TCEA1

Summary

TCEA1 (transcription elongation factor A1, HGNC:11612) is a protein-coding gene on chromosome 8q11.23, encoding Transcription elongation factor A protein 1 (P23193). Necessary for efficient RNA polymerase II transcription elongation past template-encoded arresting sites.

Predicted to enable DNA binding activity; translation elongation factor activity; and zinc ion binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within erythrocyte differentiation and positive regulation of DNA-templated transcription. Located in nucleolus and nucleoplasm. Part of transcription factor TFIID complex.

Source: NCBI Gene 6917 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• Druggable target: yes
• MANE Select transcript: NM_006756

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11612
Approved symbol	TCEA1
Name	transcription elongation factor A1
Location	8q11.23
Locus type	gene with protein product
Status	Approved
Aliases	SII, TF2S, TFIIS
Ensembl gene	ENSG00000187735
Ensembl biotype	protein_coding
OMIM	601425
Entrez	6917

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 13 protein_coding, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000396401, ENST00000517351, ENST00000518310, ENST00000518784, ENST00000519704, ENST00000520534, ENST00000521086, ENST00000521604, ENST00000521836, ENST00000522397, ENST00000522635, ENST00000911142, ENST00000911143, ENST00000911144, ENST00000911145, ENST00000911146, ENST00000920395, ENST00000920396, ENST00000959335

RefSeq mRNA: 4 — MANE Select: NM_006756 NM_001425841, NM_001425842, NM_006756, NM_201437

CCDS: CCDS47857, CCDS47858

Canonical transcript exons

ENST00000521604 — 10 exons

Exon	Start	End
ENSE00001426483	54022063	54022448
ENSE00002132465	53966556	53968112
ENSE00003471084	53999945	54000050
ENSE00003474196	53986969	53987025
ENSE00003521173	54010430	54010492
ENSE00003521566	53984363	53984517
ENSE00003562827	53970392	53970463
ENSE00003586940	53993668	53993755
ENSE00003605835	53979025	53979171
ENSE00003622116	53988114	53988259

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 98.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.0315 / max 1781.0984, expressed in 1824 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93083	22.8987	1809
93086	9.2604	1706
93085	7.5986	1290
93087	3.8506	1132
93084	1.7125	944
93082	0.7107	376

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	98.52	gold quality
calcaneal tendon	UBERON:0003701	98.29	gold quality
cranial nerve II	UBERON:0000941	98.18	gold quality
caput epididymis	UBERON:0004358	98.09	gold quality
cartilage tissue	UBERON:0002418	98.08	gold quality
cauda epididymis	UBERON:0004360	98.05	gold quality
corpus epididymis	UBERON:0004359	97.97	gold quality
upper leg skin	UBERON:0004262	97.74	gold quality
parotid gland	UBERON:0001831	97.61	gold quality
mammary duct	UBERON:0001765	97.60	gold quality
skin of hip	UBERON:0001554	97.59	gold quality
blood vessel layer	UBERON:0004797	97.47	gold quality
bronchial epithelial cell	CL:0002328	97.46	gold quality
saphenous vein	UBERON:0007318	97.40	gold quality
mammalian vulva	UBERON:0000997	97.37	gold quality
seminal vesicle	UBERON:0000998	97.36	gold quality
ventricular zone	UBERON:0003053	97.23	gold quality
urethra	UBERON:0000057	97.22	gold quality
oral cavity	UBERON:0000167	97.22	gold quality
superficial temporal artery	UBERON:0001614	97.19	gold quality
pigmented layer of retina	UBERON:0001782	97.19	gold quality
jejunal mucosa	UBERON:0000399	97.10	gold quality
epithelium of mammary gland	UBERON:0003244	97.05	gold quality
tonsil	UBERON:0002372	96.98	gold quality
lymph node	UBERON:0000029	96.95	gold quality
epithelium of bronchus	UBERON:0002031	96.93	gold quality
bronchus	UBERON:0002185	96.93	gold quality
islet of Langerhans	UBERON:0000006	96.91	gold quality
nipple	UBERON:0002030	96.86	gold quality
corpus callosum	UBERON:0002336	96.81	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	18.39
E-MTAB-6819	no	1989.76
E-GEOD-106540	no	783.42
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

