TAF2

Summary

TAF2 (TATA-box binding protein associated factor 2, HGNC:11536) is a protein-coding gene on chromosome 8q24.12, encoding Transcription initiation factor TFIID subunit 2 (Q6P1X5). 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: 86.5% 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 is stably associated with the TFIID complex. It contributes to interactions at and downstream of the transcription initiation site, interactions that help determine transcription complex response to activators.

Source: NCBI Gene 6873 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly-thin corpus callosum-intellectual disability syndrome (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 362 total — 2 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 26
• Cancer dependency (DepMap): dependent in 86.5% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_003184

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11536
Approved symbol	TAF2
Name	TATA-box binding protein associated factor 2
Location	8q24.12
Locus type	gene with protein product
Status	Approved
Aliases	TAFII150, CIF150
Ensembl gene	ENSG00000064313
Ensembl biotype	protein_coding
OMIM	604912
Entrez	6873

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 21 nonsense_mediated_decay, 8 retained_intron, 7 protein_coding, 7 protein_coding_CDS_not_defined

ENST00000378164, ENST00000519355, ENST00000521007, ENST00000523078, ENST00000523098, ENST00000523734, ENST00000523904, ENST00000526969, ENST00000529653, ENST00000684862, ENST00000685202, ENST00000685235, ENST00000685503, ENST00000685663, ENST00000685684, ENST00000685755, ENST00000685824, ENST00000685876, ENST00000685993, ENST00000686098, ENST00000686879, ENST00000688037, ENST00000688215, ENST00000688645, ENST00000689164, ENST00000689341, ENST00000689399, ENST00000689867, ENST00000689873, ENST00000689919, ENST00000690031, ENST00000690144, ENST00000690808, ENST00000690922, ENST00000691057, ENST00000691237, ENST00000691847, ENST00000691880, ENST00000692518, ENST00000692707, ENST00000692711, ENST00000692829, ENST00000692916

RefSeq mRNA: 1 — MANE Select: NM_003184 NM_003184

CCDS: CCDS34937

Canonical transcript exons

ENST00000378164 — 26 exons

Exon	Start	End
ENSE00000871622	119744288	119744393
ENSE00000871623	119746705	119746934
ENSE00000871628	119778019	119778129
ENSE00000871629	119781053	119781193
ENSE00001090699	119793366	119793451
ENSE00001090700	119801794	119802025
ENSE00001090704	119803878	119804019
ENSE00001090706	119788790	119788904
ENSE00001090707	119791324	119791459
ENSE00001090709	119785201	119785266
ENSE00001090710	119788338	119788447
ENSE00001090711	119819346	119819506
ENSE00001090714	119795532	119795631
ENSE00001090718	119783381	119783633
ENSE00001090720	119789592	119789746
ENSE00001090722	119796990	119797103
ENSE00001090723	119797662	119797846
ENSE00001276731	119730774	119732186
ENSE00001505690	119831677	119831731
ENSE00002108893	119832482	119832841
ENSE00003531383	119758073	119758142
ENSE00003564339	119756006	119756115
ENSE00003586119	119742534	119742656
ENSE00003606723	119762415	119762608
ENSE00003653634	119760599	119760738
ENSE00003676424	119806283	119806401

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 93.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.7358 / max 534.1767, expressed in 1821 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94627	32.7358	1821

