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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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GTF2IRD1
GTF2I repeat domain containing 1
Chromosome 7 Β· 7q11.23
NCBI Gene: 9569Ensembl: ENSG00000006704.11HGNC: HGNC:4661UniProt: E9PFE2
67PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTranscription Factor
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
RNA polymerase II cis-regulatory region sequence-specific DNA bindingDNA-binding transcription repressor activity, RNA polymerase II-specificprotein bindingnegative regulation of transcription by RNA polymerase IIsmoking initiationRespiratory insufficiencydiabetes mellitusinterstitial lung disease
✦AI Summary

GTF2IRD1 encodes a transcription factor that plays critical roles in neurodevelopment and is one of 25-27 genes deleted in Williams syndrome (WS) 1. The protein functions as a DNA-binding transcription regulator, with binding sites enriched at promoters and chr7 regulatory regions in the developing brain 2. GTF2IRD1 specifically binds to and regulates the expression of transthyretin (TTR), which activates ERK signaling pathways essential for proper neural progenitor cell proliferation, differentiation, and synapse formation 3. In WS pathogenesis, GTF2IRD1 haploinsufficiency contributes significantly to intellectual disability, social functioning deficits, and anxiety through multiple mechanisms 14. The gene regulates auditory processing by controlling VIPR1 expression in auditory cortex interneurons, with its deletion leading to enhanced frequency discrimination abilities characteristic of WS 5. Loss of GTF2IRD1 function also contributes to motor coordination deficits and increased ventricular volume in mouse models 6. Clinically, GTF2IRD1 serves as a key determinant of WS neuropsychological phenotype severity, and its expression patterns may influence tumor progression in growth hormone-secreting pituitary adenomas 7.

Sources cited
1
GTF2IRD1 is one of 25-27 genes deleted in Williams syndrome and affects intellectual ability, social functioning and anxiety
PMID: 34140529
2
GTF2IRD1 binding targets are enriched at promoters and for transcriptional and chromatin regulators
PMID: 32313931
3
GTF2IRD1 binds to TTR promoter regions, regulates TTR expression, and activates ERK signaling for neural development
PMID: 39671308
4
GTF2IRD1 has major impact on intellectual capacity, visuospatial abilities, and social skills in Williams syndrome
PMID: 36520254
5
Gtf2ird1 haploinsufficiency causes enhanced frequency discrimination by downregulating VIPR1 in auditory cortex interneurons
PMID: 36152627
6
GTF2IRD1 deletion contributes to increased ventricle volume in mouse models
PMID: 17270452
7
GTF2IRD1 functions as a regulatory transcription factor in growth hormone-secreting pituitary adenomas
PMID: 39784532
Disease Associationsβ“˜20
smoking initiationOpen Targets
0.33Weak
Respiratory insufficiencyOpen Targets
0.33Weak
diabetes mellitusOpen Targets
0.33Weak
interstitial lung diseaseOpen Targets
0.32Weak
type 2 diabetes mellitusOpen Targets
0.32Weak
alcohol drinkingOpen Targets
0.32Weak
major depressive disorderOpen Targets
0.31Weak
influenza A (H1N1)Open Targets
0.31Weak
systemic lupus erythematosusOpen Targets
0.30Weak
Alzheimer diseaseOpen Targets
0.30Weak
Crohn's diseaseOpen Targets
0.27Weak
Rare pervasive developmental disorderOpen Targets
0.27Weak
cervical carcinomaOpen Targets
0.24Weak
autoimmune diseaseOpen Targets
0.12Weak
colorectal carcinomaOpen Targets
0.08Suggestive
pachyonychia congenitaOpen Targets
0.07Suggestive
COVID-19Open Targets
0.06Suggestive
neoplasmOpen Targets
0.05Suggestive
atrial fibrillationOpen Targets
0.05Suggestive
atrial flutterOpen Targets
0.05Suggestive
Pathogenic Variants1
NM_005685.4(GTF2IRD1):c.973C>T (p.Arg325Cys)Likely pathogenic
Childhood-onset schizophrenia
β˜…β˜†β˜†β˜†2014β†’ Residue 325
View on ClinVar β†—
Related Genes
MNTShared pathway100%NFICShared pathway100%NFIXShared pathway100%NFYAShared pathway100%PRRX1Shared pathway100%GLIS3Shared pathway100%
Tissue Expression6 tissues
Lung
100%
Ovary
100%
Brain
94%
Heart
93%
Liver
45%
Bone Marrow
4%
Gene Interaction Network
Click a node to explore
GTF2IRD1MNTNFICNFIXNFYAPRRX1GLIS3
PROTEIN STRUCTURE
Preparing viewer…
PDB2D99 Β· NMR
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.31Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.20 [0.13–0.31]
RankingsWhere GTF2IRD1 stands among ~20K protein-coding genes
  • #6,989of 20,598
    Most Researched67
  • #5,012of 5,498
    Most Pathogenic Variants1
  • #1,212of 17,882
    Most Constrained (LOEUF)0.31 Β· top 10%
Genes detectedGTF2IRD1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Williams syndrome.
PMID: 34140529
Nat Rev Dis Primers Β· 2021
1.00
2
Single-cell and spatial transcriptomic analyses reveal heterogeneity characteristics and specific cell subtype regulators in growth hormone-secreting pituitary adenomas.
PMID: 39784532
Int J Surg Β· 2025
0.90
3
A human forebrain organoid model reveals the essential function of GTF2IRD1-TTR-ERK axis for the neurodevelopmental deficits of Williams syndrome.
PMID: 39671308
Elife Β· 2024
0.80
4
Functions of Gtf2i and Gtf2ird1 in the developing brain: transcription, DNA binding and long-term behavioral consequences.
PMID: 32313931
Hum Mol Genet Β· 2020
0.70
5
Neuropsychological Genotype-Phenotype in Patients with Williams Syndrome with Atypical Deletions: A Systematic Review.
PMID: 36520254
Neuropsychol Rev Β· 2023
0.60