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 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]

GeneReviewsOMIMResearchGenerating clinical summary…
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
1 unique Pathogenic / Likely Pathogenic· 52 VUS of 90 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
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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 OE?0.12 (0.06–0.27)
0≤0.351.4
Missense OE?0.49 (0.42–0.56)
0≤0.61.4
Synonymous OE?0.95
0≤1.21.6
LoF obs/exp: 4 / 33.9Missense obs/exp: 140 / 286.7Syn Z: 0.39

This gene — mechanism propensity

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

90 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1
VUS52
Likely Benign10
1
Pathogenic
52
VUS
10
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
1
0
1
Likely Pathogenic
0
0
0
0
0
VUS
2
49
1
0
52
Likely Benign
1
2
0
7
10
Benign
0
0
0
0
0
Total3512763

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

View in ClinVar →

161 pathogenic / likely-pathogenic (of 173) ClinVar copy-number / structural variants overlap GTF2I — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

GTF2I · protein map & ClinVar variants

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

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