126 targeting TCEA1, 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-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505

Literature-anchored findings (GeneRIF, showing 11)

• Results provide a model of the RNA polymerase II-transcription elongation factor TFIIS complex from X-ray diffraction data to 3.8 A resolution. (PMID:12914699)
• transcription factor IIF, hepatitis delta antigen, and stimulatory factor II control human RNA polymerase II (RNAP II) pausing and transcript cleavage (PMID:14506279)
• TFIIS has a role in suppression of transient pausing, which is the most important contribution of TFIIS to elongation from a stall position (PMID:15351637)
• Data shpw that SII is a major component of chromatin transcription and strongly synergizes with p300 (histone acetylation) at a step subsequent to preinitiation complex formation. (PMID:16630816)
• PLAG1 protein is overexpressed in epithelial, myoepithelial, and mesenchymal-like tumor cells in tumors with fusions to CHCHD7 and TCEA1. (PMID:16736500)
• a role for TFIIS in transcription recovery and re-establishment of the balance between hypo- and hyper-phosphorylated RNAPII after DNA damage repair (PMID:20729154)
• Results indicate that TFIIS is not limiting for the repair of transcription-blocking DNA lesions and thus the present work does not support a role for TFIIS in TC-NER. (PMID:21070792)
• RNF20, presumably via H2Bub, selectively represses oncogenic genes by interfering with chromatin recruitment of TFIIS, a factor capable of relieving stalled RNA polymerase II. RNF20 inhibits the interaction between TFIIS and the PAF1 complex. (PMID:21596312)
• A mutant form of TFIIS increased RNAPII pausing and backtracking results in R-loop formation and genome instability. (PMID:31519522)
• A ubiquitous disordered protein interaction module orchestrates transcription elongation. (PMID:34822292)
• Human DNA topoisomerase I poisoning causes R loop-mediated genome instability attenuated by transcription factor IIS. (PMID:38787953)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tcea1	ENSDARG00000003531
mus_musculus	Tcea1	ENSMUSG00000033813
rattus_norvegicus	Tcea1	ENSRNOG00000005869
rattus_norvegicus	Tcea1l1	ENSRNOG00000022323

Paralogs (3): TCEA2 (ENSG00000171703), TCEANC (ENSG00000176896), TCEA3 (ENSG00000204219)

Protein

Protein identifiers

Transcription elongation factor A protein 1 — P23193 (reviewed: P23193)

Alternative names: Transcription elongation factor S-II protein 1, Transcription elongation factor TFIIS.o

All UniProt accessions (7): A0A384MTX4, B7Z4S1, E5RFI1, E5RIS7, E5RJ93, E5RK46, P23193

UniProt curated annotations — full annotation on UniProt →

Function. Necessary for efficient RNA polymerase II transcription elongation past template-encoded arresting sites. The arresting sites in DNA have the property of trapping a certain fraction of elongating RNA polymerases that pass through, resulting in locked ternary complexes. Cleavage of the nascent transcript by S-II allows the resumption of elongation from the new 3’-terminus.

Subunit / interactions. Interacts with EAF2. Associates with UBR5 and forms a transcription regulatory complex made of CDK9, Pol II, UBR5 and TCEA1/TFIIS. Part of TBP-based Pol II pre-initiation complex (PIC), in which Pol II core assembles with general transcription factors and other specific initiation factors including GTF2E1, GTF2E2, GTF2F1, GTF2F2, TCEA1, ERCC2, ERCC3, GTF2H2, GTF2H3, GTF2H4, GTF2H5, GTF2A1, GTF2A2, GTF2B and TBP; this large multi-subunit PIC complex mediates DNA unwinding and targets Pol II core to the transcription start site where the first phosphodiester bond forms.

Subcellular location. Nucleus.

Disease relevance. A chromosomal aberration involving TCEA1 may be a cause of salivary gland pleiomorphic adenomas (PA) [181030]. Pleiomorphic adenomas are the most common benign epithelial tumors of the salivary gland. Translocation t(3;8)(p21;q12) with PLAG1.

Miscellaneous. S-II binds to RNA-polymerase II in the absence of transcription.

Similarity. Belongs to the TFS-II family.

Isoforms (2)

UniProt ID	Names	Canonical?
P23193-1	1	yes
P23193-2	2

RefSeq proteins (4): NP_001412770, NP_001412771, NP_006747, NP_958845 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001222	Znf_TFIIS	Domain
IPR003617	TFIIS/CRSP70_N_sub	Domain
IPR003618	TFIIS_cen_dom	Domain
IPR006289	TFSII	Family
IPR017923	TFIIS_N	Domain
IPR035100	TF_IIS-typ	Family
IPR035441	TFIIS/LEDGF_dom_sf	Homologous_superfamily
IPR036575	TFIIS_cen_dom_sf	Homologous_superfamily

Pfam: PF01096, PF07500, PF08711

UniProt features (46 total): helix 15, sequence conflict 6, strand 6, modified residue 5, binding site 4, domain 2, turn 2, chain 1, cross-link 1, splice variant 1, zinc finger region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

25 structures.

PDB	Method	Resolution (Å)
3NDQ	X-RAY DIFFRACTION	1.93
9MLC	ELECTRON MICROSCOPY	2.4
9EGX	ELECTRON MICROSCOPY	2.9
9EGY	ELECTRON MICROSCOPY	2.9
9EGZ	ELECTRON MICROSCOPY	2.9
7UNC	ELECTRON MICROSCOPY	3
7UND	ELECTRON MICROSCOPY	3
8A40	ELECTRON MICROSCOPY	3
9EH2	ELECTRON MICROSCOPY	3.1
8UIS	ELECTRON MICROSCOPY	3.23
9J0N	ELECTRON MICROSCOPY	3.4
9EH0	ELECTRON MICROSCOPY	3.6
5IYB	ELECTRON MICROSCOPY	3.9
5IYC	ELECTRON MICROSCOPY	3.9
5IYA	ELECTRON MICROSCOPY	5.4
9S3G	ELECTRON MICROSCOPY	6.4
9S0U	ELECTRON MICROSCOPY	6.72
5IY6	ELECTRON MICROSCOPY	7.2
6O9L	ELECTRON MICROSCOPY	7.2
5IY8	ELECTRON MICROSCOPY	7.9
5IY7	ELECTRON MICROSCOPY	8.6
1TFI	SOLUTION NMR
6ZUY	SOLUTION NMR
6ZV4	SOLUTION NMR
7CNF	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23193-F1	80.42	0.42

Functional residue map

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

Ligand- & substrate-binding residues (4): 263; 266; 291; 294

Post-translational modifications (6): 1, 57, 81, 97, 100, 55

Function

Pathways and Gene Ontology

Reactome pathways

29 pathways

ID	Pathway
R-HSA-112382	Formation of RNA Pol II elongation complex
R-HSA-167152	Formation of HIV elongation complex in the absence of HIV Tat
R-HSA-167200	Formation of HIV-1 elongation complex containing HIV-1 Tat
R-HSA-167238	Pausing and recovery of Tat-mediated HIV elongation
R-HSA-167243	Tat-mediated HIV elongation arrest and recovery
R-HSA-167246	Tat-mediated elongation of the HIV-1 transcript
R-HSA-167287	HIV elongation arrest and recovery
R-HSA-167290	Pausing and recovery of HIV elongation
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-6781823	Formation of TC-NER Pre-Incision Complex
R-HSA-6781827	Transcription-Coupled Nucleotide Excision Repair (TC-NER)
R-HSA-6782135	Dual incision in TC-NER
R-HSA-6782210	Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes
R-HSA-75955	RNA Polymerase II Transcription Elongation
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-167169	HIV Transcription Elongation
R-HSA-167172	Transcription of the HIV genome
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-5663205	Infectious disease
R-HSA-5696398	Nucleotide Excision Repair
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-73894	DNA Repair
R-HSA-74160	Gene expression (Transcription)
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 240 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, MORF_MTA1, MORF_DNMT1, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_ERYTHROCYTE_HOMEOSTASIS, MORF_HDAC1, MORF_CDK2, HSIAO_HOUSEKEEPING_GENES, IVANOVA_HEMATOPOIESIS_MATURE_CELL, WEIGEL_OXIDATIVE_STRESS_BY_TBH_AND_H2O2, MORF_HDAC2, PATIL_LIVER_CANCER, PUJANA_CHEK2_PCC_NETWORK, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_UP

GO Biological Process (7): transcription elongation by RNA polymerase II (GO:0006368), erythrocyte differentiation (GO:0030218), positive regulation of transcription by RNA polymerase II (GO:0045944), DNA-templated transcription (GO:0006351), transcription by RNA polymerase II (GO:0006366), translational elongation (GO:0006414), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (7): DNA binding (GO:0003677), transcription elongation factor activity (GO:0003711), zinc ion binding (GO:0008270), nucleic acid binding (GO:0003676), translation elongation factor activity (GO:0003746), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription factor TFIID complex (GO:0005669), nucleolus (GO:0005730)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Transcription of the HIV genome	6
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	3
RNA Polymerase II Transcription	2
RNA Polymerase II Transcription Elongation	1
Tat-mediated elongation of the HIV-1 transcript	1
HIV Transcription Elongation	1
Nucleotide Excision Repair	1
Transcriptional Regulation by TP53	1
HIV Infection	1
HIV Life Cycle	1
Viral Infection Pathways	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
DNA-templated transcription	2
binding	2
nuclear lumen	2
DNA-templated transcription elongation	1
myeloid cell differentiation	1
erythrocyte homeostasis	1
regulation of transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
gene expression	1
RNA biosynthetic process	1
translation	1
macromolecule biosynthetic process	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
nucleic acid binding	1
transcription regulator activity	1
transition metal ion binding	1
translational elongation	1
translation factor activity	1
cation binding	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
RNA polymerase II, holoenzyme	1
RNA polymerase II transcription regulator complex	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2588 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TCEA1	GTF2B	Q00403	937
TCEA1	POLR2I	P36954	909
TCEA1	POLR3K	Q9Y2Y1	902
TCEA1	XAB2	Q9HCS7	896
TCEA1	PLAG1	Q6DJT9	889
TCEA1	POLR2B	P30876	878
TCEA1	HMGN1	P05114	874
TCEA1	SUPT4H1	P63272	872
TCEA1	SUPT5H	O00267	867
TCEA1	POLR2A	P24928	835
TCEA1	POLI	Q9UNA4	817
TCEA1	TBP	P20226	808
TCEA1	SUPT6H	Q7KZ85	807
TCEA1	POLR2E	P19388	789
TCEA1	CHCHD7	Q9BUK0	752
TCEA1	POLR1H	Q9P1U0	752

IntAct

61 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
MED17	MED19	psi-mi:“MI:0914”(association)	0.840
POLR2E	POLR2D	psi-mi:“MI:0915”(physical association)	0.790
POLR2A	TCEA1	psi-mi:“MI:0915”(physical association)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
TCEA1	POLR2A	psi-mi:“MI:0914”(association)	0.710
NFKBIA	POLRMT	psi-mi:“MI:0914”(association)	0.670
POLR2C	SUPT5H	psi-mi:“MI:0914”(association)	0.640
TCEA1	LEO1	psi-mi:“MI:0407”(direct interaction)	0.580
PAF1	TCEA1	psi-mi:“MI:0407”(direct interaction)	0.580
BROX	TCEA1	psi-mi:“MI:0914”(association)	0.560
TCEA1	GPKOW	psi-mi:“MI:0915”(physical association)	0.560
BROX	TCEA1	psi-mi:“MI:0915”(physical association)	0.560
EED	EPOP	psi-mi:“MI:0914”(association)	0.530
GPR21	TMEM120B	psi-mi:“MI:0914”(association)	0.530
USP47	DENR	psi-mi:“MI:0914”(association)	0.530
HSD3B2	NARS1	psi-mi:“MI:0914”(association)	0.530
DUSP19	NARS1	psi-mi:“MI:0914”(association)	0.530
CYP1A1	SNX3	psi-mi:“MI:0914”(association)	0.530
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
TCEA1	iglC2	psi-mi:“MI:0915”(physical association)	0.370
OTUB1		psi-mi:“MI:0914”(association)	0.350
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
POLR2G	POLR2B	psi-mi:“MI:0914”(association)	0.350
TCEA1	CCNT1	psi-mi:“MI:0914”(association)	0.350

