TAF8

Summary

TAF8 (TATA-box binding protein associated factor 8, HGNC:17300) is a protein-coding gene on chromosome 6p21.1, encoding Transcription initiation factor TFIID subunit 8 (Q7Z7C8). 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 93.5% of cancer cell lines).

This gene encodes one of several TATA-binding protein (TBP)-associated factors (TAFs), which are integral subunits of the general transcription factor complex TFIID. TFIID recognizes the core promoter of many genes and nucleates the assembly of a transcription preinitiation complex containing RNA polymerase II and other initiation factors. The protein encoded by this gene contains an H4-like histone fold domain, and interacts with several subunits of TFIID including TBP and the histone-fold protein TAF10. Alternatively spliced transcript variants have been described, but their biological validity has not been determined.

Source: NCBI Gene 129685 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy (Strong, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 96 total — 6 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 17
• Cancer dependency (DepMap): dependent in 93.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_138572

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17300
Approved symbol	TAF8
Name	TATA-box binding protein associated factor 8
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32821, TAF(II)43
Ensembl gene	ENSG00000137413
Ensembl biotype	protein_coding
OMIM	609514
Entrez	129685

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 12 protein_coding, 5 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000372977, ENST00000372978, ENST00000372982, ENST00000456846, ENST00000465926, ENST00000472818, ENST00000482432, ENST00000482926, ENST00000486070, ENST00000494547, ENST00000684962, ENST00000685500, ENST00000686229, ENST00000686935, ENST00000687266, ENST00000687601, ENST00000688007, ENST00000688562, ENST00000689833, ENST00000691805

RefSeq mRNA: 3 — MANE Select: NM_138572 NM_001410906, NM_001410907, NM_138572

CCDS: CCDS43462, CCDS93918, CCDS93919

Canonical transcript exons

ENST00000372977 — 9 exons

Exon	Start	End
ENSE00001086398	42066312	42066459
ENSE00001899594	42077533	42083272
ENSE00001914048	42050524	42050586
ENSE00002196187	42068465	42068607
ENSE00003507225	42055952	42056014
ENSE00003548059	42055531	42055629
ENSE00003618239	42077100	42077239
ENSE00003630482	42057389	42057513
ENSE00003634570	42051357	42051513

Expression profiles

Bgee: expression breadth ubiquitous, 209 present calls, max score 94.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.7850 / max 182.7254, expressed in 1822 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67783	27.5959	1820
67784	1.1891	567

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	94.15	gold quality
apex of heart	UBERON:0002098	88.25	gold quality
oocyte	CL:0000023	85.85	gold quality
monocyte	CL:0000576	85.67	gold quality
leukocyte	CL:0000738	85.52	gold quality
bone marrow cell	CL:0002092	85.20	gold quality
heart left ventricle	UBERON:0002084	84.25	gold quality
gastrocnemius	UBERON:0001388	84.22	gold quality
muscle of leg	UBERON:0001383	84.12	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.89	gold quality
cardiac ventricle	UBERON:0002082	83.80	gold quality
tendon of biceps brachii	UBERON:0008188	83.70	gold quality
vermiform appendix	UBERON:0001154	83.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.74	gold quality
right atrium auricular region	UBERON:0006631	82.74	gold quality
blood	UBERON:0000178	82.69	gold quality
metanephros cortex	UBERON:0010533	82.68	gold quality
secondary oocyte	CL:0000655	82.52	gold quality
granulocyte	CL:0000094	82.48	gold quality
heart	UBERON:0000948	82.21	gold quality
lymph node	UBERON:0000029	82.13	gold quality
tendon	UBERON:0000043	82.03	gold quality
right lobe of thyroid gland	UBERON:0001119	82.02	gold quality
left lobe of thyroid gland	UBERON:0001120	81.78	gold quality
stromal cell of endometrium	CL:0002255	81.68	gold quality
sural nerve	UBERON:0015488	81.47	gold quality
popliteal artery	UBERON:0002250	81.45	gold quality
tibial artery	UBERON:0007610	81.45	gold quality
lower esophagus mucosa	UBERON:0035834	81.44	gold quality
ventricular zone	UBERON:0003053	81.42	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, SPI1, YBX3

miRNA regulators (miRDB)

112 targeting TAF8, 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-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-623	99.76	68.16	1170

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 93.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 3)

• the TAF2-TAF8-TAF10 complex demonstrates that there is a stepwise assembly pathway of nuclear holo-TFIID, regulated by nuclear import of preformed cytoplasmic submodules (PMID:25586196)
• TAF8 mutant protein with an unrelated C-terminus. The mutant TAF8 protein could not be detected in extracts from the patient’s fibroblasts, indicating a loss of TAF8 function and that the mutation is most likely causative (PMID:29648665)
• TAF8 regions important for TFIID lobe B assembly or for TAF2 interactions are required for embryonic stem cell survival. (PMID:34634302)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	taf8	ENSDARG00000026806
mus_musculus	Taf8	ENSMUSG00000023980
rattus_norvegicus	Taf8	ENSRNOG00000015249
drosophila_melanogaster	sa	FBGN0002842
drosophila_melanogaster	Taf8	FBGN0022724
caenorhabditis_elegans		WBGENE00006390

Protein

Protein identifiers

Transcription initiation factor TFIID subunit 8 — Q7Z7C8 (reviewed: Q7Z7C8)

Alternative names: Protein taube nuss, TBP-associated factor 43 kDa, TBP-associated factor 8, Transcription initiation factor TFIID 43 kDa subunit

All UniProt accessions (9): A0A0A0MRR3, A0A8I5KTT0, A0A8I5KVM3, A0A8I5KXI2, A0A8I5QJI2, A0A8I5QL33, A0A8I5QL44, B4DZU5, Q7Z7C8

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. TAF8 is involved in forming the TFIID-B module, together with TAF5. Mediates both basal and activator-dependent transcription. Plays a role in the differentiation of preadipocyte fibroblasts to adipocytes, however, does not seem to play a role in differentiation of myoblasts. Required for the integration of TAF10 in the TAF complex. May be important for survival of cells of the inner cell mass which constitute the pluripotent cell population of the early embryo.

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 with TBP, TAF1, TAF6, TAF10, TAF11 and TAF13. Component also of a small TAF complex (SMAT) containing TAF8, TAF10 and SUPT7L. Forms a heterodimer with TAF10. Interaction with TAF10 is mediated mainly via its histone fold domain while interaction with SUPT7L is via its C-terminal region.

Subcellular location. Nucleus. Cytoplasm.

Disease relevance. Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy (NEDMLHB) [MIM:619972] An autosomal recessive disorder with onset soon after birth or in early infancy. Affected individuals do not show developmental progress, are unable to sit or walk, do not acquire speech, have poor visual fixation, and show poor overall growth associated with feeding problems. Additional variable features include seizures, spasticity, and joint contractures. Brain imaging shows hypomyelination, thin corpus callosum, and cerebral and cerebellar atrophy. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Ectopic expression of the histone fold domain acts as a dominant-negative mutant resulting in differentiation inhibition.

Induction. Induced with triglyceride accumulation.

Miscellaneous. ‘Taube nuss’ means ’empty nut’ in German.

Similarity. Belongs to the TAF8 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q7Z7C8-1	1	yes
Q7Z7C8-2	2
Q7Z7C8-4	3

RefSeq proteins (3): NP_001397835, NP_001397836, NP_612639* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006565	BTP	Domain
IPR009072	Histone-fold	Homologous_superfamily
IPR019473	TFIID_su8_C	Domain
IPR037818	TAF8	Family

Pfam: PF07524, PF10406

UniProt features (23 total): helix 7, modified residue 3, splice variant 2, strand 2, region of interest 2, compositionally biased region 2, initiator methionine 1, chain 1, sequence conflict 1, domain 1, short sequence motif 1

Structure

Experimental structures (PDB)

31 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4WV6	X-RAY DIFFRACTION	1.75
4WV4	X-RAY DIFFRACTION	1.91
7EGG	ELECTRON MICROSCOPY	2.77
7EGH	ELECTRON MICROSCOPY	3.04
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
7EGI	ELECTRON MICROSCOPY	9.82

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z7C8-F1	74.32	0.33

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 (3): 271, 2, 130

Function

Pathways and Gene Ontology

Reactome pathways

12 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-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 193 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_GROWTH, BEIER_GLIOMA_STEM_CELL_DN, GOBP_INNER_CELL_MASS_CELL_PROLIFERATION, REACTOME_HIV_INFECTION, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_MAINTENANCE_OF_LOCATION, GOBP_MAINTENANCE_OF_PROTEIN_LOCALIZATION_IN_ORGANELLE, GOBP_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_BLASTOCYST_DEVELOPMENT, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION

GO Biological Process (9): DNA-templated transcription open complex formation (GO:0001112), inner cell mass cell proliferation (GO:0001833), transcription initiation at RNA polymerase II promoter (GO:0006367), cell differentiation (GO:0030154), mRNA transcription by RNA polymerase II (GO:0042789), regulation of fat cell differentiation (GO:0045598), RNA polymerase II preinitiation complex assembly (GO:0051123), maintenance of protein location in nucleus (GO:0051457), positive regulation of transcription initiation by RNA polymerase II (GO:0060261)

