TAF4

Summary

TAF4 (TATA-box binding protein associated factor 4, HGNC:11537) is a protein-coding gene on chromosome 20q13.33, encoding Transcription initiation factor TFIID subunit 4 (O00268). The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription. It is a selective cancer dependency (DepMap: 16.6% 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 one of the larger subunits of TFIID that has been shown to potentiate transcriptional activation by retinoic acid, thyroid hormone and vitamin D3 receptors. In addition, this subunit interacts with the transcription factor CREB, which has a glutamine-rich activation domain, and binds to other proteins containing glutamine-rich regions. Aberrant binding to this subunit by proteins with expanded polyglutamine regions has been suggested as one of the pathogenetic mechanisms underlying a group of neurodegenerative disorders referred to as polyglutamine diseases.

Source: NCBI Gene 6874 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual developmental disorder, autosomal dominant 73 (Strong, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 293 total — 10 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 101
• Cancer dependency (DepMap): dependent in 16.6% of screened cell lines
• MANE Select transcript: NM_003185

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11537
Approved symbol	TAF4
Name	TATA-box binding protein associated factor 4
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	TAFII130, TAFII135
Ensembl gene	ENSG00000130699
Ensembl biotype	protein_coding
OMIM	601796
Entrez	6874

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 3 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000252996, ENST00000436129, ENST00000474089, ENST00000486599, ENST00000488539, ENST00000608458, ENST00000608887, ENST00000609041, ENST00000609045, ENST00000692470

RefSeq mRNA: 1 — MANE Select: NM_003185 NM_003185

CCDS: CCDS33500

Canonical transcript exons

ENST00000252996 — 15 exons

Exon	Start	End
ENSE00000897212	62009052	62009174
ENSE00000897216	62010046	62010165
ENSE00000897221	62012815	62012934
ENSE00000897226	62014547	62014707
ENSE00001379037	62064451	62065881
ENSE00001636878	61974798	61976335
ENSE00003703109	62006510	62006758
ENSE00003703639	61997550	61997669
ENSE00003704847	61998983	61999108
ENSE00003705897	61998136	61998192
ENSE00003706957	62003160	62003274
ENSE00003708908	62007547	62007636
ENSE00003709078	62000124	62000254
ENSE00003710148	62003731	62003878
ENSE00003711468	62000552	62000721

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 89.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.3722 / max 61.1785, expressed in 1674 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188237	5.9898	1633
188236	1.0700	621
188235	0.3125	131

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	89.45	gold quality
left testis	UBERON:0004533	89.28	gold quality
testis	UBERON:0000473	88.42	gold quality
adrenal tissue	UBERON:0018303	88.42	gold quality
skeletal muscle tissue	UBERON:0001134	87.55	gold quality
bone marrow cell	CL:0002092	87.50	gold quality
ventricular zone	UBERON:0003053	86.96	gold quality
ovary	UBERON:0000992	86.55	gold quality
left ovary	UBERON:0002119	86.51	gold quality
ganglionic eminence	UBERON:0004023	86.39	gold quality
embryo	UBERON:0000922	86.38	gold quality
right ovary	UBERON:0002118	86.12	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.78	gold quality
cerebellum	UBERON:0002037	85.00	gold quality
cerebellar hemisphere	UBERON:0002245	84.93	gold quality
cerebellar cortex	UBERON:0002129	84.90	gold quality
gastrocnemius	UBERON:0001388	84.75	gold quality
tonsil	UBERON:0002372	84.45	gold quality
cortical plate	UBERON:0005343	84.18	gold quality
muscle tissue	UBERON:0002385	84.12	gold quality
muscle of leg	UBERON:0001383	84.08	gold quality
colonic epithelium	UBERON:0000397	83.95	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.89	gold quality
bone marrow	UBERON:0002371	83.80	gold quality
sural nerve	UBERON:0015488	83.64	gold quality
uterine cervix	UBERON:0000002	83.17	gold quality
duodenum	UBERON:0002114	83.08	gold quality
body of pancreas	UBERON:0001150	82.67	gold quality
body of uterus	UBERON:0009853	82.61	gold quality
cortex of kidney	UBERON:0001225	82.56	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-124858	no	21.13
E-ANND-3	no	2.24

