OF_DNA_REPAIR, YY1_Q6, PATIL_LIVER_CANCER, REACTOME_HIV_INFECTION, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, YY1_02, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_DNA_DAMAGE_RESPONSE, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY

GO Biological Process (14): regulation of DNA repair (GO:0006282), DNA-templated transcription initiation (GO:0006352), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), transcription initiation at RNA polymerase II promoter (GO:0006367), apoptotic process (GO:0006915), negative regulation of cell population proliferation (GO:0008285), mRNA transcription by RNA polymerase II (GO:0042789), positive regulation of apoptotic process (GO:0043065), negative regulation of cell cycle (GO:0045786), positive regulation of DNA-templated transcription (GO:0045893), RNA polymerase II preinitiation complex assembly (GO:0051123), positive regulation of transcription initiation by RNA polymerase II (GO:0060261), positive regulation of intrinsic apoptotic signaling pathway (GO:2001244)

GO Molecular Function (6): DNA binding (GO:0003677), transcription coactivator activity (GO:0003713), RNA polymerase II general transcription initiation factor activity (GO:0016251), aryl hydrocarbon receptor binding (GO:0017162), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515)

GO Cellular Component (9): SAGA complex (GO:0000124), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription factor TFIID complex (GO:0005669), cytosol (GO:0005829), protein-containing complex (GO:0032991), transcription factor TFTC complex (GO:0033276), SLIK (SAGA-like) complex (GO:0046695), MLL1 complex (GO:0071339)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
RNA Polymerase II Transcription	5
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
HIV Infection	1
HIV Life Cycle	1
Viral Infection Pathways	1
Generic Transcription Pathway	1
Transcriptional Regulation by TP53	1
Disease	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	4
DNA-templated transcription	3
SAGA-type complex	3
regulation of DNA-templated transcription	2
negative regulation of cellular process	2
transcription initiation at RNA polymerase II promoter	2
DUBm complex	2
cellular anatomical structure	2
RNA polymerase II, holoenzyme	2
RNA polymerase II transcription regulator complex	2
DNA repair	1
regulation of DNA metabolic process	1
regulation of cellular response to stress	1
RNA biosynthetic process	1
DNA-templated transcription initiation	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell population proliferation	1
regulation of cell population proliferation	1
mRNA transcription	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
cell cycle	1
regulation of cell cycle	1
positive regulation of RNA biosynthetic process	1
transcription preinitiation complex assembly	1
positive regulation of transcription by RNA polymerase II	1
regulation of transcription initiation by RNA polymerase II	1
positive regulation of DNA-templated transcription initiation	1
intrinsic apoptotic signaling pathway	1
positive regulation of intracellular signal transduction	1
positive regulation of apoptotic signaling pathway	1
regulation of intrinsic apoptotic signaling pathway	1
nucleic acid binding	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
general transcription initiation factor activity	1
signaling receptor binding	1

Protein interactions and networks

STRING

2123 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAF6	TAF12	Q16514	999
TAF6	TAF5	Q15542	999
TAF6	TAF9	Q16594	999
TAF6	TAF10	Q12962	998
TAF6	TAF4	O00268	990
TAF6	TAF8	Q7Z7C8	968
TAF6	TAF1	P21675	951
TAF6	TAF7	Q15545	950
TAF6	TAF11	Q15544	950
TAF6	TBP	P20226	946
TAF6	TAF9B	Q9HBM6	918
TAF6	TAF2	Q6P1X5	900
TAF6	KAT2B	Q92831	885
TAF6	SUPT20H	Q8NEM7	841
TAF6	GTF2B	Q00403	824

IntAct

138 interactions, top by confidence:

A	B	Type	Score
TAF5	TAF6	psi-mi:“MI:0407”(direct interaction)	0.760
TAF5	TAF6	psi-mi:“MI:0914”(association)	0.760
TAF5	TAF6	psi-mi:“MI:0915”(physical association)	0.760
TAF12	TAF4	psi-mi:“MI:0914”(association)	0.760
TBP	TAF4	psi-mi:“MI:0914”(association)	0.730
TAF12	TAF4	psi-mi:“MI:0915”(physical association)	0.720
TAF12	TAF4	psi-mi:“MI:0914”(association)	0.720
TAF10	TAF4	psi-mi:“MI:0914”(association)	0.650

