GTF2IRD1

Chr 7

GTF2I repeat domain containing 1

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

This protein functions as a transcription regulator involved in craniofacial and cognitive development, cell-cycle progression, and skeletal muscle differentiation. Mutations cause Williams-Beuren syndrome, a multisystem developmental disorder with craniofacial abnormalities and intellectual disability that follows an autosomal dominant inheritance pattern due to deletions at 7q11.23. The gene is highly constrained against loss-of-function variants (pLI 0.90, LOEUF 0.33), indicating that complete loss of protein function is likely deleterious.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.33
Clinical SummaryGTF2IRD1
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.
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ClinVar Variants
167 unique Pathogenic / Likely Pathogenic· 137 VUS of 408 total submissions
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GeneReview available — GTF2IRD1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.33LOEUF
pLI 0.900
Z-score 5.36
OE 0.19 (0.120.33)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.66Z-score
OE missense 0.70 (0.650.76)
444 obs / 632.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.19 (0.120.33)
00.351.4
Missense OE0.70 (0.650.76)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 10 / 51.5Missense obs/exp: 444 / 632.2Syn Z: 0.33
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedGTF2IRD1-related neurodevelopmental disorderOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.4587th %ile
GOF
0.4382th %ile
LOF
0.72top 10%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

408 submitted variants in ClinVar

Classification Summary

Pathogenic160
Likely Pathogenic7
VUS137
Likely Benign55
Benign17
Conflicting1
160
Pathogenic
7
Likely Pathogenic
137
VUS
55
Likely Benign
17
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
160
0
160
Likely Pathogenic
0
1
6
0
7
VUS
3
124
10
0
137
Likely Benign
0
10
5
40
55
Benign
0
1
3
13
17
Conflicting
1
Total313618453377

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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