HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
GIGYF2
GRB10 interacting GYF protein 2
Chromosome 2 · 2q37.1
NCBI Gene: 26058Ensembl: ENSG00000204120.17HGNC: HGNC:11960UniProt: Q6Y7W6
202PubMed Papers
21Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
Golgi apparatusendoplasmic reticulumcytoplasmic stress granuleRNA bindingneurodegenerative diseaseLeber congenital amaurosis 16schizophreniamathematical ability
✦AI Summary

GIGYF2 is a multifunctional adaptor protein that regulates gene expression through multiple mechanisms. Structurally, it contains a GYF domain that binds AGO2 1 and interacts with translation initiation factors including EIF4E2 and 4EHP 2. Mechanistically, GIGYF2 functions in mRNA surveillance pathways, participating in ribosome collision-induced quality control and nonsense-mediated decay 3. It recruits translational repressors to collided ribosomes, creating a negative-feedback loop that prevents translation of defective mRNAs 4. Additionally, as an RNA-binding protein, GIGYF2 enhances mRNA stability of specific targets like STAU1 5, and mediates microRNA-induced silencing through AGO2 interaction 1. Disease relevance is substantial. De novo loss-of-function mutations in GIGYF2 are recurrently associated with autism spectrum disorder 67, with affected individuals showing more severe phenotypes when carrying multiple genetic hits 7. GIGYF2 dysfunction is implicated in schizophrenia-associated phenotypes including altered forebrain development 8. Clinically, GIGYF2 dysregulation contributes to vascular aging through mTORC1 pathway activation 5, suggesting therapeutic potential. The GIGYF2-STAU1-mTORC1 signaling cascade represents a promising intervention target for aging-related cardiovascular diseases and neurodevelopmental disorders.

Sources cited
1
GIGYF2 identified as a novel de novo likely gene-disruptive mutation in autism spectrum disorder cohort
PMID: 27824329
2
GIGYF2 associated with macrocephaly in autism; patients with multiple genetic hits show more severe phenotypes
PMID: 30564305
3
GIGYF2 functions as versatile adaptor protein regulating transcription, mRNA surveillance, translational repression, and mRNA degradation; dysregulation implicated in metabolic diseases, vascular aging, viral infections, and neurodegeneration
PMID: 40643551
4
GIGYF2 identified as schizophrenia-associated gene with translational repressor function affecting forebrain development
PMID: 30929901
5
GIGYF2 hyperexpression in senescent endothelial cells promotes vascular aging through STAU1-mTORC1-S6K1 signaling pathway
PMID: 37517320
6
GIGYF2 and 4EHP inhibit translation initiation of defective mRNAs as part of ribosome-associated quality control; dysfunction leads to neurodevelopmental and neuropsychiatric disorders
PMID: 32726578
7
EDF1 recruits GIGYF2 and EIF4E2 to collided ribosomes to prevent translation of defective mRNAs
PMID: 32744497
8
GIGYF2 binds AGO2 and exhibits microRNA-induced silencing activity involving mRNA destabilization and translational repression
PMID: 27157137
Disease Associationsⓘ21
neurodegenerative diseaseOpen Targets
0.53Moderate
Leber congenital amaurosis 16Open Targets
0.52Moderate
schizophreniaOpen Targets
0.48Moderate
mathematical abilityOpen Targets
0.42Moderate
Parkinson diseaseOpen Targets
0.39Weak
Leber congenital amaurosisOpen Targets
0.38Weak
esophageal diseaseOpen Targets
0.38Weak
snowflake vitreoretinal degenerationOpen Targets
0.37Weak
gastroesophageal reflux diseaseOpen Targets
0.34Weak
Nasal Cavity PolypOpen Targets
0.34Weak
Hereditary late-onset Parkinson diseaseOpen Targets
0.33Weak
obesityOpen Targets
0.32Weak
attention deficit hyperactivity disorderOpen Targets
0.31Weak
cervical carcinomaOpen Targets
0.31Weak
autism spectrum disorderOpen Targets
0.31Weak
intelligenceOpen Targets
0.30Weak
coronary artery diseaseOpen Targets
0.29Weak
jaw diseaseOpen Targets
0.27Weak
retinitis pigmentosaOpen Targets
0.27Weak
epistaxisOpen Targets
0.24Weak
Parkinson disease 11UniProt
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PINK1Protein interaction99%EIF4G1Protein interaction98%EIF4EProtein interaction93%ATP13A2Protein interaction89%LRRK2Protein interaction82%DDX6Protein interaction82%
Tissue Expression6 tissues
Heart
100%
Brain
80%
Ovary
78%
Lung
69%
Bone Marrow
67%
Liver
52%
Gene Interaction Network
Click a node to explore
GIGYF2PINK1EIF4G1EIF4EATP13A2LRRK2DDX6
PROTEIN STRUCTURE
Preparing viewer…
PDB7RUP · 1.23 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.15Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.09 [0.06–0.15]
RankingsWhere GIGYF2 stands among ~20K protein-coding genes
  • #2,081of 20,598
    Most Researched202 · top quartile
  • #209of 17,882
    Most Constrained (LOEUF)0.15 · top 5%
Genes detectedGIGYF2
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
De novo genic mutations among a Chinese autism spectrum disorder cohort.
PMID: 27824329
Nat Commun · 2016
1.00
2
Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
PMID: 30564305
Mol Autism · 2018
0.90
3
GIGYF2: A Multifunctional Regulator at the Crossroads of Gene Expression, mRNA Surveillance, and Human Disease.
PMID: 40643551
Cells · 2025
0.80
4
Enteric coronavirus nsp2 is a virulence determinant that recruits NBR1 for autophagic targeting of TBK1 to diminish the innate immune response.
PMID: 38597182
Autophagy · 2024
0.80
5
Repression of mRNA translation initiation by GIGYF1 via disrupting the eIF3-eIF4G1 interaction.
PMID: 39018414
Sci Adv · 2024
0.72