BioGRID (337): TAF6 (Affinity Capture-MS), TAF6 (Protein-peptide), TAF6 (Affinity Capture-MS), CDC26 (Co-fractionation), SUPT5H (Co-fractionation), TAF1 (Co-fractionation), TAF10 (Co-fractionation), TAF3 (Co-fractionation), TAF6 (Co-fractionation), TAF6 (Co-fractionation), TAF6 (Co-fractionation), TAF6 (Co-fractionation), TAF6 (Affinity Capture-MS), TAF6 (Reconstituted Complex), TAF6 (Affinity Capture-Western)

ESM2 similar proteins: A0A571BF63, A0A8M9QN10, A2ARM1, A2CI97, A3KNA7, A4D1P6, A9C3W3, B2RYI0, E9Q7E2, F1QNV4, O95475, P49848, P56524, P70302, P83093, P84903, Q0VDN7, Q12769, Q12772, Q13586, Q2HJE1, Q32N92, Q3T1I5, Q3U1N2, Q3UGY8, Q58CP9, Q58HI1, Q5E9R0, Q5R902, Q5ZLL7, Q60429, Q62311, Q63801, Q6GQ26, Q6NZM9, Q6P4L9, Q6P4R8, Q6PIJ4, Q6ZPR5, Q7TMQ7

Diamond homologs: F4HVA6, O74462, P49847, P49848, P53040, Q62311, Q63801, Q91857, Q9MAU3, Q9Y6J9, Q8R2K4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TAF6	“form complex”	TFIID	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 105 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
HIV Transcription Initiation	11	36.6×	4e-13
RNA Polymerase II HIV Promoter Escape	11	36.6×	4e-13
RNA Polymerase II Promoter Escape	11	36.6×	4e-13
RNA Polymerase II Transcription Pre-Initiation And Promoter Opening	11	36.6×	4e-13
RNA Polymerase II Transcription Initiation	11	36.6×	4e-13
RNA Polymerase II Transcription Initiation And Promoter Clearance	11	36.6×	4e-13
Transcription of the HIV genome	11	27.2×	1e-11
Late Phase of HIV Life Cycle	10	24.0×	4e-10

GO biological processes:

GO term	Partners	Fold	FDR
DNA-templated transcription initiation	5	51.4×	2e-06
RNA polymerase II preinitiation complex assembly	13	38.8×	6e-15
transcription initiation at RNA polymerase II promoter	9	37.0×	4e-10
positive regulation of transcription initiation by RNA polymerase II	11	32.9×	8e-12
mRNA transcription by RNA polymerase II	9	32.7×	1e-09
regulation of DNA repair	6	18.2×	6e-05
transcription by RNA polymerase II	14	10.8×	4e-09
chromatin remodeling	8	6.4×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	54
Likely benign	39
Benign	21

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
180203	NM_139315.3(TAF6):c.136C>T (p.Arg46Cys)	Pathogenic
985272	NM_139315.3(TAF6):c.958C>T (p.Arg320Ter)	Pathogenic
3780690	NM_139315.3(TAF6):c.397+2T>C	Likely pathogenic
429479	NM_139315.3(TAF6):c.574+1G>A	Likely pathogenic
489277	NM_139315.3(TAF6):c.721-1G>A	Likely pathogenic

SpliceAI

1961 predictions. Top by Δscore:

