TCEA3

gene
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Also known as TFIIS.H

Summary

TCEA3 (transcription elongation factor A3, HGNC:11615) is a protein-coding gene on chromosome 1p36.12, encoding Transcription elongation factor A protein 3 (O75764). 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 regulation of transcription by RNA polymerase II. Predicted to be active in nucleus.

Source: NCBI Gene 6920 — RefSeq curated summary.

At a glance

  • GWAS associations: 60
  • Clinical variants (ClinVar): 75 total
  • MANE Select transcript: NM_003196

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:11615
Approved symbolTCEA3
Nametranscription elongation factor A3
Location1p36.12
Locus typegene with protein product
StatusApproved
AliasesTFIIS.H
Ensembl geneENSG00000204219
Ensembl biotypeprotein_coding
OMIM604128
Entrez6920

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 20 protein_coding, 2 retained_intron

ENST00000374601, ENST00000374602, ENST00000450454, ENST00000461794, ENST00000476978, ENST00000492271, ENST00000898818, ENST00000898819, ENST00000898820, ENST00000898821, ENST00000898822, ENST00000898823, ENST00000898824, ENST00000898825, ENST00000898826, ENST00000941055, ENST00000941056, ENST00000941057, ENST00000941058, ENST00000941059, ENST00000941060, ENST00000941061

RefSeq mRNA: 1 — MANE Select: NM_003196 NM_003196

CCDS: CCDS44086

Canonical transcript exons

ENST00000450454 — 11 exons

ExonStartEnd
ENSE000014639582338090923381474
ENSE000014639672339779223397955
ENSE000014639732341907723419139
ENSE000014639742342456523424748
ENSE000015920942339754523397601
ENSE000016417292339387923394033
ENSE000034640442338434623384417
ENSE000034780492341724923417390
ENSE000034849732341790423418009
ENSE000035430122340866423408726
ENSE000035595212338727323387419

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.7784 / max 414.4001, expressed in 981 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter IDTPM avgSamples expressed
109726.7101919
109730.8501367
109700.110449
109710.102949
109740.00491

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
skeletal muscle tissueUBERON:000113499.23gold quality
hindlimb stylopod muscleUBERON:000425299.12gold quality
gastrocnemiusUBERON:000138898.91gold quality
muscle of legUBERON:000138398.83gold quality
body of pancreasUBERON:000115098.65gold quality
mucosa of transverse colonUBERON:000499197.41gold quality
right lobe of liverUBERON:000111497.12gold quality
rectumUBERON:000105296.79gold quality
liverUBERON:000210796.78gold quality
right adrenal glandUBERON:000123396.65gold quality
sural nerveUBERON:001548896.65gold quality
muscle tissueUBERON:000238596.58gold quality
right adrenal gland cortexUBERON:003582796.53gold quality
left adrenal gland cortexUBERON:003582596.15gold quality
left adrenal glandUBERON:000123496.06gold quality
saliva-secreting glandUBERON:000104495.72gold quality
transverse colonUBERON:000115795.60gold quality
right uterine tubeUBERON:000130295.55gold quality
adrenal tissueUBERON:001830395.55gold quality
minor salivary glandUBERON:000183095.53gold quality
adrenal glandUBERON:000236995.36gold quality
apex of heartUBERON:000209895.05gold quality
left ovaryUBERON:000211995.02gold quality
ovaryUBERON:000099295.00gold quality
calcaneal tendonUBERON:000370194.98gold quality
fundus of stomachUBERON:000116094.80gold quality
heart left ventricleUBERON:000208494.68gold quality
body of stomachUBERON:000116194.52gold quality
stomachUBERON:000094594.39gold quality
cortex of kidneyUBERON:000122594.12gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes22.29
E-GEOD-83139no2.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting TCEA3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-3925-3P100.0069.951237
HSA-MIR-477599.9875.006394
HSA-MIR-515-5P99.9269.822343
HSA-MIR-519E-5P99.9269.622358
HSA-MIR-576-5P99.8470.462582
HSA-MIR-92A-2-5P99.7567.012164
HSA-MIR-17-3P99.5566.771311
HSA-MIR-132499.4666.571302
HSA-MIR-330-3P99.4169.952521
HSA-MIR-6731-5P99.2867.422375
HSA-MIR-808599.2867.562362
HSA-MIR-450599.2767.812678
HSA-MIR-578799.2267.862628
HSA-MIR-371A-5P99.0866.511914
HSA-MIR-6871-5P98.9066.67671
HSA-MIR-16-1-3P98.7069.231538
HSA-MIR-7155-5P98.6566.141290
HSA-MIR-6881-5P98.1667.38665
HSA-MIR-4799-3P97.7865.97893
HSA-MIR-4720-5P97.4665.67893
HSA-MIR-5588-5P97.4665.70913
HSA-MIR-5000-5P97.4066.111055
HSA-MIR-397696.6767.791187
HSA-MIR-6742-5P96.3264.01869
HSA-MIR-29C-5P87.3666.9629

