GTF3C6

Summary

GTF3C6 (general transcription factor IIIC subunit 6, HGNC:20872) is a protein-coding gene on chromosome 6q21, encoding General transcription factor 3C polypeptide 6 (Q969F1). Involved in RNA polymerase III-mediated transcription. It is a selective cancer dependency (DepMap: 15.9% of cell lines).

RNA polymerases are unable to initiate RNA synthesis in the absence of additional proteins called general transcription factors (GTFs). GTFs assemble in a complex on the DNA promoter and recruit the RNA polymerase. GTF3C family proteins (e.g., GTF3C1, MIM 603246) are essential for RNA polymerase III to make a number of small nuclear and cytoplasmic RNAs, including 5S RNA (MIM 180420), tRNA, and adenovirus-associated (VA) RNA of both cellular and viral origin.

Source: NCBI Gene 112495 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 42 total
• Cancer dependency (DepMap): dependent in 15.9% of screened cell lines
• MANE Select transcript: NM_138408

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20872
Approved symbol	GTF3C6
Name	general transcription factor IIIC subunit 6
Location	6q21
Locus type	gene with protein product
Status	Approved
Aliases	bA397G5.3, TFIIIC35
Ensembl gene	ENSG00000155115
Ensembl biotype	protein_coding
OMIM	611784
Entrez	112495

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 20 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000329970, ENST00000480191, ENST00000883260, ENST00000883261, ENST00000883262, ENST00000883263, ENST00000883264, ENST00000883265, ENST00000935759, ENST00000935760, ENST00000935761, ENST00000935762, ENST00000935763, ENST00000935764, ENST00000935765, ENST00000935766, ENST00000935767, ENST00000935768, ENST00000935769, ENST00000935770, ENST00000935771

RefSeq mRNA: 1 — MANE Select: NM_138408 NM_138408

CCDS: CCDS5087

Canonical transcript exons

ENST00000329970 — 6 exons

Exon	Start	End
ENSE00001448169	110958706	110958826
ENSE00003464079	110959172	110959252
ENSE00003491286	110960572	110960616
ENSE00003614732	110962392	110962505
ENSE00003635999	110967510	110967872
ENSE00003660700	110960414	110960477

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 59.0295 / max 1373.9073, expressed in 1820 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
69265	35.5581	1815
69266	21.5890	1805
69264	1.1843	773
69267	0.4180	149
69268	0.2800	93

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	98.13	gold quality
muscle of leg	UBERON:0001383	97.93	gold quality
heart left ventricle	UBERON:0002084	97.64	gold quality
endometrium	UBERON:0001295	97.57	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.56	gold quality
ganglionic eminence	UBERON:0004023	97.54	gold quality
monocyte	CL:0000576	97.36	gold quality
right testis	UBERON:0004534	97.35	gold quality
substantia nigra	UBERON:0002038	97.27	gold quality
amygdala	UBERON:0001876	97.19	gold quality
leukocyte	CL:0000738	97.14	gold quality
left testis	UBERON:0004533	97.14	gold quality
putamen	UBERON:0001874	97.12	gold quality
heart	UBERON:0000948	97.11	gold quality
apex of heart	UBERON:0002098	97.11	gold quality
caudate nucleus	UBERON:0001873	97.04	gold quality
ventricular zone	UBERON:0003053	97.04	gold quality
right adrenal gland	UBERON:0001233	96.97	gold quality
rectum	UBERON:0001052	96.96	gold quality
nucleus accumbens	UBERON:0001882	96.93	gold quality
right atrium auricular region	UBERON:0006631	96.92	gold quality
temporal lobe	UBERON:0001871	96.91	gold quality
right adrenal gland cortex	UBERON:0035827	96.89	gold quality
hypothalamus	UBERON:0001898	96.83	gold quality
left adrenal gland	UBERON:0001234	96.70	gold quality
prostate gland	UBERON:0002367	96.69	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.69	gold quality
gall bladder	UBERON:0002110	96.65	gold quality
testis	UBERON:0000473	96.56	gold quality
mucosa of transverse colon	UBERON:0004991	96.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-9	yes	8.60
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 15.9% of screened cell lines.

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gtf3c6	ENSDARG00000043301
mus_musculus	Gtf3c6	ENSMUSG00000019837
rattus_norvegicus	Gtf3c6	ENSRNOG00000000586
drosophila_melanogaster	CG42516	FBGN0260390

Protein

Protein identifiers

General transcription factor 3C polypeptide 6 — Q969F1 (reviewed: Q969F1)

Alternative names: Transcription factor IIIC 35 kDa subunit, Transcription factor IIIC subunit 6

All UniProt accessions (1): Q969F1

UniProt curated annotations — full annotation on UniProt →

Function. Involved in RNA polymerase III-mediated transcription. Integral, tightly associated component of the DNA-binding TFIIIC2 subcomplex that directly binds tRNA and virus-associated RNA promoters.

Subunit / interactions. Part of the TFIIIC subcomplex TFIIIC2, consisting of six subunits, GTF3C1, GTF3C2, GTF3C3, GTF3C4, GTF3C5 and GTF3C6. Interacts with GTF3C4 and GTF3C5.

Subcellular location. Nucleus.

Similarity. Belongs to the TFIIIC subunit 6 family.

RefSeq proteins (1): NP_612417* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019481	TFIIIC_triple_barrel	Domain
IPR042771	GTF3C6-like	Family

Pfam: PF10419

UniProt features (7 total): region of interest 2, modified residue 2, initiator methionine 1, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8CLK	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q969F1-F1	66.32	0.28

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 (2): 2, 9

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-749476	RNA Polymerase III Abortive And Retractive Initiation
R-HSA-76061	RNA Polymerase III Transcription Initiation From Type 1 Promoter
R-HSA-76066	RNA Polymerase III Transcription Initiation From Type 2 Promoter
R-HSA-74158	RNA Polymerase III Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-76046	RNA Polymerase III Transcription Initiation

MSigDB gene sets: 105 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_TRNA_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, GOBP_RRNA_TRANSCRIPTION, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, ACEVEDO_LIVER_CANCER_UP, GOCC_NUCLEAR_BODY, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX, MARSON_BOUND_BY_FOXP3_STIMULATED, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_III_PROMOTER

GO Biological Process (3): transcription by RNA polymerase III (GO:0006383), 5S class rRNA transcription by RNA polymerase III (GO:0042791), tRNA transcription by RNA polymerase III (GO:0042797)

GO Molecular Function (3): RNA polymerase III general transcription initiation factor activity (GO:0000995), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (4): transcription factor TFIIIC complex (GO:0000127), nucleoplasm (GO:0005654), nuclear body (GO:0016604), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
RNA Polymerase III Transcription	2
RNA Polymerase III Transcription Initiation	2
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase III	3
DNA-templated transcription	1
rRNA transcription	1
tRNA transcription	1
general transcription initiation factor activity	1
nucleic acid binding	1
binding	1
RNA polymerase III transcription regulator complex	1
nuclear lumen	1
cellular anatomical structure	1
nucleoplasm	1
intracellular membraneless organelle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

454 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GTF3C6	GTF3C5	Q9Y5Q8	973
GTF3C6	GTF3C4	Q9UKN8	947
GTF3C6	GTF3C1	Q12789	854
GTF3C6	GTF3C3	Q9Y5Q9	647
GTF3C6	GUCY2C	P25092	635
GTF3C6	TCF7	P36402	586
GTF3C6	GOLGA6L1	Q8N7Z2	573
GTF3C6	MT-CYB	P00156	568
GTF3C6	BASP1	P80723	546
GTF3C6	GOLGA8O	A6NCC3	542
GTF3C6	GOLGA8Q	H3BV12	530
GTF3C6	GOLGA8N	F8WBI6	518
GTF3C6	SERBP1	Q8NC51	506
GTF3C6	RPF2	Q9H7B2	488
GTF3C6	GTF3C2	Q8WUA4	448

IntAct

20 interactions, top by confidence:

A	B	Type	Score
GTF3C1	GTF3C2	psi-mi:“MI:0914”(association)	0.670
GTF3C6	SPATC1L	psi-mi:“MI:0915”(physical association)	0.560
ZNF460	ZNF324	psi-mi:“MI:0914”(association)	0.530
GTF3C6	GTF3C5	psi-mi:“MI:0915”(physical association)	0.500
GTF3C6	GTF3C4	psi-mi:“MI:0915”(physical association)	0.500
PCNA	GTF3C6	psi-mi:“MI:0915”(physical association)	0.370
CD44	TCAF2	psi-mi:“MI:0914”(association)	0.350
BIN3	NME2P1	psi-mi:“MI:0914”(association)	0.350
GTF3C6	GTF3C1	psi-mi:“MI:0914”(association)	0.350
ZCCHC10	C1orf226	psi-mi:“MI:0914”(association)	0.350
ZNF460	ZNF320	psi-mi:“MI:0914”(association)	0.350
SPANXN2	ZNF320	psi-mi:“MI:0914”(association)	0.350
RPL15	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
ZNF785	CASK	psi-mi:“MI:0914”(association)	0.350
P/V	ESYT2	psi-mi:“MI:0914”(association)	0.350
	TTC8	psi-mi:“MI:0914”(association)	0.350
SPATC1L	GTF3C6	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (38): GTF3C6 (Affinity Capture-RNA), GTF3C6 (Affinity Capture-MS), GTF3C6 (Affinity Capture-MS), GTF3C6 (Affinity Capture-MS), GTF3C6 (Affinity Capture-RNA), GTF3C6 (Affinity Capture-MS), GTF3C6 (Affinity Capture-MS), SPATC1L (Two-hybrid), GTF3C6 (Affinity Capture-MS), GTF3C6 (Affinity Capture-MS), GTF3C6 (Affinity Capture-RNA), GTF3C6 (Affinity Capture-MS), GTF3C6 (Affinity Capture-MS), GTF3C6 (Affinity Capture-MS), GTF3C6 (Affinity Capture-MS)

ESM2 similar proteins: A0P8Z5, A5A6N3, A6QPH9, D4A7U2, E2IUK4, E2RSQ2, G3HKI1, P28715, P35689, P97432, Q08DY8, Q13426, Q14159, Q14596, Q2HJ93, Q2KIY6, Q3U2E2, Q3UKU1, Q3ZK22, Q4R3D6, Q4R8B9, Q4R914, Q501R9, Q5F3F2, Q5RC94, Q5RD40, Q5RFG8, Q5RFL7, Q5TAB7, Q5VVJ2, Q5XI52, Q68FE8, Q69Z66, Q6N043, Q6P2K3, Q76CY8, Q7Z6J8, Q8IWR0, Q8N7W2, Q8NA31

Diamond homologs: Q969F1, Q9D8P7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GTF3C6	“form complex”	TFIIIC	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

640 predictions. Top by Δscore:

Variant	Effect	Δscore
6:110958818:G:GT	donor_gain	1.0000
6:110958824:G:GT	donor_gain	1.0000
6:110958827:GTA:G	donor_gain	1.0000
6:110958897:G:GT	donor_gain	1.0000
6:110960408:TTGTA:T	acceptor_loss	1.0000
6:110960409:TGTA:T	acceptor_loss	1.0000
6:110960410:GTAG:G	acceptor_loss	1.0000
6:110960411:TA:T	acceptor_loss	1.0000
6:110960412:A:AT	acceptor_loss	1.0000
6:110960412:AG:A	acceptor_gain	1.0000
6:110960413:GG:G	acceptor_gain	1.0000
6:110960413:GGGC:G	acceptor_gain	1.0000
6:110960475:AAGG:A	donor_loss	1.0000
6:110960476:AGGTA:A	donor_loss	1.0000
6:110960477:GG:G	donor_loss	1.0000
6:110960478:GTAGG:G	donor_loss	1.0000
6:110960479:T:A	donor_loss	1.0000
6:110960570:A:AG	acceptor_gain	1.0000
6:110960571:G:GA	acceptor_gain	1.0000
6:110960571:GA:G	acceptor_gain	1.0000
6:110960617:G:GC	donor_loss	1.0000
6:110960618:TAAG:T	donor_loss	1.0000
6:110962384:T:A	acceptor_gain	1.0000
6:110962387:TCCA:T	acceptor_loss	1.0000
6:110962388:CCA:C	acceptor_loss	1.0000
6:110962390:A:AG	acceptor_gain	1.0000
6:110962390:AGC:A	acceptor_loss	1.0000
6:110962390:AGCT:A	acceptor_gain	1.0000
6:110962391:G:GG	acceptor_gain	1.0000
6:110962391:GC:G	acceptor_gain	1.0000

AlphaMissense

1429 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:110960460:T:C	F62S	0.998
6:110960466:G:A	G64E	0.998
6:110960590:T:A	V74D	0.998
6:110960432:C:T	P53S	0.997
6:110960433:C:A	P53H	0.997
6:110960459:T:C	F62L	0.997
6:110960461:T:A	F62L	0.997
6:110960461:T:G	F62L	0.997
6:110959194:T:C	L27S	0.996
6:110960439:T:C	L55P	0.996
6:110960465:G:T	G64W	0.996
6:110960580:G:A	G71R	0.996
6:110960580:G:C	G71R	0.996
6:110960581:G:A	G71E	0.996
6:110960596:T:C	F76S	0.996
6:110960433:C:G	P53R	0.995
6:110960465:G:A	G64R	0.995
6:110960465:G:C	G64R	0.995
6:110962427:T:G	Y95D	0.995
6:110962452:T:C	L103P	0.995
6:110960460:T:G	F62C	0.994
6:110960580:G:T	G71W	0.994
6:110962452:T:A	L103H	0.994
6:110960442:A:C	Q56P	0.993
6:110960457:T:A	V61D	0.993
6:110960462:G:C	A63P	0.992
6:110960466:G:T	G64V	0.992
6:110962428:A:C	Y95S	0.992
6:110962458:T:A	M105K	0.992
6:110962458:T:G	M105R	0.992

dbSNP variants (sampled 300 via entrez): RS1000077608 (6:110961830 C>T), RS1000285598 (6:110967290 C>T), RS1000428351 (6:110962623 C>G), RS1000635946 (6:110967723 G>A,C,T), RS1000911119 (6:110957307 G>A), RS1001026355 (6:110963125 C>G,T), RS1001259737 (6:110956960 G>A,T), RS1001572963 (6:110962457 A>C,G), RS1001625484 (6:110962128 TC>T), RS1001683053 (6:110968336 C>T), RS1001768669 (6:110959610 G>C), RS1001791132 (6:110967851 A>ACT), RS1002137215 (6:110968197 T>A,C), RS1002158222 (6:110958313 A>C,T), RS1002575824 (6:110963539 G>C)

Disease associations

OMIM: gene MIM:611784 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_332	Refractive error	3.000000e-10

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
(+)-JQ1 compound	decreases expression	6
Valproic Acid	decreases expression	3
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Acetaminophen	decreases expression	2
dicrotophos	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	increases abundance, decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases expression	1
Camptothecin	increases expression	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects expression	1
Lead	affects expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1
Aflatoxin B1	increases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	increases abundance, decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2YF	Abcam HEK293T GTF3C6 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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