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
ATF7	Repression
CDKN1A	Unknown

Upstream regulators (CollecTRI, top): CREM

miRNA regulators (miRDB)

158 targeting TAF4, 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-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4747-5P	100.00	67.90	2681
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-5011-5P	100.00	83.46	5820
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 16.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 14)

• huntingtin interacts with Sp1 and TAFII130; transcriptional activity of SP1 and TAFII130 disrupted in early Huntingtin’s Disease (PMID:11988536)
• Data present the crystal structure of a complex formed by the interacting domains from two subunits of the general transcription factor TFIID, the human TATA binding protein-associated factors hTAF4 (hTAF(II)135) and hTAF12 (hTAF(II)20). (PMID:12237304)
• trans-activation of promoters by simian virus 40 small t-antigen may depend on a consensus TATA motif and such promoters recruit the general transcription factor hTAF(II)130/135 (PMID:12810884)
• TAF4b incorporation into TFIID induces an open conformation at the lobe involved in TFIIA & putative activator interactions, correlating with differential activator-dependent transcription & promoter recognition by 4b/4-IID. (PMID:18206971)
• Findings suggest that DNA binding by TAF4/4b-TAF12 facilitates the association of TFIID with the core promoter of a subset of genes. (PMID:19635797)
• These interactions are important to the transcriptional activation of these genes by Rta since introducing TAF4 shRNA substantially reduces the ability of Rta to activate these promoters (PMID:23326574)
• TAF4 isoforms generated by the alternative splicing participate in the conversion of the cellular transcriptional programs from the maintenance of stem cell state to differentiation (PMID:24098348)
• Inactivation of hTAF4-TAFH domain accelerates differentiation of human neural progenitor cells. (PMID:24696168)
• Targeted splicing of hTAF4-TAFH coordinates AS of other TFIID subunits, underscoring the role of TAF4 in synchronised changes of Pol II complex composition essential for efficient cellular reprogramming. (PMID:27499390)
• the two Q-domains of Sp1 and four Q-domains of TAF4 were disordered under physiological conditions. (PMID:27515574)
• Data suggest that many TATA-box-containing promoters contain a TFIIA recognition element (IIARE) that activates transcription by increasing the recruitment of RNA polymerase II, TFIIA (TF2A1/TF2A2 subunits), TAF4, and P300. (TAF4 = TATA box binding protein (TBP)-associated factor, RNA polymerase II, C1; P300 = E1A binding protein p300) (PMID:28539359)
• Identification of heteromolecular binding sites in transcription factors Sp1 and TAF4 using high-resolution nuclear magnetic resonance spectroscopy has been reported. (PMID:28857320)
• alphaalpha-hub coregulator structure and flexibility determine transcription factor binding and selection in regulatory interactomes. (PMID:35452682)
• De novo putative loss-of-function variants in TAF4 are associated with a neuro-developmental disorder. (PMID:35904126)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	taf4a	ENSDARG00000068192
mus_musculus	Taf4	ENSMUSG00000039117
rattus_norvegicus	Taf4	ENSRNOG00000054497
caenorhabditis_elegans	taf-4	WBGENE00006385

Paralogs (1): TAF4B (ENSG00000141384)

Protein

Protein identifiers

Transcription initiation factor TFIID subunit 4 — O00268 (reviewed: O00268)

Alternative names: RNA polymerase II TBP-associated factor subunit C, TBP-associated factor 4, Transcription initiation factor TFIID 130 kDa subunit, Transcription initiation factor TFIID 135 kDa subunit

All UniProt accessions (5): O00268, A0A8I5KRH3, A0A8I5KW49, V9GY03, V9GY14

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. TAF4 may maintain an association between the TFIID and TFIIA complexes, while bound to the promoter, together with TBP, during PIC assembly. Potentiates transcriptional activation by the AF-2S of the retinoic acid, vitamin D3 and thyroid hormone.

