GTF2I

Chr 7

general transcription factor IIi

Also known as: BAP135, BTKAP1, DIWS, GTFII-I, IB291, SPIN, TFII-I, WBS

NCBI Gene: 2969ENSG00000263001UniProt: P78347

This gene encodes a phosphoprotein containing six characteristic repeat motifs. The encoded protein binds to the initiator element (Inr) and E-box element in promoters and functions as a regulator of transcription. This locus, along with several other neighboring genes, is deleted in Williams-Beuren syndrome. There are many closely related genes and pseudogenes for this gene on chromosome 7. This gene also has pseudogenes on chromosomes 9, 13, and 21. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Jul 2013]

228
ClinVar variants
159
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— GTF2I
⚡
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
159 Pathogenic / Likely Pathogenic· 60 VUS of 228 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.27LOEUF
pLI 0.996
Z-score 4.76
OE 0.12 (0.06–0.27)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
3.08Z-score
OE missense 0.49 (0.42–0.56)
140 obs / 286.7 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.0.12 (0.06–0.27)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.49 (0.42–0.56)
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.0.95
0≤1.21.6
LoF obs/exp: 4 / 33.9Missense obs/exp: 140 / 286.7Syn Z: 0.39

ClinVar Variant Classifications

228 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic153
Likely Pathogenic6
VUS60
Likely Benign9
153
Pathogenic
6
Likely Pathogenic
60
VUS
9
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
153
0
153
Likely Pathogenic
0
0
6
0
6
VUS
1
47
12
0
60
Likely Benign
1
2
2
4
9
Benign
0
0
0
0
0
Total2491734228

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

View in ClinVar →

Protein Context — Lollipop Plot

GTF2I · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
📖
GeneReview available — GTF2I
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Williams syndrome.
Kozel BA et al.·Nat Rev Dis Primers
2021Review
Genotypic and Phenotypic Characteristics of Acute Promyelocytic Leukemia Translocation Variants.
Mannan A et al.·Hematol Oncol Stem Cell Ther
2020Review
The contribution of GTF2I haploinsufficiency to Williams syndrome.
Chailangkarn T et al.·Mol Cell Probes
2018Review
Neuropsychological Genotype-Phenotype in Patients with Williams Syndrome with Atypical Deletions: A Systematic Review.
Serrano-Juárez CA et al.·Neuropsychol Rev
2023Review
Novel CDKL5 targets identified in human iPSC-derived neurons.
Massey S et al.·Cell Mol Life Sci
2024
GTF2I mutation in micronodular thymoma with lymphoid stroma.
Bille A et al.·J Clin Pathol
2024
Molecular profiling of rare thymoma using next-generation sequencing: meta-analysis.
Kostic Peric J et al.·Radiol Oncol
2023Meta-analysis
Loss of GTF2I promotes neuronal apoptosis and synaptic reduction in human cellular models of neurodevelopment.
Adams JW et al.·Cell Rep
2024Functional
Common and rare carcinomas of the thymus.
Roden AC et al.·Virchows Arch
2021Review
Prenatal diagnosis, ultrasound findings and pregnancy outcome of 7q11.23 deletion and duplication syndromes: what are the fetal features?
Luo X et al.·BMC Pregnancy Childbirth
2024
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