BioGRID (177): TCEA1 (Affinity Capture-MS), TCEA1 (Affinity Capture-MS), TCEA1 (Affinity Capture-MS), TCEA1 (Affinity Capture-MS), TCEA1 (Affinity Capture-MS), TCEA1 (Affinity Capture-MS), TCEA1 (Affinity Capture-MS), TCEA1 (Affinity Capture-MS), DUS3L (Co-fractionation), NFATC2IP (Co-fractionation), TCEA1 (Co-fractionation), TCEA1 (Co-fractionation), TCEA1 (Co-fractionation), TCEA1 (Co-fractionation), TCEA1 (Co-fractionation)

ESM2 similar proteins: A0A1B0GTH9, A6QQM4, A7SKE9, B4KLC0, B4LRY2, B4Q5Z1, E0X9N4, O60308, P0CR50, P0CR51, P10711, P23193, Q02336, Q09464, Q0VA16, Q15560, Q17CJ5, Q1HE00, Q28CY2, Q29RL9, Q3B7L8, Q3EA33, Q4KLL0, Q4R4J1, Q4V7D7, Q5EB92, Q5RAY5, Q5U2P3, Q5ZM16, Q63799, Q641B2, Q6DJI8, Q6DRC4, Q6GPP0, Q6IDS6, Q6NZZ9, Q6P616, Q7QJV0, Q7ZXB5, Q8BHS3

Diamond homologs: A5PK23, O95402, P10711, P23193, Q29CV2, Q29RL9, Q4KLL0, Q63799, Q7TN02, Q90YL3, Q90YY5, Q9QVN7, Q9V4F9, A6ZZW1, O44498, O75764, P20232, P36106, P52652, Q2KI09, Q6FJ00, Q6ZMY3, Q9U263, A5PKE4, B0UYI1, F4J4Y5, P23881, Q148K0, Q5XIC7, Q8R2M0, Q96MN5, Q9FHK9, B1ASB6, Q15560, Q92576, O13896, O27369, O29033, P07273, P36958

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TCEA1	up-regulates	UBR5	binding
PAF1C	“up-regulates activity”	TCEA1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 76 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
FGFR2 mutant receptor activation	5	70.5×	5e-08
Signaling by FGFR2 IIIa TM	6	66.8×	2e-09
Abortive elongation of HIV-1 transcript in the absence of Tat	7	64.4×	1e-10
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection	8	60.4×	1e-11
RNA Pol II CTD phosphorylation and interaction with CE	8	60.4×	1e-11
mRNA Capping	8	56.4×	2e-11
Pausing and recovery of Tat-mediated HIV elongation	8	54.6×	2e-11
Tat-mediated HIV elongation arrest and recovery	8	54.6×	2e-11

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription elongation by RNA polymerase II	9	39.2×	6e-10
transcription elongation by RNA polymerase II	6	38.6×	2e-06
transcription initiation at RNA polymerase II promoter	5	27.1×	9e-05
positive regulation of transcription initiation by RNA polymerase II	6	23.6×	3e-05
RNA polymerase II preinitiation complex assembly	5	19.7×	3e-04
transcription by RNA polymerase II	10	10.2×	8e-06
Wnt signaling pathway	6	8.7×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

2077 predictions. Top by Δscore:

Variant	Effect	Δscore
8:53977818:A:AC	donor_gain	1.0000
8:53979021:AAAC:A	donor_loss	1.0000
8:53979022:AAC:A	donor_loss	1.0000
8:53979023:AC:A	donor_loss	1.0000
8:53979024:CC:C	donor_loss	1.0000
8:53987026:C:CC	acceptor_gain	1.0000
8:53988112:ACCC:A	donor_gain	1.0000
8:53988113:CCCC:C	donor_gain	1.0000
8:53988260:C:CC	acceptor_gain	1.0000
8:53993656:A:AC	donor_gain	1.0000
8:53993657:C:CC	donor_gain	1.0000
8:53993663:AGTAC:A	donor_loss	1.0000
8:53993665:TA:T	donor_loss	1.0000
8:53993666:AC:A	donor_loss	1.0000
8:53993751:CCCAT:C	acceptor_gain	1.0000
8:53993752:CCAT:C	acceptor_gain	1.0000
8:53993752:CCATC:C	acceptor_gain	1.0000
8:53993753:CAT:C	acceptor_gain	1.0000
8:53993753:CATC:C	acceptor_gain	1.0000
8:53993754:ATCT:A	acceptor_loss	1.0000
8:53993755:TCTG:T	acceptor_loss	1.0000
8:53993756:C:CC	acceptor_gain	1.0000
8:53993756:CTG:C	acceptor_loss	1.0000
8:53999947:A:AC	donor_gain	1.0000
8:53999948:A:C	donor_gain	1.0000
8:54000046:GTGGA:G	acceptor_gain	1.0000
8:54000047:TGGA:T	acceptor_gain	1.0000
8:54000048:GGA:G	acceptor_gain	1.0000
8:54000049:GA:G	acceptor_gain	1.0000
8:54000051:C:CC	acceptor_gain	1.0000

AlphaMissense

2001 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:53970395:C:A	W298C	1.000
8:53970395:C:G	W298C	1.000
8:53970396:C:G	W298S	1.000
8:53970397:A:G	W298R	1.000
8:53970397:A:T	W298R	1.000
8:53970407:A:C	C294W	1.000
8:53970408:C:G	C294S	1.000
8:53970409:A:G	C294R	1.000
8:53970409:A:T	C294S	1.000
8:53970416:A:C	C291W	1.000
8:53970417:C:A	C291F	1.000
8:53970417:C:G	C291S	1.000
8:53970417:C:T	C291Y	1.000
8:53970418:A:G	C291R	1.000
8:53970418:A:T	C291S	1.000
8:53970423:A:T	V289D	1.000
8:53970425:A:C	F288L	1.000
8:53970425:A:T	F288L	1.000
8:53970426:A:C	F288C	1.000
8:53970426:A:G	F288S	1.000
8:53970427:A:G	F288L	1.000
8:53970429:G:T	T287K	1.000
8:53970434:C:A	M285I	1.000
8:53970434:C:G	M285I	1.000
8:53970434:C:T	M285I	1.000
8:53970435:A:C	M285R	1.000
8:53970435:A:T	M285K	1.000
8:53970438:G:T	P284Q	1.000
8:53970439:G:A	P284S	1.000
8:53970440:T:A	E283D	1.000

dbSNP variants (sampled 300 via entrez): RS1000118982 (8:54013425 C>G), RS1000139827 (8:53983064 A>C,T), RS1000147985 (8:54004337 C>T), RS1000204474 (8:53982762 G>A), RS1000212019 (8:54022278 C>G), RS1000221802 (8:54005027 C>T), RS1000318861 (8:54009605 C>A), RS1000322244 (8:54010670 A>T), RS1000421866 (8:53998114 T>G), RS1000433804 (8:54016161 G>A), RS1000478718 (8:53976916 A>G), RS1000542113 (8:54020953 T>C,G), RS1000582320 (8:54021948 G>A,T), RS1000585996 (8:54006530 AAAG>A), RS1000679237 (8:54018350 C>G)

Disease associations

OMIM: gene MIM:601425 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066940 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.60	Kd	25.13	nM	CHEMBL5653589
7.60	ED50	25.13	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149560: Binding affinity to human TCEA1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0251	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	6
bisphenol A	affects expression, increases expression	2
Arsenic	increases abundance, increases expression, affects cotreatment	2
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
quercitrin	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
perfluorooctanoic acid	increases expression	1
benzo(e)pyrene	increases methylation	1
versicolorin A	increases expression	1
coumarin	decreases phosphorylation	1
perfluorooctane sulfonic acid	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
K 7174	increases expression	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	decreases methylation	1
Air Pollutants	increases abundance, increases expression	1
Azacitidine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1
Bucladesine	decreases expression, affects cotreatment	1
Diethylhexyl Phthalate	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	affects cotreatment, decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652602	Binding	Binding affinity to human TCEA1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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