GTF2IRD1

Chr 7

GTF2I repeat domain containing 1

Also known as: BEN, CREAM1, GTF3, MUSTRD1, RBAP2, WBS, WBSCR11, WBSCR12

NCBI Gene: 9569ENSG00000006704UniProt: Q9UHL9

The protein encoded by this gene contains five GTF2I-like repeats and each repeat possesses a potential helix-loop-helix (HLH) motif. It may have the ability to interact with other HLH-proteins and function as a transcription factor or as a positive transcriptional regulator under the control of Retinoblastoma protein. This gene plays a role in craniofacial and cognitive development and mutations have been associated with Williams-Beuren syndrome, a multisystem developmental disorder caused by deletion of multiple genes at 7q11.23. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2010]

374
ClinVar variants
165
Pathogenic / LP
0.90
pLI score· haploinsufficient
0
Active trials
Clinical Summary— GTF2IRD1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.90). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
165 Pathogenic / Likely Pathogenic· 137 VUS of 374 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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.
0.33LOEUF
pLI 0.900
Z-score 5.36
OE 0.19 (0.12–0.33)
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.
2.66Z-score
OE missense 0.70 (0.65–0.76)
444 obs / 632.2 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.0.19 (0.12–0.33)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.65–0.76)
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.0.97
0≤1.21.6
LoF obs/exp: 10 / 51.5Missense obs/exp: 444 / 632.2Syn Z: 0.33

ClinVar Variant Classifications

374 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic158
Likely Pathogenic7
VUS137
Likely Benign54
Benign17
Conflicting1
158
Pathogenic
7
Likely Pathogenic
137
VUS
54
Likely Benign
17
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
158
0
158
Likely Pathogenic
0
1
6
0
7
VUS
0
124
13
0
137
Likely Benign
0
10
5
39
54
Benign
0
1
3
13
17
Conflicting
—1
Total013618552374

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

View in ClinVar →

Protein Context — Lollipop Plot

GTF2IRD1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

GTF2IRD1-related neurodevelopmental disorder

limited
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variant

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — GTF2IRD1
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
Single-cell and spatial transcriptomic analyses reveal heterogeneity characteristics and specific cell subtype regulators in growth hormone-secreting pituitary adenomas.
Zhang Y et al.·Int J Surg
2025
Neuropsychological Genotype-Phenotype in Patients with Williams Syndrome with Atypical Deletions: A Systematic Review.
Serrano-Juárez CA et al.·Neuropsychol Rev
2023Review
Animal models of Williams syndrome.
Osborne LR·Am J Med Genet C Semin Med Genet
2010Review
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
GTF2IRD1 overexpression promotes tumor progression and correlates with less CD8+ T cells infiltration in pancreatic cancer.
Zhuang H et al.·Biosci Rep
2020
GTF2IRD1 on chromosome 7 is a novel oncogene regulating the tumor-suppressor gene TGFβR2 in colorectal cancer.
Nambara S et al.·Cancer Sci
2020
Expression of Gtf2ird1, the Williams syndrome-associated gene, during mouse development.
Palmer SJ et al.·Gene Expr Patterns
2007Functional
Mutation of Gtf2ird1 from the Williams-Beuren syndrome critical region results in facial dysplasia, motor dysfunction, and altered vocalisations.
Howard ML et al.·Neurobiol Dis
2012
Is it Williams syndrome? GTF2IRD1 implicated in visual-spatial construction and GTF2I in sociability revealed by high resolution arrays.
Dai L et al.·Am J Med Genet A
2009
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Enhancement of circular RNA 0002577 in serum exosomes in patients with endometrial cancer accelerates disease progression via general transcription factor II-I repeat domain-containing 1 (GTF2IRD1).
Li Y et al.·J Gynecol Oncol
2025Cohort
A human forebrain organoid model reveals the essential function of GTF2IRD1-TTR-ERK axis for the neurodevelopmental deficits of Williams syndrome.
Zhao X et al.·Elife
2024🔓 Open AccessFunctional
DNA methylation profiles in individuals with rare, atypical 7q11.23 CNVs correlate with GTF2I and GTF2IRD1 copy number.
Strong E et al.·NPJ Genom Med
2023🔓 Open Access
Extensive characterization of a Williams syndrome murine model shows Gtf2ird1-mediated rescue of select sensorimotor tasks, but no effect on enhanced social behavior.
Nygaard KR et al.·Genes Brain Behav
2023🔓 Open AccessFunctional
Biallelic GTF2IRD1 variants in brothers with profound neurodevelopmental disorder: A possible novel disorder involving a critical gene for Williams syndrome.
Cummings CT et al.·Am J Med Genet A
2023🔓 Open Access
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