GTF2IRD2

Chr 7

GTF2I repeat domain containing 2

Also known as: FP630, GTF2IRD2 alpha, GTF2IRD2A

NCBI Gene: 84163ENSG00000196275UniProt: Q86UP8

This gene is one of several closely related genes on chromosome 7 encoding proteins containing helix-loop-helix motifs. These proteins may function as regulators of transcription. The encoded protein is unique in that its C-terminus is derived from CHARLIE8 transposable element sequence. This gene is located in a region of chromosome 7 that is deleted in Williams-Beuren syndrome, and loss of this locus may contribute to the cognitive phenotypes observed in this disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

92
ClinVar variants
55
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GTF2IRD2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
55 Pathogenic / Likely Pathogenic· 28 VUS of 92 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
Tolerant — LoF & missense variants common in population
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.
1.17LOEUF
pLI 0.000
Z-score 1.02
OE 0.75 (0.49–1.17)
Tolerant

Highly tolerant — LoF variants common in population

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.
1.12Z-score
OE missense 0.82 (0.74–0.91)
260 obs / 316.0 exp
Tolerant

Mild missense constraint

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.0.75 (0.49–1.17)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.74–0.91)
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.0.78
0≤1.21.6
LoF obs/exp: 14 / 18.8Missense obs/exp: 260 / 316.0Syn Z: 1.97

ClinVar Variant Classifications

92 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic53
Likely Pathogenic2
VUS28
Likely Benign6
Benign2
Conflicting1
53
Pathogenic
2
Likely Pathogenic
28
VUS
6
Likely Benign
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
53
0
53
Likely Pathogenic
0
0
2
0
2
VUS
0
19
9
0
28
Likely Benign
0
1
1
4
6
Benign
0
1
0
1
2
Conflicting
—1
Total02165592

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

View in ClinVar →

Protein Context — Lollipop Plot

GTF2IRD2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Neuropsychological Genotype-Phenotype in Patients with Williams Syndrome with Atypical Deletions: A Systematic Review.
Serrano-Juárez CA et al.·Neuropsychol Rev
2023Review
Cognitive, Behavioral, and Adaptive Profiles in Williams Syndrome With and Without Loss of GTF2IRD2.
Serrano-Juárez CA et al.·J Int Neuropsychol Soc
2018
A role for transcription factor GTF2IRD2 in executive function in Williams-Beuren syndrome.
Porter MA et al.·PLoS One
2012
Williams-Beuren syndrome in Mexican patients confirmed by FISH and assessed by aCGH.
Ramírez-Velazco A et al.·J Genet
2019Cohort
Chromosomal Microarray Analysis in Taiwanese Patients with Williams-Beuren Syndrome.
Kuo HT et al.·Cytogenet Genome Res
2019Cohort
An Exploration of Social Cognition in Children with Different Degrees of Genetic Deletion in Williams Syndrome.
Serrano-Juárez CA et al.·J Autism Dev Disord
2021
Hemizygosity at the NCF1 gene in patients with Williams-Beuren syndrome decreases their risk of hypertension.
Del Campo M et al.·Am J Hum Genet
2006Cohort
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