Literature-anchored findings (GeneRIF, showing 6)

  • Study demonstrates a strong synergy between hPAF1C and elongation factor SII/TFIIS and an underlying mechanism involving direct hPAF1C-SII interactions and cooperative binding to RNA polymerase II. (PMID:20178742)
  • Tcea3 binds to TGF-beta I receptor and activates TGF-beta signaling pathway. (PMID:23357533)
  • TCEA3 attenuates the proliferation and induces apoptosis of gastric cancer cells (PMID:26498664)
  • Findings reveal a novel mechanism by which p53 utilizes TFIIS.h to selectively promote the transcriptional elongation of the bax gene, upsurging cell death in response to severe DNA damage. (PMID:27005522)
  • The transcription elongation factor TCEA3 induces apoptosis in rhabdomyosarcoma. (PMID:31988307)
  • Oncogenic tRNA-derived fragment tRF-Leu-CAG promotes tumorigenesis of lung cancer via targeting TCEA3 and increasing autophagy. (PMID:39198937)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_reriotcea3ENSDARG00000004724
mus_musculusTcea3ENSMUSG00000001604
rattus_norvegicusTcea3ENSRNOG00000011794

Paralogs (3): TCEA2 (ENSG00000171703), TCEANC (ENSG00000176896), TCEA1 (ENSG00000187735)

Protein

Protein identifiers

Transcription elongation factor A protein 3O75764 (reviewed: O75764)

Alternative names: Transcription elongation factor S-II protein 3, Transcription elongation factor TFIIS.h

All UniProt accessions (3): O75764, S4R3M9, S4R419

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.

Subcellular location. Nucleus.

Similarity. Belongs to the TFS-II family.

Isoforms (2)

UniProt IDNamesCanonical?
O75764-11yes
O75764-22

RefSeq proteins (1): NP_003187* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR001222Znf_TFIISDomain
IPR003617TFIIS/CRSP70_N_subDomain
IPR003618TFIIS_cen_domDomain
IPR006289TFSIIFamily
IPR017923TFIIS_NDomain
IPR035100TF_IIS-typFamily
IPR035441TFIIS/LEDGF_dom_sfHomologous_superfamily
IPR036575TFIIS_cen_dom_sfHomologous_superfamily

Pfam: PF01096, PF07500, PF08711

UniProt features (16 total): binding site 4, compositionally biased region 3, domain 2, modified residue 2, splice variant 2, chain 1, zinc finger region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-O75764-F174.570.34

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): 338; 341; 310; 313

Post-translational modifications (2): 115, 140

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 103 (showing top): BENPORATH_ES_WITH_H3K27ME3, MAZ_Q6, MEF2_02, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_DN, SANSOM_APC_TARGETS_DN, HNF1_01, MEF2_Q6_01, CTAWWWATA_RSRFC4_Q2, WENG_POR_TARGETS_GLOBAL_UP, MEF2_03, MASSARWEH_TAMOXIFEN_RESISTANCE_UP, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, NUYTTEN_NIPP1_TARGETS_DN, DODD_NASOPHARYNGEAL_CARCINOMA_DN

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), transcription elongation by RNA polymerase II (GO:0006368), DNA-templated transcription (GO:0006351)

