GTF3C1

Chr 16

general transcription factor IIIC subunit 1

Also known as: TFIIIC, TFIIIC220, TFIIICalpha

Encodes a component of transcription factor TFIIIC that is required for RNA polymerase III-mediated transcription of tRNA, 5S rRNA, and other stable RNAs. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability and seizures. This gene is highly constrained against loss-of-function mutations (pLI ~1.0), indicating that haploinsufficiency is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.17
Clinical SummaryGTF3C1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
3 unique Pathogenic / Likely Pathogenic· 177 VUS of 200 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.17LOEUF
pLI 1.000
Z-score 8.52
OE 0.10 (0.070.17)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.26Z-score
OE missense 0.74 (0.700.78)
950 obs / 1278.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.10 (0.070.17)
00.351.4
Missense OE0.74 (0.700.78)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 11 / 105.5Missense obs/exp: 950 / 1278.2Syn Z: -0.79
DN
0.2299th %ile
GOF
0.1899th %ile
LOF
0.78top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.17

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

200 submitted variants in ClinVar

Classification Summary

Pathogenic2
Likely Pathogenic1
VUS177
Likely Benign20
2
Pathogenic
1
Likely Pathogenic
177
VUS
20
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
2
0
2
Likely Pathogenic
0
0
1
0
1
VUS
0
175
2
0
177
Likely Benign
0
18
0
2
20
Benign
0
0
0
0
0
Total019352200

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GTF3C1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC