GTF3C1

Chr 16

general transcription factor IIIC subunit 1

Also known as: TFIIIC, TFIIIC220, TFIIICalpha

NCBI Gene: 2975 ENSG00000077235 UniProt: Q12789 OMIM: 603246

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.

OMIM ResearchSummary from RefSeq, UniProt

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. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.17

Clinical Summary— GTF3C1

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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.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 154 VUS of 232 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.17LOEUF

pLI 1.000

Z-score 8.52

OE 0.10 (0.07–0.17)

Highly constrained

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

Missense Constraint?

3.26Z-score

OE missense 0.74 (0.70–0.78)

950 obs / 1278.2 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.10 (0.07–0.17)

0≤0.351.4

Missense OE?0.74 (0.70–0.78)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 11 / 105.5Missense obs/exp: 950 / 1278.2Syn Z: -0.79

This gene — mechanism propensity

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

232 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic2

VUS154

Likely Benign17

Benign9

Likely Pathogenic

154

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	2	0	0	2
VUS	152	0	2	154
Likely Benign	17	0	0	17
Benign	2	1	6	9
Total	173	1	8	182

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

View in ClinVar →

31 pathogenic / likely-pathogenic (of 42) ClinVar copy-number / structural variants overlap GTF3C1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →