HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
7 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
GKAP1
G kinase anchoring protein 1
Chromosome 9 · 9q21.32
NCBI Gene: 80318Ensembl: ENSG00000165113.14HGNC: HGNC:17496UniProt: Q5VSY0
25PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingidentical protein bindingsignal transductionreceptor guanylyl cyclase signaling pathwayneurodegenerative diseasemultiple sclerosiseye diseaseAlzheimer disease
✦AI Summary

GKAP1 (G kinase anchoring protein 1) is a scaffolding protein located on chromosome 9 that regulates insulin signaling in adipocytes. Its primary function involves modulating insulin receptor substrate-1 (IRS-1) availability to insulin receptor tyrosine kinase, thereby controlling insulin-dependent IRS-1 phosphorylation 1. GKAP1 binding to IRS-1 is required for insulin-induced glucose transporter 4 (GLUT4) translocation to the cell membrane, a critical step in glucose uptake 1. Mechanistically, GKAP1 associates with IRS-1 protein complexes and facilitates downstream MAPK and PI3K signaling pathway activation 2. GKAP1 is also involved in tumor necrosis factor-α-mediated impairment of insulin signaling, as TNF-α decreases GKAP1 protein levels through cGMP-dependent kinase regulation, contributing to insulin resistance 1. Beyond metabolic function, GKAP1 has disease relevance as a fusion partner in several cancers. GKAP1-NTRK2 fusion proteins have been identified in pediatric gliomas, generating constitutively activated receptor tyrosine kinases responsive to TRK inhibitor therapy 23. GKAP1 is also located within a minimally deleted region in acute myeloid leukemia with del(9q) cytogenetics 4 and has been implicated as a candidate gene in bladder exstrophy-epispadias complex and esophageal squamous cell carcinoma 56.

Sources cited
1
GKAP42 (GKAP1) binding to IRS-1 is required for insulin-induced GLUT4 translocation; TNF-α decreases GKAP42 protein levels via cGK-Iα causing insulin resistance
PMID: 25586176
2
GKAP1-NTRK2 fusion protein is constitutively activated and upregulates MAPK and PI3K signaling; responsive to TRK inhibitor larotrectinib in pediatric glioma
PMID: 33820494
3
GKAP1 is identified as a fusion partner of NTRK2 in pediatric and adult gliomas with variable TRK inhibitor response
PMID: 39014476
4
GKAP1 is part of the minimally deleted region in acute myeloid leukemia with del(9q); expression is significantly reduced in del(9q) patients
PMID: 30476680
5
GKAP1 harbors de novo variants identified in cloacal exstrophy exome analysis as a candidate gene
PMID: 37509153
6
GKAP1 missense variant shared by three unrelated esophageal squamous cell carcinoma patients in candidate susceptibility variant study
PMID: 28165652
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.35Weak
multiple sclerosisOpen Targets
0.33Weak
eye diseaseOpen Targets
0.30Weak
Alzheimer diseaseOpen Targets
0.26Weak
Parkinson diseaseOpen Targets
0.26Weak
lysosomal storage diseaseOpen Targets
0.26Weak
neuroinflammatory disorderOpen Targets
0.23Weak
age-related macular degenerationOpen Targets
0.08Suggestive
X-linked retinal dysplasiaOpen Targets
0.08Suggestive
azoospermiaOpen Targets
0.08Suggestive
retinitis pigmentosaOpen Targets
0.07Suggestive
choroidal dystrophy, central areolar, 1Open Targets
0.06Suggestive
Familial exudative vitreoretinopathyOpen Targets
0.06Suggestive
severe early-childhood-onset retinal dystrophyOpen Targets
0.06Suggestive
Stargardt diseaseOpen Targets
0.06Suggestive
reticular dystrophy of the retinal pigment epitheliumOpen Targets
0.06Suggestive
X-linked non-syndromic intellectual disabilityOpen Targets
0.06Suggestive
age related macular degeneration 11Open Targets
0.06Suggestive
age related macular degeneration 4Open Targets
0.06Suggestive
age related macular degeneration 6Open Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
C1QTNF12Shared pathway20%GUCY2CShared pathway20%GUCA1BShared pathway20%NHERF4Shared pathway17%PRKG1Shared pathway14%SNX5Shared pathway13%
Tissue Expression6 tissues
Heart
100%
Brain
95%
Ovary
86%
Liver
70%
Bone Marrow
45%
Lung
28%
Gene Interaction Network
Click a node to explore
GKAP1C1QTNF12GUCY2CGUCA1BNHERF4PRKG1SNX5
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q5VSY0
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.82LoF Tolerant
pLIⓘ
0.21Tolerant
Observed/Expected LoF0.44 [0.25–0.82]
RankingsWhere GKAP1 stands among ~20K protein-coding genes
  • #12,983of 20,598
    Most Researched25
  • #6,972of 17,882
    Most Constrained (LOEUF)0.82
Genes detectedGKAP1
Sources retrieved7 papers
Response time—
📄 Sources
7▼
1
NTRK-fused central nervous system tumours: clinicopathological and genetic insights and response to TRK inhibitors.
PMID: 39014476
Acta Neuropathol Commun · 2024
1.00
2
Exome Survey and Candidate Gene Re-Sequencing Identifies Novel Exstrophy Candidate Genes and Implicates
PMID: 37509153
Biomolecules · 2023
0.86
3
Candidate susceptibility variants for esophageal squamous cell carcinoma.
PMID: 28165652
Genes Chromosomes Cancer · 2017
0.71
4
Discovery of a rare
PMID: 33820494
Cancer Biol Ther · 2021
0.57
5
Characterization of acute myeloid leukemia with del(9q) - Impact of the genes in the minimally deleted region.
PMID: 30476680
Leuk Res · 2019
0.43