GO Molecular Function (5): DNA binding (GO:0003677), zinc ion binding (GO:0008270), nucleic acid binding (GO:0003676), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
transcription by RNA polymerase II2
binding2
regulation of DNA-templated transcription1
DNA-templated transcription elongation1
gene expression1
RNA biosynthetic process1
nucleic acid binding1
transition metal ion binding1
cation binding1
intracellular membrane-bounded organelle1

Protein interactions and networks

STRING

1680 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
TCEA3GTF2BQ00403894
TCEA3SUPT4H1P63272872
TCEA3SUPT5HO00267868
TCEA3POLR2IP36954834
TCEA3TBPP20226808
TCEA3SUPT6HQ7KZ85806
TCEA3POLR2BP30876802
TCEA3PLAG1Q6DJT9763
TCEA3POLR1HQ9P1U0750
TCEA3POLIQ9UNA4729
TCEA3POLR3KQ9Y2Y1719
TCEA3POLR2AP24928717
TCEA3LEO1Q8WVC0713
TCEA3ELOA2Q8IYF1706
TCEA3ELOAQ14241694

IntAct

8 interactions, top by confidence:

ABTypeScore
TCEA3LEO1psi-mi:“MI:0915”(physical association)0.560
SAV1TCEA3psi-mi:“MI:0915”(physical association)0.370
RPH3ALTCEA3psi-mi:“MI:0915”(physical association)0.370
Mpsi-mi:“MI:0914”(association)0.350
TCEA1TCEA3psi-mi:“MI:0914”(association)0.350
LEO1TCEA3psi-mi:“MI:0915”(physical association)0.000

BioGRID (12): TCEA3 (Two-hybrid), TCEA3 (Protein-RNA), TCEA3 (Affinity Capture-RNA), TCEA3 (Affinity Capture-MS), USP47 (Affinity Capture-Western), TCEA3 (Affinity Capture-Western), TCEA3 (Affinity Capture-MS), TCEA3 (Affinity Capture-MS), TCEA3 (Cross-Linking-MS (XL-MS)), TCEA3 (Cross-Linking-MS (XL-MS)), TCEA3 (Cross-Linking-MS (XL-MS)), TCEA3 (Two-hybrid)

ESM2 similar proteins: A2VE39, B0UYI1, D2HRF1, O46563, O60308, O75764, P10711, P23193, P23881, P54729, Q0P5J9, Q148K0, Q15560, Q29RL9, Q2KI09, Q4KLL0, Q5R8Y3, Q5R952, Q5R981, Q5U2Z5, Q5XGZ8, Q5XIC7, Q5ZM30, Q63799, Q6GQ76, Q7ZYU8, Q803R5, Q84ZC0, Q8BVE3, Q8BW49, Q8N1G2, Q8R2M0, Q8R3N6, Q8VDS4, Q8VI84, Q8WTT2, Q91Y26, Q95LY5, Q96MN5, Q96P16

Diamond homologs: A6ZZW1, O44498, O75764, P10711, P20232, P23193, P36106, P52652, Q29RL9, Q2KI09, Q4KLL0, Q6FJ00, Q6ZMY3, Q9U263, A5PKE4, B0UYI1, F4J4Y5, P23881, Q148K0, Q5XIC7, Q8R2M0, Q96MN5, Q9FHK9, Q14241, Q63187, Q8CB77, O13896, O27369, O29033, P07273, P36958, P49373, Q04307, Q07271, Q2M2S7, Q56254, Q58548, Q5JF34, Q5UQS8, Q980K2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance57
Likely benign1
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2446 predictions. Top by Δscore:

VariantEffectΔscore
1:23387267:CCTTA:Cdonor_loss1.0000
1:23387268:CTTA:Cdonor_loss1.0000
1:23387269:TTAC:Tdonor_loss1.0000
1:23387270:TACCT:Tdonor_loss1.0000
1:23387271:A:ACdonor_gain1.0000
1:23387271:AC:Adonor_gain1.0000
1:23387271:ACCTG:Adonor_loss1.0000
1:23387272:C:CCdonor_gain1.0000
1:23387272:CC:Cdonor_gain1.0000
1:23387272:CCT:Cdonor_gain1.0000
1:23387272:CCTG:Cdonor_gain1.0000
1:23387272:CCTGG:Cdonor_gain1.0000
1:23387416:TTTC:Tacceptor_gain1.0000
1:23397450:T:TAdonor_gain1.0000
1:23397459:T:TAdonor_gain1.0000
1:23417387:GAGT:Gacceptor_gain1.0000
1:23417391:C:CCacceptor_gain1.0000
1:23417391:C:CGacceptor_loss1.0000
1:23417392:T:Gacceptor_loss1.0000
1:23418010:C:CCacceptor_gain1.0000
1:23424559:CCTCA:Cdonor_loss1.0000
1:23424560:CTCA:Cdonor_loss1.0000
1:23424561:TCAC:Tdonor_loss1.0000
1:23424562:CACCG:Cdonor_loss1.0000
1:23424563:A:ACdonor_gain1.0000
1:23424563:ACCGT:Adonor_loss1.0000
1:23424564:C:CCdonor_gain1.0000
1:23424573:T:TAdonor_gain1.0000
1:23381475:C:CCacceptor_gain0.9900
1:23387415:ATTTC:Aacceptor_gain0.9900

AlphaMissense

2297 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
1:23384349:C:AW345C1.000
1:23384349:C:GW345C1.000
1:23384351:A:GW345R1.000
1:23384351:A:TW345R1.000
1:23384362:C:GC341S1.000
1:23384363:A:GC341R1.000
1:23384363:A:TC341S1.000
1:23384370:G:CC338W1.000
1:23384371:C:AC338F1.000
1:23384371:C:GC338S1.000
1:23384371:C:TC338Y1.000
1:23384372:A:GC338R1.000
1:23384372:A:TC338S1.000
1:23384377:A:TV336D1.000
1:23384379:A:CF335L1.000
1:23384379:A:TF335L1.000
1:23384381:A:GF335L1.000
1:23384392:G:TP331H1.000
1:23384398:T:AD329V1.000
1:23384399:C:GD329H1.000
1:23384412:C:AQ324H1.000
1:23384412:C:GQ324H1.000
1:23387273:C:AQ322H1.000
1:23387273:C:GQ322H1.000
1:23387281:A:CY320D1.000
1:23387285:G:CC318W1.000
1:23387301:C:GC313S1.000
1:23387302:A:TC313S1.000
1:23387310:C:GC310S1.000
1:23387311:A:GC310R1.000

dbSNP variants (sampled 300 via entrez): RS1000375672 (1:23403715 G>A), RS1000421758 (1:23391935 A>C), RS1000426431 (1:23407950 T>G), RS1000579563 (1:23403062 C>A), RS1000645599 (1:23422389 G>A), RS1001088626 (1:23389845 G>A), RS1001110197 (1:23397253 A>C), RS1001161798 (1:23415858 A>G), RS1001163610 (1:23413377 C>T), RS1001207 (1:23422655 G>A), RS1001223029 (1:23407002 C>T), RS1001257711 (1:23400470 A>G), RS1001323910 (1:23412956 G>A,T), RS1001375235 (1:23419434 A>T), RS1001479559 (1:23396981 G>A)

Disease associations

OMIM: gene MIM:604128 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

60 associations (top):