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	93.19	gold quality
endothelial cell	CL:0000115	93.16	gold quality
calcaneal tendon	UBERON:0003701	93.02	gold quality
corpus epididymis	UBERON:0004359	92.02	gold quality
cauda epididymis	UBERON:0004360	92.02	gold quality
choroid plexus epithelium	UBERON:0003911	91.51	gold quality
ventricular zone	UBERON:0003053	91.26	gold quality
skin of hip	UBERON:0001554	91.14	gold quality
caput epididymis	UBERON:0004358	91.14	gold quality
epithelium of nasopharynx	UBERON:0001951	91.02	gold quality
germinal epithelium of ovary	UBERON:0001304	90.98	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.62	gold quality
seminal vesicle	UBERON:0000998	90.48	gold quality
tendon	UBERON:0000043	89.87	gold quality
gingival epithelium	UBERON:0001949	89.76	gold quality
oocyte	CL:0000023	89.54	gold quality
upper leg skin	UBERON:0004262	89.44	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.41	gold quality
ganglionic eminence	UBERON:0004023	89.35	gold quality
gingiva	UBERON:0001828	89.29	gold quality
secondary oocyte	CL:0000655	89.25	gold quality
colonic epithelium	UBERON:0000397	89.08	gold quality
tibia	UBERON:0000979	89.04	gold quality
oviduct epithelium	UBERON:0004804	89.04	gold quality
epithelial cell of pancreas	CL:0000083	88.91	gold quality
mucosa of sigmoid colon	UBERON:0004993	88.91	gold quality
cervix squamous epithelium	UBERON:0006922	88.77	gold quality
visceral pleura	UBERON:0002401	88.75	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.60	gold quality
parietal pleura	UBERON:0002400	88.53	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-137537	no	3.28
E-CURD-112	no	2.29
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2, RARB, TAF1

miRNA regulators (miRDB)

94 targeting TAF2, 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-6867-5P	100.00	82.21	3464
HSA-MIR-5692A	100.00	74.40	6850
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 86.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• This study suggested that the Microcephaly thin corpus callosum intellectual disability syndrome is caused by the more conserved mutation p.Thr186Arg, with the second sequence change identified, p.Pro416His. (PMID:24084144)
• 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)
• Phenotype associated with TAF2 biallelic mutations: A clinical description of four individuals and review of the literature. (PMID:34474177)
• TAF8 regions important for TFIID lobe B assembly or for TAF2 interactions are required for embryonic stem cell survival. (PMID:34634302)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	taf2	ENSDARG00000102307
mus_musculus	Taf2	ENSMUSG00000037343
rattus_norvegicus	Taf2	ENSRNOG00000034022
drosophila_melanogaster	Taf2	FBGN0011836
caenorhabditis_elegans		WBGENE00006383

Protein

Protein identifiers

Transcription initiation factor TFIID subunit 2 — Q6P1X5 (reviewed: Q6P1X5)

Alternative names: 150 kDa cofactor of initiator function, RNA polymerase II TBP-associated factor subunit B, TBP-associated factor 150 kDa, Transcription initiation factor TFIID 150 kDa subunit

All UniProt accessions (22): Q6P1X5, A0A8I5KNG3, A0A8I5KPW0, A0A8I5KR26, A0A8I5KRI4, A0A8I5KSY6, A0A8I5KU60, A0A8I5KUD2, A0A8I5KUQ2, A0A8I5KV60, A0A8I5KVC1, A0A8I5KXP3, A0A8I5KXS3, A0A8I5KY57, A0A8I5QJD7, A0A8I5QJI9, A0A8I5QJJ6, A0A8I5QJR0, E5RI28, H0YB55, H0YC37, H0YEX2

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. TAF2 forms a promoter DNA binding subcomplex of TFIID, together with TAF7 and TAF1.

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 TAF2C1. Component of the TFTC-HAT complex.

Subcellular location. Nucleus.

Tissue specificity. Expressed in all tissues tested.

Disease relevance. Neurodevelopmental disorder with feeding difficulties, thin corpus callosum, and foot deformity (NEDFCF) [MIM:615599] An autosomal recessive disorder characterized by impaired intellectual development, microcephaly, delayed psychomotor development, pyramidal signs, thin corpus callosum, and foot deformity. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. PubMed:9418870 was unable to show an association between TAF2 and TFIID.

Similarity. Belongs to the TAF2 family.

RefSeq proteins (1): NP_003175* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016024	ARM-type_fold	Homologous_superfamily
IPR027268	Peptidase_M4/M1_CTD_sf	Homologous_superfamily
IPR037813	TAF2	Family
IPR042097	Aminopeptidase_N-like_N_sf	Homologous_superfamily
IPR057345	Ig-like_TAF2	Domain
IPR057991	TPR_TAF2_C	Domain

Pfam: PF25316, PF25577

UniProt features (108 total): strand 39, helix 35, turn 8, sequence variant 8, sequence conflict 6, modified residue 5, region of interest 3, compositionally biased region 3, chain 1

Structure

Experimental structures (PDB)

28 structures.