GO Molecular Function (3): RNA polymerase II general transcription initiation factor activity (GO:0016251), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription factor TFIID complex (GO:0005669), perinuclear region of cytoplasm (GO:0048471), sperm midpiece (GO:0097225), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-6 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
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
transcription by RNA polymerase II	3
DNA-templated transcription initiation	2
transcription initiation at RNA polymerase II promoter	2
protein-DNA complex remodeling	1
blastocyst growth	1
cell population proliferation	1
cellular developmental process	1
mRNA transcription	1
fat cell differentiation	1
regulation of cell differentiation	1
transcription preinitiation complex assembly	1
nucleus	1
protein localization to nucleus	1
maintenance of protein localization in organelle	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
general transcription initiation factor activity	1
protein dimerization activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
RNA polymerase II, holoenzyme	1
RNA polymerase II transcription regulator complex	1
cytoplasm	1
sperm flagellum	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1072 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAF8	TAF10	Q12962	998
TAF8	TAF11	Q15544	970
TAF8	TAF6	P49848	968
TAF8	TAF12	Q16514	967
TAF8	TAF2	Q6P1X5	945
TAF8	SUPT7L	O94864	939
TAF8	TAF5	Q15542	935
TAF8	TAF4	O00268	888
TAF8	TAF9	Q16594	881
TAF8	TAF7	Q15545	880
TAF8	TBP	P20226	832
TAF8	TAF1	P21675	825
TAF8	SUPT3H	O75486	761
TAF8	TAF13	Q15543	758
TAF8	TAF7L	Q5H9L4	644

IntAct

30 interactions, top by confidence:

A	B	Type	Score
TAF12	TAF4	psi-mi:“MI:0914”(association)	0.760
TAF8	ZDHHC17	psi-mi:“MI:0915”(physical association)	0.660
TAF10	TAF4	psi-mi:“MI:0914”(association)	0.650
TAF10	TAF4	psi-mi:“MI:0915”(physical association)	0.650
TAF8	TAF4	psi-mi:“MI:0914”(association)	0.530
SPATA25	TAF4	psi-mi:“MI:0914”(association)	0.530
TAF7L	TAF4	psi-mi:“MI:0914”(association)	0.530
FMR1	ACOT7	psi-mi:“MI:0914”(association)	0.500
GTF2A2	TAF4	psi-mi:“MI:0915”(physical association)	0.490
KIF7	TBC1D31	psi-mi:“MI:0914”(association)	0.350
BTBD8	HSPA8	psi-mi:“MI:0914”(association)	0.350
	TAF4	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ENG	IGKV2-28	psi-mi:“MI:0914”(association)	0.350
MED26		psi-mi:“MI:0914”(association)	0.350
ZCCHC10	C1orf226	psi-mi:“MI:0914”(association)	0.350
MOAP1	TAF4	psi-mi:“MI:0914”(association)	0.350
RAVER1	KDM6A	psi-mi:“MI:2364”(proximity)	0.270
FEV	TAF4	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (127): TAF8 (Two-hybrid), TAF8 (Protein-peptide), TAF6 (Affinity Capture-MS), TAF5 (Affinity Capture-MS), TAF4B (Affinity Capture-MS), TAF4 (Affinity Capture-MS), TAF9B (Affinity Capture-MS), TAF9 (Affinity Capture-MS), TAF10 (Affinity Capture-MS), ZDHHC17 (Affinity Capture-MS), TAF12 (Affinity Capture-MS), TAF1 (Affinity Capture-MS), TAF2 (Affinity Capture-MS), TAF7 (Affinity Capture-MS), TAF8 (Affinity Capture-MS)

ESM2 similar proteins: A4IFQ0, A6QL63, A6QR06, A7MAZ4, O75486, P54198, Q08BT5, Q0VA03, Q13769, Q14161, Q15022, Q1LVW0, Q28J24, Q3B7L5, Q5BJQ7, Q5RDB9, Q5ZJA9, Q5ZMS1, Q61666, Q62784, Q66H91, Q68FF6, Q68FX7, Q6DEW4, Q6GMF2, Q6GQW0, Q6ZPY2, Q76JQ2, Q7Z7C8, Q7ZYA2, Q80U70, Q8BIK4, Q8BKT7, Q8C0Q9, Q8NFG4, Q8QZS3, Q96BN2, Q96MD2, Q96PE3, Q99LM9

Diamond homologs: A7MAZ4, Q28J24, Q5F489, Q5HZG4, Q5VWG9, Q5ZMS1, Q6P0T2, Q7Z7C8, Q7ZYA2, Q9EQH4, Q9VWY6, O74508, Q03012, Q5AHB8, Q5EA28, Q5EAW9, Q5ZKY4, Q6BNL6, Q8C0D7, Q92576, Q9CWW7, Q9P0U4, Q9UNL4, Q9VJY8, Q9W352, Q9SYZ9

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TAF8	“form complex”	TFIID	binding
TAF8	“form complex”	“SAGA complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 24 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	5	97.1×	1e-08
RNA Polymerase II HIV Promoter Escape	5	97.1×	1e-08
RNA Polymerase II Promoter Escape	5	97.1×	1e-08
RNA Polymerase II Transcription Pre-Initiation And Promoter Opening	5	97.1×	1e-08
RNA Polymerase II Transcription Initiation	5	97.1×	1e-08
RNA Polymerase II Transcription Initiation And Promoter Clearance	5	97.1×	1e-08
Transcription of the HIV genome	5	72.1×	6e-08
Late Phase of HIV Life Cycle	5	70.0×	6e-08

GO biological processes:

GO term	Partners	Fold	FDR
RNA polymerase II preinitiation complex assembly	7	95.1×	1e-10
transcription initiation at RNA polymerase II promoter	5	93.6×	2e-07
positive regulation of transcription initiation by RNA polymerase II	5	68.0×	6e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	3
Uncertain significance	50
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
1686246	NM_138572.3(TAF8):c.719_720del (p.Thr240fs)	Pathogenic
1686247	NM_138572.3(TAF8):c.806_809del (p.Asn269fs)	Pathogenic
1698452	NM_138572.3(TAF8):c.45+4A>G	Pathogenic
1698453	NM_138572.3(TAF8):c.489G>A (p.Pro163=)	Pathogenic
3776294	NM_138572.3(TAF8):c.796G>T (p.Glu266Ter)	Pathogenic
638647	NM_138572.3(TAF8):c.781-1G>A	Pathogenic
3067953	NM_138572.3(TAF8):c.365-1G>T	Likely pathogenic
3910783	NM_138572.3(TAF8):c.400del (p.Leu134fs)	Likely pathogenic
493566	GRCh37/hg19 6p21.1(chr6:42039993-42270812)x3	Likely pathogenic

SpliceAI

1492 predictions. Top by Δscore:

Variant	Effect	Δscore
6:42051509:GAGCT:G	donor_gain	1.0000
6:42051510:AGCT:A	donor_gain	1.0000
6:42051511:GCT:G	donor_gain	1.0000
6:42051511:GCTG:G	donor_gain	1.0000
6:42051512:CT:C	donor_gain	1.0000
6:42051513:TG:T	donor_loss	1.0000
6:42051514:G:GG	donor_gain	1.0000
6:42051514:GT:G	donor_loss	1.0000
6:42051515:T:A	donor_loss	1.0000
6:42051516:GAG:G	donor_loss	1.0000
6:42051517:AG:A	donor_loss	1.0000
6:42055529:A:AG	acceptor_gain	1.0000
6:42055530:G:GG	acceptor_gain	1.0000
6:42055530:GA:G	acceptor_gain	1.0000
6:42055530:GAC:G	acceptor_gain	1.0000
6:42055530:GACA:G	acceptor_gain	1.0000
6:42055625:GATGG:G	donor_gain	1.0000
6:42055628:GG:G	donor_gain	1.0000
6:42055629:GG:G	donor_gain	1.0000
6:42055949:TAGGT:T	acceptor_loss	1.0000
6:42055950:A:AC	acceptor_loss	1.0000
6:42055950:A:AG	acceptor_gain	1.0000
6:42055951:G:A	acceptor_loss	1.0000
6:42055951:G:GG	acceptor_gain	1.0000
6:42056011:GCTC:G	donor_gain	1.0000
6:42056015:G:GG	donor_gain	1.0000
6:42057387:A:AG	acceptor_gain	1.0000
6:42057388:G:GG	acceptor_gain	1.0000
6:42066460:G:GG	donor_gain	1.0000
6:42068455:A:AG	acceptor_gain	1.0000

AlphaMissense

2020 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:42051412:G:C	R34T	1.000
6:42051412:G:T	R34M	1.000
6:42051413:G:C	R34S	1.000
6:42051413:G:T	R34S	1.000
6:42051421:T:C	L37P	1.000
6:42051435:A:C	S42R	1.000
6:42051437:C:A	S42R	1.000
6:42051437:C:G	S42R	1.000
6:42051445:T:C	L45P	1.000
6:42051469:C:A	A53D	1.000
6:42051493:T:C	L61P	1.000
6:42055545:G:A	G73R	1.000
6:42055545:G:C	G73R	1.000
6:42055545:G:T	G73W	1.000
6:42055546:G:A	G73E	1.000
6:42055554:G:C	A76P	1.000
6:42055582:G:C	R85T	1.000
6:42055582:G:T	R85M	1.000
6:42055583:G:C	R85S	1.000
6:42055583:G:T	R85S	1.000
6:42055602:G:C	D92H	1.000
6:42055602:G:T	D92Y	1.000
6:42055603:A:C	D92A	1.000
6:42055603:A:G	D92G	1.000
6:42055603:A:T	D92V	1.000
6:42055618:T:C	L97P	1.000
6:42057484:C:T	P154S	1.000
6:42057485:C:A	P154H	1.000
6:42057493:C:A	H157N	1.000
6:42057493:C:G	H157D	1.000

dbSNP variants (sampled 300 via entrez): RS1000049249 (6:42085328 G>A), RS1000088029 (6:42063115 G>A,T), RS1000120799 (6:42084309 T>A), RS1000137742 (6:42080202 T>C), RS1000241820 (6:42053850 A>G), RS1000378234 (6:42080578 G>C), RS1000396821 (6:42075143 G>A), RS1000474248 (6:42081612 G>A), RS1000519934 (6:42053049 A>C), RS1000573002 (6:42082804 A>C), RS1000713748 (6:42081793 C>T), RS1000748547 (6:42071921 C>A), RS1000965867 (6:42049134 C>T), RS1000975386 (6:42070743 C>T), RS1001100433 (6:42065219 G>A)

Disease associations

OMIM: gene MIM:609514 | disease phenotypes: MIM:619972

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy	Strong	Autosomal recessive

Mondo (3): neurodevelopmental disorder (MONDO:0700092), neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy (MONDO:0859266), microcephaly (MONDO:0001149)

Orphanet (0):

HPO phenotypes

17 total (18 of 17 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000248	Brachycephaly
HP:0000343	Long philtrum
HP:0000508	Ptosis
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001762	Talipes equinovarus
HP:0002191	Progressive spasticity
HP:0003593	Infantile onset
HP:0006956	Lateral ventricle dilatation
HP:0010804	Tented upper lip vermilion
HP:0011344	Severe global developmental delay
HP:0025336	Delayed ability to sit
HP:0032989	Delayed ability to roll over
HP:0040010	Small posterior fossa
HP:0200012	Short corpus callosum
HP:0000252	Microcephaly

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST003064_7	Exploratory eye movement dysfunction in schizophrenia (cognitive search score)	7.000000e-06
GCST003065_9	Exploratory eye movement dysfunction in schizophrenia (responsive search score)	3.000000e-06
GCST003068_6	Exploratory eye movement dysfunction in schizophrenia (number of eye fixations)	4.000000e-06
GCST004232_87	HDL cholesterol levels	2.000000e-07
GCST009066_9	Mosaic loss of chromosome Y (Y chromosome dosage)	4.000000e-12
GCST009067_11	Mosaic loss of chromosome Y (Y chromosome dosage)	9.000000e-36
GCST012146_12	Hemoglobin levels	1.000000e-07
GCST90002388_92	Lymphocyte count	2.000000e-32
GCST90002389_321	Lymphocyte percentage of white cells	2.000000e-14
GCST90002399_296	Neutrophil percentage of white cells	5.000000e-09

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007700	exploratory eye movement measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007783	mosaic loss of chromosome Y measurement
EFO:0004509	hemoglobin measurement
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
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

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	5
Air Pollutants	affects expression, increases abundance, affects methylation, increases expression	3
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Particulate Matter	affects methylation, increases abundance, increases expression, affects expression	2
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
beta-lapachone	decreases expression	1
arsenite	decreases reaction, affects binding	1
butyraldehyde	decreases expression	1
cupric oxide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1
Doxorubicin	decreases expression	1
Ketoconazole	increases expression	1
Ozone	increases abundance, affects expression	1
Smoke	decreases expression	1
Urethane	increases expression	1
Aflatoxin B1	increases methylation	1
Asbestos, Crocidolite	affects expression	1

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A6Z6	SEES3-1V human TAF8, clone1	Embryonic stem cell	Male
CVCL_A6Z7	SEES3-1V human TAF8, clone2	Embryonic stem cell	Male
CVCL_A6Z8	SEES3-1V human TAF8, clone3	Embryonic stem cell	Male
CVCL_C0LQ	GM28350	Finite cell line	Male

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