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. Component of the TFTC-HAT complex, at least composed of TAF5L, TAF6L, TADA3L, SUPT3H, TAF2, TAF4, TAF5, GCN5L2/GCN5, TAF10, TAF12 and TRRAP. 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. Interacts with ATF7; the interaction inhibits ATF7-mediated tranactivation. (Microbial infection) Interacts with SV40 Large T antigen.

Subcellular location. Nucleus.

Disease relevance. Intellectual developmental disorder, autosomal dominant 73 (MRD73) [MIM:620450] An autosomal dominant disorder characterized by intellectual disability ranging from mild to severe, developmental delay, speech delay, behavioral abnormalities, and non-specific dysmorphic facial features. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TAF4 family.

RefSeq proteins (1): NP_003176* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003894	TAFH_NHR1	Domain
IPR007900	TAF4_C	Domain
IPR009072	Histone-fold	Homologous_superfamily
IPR037249	TAFH/NHR1_dom_sf	Homologous_superfamily
IPR045144	TAF4	Family

Pfam: PF05236, PF07531

UniProt features (66 total): compositionally biased region 15, helix 15, modified residue 11, region of interest 7, sequence variant 5, sequence conflict 5, strand 4, turn 2, chain 1, domain 1

Structure

Experimental structures (PDB)

31 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
2P6V	X-RAY DIFFRACTION	2
1H3O	X-RAY DIFFRACTION	2.3
7EGG	ELECTRON MICROSCOPY	2.77
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
8WAL	ELECTRON MICROSCOPY	8.52
7EGJ	ELECTRON MICROSCOPY	8.64
7EGE	ELECTRON MICROSCOPY	9
6MZD	ELECTRON MICROSCOPY	9.8
7EGI	ELECTRON MICROSCOPY	9.82

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00268-F1	54.71	0.16

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): 109, 424, 435, 594, 595, 597, 605, 611, 621, 631, 658

Function

Pathways and Gene Ontology

Reactome pathways

20 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
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: 0 (showing top):

GO Biological Process (12): ovarian follicle development (GO:0001541), 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), mRNA transcription by RNA polymerase II (GO:0042789), 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), DNA-templated transcription (GO:0006351), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (7): DNA binding (GO:0003677), aryl hydrocarbon receptor binding (GO:0017162), protein heterodimerization activity (GO:0046982), core promoter sequence-specific DNA binding (GO:0001046), protein binding (GO:0005515), RNA polymerase II general transcription initiation factor activity (GO:0016251), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629)

GO Cellular Component (10): chromatin (GO:0000785), male germ cell nucleus (GO:0001673), 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), MLL1 complex (GO:0071339), transcription regulator complex (GO:0005667)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
RNA Polymerase II Transcription	4
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
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	4
transcription by RNA polymerase II	4
cellular anatomical structure	3
RNA biosynthetic process	2
regulation of DNA-templated transcription	2
transcription initiation at RNA polymerase II promoter	2
RNA polymerase II, holoenzyme	2
RNA polymerase II transcription regulator complex	2
female gonad development	1
anatomical structure development	1
DNA repair	1
regulation of DNA metabolic process	1
regulation of cellular response to stress	1
DNA-templated transcription initiation	1
mRNA transcription	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
gene expression	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
nucleic acid binding	1
signaling receptor binding	1
RNA polymerase II-specific DNA-binding transcription factor binding	1
protein dimerization activity	1
transcription cis-regulatory region binding	1
binding	1
general transcription initiation factor activity	1
DNA-binding transcription factor binding	1
chromosome	1
germ cell nucleus	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
cellular_component	1
SAGA-type complex	1
MLL1/2 complex	1
protein-containing complex	1

