GTF2I

Chr 7

general transcription factor IIi

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

NCBI Gene: 2969ENSG00000263001UniProt: P78347OMIM: 601679

This gene encodes a transcriptional regulator that binds to initiator and E-box elements in gene promoters and coordinates formation of multiprotein transcriptional complexes. Deletions encompassing GTF2I cause Williams-Beuren syndrome, a multisystem disorder with intellectual disability, distinctive facial features, cardiovascular abnormalities, and hypercalcemia. The gene is highly constrained against loss-of-function variants in the general population.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.27
Clinical Summary— GTF2I
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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
161 unique Pathogenic / Likely Pathogenic· 62 VUS of 262 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — GTF2I
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
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
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
LoF OE0.12 (0.06–0.27)
0≤0.351.4
Missense OE0.49 (0.42–0.56)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 4 / 33.9Missense obs/exp: 140 / 286.7Syn Z: 0.39
DN
0.3792th %ile
GOF
0.3491th %ile
LOF
0.76top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.27

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

262 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic155
Likely Pathogenic6
VUS62
Likely Benign12
155
Pathogenic
6
Likely Pathogenic
62
VUS
12
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
155
0
155
Likely Pathogenic
0
0
6
0
6
VUS
2
49
11
0
62
Likely Benign
1
2
2
7
12
Benign
0
0
0
0
0
Total3511747235

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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Case Report: Molecular diagnostics and clinical courses of two adult spinal pilocytic astrocytoma long-term survivors with GTF2I::BRAF fusion.
Argao L et al.·Front Oncol
2026Open AccessCase report
Heterozygous alterations of GTF2I at the Williams-Beuren syndrome's locus cause a neurodevelopmental disorder.
Jury J et al.·J Med Genet
2025
Gtf2i-encoded transcription factor Tfii-i regulates myelination via Sox10 and Mbp regulatory elements.
Levy G et al.·Nat Commun
2025Open Access
Transcription factor GTF2I regulates osteoclast differentiation through mediating miR-134-5p and MAT2A expressions.
Tang L et al.·J Cell Commun Signal
2025Open Access
Risk Allele rs117026326-Mediated Alternative Splicing of GTF2I Promotes B Cell Proliferation in Primary Sjögren's Syndrome.
Luo C et al.·J Immunol Res
2025Open Access
Top 5 resultsSearch Europe PMC ↗

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