PDB	Method	Resolution (Å)
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
6MZL	ELECTRON MICROSCOPY	23

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P1X5-F1	74.09	0.21

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 1196, 1198, 1185, 1188, 1194

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: 245 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, MORF_MSH3, GOBP_POSITIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, MORF_BRCA1, MORF_ATRX, GOBP_CELL_CYCLE_PHASE_TRANSITION, MORF_ESR1, LHX3_01, GOBP_REGULATION_OF_DNA_REPAIR, PUJANA_CHEK2_PCC_NETWORK, REACTOME_HIV_INFECTION, ONKEN_UVEAL_MELANOMA_UP, MORF_PPP5C, MORF_FANCG, GOBP_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION

GO Biological Process (9): G2/M transition of mitotic cell cycle (GO:0000086), regulation of DNA repair (GO:0006282), regulation of transcription by RNA polymerase II (GO:0006357), 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), response to paraquat (GO:1901562)

GO Molecular Function (4): transcription cis-regulatory region binding (GO:0000976), chromatin binding (GO:0003682), RNA polymerase II general transcription initiation factor activity (GO:0016251), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription factor TFIID complex (GO:0005669), transcription factor TFTC complex (GO:0033276)

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
transcription by RNA polymerase II	4
regulation of DNA-templated transcription	2
transcription initiation at RNA polymerase II promoter	2
binding	2
RNA polymerase II, holoenzyme	2
RNA polymerase II transcription regulator complex	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G2/M phase transition	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
DNA-templated 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
response to chemical	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
general transcription initiation factor activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
SAGA-type complex	1

Protein interactions and networks

STRING

2082 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAF2	TAF1	P21675	996
TAF2	TAF5	Q15542	977
TAF2	TAF7	Q15545	975
TAF2	TAF4	O00268	961
TAF2	BTAF1	O14981	959
TAF2	TAF8	Q7Z7C8	945
TAF2	TBP	P20226	905
TAF2	TAF6	P49848	900
TAF2	TAF10	Q12962	878
TAF2	TAF12	Q16514	866
TAF2	TAF9	Q16594	859
TAF2	TAF11	Q15544	842
TAF2	TAF13	Q15543	825
TAF2	TAF5L	O75529	718
TAF2	TAF3	Q5VWG9	717
TAF2	GTF2B	Q00403	717

IntAct

74 interactions, top by confidence:

A	B	Type	Score
TAF12	TAF4	psi-mi:“MI:0914”(association)	0.760
TBP	TAF4	psi-mi:“MI:0914”(association)	0.730
TAF10	TAF4	psi-mi:“MI:0915”(physical association)	0.650
TAF2	PUF60	psi-mi:“MI:0915”(physical association)	0.560
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
EPB41L3	AP3B1	psi-mi:“MI:0914”(association)	0.530
GTF2A2	TAF4	psi-mi:“MI:0915”(physical association)	0.490
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
TAF1	TAF2	psi-mi:“MI:0915”(physical association)	0.400
Samm50	ZC3H18	psi-mi:“MI:0914”(association)	0.350
Kif4	RNF213	psi-mi:“MI:0914”(association)	0.350
	TAF4	psi-mi:“MI:0914”(association)	0.350
KAT2A	TAF4	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
AK9	MYO9A	psi-mi:“MI:0914”(association)	0.350
TAF7L	TAF4	psi-mi:“MI:0914”(association)	0.350
RFC4	RAD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (213): TAF2 (Protein-peptide), TAF2 (Affinity Capture-MS), TAF2 (Affinity Capture-MS), TAF2 (Co-fractionation), TAF2 (Proximity Label-MS), TAF2 (Affinity Capture-MS), TAF2 (Affinity Capture-MS), TAF2 (Affinity Capture-MS), TAF2 (Affinity Capture-MS), TAF2 (Affinity Capture-MS), TAF2 (Affinity Capture-MS), TAF2 (Affinity Capture-MS), TAF2 (Affinity Capture-Western), TAF2 (Affinity Capture-Western), TAF2 (Affinity Capture-Western)

ESM2 similar proteins: A0A286ZK88, A1L1L6, A7MB28, A8WGF4, B8BJ39, D0G6S1, O00399, O54956, P11029, P11497, Q13085, Q148G7, Q28007, Q28943, Q28DR7, Q2HJF8, Q2RAK2, Q4R4U1, Q502J7, Q5FVD6, Q5R559, Q5R5F8, Q5R7D8, Q5R8Q7, Q5SWU9, Q5ZIT8, Q5ZM73, Q6AYR2, Q6NVC5, Q6NWV3, Q6P1X5, Q6PC62, Q7TPD1, Q7TSL3, Q86XK2, Q8BG51, Q8BH44, Q8C176, Q8CHR6, Q8IWZ6

Diamond homologs: Q24325, Q32PW3, Q5ZIT8, Q6P1X5, Q8C176, Q9TYN3

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TAF2	“form complex”	TFIID	binding
TAF2	“form complex”	“SAGA complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 75 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	10	45.7×	6e-13
RNA Polymerase II HIV Promoter Escape	10	45.7×	6e-13
RNA Polymerase II Promoter Escape	10	45.7×	6e-13
RNA Polymerase II Transcription Pre-Initiation And Promoter Opening	10	45.7×	6e-13
RNA Polymerase II Transcription Initiation	10	45.7×	6e-13
RNA Polymerase II Transcription Initiation And Promoter Clearance	10	45.7×	6e-13
Transcription of the HIV genome	11	37.3×	6e-13
Late Phase of HIV Life Cycle	10	32.9×	1e-11

GO biological processes:

GO term	Partners	Fold	FDR
transcription initiation at RNA polymerase II promoter	9	51.1×	2e-11
RNA polymerase II preinitiation complex assembly	12	49.4×	4e-15
positive regulation of transcription initiation by RNA polymerase II	11	45.3×	2e-13
mRNA transcription by RNA polymerase II	8	40.0×	3e-09
regulation of DNA repair	5	20.9×	3e-04
transcription by RNA polymerase II	10	10.7×	3e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	173
Likely benign	121
Benign	29

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
4847345	NC_000008.10:g.(?120743013)(120845082_?)del	Pathogenic
92249	NM_003184.4(TAF2):c.1945T>C (p.Trp649Arg)	Pathogenic
1319159	NM_003184.4(TAF2):c.2612dup (p.Ala872fs)	Likely pathogenic
4532089	NM_003184.4(TAF2):c.2768+1G>T	Likely pathogenic
4849178	NM_003184.4(TAF2):c.793-2A>G	Likely pathogenic

SpliceAI

4444 predictions. Top by Δscore:

Variant	Effect	Δscore
8:119741831:C:CA	donor_gain	1.0000
8:119742528:TTTTA:T	donor_loss	1.0000
8:119742529:TTTAC:T	donor_loss	1.0000
8:119742530:TTAC:T	donor_loss	1.0000
8:119742531:TA:T	donor_loss	1.0000
8:119742532:ACCT:A	donor_loss	1.0000
8:119742533:C:A	donor_loss	1.0000
8:119742652:GAGCC:G	acceptor_gain	1.0000
8:119742654:GCC:G	acceptor_gain	1.0000
8:119742655:CC:C	acceptor_gain	1.0000
8:119742655:CCC:C	acceptor_gain	1.0000
8:119742656:CC:C	acceptor_gain	1.0000
8:119742656:CCT:C	acceptor_loss	1.0000
8:119742657:C:CC	acceptor_gain	1.0000
8:119742657:CT:C	acceptor_loss	1.0000
8:119742658:T:A	acceptor_loss	1.0000
8:119742662:A:AC	acceptor_gain	1.0000
8:119742666:C:CT	acceptor_gain	1.0000
8:119742666:C:T	acceptor_gain	1.0000
8:119742667:A:T	acceptor_gain	1.0000
8:119744284:TTACC:T	donor_loss	1.0000
8:119744285:TAC:T	donor_gain	1.0000
8:119744286:AC:A	donor_loss	1.0000
8:119744287:C:CG	donor_loss	1.0000
8:119744391:AAA:A	acceptor_gain	1.0000
8:119744392:AA:A	acceptor_gain	1.0000
8:119744394:C:CC	acceptor_gain	1.0000
8:119744409:A:C	acceptor_gain	1.0000
8:119744879:A:AC	donor_gain	1.0000
8:119744880:C:CC	donor_gain	1.0000

AlphaMissense

8027 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:119746832:A:G	L994S	1.000
8:119746862:G:T	P984H	1.000
8:119756024:A:G	W954R	1.000
8:119756024:A:T	W954R	1.000
8:119756026:A:G	L953P	1.000
8:119760628:G:T	A890D	1.000
8:119760637:C:A	R887M	1.000
8:119760712:T:G	Q862P	1.000
8:119760715:A:G	L861P	1.000
8:119760721:C:G	R859P	1.000
8:119760728:C:G	A857P	1.000
8:119760735:A:C	C854W	1.000
8:119760736:C:T	C854Y	1.000
8:119760737:A:G	C854R	1.000
8:119762454:T:A	E840V	1.000
8:119762484:A:G	L830P	1.000
8:119762556:A:T	V806D	1.000
8:119762568:A:G	L802P	1.000
8:119762572:C:G	A801P	1.000
8:119762587:C:G	A796P	1.000
8:119762601:T:A	D791V	1.000
8:119762602:C:G	D791H	1.000
8:119778022:A:C	N787K	1.000
8:119778022:A:T	N787K	1.000
8:119778031:G:C	N784K	1.000
8:119778031:G:T	N784K	1.000
8:119778037:A:C	N782K	1.000
8:119778037:A:T	N782K	1.000
8:119778082:A:C	C767W	1.000
8:119778100:T:A	R761S	1.000

dbSNP variants (sampled 300 via entrez): RS1000044138 (8:119805871 T>C), RS1000087373 (8:119743586 A>G), RS1000106484 (8:119763801 C>A,T), RS1000136378 (8:119794040 A>G), RS1000145676 (8:119788017 T>A), RS1000222966 (8:119737771 G>C), RS1000240301 (8:119819164 C>A,T), RS1000250277 (8:119768620 A>C), RS1000356885 (8:119738089 T>C), RS1000380883 (8:119769400 C>A,T), RS1000399090 (8:119787618 G>C), RS1000432644 (8:119817573 T>A), RS1000454000 (8:119818897 T>C,G), RS1000482335 (8:119786839 T>C), RS1000503245 (8:119743658 A>G,T)

Disease associations

OMIM: gene MIM:604912 | disease phenotypes: MIM:615599

GenCC curated gene-disease

Disease	Classification	Inheritance
microcephaly-thin corpus callosum-intellectual disability syndrome	Strong	Autosomal recessive

Mondo (2): microcephaly-thin corpus callosum-intellectual disability syndrome (MONDO:0014273), microcephaly (MONDO:0001149)

Orphanet (1): Microcephaly-thin corpus callosum-intellectual disability syndrome (Orphanet:397951)

HPO phenotypes

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

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000577	Exotropia
HP:0000639	Nystagmus
HP:0000666	Horizontal nystagmus
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0001647	Bicuspid aortic valve
HP:0001650	Aortic valve stenosis
HP:0001760	Abnormal foot morphology
HP:0002059	Cerebral atrophy
HP:0002079	Hypoplasia of the corpus callosum
HP:0002188	Delayed CNS myelination
HP:0002465	Poor speech
HP:0003487	Babinski sign
HP:0003593	Infantile onset
HP:0005484	Secondary microcephaly
HP:0007256	Abnormal pyramidal sign
HP:0007703	Abnormal retinal pigmentation
HP:0011461	Fetal onset
HP:0012448	Delayed myelination

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005787_13	Heart rate response to exercise	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009184	heart rate response to exercise

MeSH disease descriptors (1)

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases abundance, increases expression, affects cotreatment	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Irinotecan	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects expression	1
Lead	affects splicing	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Selenium	decreases expression	1
Valproic Acid	affects expression	1
Lactic Acid	decreases expression	1
Chlorodiphenyl (54% Chlorine)	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia
NCT04816175	Not specified	COMPLETED	Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay
NCT05322980	Not specified	COMPLETED	Summary of Infants Weighing 500 Grams or Less
NCT06019182	Not specified	RECRUITING	MEHMO Natural History and Biomarkers
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.