StudyTraitp-value
GCST002500_48QT interval1.000000e-14
GCST005171_56QT interval2.000000e-07
GCST005985_1Creatinine levels3.000000e-11
GCST006613_151Triglycerides2.000000e-11
GCST006614_90Total cholesterol levels4.000000e-08
GCST007324_80Adventurousness4.000000e-09
GCST007876_64Estimated glomerular filtration rate8.000000e-15
GCST010204_159Low density lipoprotein cholesterol levels4.000000e-09
GCST010241_81Apolipoprotein A1 levels2.000000e-13
GCST010242_325HDL cholesterol levels2.000000e-13
GCST010796_2023Electrocardiogram morphology (amplitude at temporal datapoints)3.000000e-08
GCST010796_2024Electrocardiogram morphology (amplitude at temporal datapoints)8.000000e-11
GCST010796_2025Electrocardiogram morphology (amplitude at temporal datapoints)4.000000e-10
GCST010796_2076Electrocardiogram morphology (amplitude at temporal datapoints)4.000000e-16
GCST010796_2077Electrocardiogram morphology (amplitude at temporal datapoints)8.000000e-16
GCST010796_2078Electrocardiogram morphology (amplitude at temporal datapoints)1.000000e-15
GCST010796_2079Electrocardiogram morphology (amplitude at temporal datapoints)2.000000e-15
GCST010796_2080Electrocardiogram morphology (amplitude at temporal datapoints)6.000000e-15
GCST010796_2081Electrocardiogram morphology (amplitude at temporal datapoints)5.000000e-14
GCST010796_2082Electrocardiogram morphology (amplitude at temporal datapoints)8.000000e-13
GCST010796_2083Electrocardiogram morphology (amplitude at temporal datapoints)6.000000e-13
GCST010796_2084Electrocardiogram morphology (amplitude at temporal datapoints)7.000000e-13
GCST010796_2085Electrocardiogram morphology (amplitude at temporal datapoints)3.000000e-12
GCST010796_2086Electrocardiogram morphology (amplitude at temporal datapoints)8.000000e-12
GCST010796_2087Electrocardiogram morphology (amplitude at temporal datapoints)2.000000e-11
GCST010796_2088Electrocardiogram morphology (amplitude at temporal datapoints)3.000000e-10
GCST010796_2089Electrocardiogram morphology (amplitude at temporal datapoints)2.000000e-09
GCST010796_2090Electrocardiogram morphology (amplitude at temporal datapoints)2.000000e-09
GCST010796_2091Electrocardiogram morphology (amplitude at temporal datapoints)4.000000e-09
GCST010796_2092Electrocardiogram morphology (amplitude at temporal datapoints)3.000000e-18

EFO canonical traits (10, from GWAS)

EFO IDTrait name
EFO:0004682QT interval
EFO:0004530triglyceride measurement
EFO:0004574total cholesterol measurement
EFO:0008579risk-taking behaviour
EFO:0004611low density lipoprotein cholesterol measurement
EFO:0004614apolipoprotein A 1 measurement
EFO:0004612high density lipoprotein cholesterol measurement
EFO:0004327electrocardiography
EFO:0007991eosinophil percentage of leukocytes
EFO:0007788BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Estradiolaffects cotreatment, increases expression, decreases expression, affects expression4
bisphenol Aaffects expression, increases expression2
(+)-JQ1 compounddecreases expression2
Acetaminophendecreases expression, increases expression2
Arsenicaffects methylation, decreases expression, increases abundance2
Benzo(a)pyreneaffects methylation, decreases expression, decreases methylation2
Tetrachlorodibenzodioxindecreases expression2
Valproic Acidincreases expression, decreases expression2
Cyclosporinedecreases expression2
FR900359affects phosphorylation1
propionaldehydeincreases expression1
pirinixic acidaffects binding, decreases expression, increases activity1
deoxynivalenoldecreases expression1
sodium arsenatedecreases expression, increases abundance1
tris(1,3-dichloro-2-propyl)phosphatedecreases expression1
perfluorooctanoic aciddecreases expression1
nickel sulfatedecreases expression1
butylparabenincreases expression1
S-(1,2-dichlorovinyl)cysteineaffects cotreatment, decreases expression1
perfluorooctane sulfonic aciddecreases expression1
perfluoro-n-nonanoic aciddecreases expression1
entinostatincreases expression1
K 7174decreases expression1
perfluorohexanesulfonic aciddecreases expression1
nutlin 3affects cotreatment, increases expression1
ICG 001increases expression1
abrineincreases expression1
jinfukangaffects cotreatment, increases expression1
NSC 689534affects binding, decreases expression1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acidincreases expression1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

CellosaurusNameCategorySex
CVCL_A7B0SEES3-1V human TCEA3, clone1Embryonic stem cellMale
CVCL_A7B1SEES3-1V human TCEA3, clone2Embryonic stem cellMale
CVCL_A7B2SEES3-1V human TCEA3, clone3Embryonic stem cellMale

Clinical trials (associated diseases)

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

  • Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): type 2 diabetes mellitus