GTF3C3

Chr 2AR

general transcription factor IIIC subunit 3

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

NCBI Gene: 9330ENSG00000119041UniProt: Q9Y5Q9

The protein encoded by this gene is part of the TFIIIC2 complex, which binds to the promoters of small nuclear and cytoplasmic RNA genes in order to recruit RNA polymerase III. The TFIIIC2 complex is composed of six subunits. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with dysmorphic facies, brain anomalies, and seizuresMIM #621201
AR
137
ClinVar variants
46
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GTF3C3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
46 Pathogenic / Likely Pathogenic· 77 VUS of 137 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.59LOEUF
pLI 0.000
Z-score 3.82
OE 0.40 (0.28–0.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.57Z-score
OE missense 0.67 (0.61–0.73)
321 obs / 479.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.40 (0.28–0.59)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.67 (0.61–0.73)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.81
0≤1.21.6
LoF obs/exp: 19 / 47.4Missense obs/exp: 321 / 479.6Syn Z: 1.89

ClinVar Variant Classifications

137 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic3
VUS77
Likely Benign12
Benign2
43
Pathogenic
3
Likely Pathogenic
77
VUS
12
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
7
36
0
43
Likely Pathogenic
0
1
2
0
3
VUS
0
72
5
0
77
Likely Benign
0
3
4
5
12
Benign
0
1
1
0
2
Total084485137

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

View 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.

Gene2Phenotype Curations

GTF3C3-related neurodevelopmental disorder with hypoplasia of corpus callosum and/or cerebellar atrophy

moderate
ARLoss Of FunctionAltered Gene Product Structure, Decreased Gene Product Level
Dev. Disorders
G2P ↗
splice region variantmissense variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with dysmorphic facies, brain anomalies, and seizures

MIM #621201

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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