GTF3C1

Summary

GTF3C1 (general transcription factor IIIC subunit 1, HGNC:4664) is a protein-coding gene on chromosome 16p12.1, encoding General transcription factor 3C polypeptide 1 (Q12789). Required for RNA polymerase III-mediated transcription. It is a selective cancer dependency (DepMap: 85.4% of cell lines).

Enables RNA polymerase III general transcription initiation factor activity. Predicted to be involved in 5S class rRNA transcription by RNA polymerase III and transcription initiation at RNA polymerase III promoter. Located in nucleolus and nucleoplasm. Part of transcription factor TFIIIC complex.

Source: NCBI Gene 2975 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 331 total — 2 likely-pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 85.4% of screened cell lines
• MANE Select transcript: NM_001520

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4664
Approved symbol	GTF3C1
Name	general transcription factor IIIC subunit 1
Location	16p12.1
Locus type	gene with protein product
Status	Approved
Aliases	TFIIIC220
Ensembl gene	ENSG00000077235
Ensembl biotype	protein_coding
OMIM	603246
Entrez	2975

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 14 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000356183, ENST00000561623, ENST00000562609, ENST00000564664, ENST00000564747, ENST00000566779, ENST00000567806, ENST00000567843, ENST00000568569, ENST00000569394, ENST00000569653, ENST00000570129, ENST00000571886, ENST00000864208, ENST00000917815, ENST00000917816, ENST00000917817, ENST00000917818, ENST00000917819, ENST00000917820, ENST00000917821, ENST00000944843, ENST00000944844

RefSeq mRNA: 2 — MANE Select: NM_001520 NM_001286242, NM_001520

CCDS: CCDS32414, CCDS66988

Canonical transcript exons

ENST00000356183 — 37 exons

Exon	Start	End
ENSE00000681769	27481079	27481191
ENSE00000681785	27485997	27486154
ENSE00000681792	27488227	27488415
ENSE00000681797	27488554	27488635
ENSE00000681802	27489043	27489178
ENSE00000681807	27489602	27489743
ENSE00000681810	27492338	27492515
ENSE00000681813	27492617	27492713
ENSE00000681819	27493199	27493296
ENSE00000681826	27494763	27494908
ENSE00000681832	27495211	27495492
ENSE00000681864	27501191	27501344
ENSE00000681870	27502859	27502995
ENSE00000681875	27505899	27506116
ENSE00000681880	27506847	27507156
ENSE00000681895	27508540	27508655
ENSE00000681905	27511749	27511901
ENSE00000681928	27528598	27528721
ENSE00000681940	27533291	27533387
ENSE00000830167	27497637	27497821
ENSE00000893380	27545314	27545523
ENSE00000893384	27537784	27537927
ENSE00001404367	27538180	27538356
ENSE00001504548	27498630	27498733
ENSE00001646319	27463541	27463592
ENSE00001741439	27460613	27461562
ENSE00001743747	27465260	27465540
ENSE00001762531	27464320	27464836
ENSE00002592016	27549670	27549913
ENSE00002699460	27469291	27469550
ENSE00003489091	27478469	27478531
ENSE00003503277	27484211	27484353
ENSE00003544772	27462294	27462486
ENSE00003596400	27470108	27470395
ENSE00003625077	27476451	27476544
ENSE00003649703	27483044	27483125
ENSE00003693243	27471748	27471920

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 98.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.3872 / max 335.0840, expressed in 1819 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156849	47.8068	1819
156847	0.5168	49
156846	0.0635	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	98.36	gold quality
adenohypophysis	UBERON:0002196	97.56	gold quality
pituitary gland	UBERON:0000007	97.15	gold quality
skin of leg	UBERON:0001511	97.00	gold quality
skin of abdomen	UBERON:0001416	96.98	gold quality
sural nerve	UBERON:0015488	96.96	gold quality
right lobe of thyroid gland	UBERON:0001119	96.57	gold quality
esophagus mucosa	UBERON:0002469	96.39	gold quality
ventricular zone	UBERON:0003053	96.36	gold quality
left lobe of thyroid gland	UBERON:0001120	96.33	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.29	gold quality
apex of heart	UBERON:0002098	96.06	gold quality
thyroid gland	UBERON:0002046	95.89	gold quality
cerebellar hemisphere	UBERON:0002245	95.83	gold quality
cerebellar cortex	UBERON:0002129	95.78	gold quality
stromal cell of endometrium	CL:0002255	95.76	gold quality
right uterine tube	UBERON:0001302	95.75	gold quality
ganglionic eminence	UBERON:0004023	95.47	gold quality
ectocervix	UBERON:0012249	95.07	gold quality
zone of skin	UBERON:0000014	94.93	gold quality
esophagus	UBERON:0001043	94.82	gold quality
right frontal lobe	UBERON:0002810	94.80	gold quality
cerebellum	UBERON:0002037	94.64	gold quality
body of uterus	UBERON:0009853	94.51	gold quality
tibial nerve	UBERON:0001323	94.22	gold quality
gastrocnemius	UBERON:0001388	94.19	gold quality
nucleus accumbens	UBERON:0001882	94.12	gold quality
endocervix	UBERON:0000458	94.10	gold quality
granulocyte	CL:0000094	93.94	gold quality
right atrium auricular region	UBERON:0006631	93.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.19

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFIC

miRNA regulators (miRDB)

37 targeting GTF3C1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-2276-3P	98.76	67.75	1384
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-3929	98.32	65.58	1026
HSA-MIR-6728-5P	97.79	66.33	891
HSA-MIR-6747-3P	97.73	64.84	1596

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 85.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 8)

• The partial purification of pol III transcription factors from PE and EC cells revealed that TFIIIC2 activity could be purified from both cell types, whereas TFIIIC1 activity was dramatically reduced in extracts from PE cells. (PMID:11741993)
• TFIIIC is composed of six subunits, five of which are conserved in humans. We report the identification, molecular cloning, and characterization of the sixth subunit of human TFIIIC, TFIIIC35 (PMID:17409385)
• Results identify TFIIIC as a recruitment factor for p300 and thus may have important implications for the emerging concept that tRNA genes or TFIIIC binding sites act as chromatin barriers to prohibit spreading of silenced heterochromatin domains. (PMID:18644873)
• Maf1, a repressor that binds and inhibits pol III, is phosphorylated in a mTOR-dependent manner both in vitro and in vivo at serine 75, a site that contributes to its function as a transcriptional inhibitor. (PMID:20543138)
• These findings reveal a novel and essential regulatory function of both SINEs and TFIIIC in mediating gene relocation and transcription (PMID:23966877)
• TFIIIC as a Potential Epigenetic Modulator of Histone Acetylation in Human Stem Cells. (PMID:36835038)
• The Conserved Chromatin Remodeler SMARCAD1 Interacts with TFIIIC and Architectural Proteins in Human and Mouse. (PMID:37761933)
• The Largest Subunit of Human TFIIIC Complex, TFIIIC220, a Lysine Acetyltransferase Targets Histone H3K18. (PMID:37963603)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000099619
danio_rerio		ENSDARG00000102091
mus_musculus	Gtf3c1	ENSMUSG00000032777
rattus_norvegicus	Gtf3c1	ENSRNOG00000016218
drosophila_melanogaster	CG7099	FBGN0032517
caenorhabditis_elegans		WBGENE00021423

Protein

Protein identifiers

General transcription factor 3C polypeptide 1 — Q12789 (reviewed: Q12789)

Alternative names: TF3C-alpha, TFIIIC box B-binding subunit, Transcription factor IIIC 220 kDa subunit, Transcription factor IIIC subunit alpha

All UniProt accessions (5): Q12789, H3BRD0, H3BU37, H3BU55, I3L1Z3

UniProt curated annotations — full annotation on UniProt →

Function. Required for RNA polymerase III-mediated transcription. Component of TFIIIC that initiates transcription complex assembly on tRNA and is required for transcription of 5S rRNA and other stable nuclear and cytoplasmic RNAs. Binds to the box B promoter element.

Subunit / interactions. Part of the TFIIIC subcomplex TFIIIC2, consisting of six subunits, GTF3C1, GTF3C2, GTF3C3, GTF3C4, GTF3C5 and GTF3C6. Interacts with IGHMBP2. Interacts with MAF1.

Subcellular location. Nucleus.

Similarity. Belongs to the TFIIIC subunit 1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q12789-2	1	yes
Q12789-3	2

RefSeq proteins (2): NP_001273171, NP_001511* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007309	TFIIIC_Bblock-bd	Domain
IPR035625	Tfc3-like_eWH	Domain
IPR044210	Tfc3-like	Family
IPR056428	WH_GTF3C1	Domain
IPR056467	eWH_GTF3C1	Domain

Pfam: PF04182, PF23704, PF24101

UniProt features (96 total): helix 25, strand 16, modified residue 14, compositionally biased region 11, sequence conflict 9, region of interest 8, cross-link 4, turn 4, sequence variant 3, chain 1, splice variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8CLI	ELECTRON MICROSCOPY	3.2
8CLJ	ELECTRON MICROSCOPY	3.2
8CLL	ELECTRON MICROSCOPY	3.4
8CLK	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12789-F1	65.68	0.05

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 (18): 667, 739, 1062, 1068, 1253, 1611, 1632, 1653, 1856, 1865, 1868, 1896, 1911, 1969, 529, 770, 833, 1142

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: 136 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, ATF_B, GRUETZMANN_PANCREATIC_CANCER_DN, TGCGCANK_UNKNOWN, YANG_BREAST_CANCER_ESR1_LASER_UP, GOBP_TRNA_METABOLIC_PROCESS, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_RRNA_TRANSCRIPTION, EFC_Q6, CREB_Q4, WANG_ESOPHAGUS_CANCER_VS_NORMAL_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, KLEIN_PRIMARY_EFFUSION_LYMPHOMA_UP, MARTIN_NFKB_TARGETS_UP

GO Biological Process (6): transcription by RNA polymerase III (GO:0006383), transcription initiation at RNA polymerase III promoter (GO:0006384), rRNA transcription (GO:0009303), tRNA transcription (GO:0009304), 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 (6): transcription factor TFIIIC complex (GO:0000127), nucleoplasm (GO:0005654), nucleolus (GO:0005730), membrane (GO:0016020), ribonucleoprotein complex (GO:1990904), 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	4
DNA-templated transcription	3
nuclear lumen	2
cellular anatomical structure	2
DNA-templated transcription initiation	1
rRNA metabolic process	1
tRNA metabolic process	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
intracellular membraneless organelle	1
protein-containing complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1544 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GTF3C1	BDP1	A6H8Y1	998
GTF3C1	GTF3A	Q92664	995
GTF3C1	BRF1	Q92994	981
GTF3C1	GTF3C2	Q8WUA4	969
GTF3C1	GTF3C4	Q9UKN8	960
GTF3C1	GTF3C5	Q9Y5Q8	955
GTF3C1	GTF3C3	Q9Y5Q9	916
GTF3C1	BBOX1	O75936	882
GTF3C1	GTF3C6	Q969F1	854
GTF3C1	TBP	P20226	827
GTF3C1	ABT1	Q9ULW3	820
GTF3C1	IGHMBP2	P38935	752
GTF3C1	POLI	Q9UNA4	691
GTF3C1	ATP2A3	Q93084	689
GTF3C1	PRDM5	Q9NQX1	625

IntAct

204 interactions, top by confidence:

A	B	Type	Score
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
FBL	NOP56	psi-mi:“MI:0914”(association)	0.800
GTF3C2	GTF3C1	psi-mi:“MI:0915”(physical association)	0.670
GTF3C1	GTF3C2	psi-mi:“MI:0914”(association)	0.670
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
SDC2	PDPK1	psi-mi:“MI:0914”(association)	0.640
GTF3C3	POLR3D	psi-mi:“MI:0914”(association)	0.640
RBM34	RRP8	psi-mi:“MI:0914”(association)	0.640
ZNF764	ZNF316	psi-mi:“MI:0914”(association)	0.640
GTF3C1	MAGEA4	psi-mi:“MI:0915”(physical association)	0.560
GTF3C1	AGTRAP	psi-mi:“MI:0915”(physical association)	0.560
CMTM5	GTF3C1	psi-mi:“MI:0915”(physical association)	0.560
MAGEA4	GTF3C1	psi-mi:“MI:0915”(physical association)	0.560
AGTRAP	GTF3C1	psi-mi:“MI:0915”(physical association)	0.560
GTF3C1	CMTM5	psi-mi:“MI:0915”(physical association)	0.560
PLK1	C1orf226	psi-mi:“MI:0914”(association)	0.560
ZNF764	IPO8	psi-mi:“MI:0914”(association)	0.530
ZNF764	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
FBL	ZNF316	psi-mi:“MI:0914”(association)	0.530
NHLH2	AP3B1	psi-mi:“MI:0914”(association)	0.530
CASQ2	PES1	psi-mi:“MI:0914”(association)	0.530
GTF3C2	C1QBP	psi-mi:“MI:0914”(association)	0.530
PTGES3	AIP	psi-mi:“MI:0914”(association)	0.530

BioGRID (326): MAGEA4 (Two-hybrid), AGTRAP (Two-hybrid), CMTM5 (Two-hybrid), GTF3C1 (Affinity Capture-MS), GTF3C1 (Affinity Capture-MS), GTF3C1 (Affinity Capture-MS), GTF3C1 (Affinity Capture-MS), GTF3C1 (Affinity Capture-MS), MTOR (Affinity Capture-Western), RPTOR (Affinity Capture-Western), GTF3C1 (Affinity Capture-Western), GTF3C1 (Affinity Capture-Western), GTF3C1 (Affinity Capture-MS), GTF3C1 (Affinity Capture-MS), GTF3C1 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8VHF7, A0JM23, A2QRA0, A4IIA7, A4IIV4, A6NFN9, A6NHR9, A7MBF6, F4IG73, F4JSE7, O17482, O95876, P12540, P21784, P34089, P38899, P55895, P56696, Q08AW4, Q0D2D7, Q12789, Q13829, Q28DC9, Q2WGJ8, Q3E7Y5, Q3UUE9, Q4R907, Q4VXA5, Q5BK83, Q5EA90, Q5F476, Q5HZS2, Q5M9F0, Q5RAX4, Q5RBH4, Q5RD21, Q6AYL6, Q6DGA7, Q6PIY5, Q70XZ2

Diamond homologs: Q12789, Q63505, Q8K284

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GTF3C1	“form complex”	TFIIIC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 248 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
RNA Polymerase III Transcription Initiation From Type 2 Promoter	7	18.2×	1e-05
RNA Polymerase III Transcription Initiation From Type 1 Promoter	7	17.5×	1e-05
RNA Polymerase III Transcription Initiation	7	14.4×	4e-05
RNA Polymerase III Transcription	7	14.0×	4e-05
RNA Polymerase III Abortive And Retractive Initiation	8	13.7×	1e-05
Syndecan interactions	5	13.0×	1e-03
Influenza Viral RNA Transcription and Replication	6	7.9×	3e-03
Formation of the ternary complex, and subsequently, the 43S complex	6	7.9×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	5	17.8×	1e-03
negative regulation of double-strand break repair via homologous recombination	5	14.5×	3e-03
ribosomal large subunit biogenesis	6	12.4×	1e-03
cytoplasmic translation	10	8.6×	2e-04
ribosomal small subunit biogenesis	8	8.5×	1e-03
rRNA processing	9	5.9×	3e-03
mRNA splicing, via spliceosome	12	5.1×	1e-03
RNA splicing	12	4.9×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	244
Likely benign	26
Benign	9

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
402157	NM_001520.4(GTF3C1):c.4096G>A (p.Glu1366Lys)	Likely pathogenic
916561	NM_001520.4(GTF3C1):c.6040C>A (p.Pro2014Thr)	Likely pathogenic

SpliceAI

5406 predictions. Top by Δscore:

Variant	Effect	Δscore
16:27461560:GCCC:G	acceptor_loss	1.0000
16:27461561:CC:C	acceptor_gain	1.0000
16:27461562:CC:C	acceptor_gain	1.0000
16:27461563:C:CC	acceptor_gain	1.0000
16:27461563:CTGG:C	acceptor_loss	1.0000
16:27462331:C:CA	donor_gain	1.0000
16:27462483:GTCC:G	acceptor_gain	1.0000
16:27462484:TCC:T	acceptor_gain	1.0000
16:27462484:TCCC:T	acceptor_loss	1.0000
16:27462485:CC:C	acceptor_gain	1.0000
16:27462485:CCC:C	acceptor_gain	1.0000
16:27462486:CC:C	acceptor_gain	1.0000
16:27462487:C:CC	acceptor_gain	1.0000
16:27462487:CTG:C	acceptor_loss	1.0000
16:27462488:T:A	acceptor_loss	1.0000
16:27463536:CCCA:C	donor_loss	1.0000
16:27463537:CCAC:C	donor_loss	1.0000
16:27463538:CA:C	donor_loss	1.0000
16:27463539:A:C	donor_loss	1.0000
16:27463540:C:CA	donor_loss	1.0000
16:27463591:CC:C	acceptor_gain	1.0000
16:27463592:CC:C	acceptor_gain	1.0000
16:27463593:C:CC	acceptor_gain	1.0000
16:27465536:AGCGG:A	acceptor_gain	1.0000
16:27465537:GCGG:G	acceptor_gain	1.0000
16:27465538:CGG:C	acceptor_gain	1.0000
16:27465538:CGGC:C	acceptor_gain	1.0000
16:27465539:GG:G	acceptor_gain	1.0000
16:27465540:GCTG:G	acceptor_loss	1.0000
16:27465541:C:CC	acceptor_gain	1.0000

AlphaMissense

13895 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:27498726:A:G	L690P	1.000
16:27501255:A:G	L666P	1.000
16:27502892:A:T	V625D	1.000
16:27502896:C:G	A624P	1.000
16:27502907:A:G	L620P	1.000
16:27502916:C:G	R617P	1.000
16:27502917:G:T	R617S	1.000
16:27507144:C:G	D419H	1.000
16:27508634:C:T	G383E	1.000
16:27508635:C:G	G383R	1.000
16:27508635:C:T	G383R	1.000
16:27537811:A:G	L242P	1.000
16:27537814:A:G	L241P	1.000
16:27538246:A:G	L181P	1.000
16:27462452:A:G	W1987R	0.999
16:27462452:A:T	W1987R	0.999
16:27484279:T:A	K1311N	0.999
16:27484279:T:G	K1311N	0.999
16:27484280:T:A	K1311I	0.999
16:27486062:A:G	W1265R	0.999
16:27486062:A:T	W1265R	0.999
16:27489081:A:G	W1131R	0.999
16:27489081:A:T	W1131R	0.999
16:27501216:A:T	V679D	0.999
16:27501318:T:A	E645V	0.999
16:27502904:A:C	I621S	0.999
16:27502904:A:T	I621N	0.999
16:27502922:A:G	L615P	0.999
16:27507116:T:G	Y428S	0.999
16:27507117:A:C	Y428D	0.999

dbSNP variants (sampled 300 via entrez): RS1000080215 (16:27510167 C>T), RS1000119041 (16:27479626 G>A), RS1000120306 (16:27476369 G>A,C), RS1000153841 (16:27493589 A>G), RS1000162721 (16:27527859 C>G,T), RS1000217940 (16:27488148 T>A), RS1000229924 (16:27532659 C>G,T), RS1000242771 (16:27538845 G>A), RS1000244998 (16:27543605 C>A), RS1000345236 (16:27538546 A>G), RS1000354606 (16:27514992 G>A), RS1000380404 (16:27499386 G>A), RS1000419975 (16:27482120 G>A), RS1000446649 (16:27515207 G>A), RS1000458928 (16:27543946 G>A)

Disease associations

OMIM: gene MIM:603246 | disease phenotypes: MIM:189960

GenCC curated gene-disease

Mondo (1): esophageal atresia/tracheoesophageal fistula (MONDO:0008586)

Orphanet (1): Esophageal atresia (Orphanet:1199)

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST009798_29	Asthma	3.000000e-08
GCST009798_58	Asthma	3.000000e-09
GCST009798_64	Asthma	4.000000e-17
GCST90002389_307	Lymphocyte percentage of white cells	1.000000e-14
GCST90002396_582	Mean reticulocyte volume	2.000000e-12
GCST90002397_234	Mean spheric corpuscular volume	7.000000e-16
GCST90002398_295	Neutrophil count	6.000000e-12
GCST90002399_263	Neutrophil percentage of white cells	9.000000e-10
GCST90002403_670	Red blood cell count	3.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0010701	mean reticulocyte volume
EFO:0004833	neutrophil count
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004305	erythrocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C531835	Esophageal atresia with or without tracheoesophageal fistula (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725071 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.16	IC50	70	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178752: Inhibition of GTF3C1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.0700	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation, decreases reaction, increases abundance	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
ginger extract	decreases expression, decreases reaction, increases abundance	1
dicrotophos	increases expression	1
geraniol	increases expression	1
methylselenic acid	decreases expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
trichostatin A	affects expression	1
perfluorooctanoic acid	decreases expression	1
coumarin	decreases phosphorylation	1
beta-methylcholine	affects expression	1
ICG 001	decreases expression	1
(+)-JQ1 compound	increases 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
Fulvestrant	increases methylation	1
Benzo(a)pyrene	increases mutagenesis	1
Caffeine	affects phosphorylation	1
Cyclophosphamide	affects cotreatment, affects expression	1
Diazinon	increases methylation	1
Doxorubicin	affects cotreatment, affects expression	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Oils, Volatile	decreases expression, decreases reaction, increases abundance	1
Ribonucleotides	affects binding	1
Selenium	increases expression	1
Tobacco Smoke Pollution	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Gold Compounds	increases expression	1
Palmitic Acid	increases phosphorylation	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697482	Binding	Inhibition of GTF3C1 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03792360	PHASE1	WITHDRAWN	Adipose Derived SVF for Aero-digestive & Enterocutaneous Fistulae
NCT02033772	Not specified	COMPLETED	Prospective Data Collection of Patients < 6 Months of Age Undergoing Thoracoscopic Surgery
NCT02364843	Not specified	TERMINATED	A Physiological Study to Determine the Enteral Threonine Requirements in Infants Aged 1 to 6 Months
NCT03455881	Not specified	UNKNOWN	Phenotypic and Genetic Assessment of Tracheal and Esophageal Birth Defects in Patients
NCT03730454	Not specified	ACTIVE_NOT_RECRUITING	Transanastomotic Tube for Proximal Esophageal Atresia With Distal Tracheoesophageal Fistula Repair