Variant	Effect	Δscore
7:100108363:GGAC:G	donor_loss	1.0000
7:100108364:GAC:G	donor_loss	1.0000
7:100108366:C:CT	donor_loss	1.0000
7:100108536:TGTTT:T	acceptor_gain	1.0000
7:100108538:TTT:T	acceptor_gain	1.0000
7:100108539:TT:T	acceptor_gain	1.0000
7:100108540:TCT:T	acceptor_loss	1.0000
7:100108541:C:CC	acceptor_gain	1.0000
7:100108541:C:G	acceptor_loss	1.0000
7:100108542:T:A	acceptor_loss	1.0000
7:100110070:TAAC:T	acceptor_gain	1.0000
7:100110072:ACC:A	acceptor_loss	1.0000
7:100110073:CC:C	acceptor_loss	1.0000
7:100110073:CCTGT:C	acceptor_gain	1.0000
7:100110074:C:CC	acceptor_gain	1.0000
7:100110075:T:C	acceptor_loss	1.0000
7:100110182:T:TA	donor_gain	1.0000
7:100110186:C:CA	donor_gain	1.0000
7:100110198:A:C	donor_gain	1.0000
7:100110211:G:C	donor_gain	1.0000
7:100110215:AG:A	donor_gain	1.0000
7:100110216:G:C	donor_gain	1.0000
7:100111136:CACCT:C	donor_loss	1.0000
7:100111137:A:AC	donor_gain	1.0000
7:100111137:AC:A	donor_gain	1.0000
7:100111138:C:CA	donor_loss	1.0000
7:100111138:C:CC	donor_gain	1.0000
7:100111138:CC:C	donor_gain	1.0000
7:100111317:TGGAC:T	acceptor_gain	1.0000
7:100111318:GGAC:G	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000159860 (7:100116961 T>C), RS1000349935 (7:100122528 T>C), RS1000392813 (7:100128116 G>T), RS1000694652 (7:100126631 A>G), RS1000697193 (7:100124092 C>T), RS1000757558 (7:100118519 T>C), RS1001198871 (7:100120019 G>T), RS1001289113 (7:100110971 C>T), RS1001363639 (7:100114357 G>A), RS1001591007 (7:100114979 C>T), RS1001625842 (7:100121687 G>A,T), RS1001735567 (7:100125562 G>A), RS1001908091 (7:100121414 G>A), RS1001909220 (7:100120092 C>G), RS1002034713 (7:100114073 C>A,T)

Disease associations

OMIM: gene MIM:602955 | disease phenotypes: MIM:617126, MIM:122470

GenCC curated gene-disease

Disease	Classification	Inheritance
Alazami-Yuan syndrome	Strong	Autosomal recessive

Mondo (4): Alazami-Yuan syndrome (MONDO:0014931), Cornelia de Lange syndrome 1 (MONDO:0007387), syndromic intellectual disability (MONDO:0000508), intellectual disability (MONDO:0001071)

Orphanet (4): Alazami-Yuan syndrome (Orphanet:694946), Cornelia de Lange syndrome (Orphanet:199), Rare genetic syndromic intellectual disability (Orphanet:183763), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

26 total (26 of 26 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000160	Narrow mouth
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000294	Low anterior hairline
HP:0000343	Long philtrum
HP:0000426	Prominent nasal bridge
HP:0000430	Underdeveloped nasal alae
HP:0000448	Prominent nose
HP:0000527	Long eyelashes
HP:0000574	Thick eyebrow
HP:0000664	Synophrys
HP:0000678	Dental crowding
HP:0000752	Hyperactivity
HP:0000954	Single transverse palmar crease
HP:0001007	Hirsutism
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001319	Neonatal hypotonia
HP:0002465	Poor speech
HP:0002553	Highly arched eyebrow
HP:0004322	Short stature
HP:0009765	Low hanging columella
HP:0010055	Broad hallux

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005196_147	Coronary artery disease	2.000000e-06
GCST010002_259	Refractive error	3.000000e-16
GCST010702_48	Subcortical volume (MOSTest)	6.000000e-10
GCST010703_289	Brain morphology (MOSTest)	6.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465548 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Ozone	affects cotreatment, increases expression, increases abundance	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	decreases methylation	1
beta-lapachone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	affects cotreatment, decreases methylation	1
jinfukang	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	increases expression	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Arsenic	affects methylation	1
Aspirin	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Diazinon	increases methylation	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Gallic Acid	increases expression	1
Ivermectin	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases methylation	1
Vitamin E	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	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
CHEMBL5338435	Binding	Binding affinity to Taf6 (unknown origin) at 200 uM preincubated for 2 hrs followed by pronase addition and measured after 30 mins by coomassie blue staining based SDS-PAGE gel analysis	Structurally Diverse Alkaloids with Anti-Renal-Fibrosis Activity from the Centipede Scolopendra subspinipes mutilans. — J Nat Prod

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A6Z0	SEES3-1V human TAF6, clone1	Embryonic stem cell	Male
CVCL_A6Z1	SEES3-1V human TAF6, clone2	Embryonic stem cell	Male
CVCL_A6Z2	SEES3-1V human TAF6, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders