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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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AKAP11
A-kinase anchoring protein 11
Chromosome 13 · 13q14.11
NCBI Gene: 11215Ensembl: ENSG00000023516.10HGNC: HGNC:369UniProt: Q9UKA4
82PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytosolprotein bindingcell surface receptor protein serine/threonine kinase signaling pathwayintracellular protein localizationneurodegenerative diseaseAlzheimer diseaseParkinson diseaselysosomal storage disease
✦AI Summary

AKAP11 (A-kinase anchoring protein 11) serves as a critical scaffold protein that anchors protein kinase A (PKA) regulatory subunits and couples PKA signaling to autophagy regulation in neurons 1. The protein functions as an autophagy receptor that mediates selective degradation of the PKA-RI complex through interactions with autophagy-related proteins VAPA/B and SPHKAP 12. AKAP11 contains an LC3-interacting region (LIR) that enables PKA regulation by upstream signals and autophagy-dependent degradation, with autophagosomes serving as platforms for PKA signaling modulation 2. Loss of AKAP11 disrupts compartment-specific PKA and GSK3α/β activities, impairing synaptic transmission and neurotransmission 1. AKAP11 is clinically significant as protein-truncating variants confer substantial risk for both bipolar disorder and schizophrenia through loss-of-function mechanisms 34. The gene emerged as a definitive shared risk factor with an odds ratio of 7.06 for bipolar disorder 3. Mouse models with AKAP11 deficiency exhibit EEG abnormalities characteristic of schizophrenia patients, including increased gamma power and attenuated auditory responses 5. The protein's interaction with GSK3β, lithium's hypothesized target, provides mechanistic insight into mood stabilizer action 34.

Sources cited
1
AKAP11 functions as an autophagy receptor coupling PKA regulation to synaptic transmission and mediates PKA-RI complex degradation
PMID: 41315293
2
AKAP11 contains LC3-interacting region enabling PKA regulation and autophagy-dependent degradation via autophagosomes
PMID: 40263600
3
AKAP11 protein-truncating variants confer bipolar disorder risk with odds ratio 7.06 and interact with GSK3B
PMID: 35410376
4
AKAP11 loss-of-function variants confer bipolar disorder risk and interact with GSK3β
PMID: 40133559
5
AKAP11-deficient mice exhibit EEG abnormalities resembling schizophrenia patients
PMID: 36914641
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.52Moderate
Alzheimer diseaseOpen Targets
0.50Moderate
Parkinson diseaseOpen Targets
0.50Moderate
lysosomal storage diseaseOpen Targets
0.50Moderate
multiple sclerosisOpen Targets
0.50Moderate
neuroinflammatory disorderOpen Targets
0.37Weak
spinal stenosisOpen Targets
0.34Weak
Crohn's diseaseOpen Targets
0.33Weak
type 1 diabetes mellitusOpen Targets
0.30Weak
cataractOpen Targets
0.29Weak
trauma complicationOpen Targets
0.29Weak
osteoporosisOpen Targets
0.24Weak
osteoarthritis, kneeOpen Targets
0.23Weak
bone diseaseOpen Targets
0.20Weak
skeletal system diseaseOpen Targets
0.19Weak
Abnormality of the skeletal systemOpen Targets
0.19Weak
total knee arthroplastyOpen Targets
0.17Weak
otosclerosisOpen Targets
0.16Weak
childhood onset asthmaOpen Targets
0.14Weak
lichen planusOpen Targets
0.14Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PRKACBProtein interaction95%PRKACAProtein interaction94%IQGAP2Protein interaction89%AKAP1Protein interaction86%GSK3BProtein interaction85%PRKAR1AProtein interaction82%
Tissue Expression6 tissues
Brain
100%
Heart
32%
Ovary
23%
Bone Marrow
17%
Lung
17%
Liver
13%
Gene Interaction Network
Click a node to explore
AKAP11PRKACBPRKACAIQGAP2AKAP1GSK3BPRKAR1A
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9UKA4
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.32Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.24 [0.18–0.32]
RankingsWhere AKAP11 stands among ~20K protein-coding genes
  • #5,771of 20,598
    Most Researched82
  • #1,283of 17,882
    Most Constrained (LOEUF)0.32 · top 10%
Genes detectedAKAP11
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Bipolar and schizophrenia risk gene AKAP11 encodes an autophagy receptor coupling the regulation of PKA kinase network homeostasis to synaptic transmission.
PMID: 41315293
Nat Commun · 2025
1.00
2
Exome sequencing in bipolar disorder identifies AKAP11 as a risk gene shared with schizophrenia.
PMID: 35410376
Nat Genet · 2022
0.90
3
Bipolar and schizophrenia risk gene
PMID: 40162211
Res Sq · 2025
0.80
4
Bipolar and schizophrenia risk gene
PMID: 39803523
bioRxiv · 2025
0.70
5
Mouse mutants in schizophrenia risk genes GRIN2A and AKAP11 show EEG abnormalities in common with schizophrenia patients.
PMID: 36914641
Transl Psychiatry · 2023
0.60