Protein interactions and networks

STRING

1404 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAF4	TAF5	Q15542	998
TAF4	TAF12	Q16514	997
TAF4	TAF9	Q16594	993
TAF4	TAF6	P49848	990
TAF4	CREB1	P16220	985
TAF4	TAF2	Q6P1X5	961
TAF4	TBP	P20226	959
TAF4	HTT	P42858	948
TAF4	TAF1	P21675	942
TAF4	TAF10	Q12962	919
TAF4	TAF8	Q7Z7C8	888
TAF4	TAF7	Q15545	841
TAF4	TAF11	Q15544	822
TAF4	TAF3	Q5VWG9	791
TAF4	KAT2B	Q92831	767

IntAct

120 interactions, top by confidence:

A	B	Type	Score
TAF12	TAF4	psi-mi:“MI:0407”(direct interaction)	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
TAF4	TAF12	psi-mi:“MI:0407”(direct interaction)	0.720
TAF4	TAF12	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
TAF10	TAF4	psi-mi:“MI:0915”(physical association)	0.650
TAF4	CREBZF	psi-mi:“MI:0407”(direct interaction)	0.560
TAF4	CREB3	psi-mi:“MI:0407”(direct interaction)	0.560

BioGRID (225): TAF4 (Affinity Capture-MS), TAF4 (Protein-peptide), TAF4 (Affinity Capture-MS), TAF4 (Affinity Capture-MS), TAF4 (Affinity Capture-MS), ANAPC1 (Co-fractionation), ANAPC7 (Co-fractionation), CDC16 (Co-fractionation), NAP1L4 (Co-fractionation), TAF1 (Co-fractionation), TAF10 (Co-fractionation), TAF4 (Co-fractionation), TAF4 (Co-fractionation), TAF4 (Co-fractionation), TAF4 (Co-fractionation)

ESM2 similar proteins: A4D2P6, A5PJV8, A6NFD8, D4AE48, O00268, O00287, O35274, O35779, O43566, P04198, P12755, P55199, Q08DA0, Q0D2I5, Q2KJ58, Q504T8, Q5XKK7, Q60698, Q61976, Q6NZ67, Q6P582, Q6R891, Q6T4P5, Q7Z6J2, Q80YR4, Q86UD0, Q86UK7, Q8BXL9, Q8CEG5, Q8R4T5, Q8TF61, Q8VCG9, Q969F2, Q969G9, Q96HZ4, Q96SB3, Q99PV5, Q9BQ61, Q9BUN5, Q9BZE9

Diamond homologs: G5E8Z2, O00268, O61707, P47825, Q92750, O43439, O54972, O70374, O75081, O75398, O77562, O88450, Q06455, Q5F3B1, Q61909, Q9IAB2, Q9Z1T5

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TAF4	“form complex”	TFIID	binding
TAF4	“down-regulates activity”	ATF7	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 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	43.5×	5e-14
RNA Polymerase II HIV Promoter Escape	11	43.5×	5e-14
RNA Polymerase II Promoter Escape	11	43.5×	5e-14
RNA Polymerase II Transcription Pre-Initiation And Promoter Opening	11	43.5×	5e-14
RNA Polymerase II Transcription Initiation	11	43.5×	5e-14
RNA Polymerase II Transcription Initiation And Promoter Clearance	11	43.5×	5e-14
Transcription of the HIV genome	11	32.3×	1e-12
Late Phase of HIV Life Cycle	10	28.5×	7e-11

GO biological processes:

GO term	Partners	Fold	FDR
RNA polymerase II preinitiation complex assembly	13	44.7×	9e-16
transcription initiation at RNA polymerase II promoter	9	42.7×	1e-10
positive regulation of transcription initiation by RNA polymerase II	11	37.9×	2e-12
mRNA transcription by RNA polymerase II	8	33.5×	1e-08
regulation of DNA repair	7	24.5×	1e-06
regulation of RNA splicing	6	16.6×	1e-04
transcription by RNA polymerase II	10	8.9×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	8
Uncertain significance	209
Likely benign	43
Benign	3

Top pathogenic / likely-pathogenic (18)

