GTF3C3

Chr 2AR

general transcription factor IIIC subunit 3

Also known as: NEDFBS, TFIIIC102, TFIIICgamma, TFiiiC2-102

The protein is an integral component of the TFIIIC2 complex that directly binds tRNA and viral RNA promoters to recruit RNA polymerase III for transcription of small nuclear and cytoplasmic RNAs. Biallelic mutations cause autosomal recessive neurodevelopmental disorder with dysmorphic facies, brain anomalies, and seizures. The gene is highly constrained against loss-of-function variants (LOEUF 0.588), indicating intolerance to reduced protein function.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.591 OMIM phenotype
Clinical SummaryGTF3C3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.59LOEUF
pLI 0.000
Z-score 3.82
OE 0.40 (0.280.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.57Z-score
OE missense 0.67 (0.610.73)
321 obs / 479.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.40 (0.280.59)
00.351.4
Missense OE0.67 (0.610.73)
00.61.4
Synonymous OE0.81
01.21.6
LoF obs/exp: 19 / 47.4Missense obs/exp: 321 / 479.6Syn Z: 1.89
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateGTF3C3-related neurodevelopmental disorder with hypoplasia of corpus callosum and/or cerebellar atrophyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6745th %ile
GOF
0.6051th %ile
LOF
0.2969th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GTF3C3 · 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.

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