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7 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GTF3C1
general transcription factor IIIC subunit 1
Chromosome 16 · 16p12.1
NCBI Gene: 2975Ensembl: ENSG00000077235.19HGNC: HGNC:4664UniProt: Q12789
169PubMed Papers
20Diseases
0Drugs
2Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleoplasmmembranetranscription factor TFIIIC complexRNA polymerase III general transcription initiation factor activityneurodegenerative diseaselysosomal storage diseasealopecia areataAbnormal brain morphology
✦AI Summary

GTF3C1 (general transcription factor IIIC subunit 1) is a core component of the TFIIIC complex required for RNA polymerase III-mediated transcription. It binds to box B promoter elements and initiates transcription complex assembly on tRNA genes and other pol III targets, including 5S rRNA and stable nuclear/cytoplasmic RNAs 1. Mechanistically, GTF3C1 functions within the TFIIIC2 complex where it interacts with regulatory proteins like SIRT7 to modulate pol III function and tRNA synthesis 1. The protein plays a critical role in ribosome biogenesis and protein synthesis regulation through its involvement in the mTOR signaling pathway. GTF3C1 has emerging relevance in multiple disease contexts. It was identified as a plausible candidate gene in esophageal atresia/tracheoesophageal fistula (EA/TEF) etiology, a rare congenital birth defect 2. Additionally, GTF3C1 expression associates with clinical outcomes: elevated expression correlates with poor prognosis in colorectal cancer patients and links to oncogenic pathways including WNT/β-catenin signaling 3. In triple-negative breast cancer, GTF3C1 was among 13 immune-related genes forming a prognostic signature predictive of distant recurrence-free survival 4. These findings suggest GTF3C1 may serve as both a developmental regulator and a potential prognostic biomarker in cancer biology.

Sources cited
1
GTF3C1 is a component of TFIIIC2 complex that interacts with SIRT7 and regulates pol III transcription, tRNA levels, and ribosome biogenesis
PMID: 24113281
2
GTF3C1 identified as plausible candidate gene in esophageal atresia/tracheoesophageal fistula etiology through exome sequencing
PMID: 32641753
3
GTF3C1 expression correlates with poor prognosis in colorectal cancer and associates with cell cycle, oxidative stress, and WNT/β-catenin signaling pathways
PMID: 33925358
4
GTF3C1 is one of 13 immune-related genes associated with distant recurrence-free survival prognosis in triple-negative breast cancer patients
PMID: 32812178
5
GTF3C1 upregulated in chemotherapy-resistant breast tumors compared to chemotherapy-sensitive tumors treated with doxorubicin and cyclophosphamide
PMID: 16322899
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.54Moderate
lysosomal storage diseaseOpen Targets
0.36Weak
alopecia areataOpen Targets
0.34Weak
Abnormal brain morphologyOpen Targets
0.27Weak
esophageal atresia/tracheoesophageal fistulaOpen Targets
0.26Weak
Tracheoesophageal fistulaOpen Targets
0.26Weak
schizophreniaOpen Targets
0.15Weak
adolescent idiopathic scoliosisOpen Targets
0.12Weak
benign chondrogenic neoplasmOpen Targets
0.12Weak
hypertrophic cardiomyopathyOpen Targets
0.09Suggestive
gastritisOpen Targets
0.07Suggestive
preeclampsiaOpen Targets
0.07Suggestive
jaw diseaseOpen Targets
0.03Suggestive
neuroblastomaOpen Targets
0.02Suggestive
brain aneurysmOpen Targets
0.02Suggestive
colorectal carcinomaOpen Targets
0.01Suggestive
breast cancerOpen Targets
0.01Suggestive
neoplasmOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
posterior cortical atrophyOpen Targets
0.01Suggestive
Pathogenic Variants2
NM_001520.4(GTF3C1):c.4096G>A (p.Glu1366Lys)Likely pathogenic
Abnormal brain morphology
★☆☆☆→ Residue 1366
NM_001520.4(GTF3C1):c.6040C>A (p.Pro2014Thr)Likely pathogenic
Esophageal atresia/tracheoesophageal fistula
☆☆☆☆2019→ Residue 2014
View on ClinVar ↗
Related Genes
TBPProtein interaction100%BDP1Protein interaction100%POLR3FProtein interaction97%GTF3C3Protein interaction91%BBOX1Protein interaction88%POLR1CProtein interaction86%
Tissue Expression6 tissues
Heart
100%
Brain
96%
Ovary
77%
Lung
69%
Bone Marrow
60%
Liver
56%
Gene Interaction Network
Click a node to explore
GTF3C1TBPBDP1POLR3FGTF3C3BBOX1POLR1C
PROTEIN STRUCTURE
Preparing viewer…
PDB8CLI · 3.20 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.36Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.27 [0.21–0.36]
RankingsWhere GTF3C1 stands among ~20K protein-coding genes
  • #2,623of 20,598
    Most Researched169 · top quartile
  • #4,259of 5,498
    Most Pathogenic Variants2
  • #1,578of 17,882
    Most Constrained (LOEUF)0.36 · top 10%
Genes detectedGTF3C1
Sources retrieved7 papers
Response time—
📄 Sources
7▼
1
Gene expression patterns for doxorubicin (Adriamycin) and cyclophosphamide (cytoxan) (AC) response and resistance.
PMID: 16322899
Breast Cancer Res Treat · 2006
1.00
2
Novel candidate genes in esophageal atresia/tracheoesophageal fistula identified by exome sequencing.
PMID: 32641753
Eur J Hum Genet · 2021
0.86
3
Application of quantitative trait locus mapping and transcriptomics to studies of the senescence-accelerated phenotype in rats.
PMID: 25563673
BMC Genomics · 2014
0.71
4
Sirtuin 7 plays a role in ribosome biogenesis and protein synthesis.
PMID: 24113281
Mol Cell Proteomics · 2014
0.57
5
Prognostication of a 13-immune-related-gene signature in patients with early triple-negative breast cancer.
PMID: 32812178
Breast Cancer Res Treat · 2020
0.43