Variant ID	HGVS	Classification
3173503	NM_003185.4(TAF4):c.1519C>T (p.Gln507Ter)	Pathogenic
3173508	NM_003185.4(TAF4):c.2719C>T (p.Gln907Ter)	Pathogenic
3242345	NM_003185.4(TAF4):c.2845C>T (p.Gln949Ter)	Pathogenic
3242346	NM_003185.4(TAF4):c.1348C>T (p.Gln450Ter)	Pathogenic
3242347	NM_003185.4(TAF4):c.2185C>T (p.Gln729Ter)	Pathogenic
3242348	NM_003185.4(TAF4):c.2453dup (p.Asn818fs)	Pathogenic
3242349	NM_003185.4(TAF4):c.2664del (p.Lys888fs)	Pathogenic
4729492	NM_003185.4(TAF4):c.898_910del (p.Pro300fs)	Pathogenic
4818966	NM_003185.4(TAF4):c.2425dup (p.Ser809fs)	Pathogenic
4819103	NM_003185.4(TAF4):c.633dup (p.Ala212fs)	Pathogenic
1687439	NM_003185.4(TAF4):c.853_860del (p.Gly285fs)	Likely pathogenic
3236097	NM_003185.4(TAF4):c.213_268del (p.Gly72fs)	Likely pathogenic
3376435	NM_003185.4(TAF4):c.808_818del (p.Pro270fs)	Likely pathogenic
3587593	NM_003185.4(TAF4):c.962del (p.Gly321fs)	Likely pathogenic
3765856	NM_003185.4(TAF4):c.1290del (p.Val431fs)	Likely pathogenic
3767129	NM_003185.4(TAF4):c.1529del (p.Gly510fs)	Likely pathogenic
3773682	NM_003185.4(TAF4):c.3160_3163del (p.Arg1054fs)	Likely pathogenic
4291844	NM_003185.4(TAF4):c.756del (p.Ala253fs)	Likely pathogenic

SpliceAI

4369 predictions. Top by Δscore:

Variant	Effect	Δscore
20:61995377:T:TA	donor_gain	1.0000
20:61995380:A:C	donor_gain	1.0000
20:61997544:CCGTA:C	donor_loss	1.0000
20:61997545:CGTA:C	donor_loss	1.0000
20:61997547:TACC:T	donor_loss	1.0000
20:61997549:C:CA	donor_loss	1.0000
20:61997549:CCT:C	donor_gain	1.0000
20:61997585:T:A	donor_gain	1.0000
20:61997667:CAT:C	acceptor_gain	1.0000
20:61997667:CATC:C	acceptor_loss	1.0000
20:61997667:CATCT:C	acceptor_gain	1.0000
20:61997670:C:CC	acceptor_gain	1.0000
20:61997671:T:C	acceptor_gain	1.0000
20:61997671:T:TC	acceptor_gain	1.0000
20:61997673:T:C	acceptor_gain	1.0000
20:61997673:T:TC	acceptor_gain	1.0000
20:61997675:A:C	acceptor_gain	1.0000
20:61997676:T:TC	acceptor_gain	1.0000
20:61997677:T:C	acceptor_gain	1.0000
20:61997678:T:C	acceptor_gain	1.0000
20:61997678:T:TC	acceptor_gain	1.0000
20:61997720:CTTA:C	acceptor_gain	1.0000
20:61998137:T:TA	donor_gain	1.0000
20:61998188:CGAGA:C	acceptor_gain	1.0000
20:61998189:GAGA:G	acceptor_gain	1.0000
20:61998190:AGA:A	acceptor_gain	1.0000
20:61998191:GA:G	acceptor_gain	1.0000
20:61998193:C:CC	acceptor_gain	1.0000
20:61998199:T:C	acceptor_gain	1.0000
20:61998199:T:TC	acceptor_gain	1.0000

AlphaMissense

6855 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:61976175:A:G	L1084P	1.000
20:61976188:A:C	Y1080D	1.000
20:61976190:A:G	L1079P	1.000
20:61976238:A:G	L1063P	1.000
20:61976241:T:A	D1062V	1.000
20:61976241:T:C	D1062G	1.000
20:61976241:T:G	D1062A	1.000
20:61976253:A:T	V1058D	1.000
20:61997596:C:A	R1015M	1.000
20:61997602:C:T	G1013E	1.000
20:61997603:C:G	G1013R	1.000
20:61997603:C:T	G1013R	1.000
20:61997605:A:T	I1012N	1.000
20:61997608:G:T	A1011E	1.000
20:61997609:C:G	A1011P	1.000
20:61997612:C:G	A1010P	1.000
20:61997614:A:G	L1009P	1.000
20:61997617:G:T	A1008E	1.000
20:61997618:C:G	A1008P	1.000
20:61997625:G:C	N1005K	1.000
20:61997625:G:T	N1005K	1.000
20:61997630:C:G	A1004P	1.000
20:61997635:C:G	R1002P	1.000
20:61997653:A:G	L996P	1.000
20:61997665:T:G	Q992P	1.000
20:61997668:A:G	M991T	1.000
20:61998139:C:A	K989N	1.000
20:61998139:C:G	K989N	1.000
20:61998141:T:C	K989E	1.000
20:61998144:C:G	A988P	1.000

dbSNP variants (sampled 300 via entrez): RS1000003021 (20:61998821 A>T), RS1000061128 (20:62064405 C>A,T), RS1000062720 (20:62039670 T>C), RS1000067117 (20:62014446 C>T), RS1000071229 (20:61979912 G>A), RS1000084670 (20:61999366 C>T), RS1000117308 (20:62007274 C>A), RS1000168735 (20:62056770 C>T), RS1000170472 (20:61991538 G>A), RS1000201195 (20:61991129 A>G), RS1000212067 (20:62025162 T>C,G), RS1000228566 (20:62064070 G>A), RS1000252583 (20:62045879 T>A,C), RS1000310250 (20:61985559 G>A), RS1000375370 (20:62029916 A>G)

Disease associations

OMIM: gene MIM:601796 | disease phenotypes: MIM:620450

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder, autosomal dominant 73	Strong	Autosomal dominant

Mondo (2): intellectual developmental disorder, autosomal dominant 73 (MONDO:0957536), neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

101 total (30 of 101 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000072	Hydroureter
HP:0000098	Tall stature
HP:0000179	Thick lower lip vermilion
HP:0000185	Cleft soft palate
HP:0000218	High palate
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000289	Broad philtrum
HP:0000319	Smooth philtrum
HP:0000322	Short philtrum
HP:0000331	Short chin
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000403	Recurrent otitis media
HP:0000405	Conductive hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000430	Underdeveloped nasal alae
HP:0000431	Wide nasal bridge
HP:0000444	Convex nasal ridge
HP:0000445	Wide nose
HP:0000448	Prominent nose
HP:0000463	Anteverted nares
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000540	Hypermetropia

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST003486_11	Response to fenofibrate (LDL cholesterol levels)	9.000000e-06
GCST004904_9	Body mass index	4.000000e-09
GCST009391_1802	Metabolite levels	6.000000e-06
GCST009391_6	Metabolite levels	1.000000e-06
GCST011983_22	Fasting glucose	2.000000e-06
GCST90002397_291	Mean spheric corpuscular volume	9.000000e-12
GCST90002403_530	Red blood cell count	3.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007804	LDL cholesterol change measurement
EFO:0004340	body mass index
EFO:0010403	triacylglycerol 48:0 measurement
EFO:0007813	cotinine measurement
EFO:0004305	erythrocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression, decreases expression	2
GSK-J4	increases expression	1
dicrotophos	increases expression	1
bisphenol A	increases methylation	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
aflatoxin B2	decreases methylation	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	increases phosphorylation	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Formaldehyde	decreases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Ozone	increases abundance, affects expression	1
Pesticides	affects methylation	1
Smoke	decreases expression	1
Tamoxifen	increases expression	1
Tretinoin	decreases expression	1
Tunicamycin	decreases expression	1
Valproic Acid	increases methylation	1
Zinc	affects expression	1
Josamycin	affects response to substance	1
Cyclosporine	decreases methylation	1
Aflatoxin B1	decreases methylation, increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice