GTF3C4

Chr 9

general transcription factor IIIC subunit 4

Also known as: KAT12, TF3C-delta, TFIII90, TFIIIC290, TFIIIC90, TFIIICDELTA

NCBI Gene: 9329ENSG00000125484UniProt: Q9UKN8OMIM: 604892

The protein functions as an essential component of transcription factor TFIIIC complex, enabling RNA polymerase III to transcribe small nuclear and cytoplasmic RNAs including 5S rRNA and tRNA, and also has histone H3K14 acetyltransferase activity. GTF3C4 mutations have not been definitively associated with human disease, though the low LOEUF score (0.444) suggests intolerance to loss-of-function variants. The inheritance pattern and specific pathogenic mechanisms remain to be established through future clinical studies.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.44
Clinical Summary— GTF3C4
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
36 unique Pathogenic / Likely Pathogenic· 87 VUS of 137 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.44LOEUF
pLI 0.259
Z-score 3.85
OE 0.24 (0.13–0.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.42Z-score
OE missense 0.68 (0.62–0.75)
302 obs / 445.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.24 (0.13–0.44)
0≤0.351.4
Missense OE0.68 (0.62–0.75)
0≤0.61.4
Synonymous OE0.99
0≤1.21.6
LoF obs/exp: 7 / 29.6Missense obs/exp: 302 / 445.5Syn Z: 0.15

ClinVar Variant Classifications

137 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic1
VUS87
Likely Benign4
35
Pathogenic
1
Likely Pathogenic
87
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
35
0
35
Likely Pathogenic
0
0
1
0
1
VUS
0
69
18
0
87
Likely Benign
0
3
0
1
4
Benign
0
0
0
0
0
Total072541127

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

View in ClinVar →

Protein Context — Lollipop Plot

GTF3C4 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients