HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
10 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.
AKAP5
A-kinase anchoring protein 5
Chromosome 14 · 14q23.3
NCBI Gene: 9495Ensembl: ENSG00000179841.8HGNC: HGNC:375UniProt: P24588
111PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
calcineurin-NFAT signaling cascadeprotein bindingmembrane raftpositive regulation of long-term synaptic potentiationrhabdomyolysisMODYtype 1 diabetes mellitusmaturity-onset diabetes of the young type 4
✦AI Summary

AKAP5 is a multivalent scaffold protein that anchors protein kinase A (PKA) and other signaling molecules to specific subcellular locations, particularly at neuronal synapses and cardiac myocytes 1. The protein forms signaling complexes by binding PKA, calcineurin (PP2B), and G-protein-coupled receptors like β1- and β2-adrenergic receptors through multiple short linear motifs (SLiMs) 23. AKAP5 is essential for proper receptor trafficking, as demonstrated by impaired β1-adrenergic receptor recycling in AKAP5-deficient cells 3. In neurons, AKAP5 is crucial for synaptic plasticity and learning, with knockout mice showing delocalized PKA, disrupted dendritic signaling, and defects in operant learning 4. The protein also regulates vascular function by facilitating purinergic modulation of L-type calcium channels through formation of nanocomplexes containing P2Y11 receptors, adenylyl cyclase, and PKA 5. Additionally, AKAP5 enhances HERG channel regulation by anchoring PKA, which has implications for cardiac arrhythmias 6. Human genetic variation in AKAP5 (Pro100Leu polymorphism) is associated with differences in aggressive behavior and anger control, suggesting roles in emotional processing 7. The protein's ability to create dynamic, multivalent signaling platforms makes it critical for coordinating complex cellular responses.

Sources cited
1
AKAP5 is a multivalent scaffold protein that binds β2-adrenergic receptor and orchestrates interactions of protein kinases, phosphatases, and cytoskeletal elements
PMID: 25789584
2
AKAP5 contains multiple short linear motifs (SLiMs) that anchor PKA and Calcineurin with varying affinities
PMID: 35697294
3
AKAP5 is essential for β1-adrenergic receptor recycling and regulates cardiac signaling pathways
PMID: 24121510
4
AKAP5 knockout mice show delocalized PKA, disrupted synaptic plasticity, and learning defects
PMID: 20428246
5
AKAP5 facilitates purinergic modulation of vascular L-type Ca2+ channels through nanocomplex formation
PMID: 33082339
6
AKAP5 anchors PKA to enhance HERG channel regulation with implications for cardiac arrhythmias
PMID: 32173522
7
Human AKAP5 genetic variation (Pro100Leu) is associated with aggressive behavior and anger control differences
PMID: 22232585
Disease Associationsⓘ20
rhabdomyolysisOpen Targets
0.28Weak
MODYOpen Targets
0.10Suggestive
type 1 diabetes mellitusOpen Targets
0.09Suggestive
maturity-onset diabetes of the young type 4Open Targets
0.07Suggestive
hyperinsulinism due to INSR deficiencyOpen Targets
0.07Suggestive
diabetes mellitusOpen Targets
0.07Suggestive
maturity-onset diabetes of the young type 2Open Targets
0.07Suggestive
maturity-onset diabetes of the young type 6Open Targets
0.07Suggestive
diabetes mellitus, transient neonatal, 2Open Targets
0.07Suggestive
hyperinsulinism due to glucokinase deficiencyOpen Targets
0.07Suggestive
exercise-induced hyperinsulinismOpen Targets
0.07Suggestive
hypothyroidismOpen Targets
0.07Suggestive
hyperproinsulinemiaOpen Targets
0.07Suggestive
maturity-onset diabetes of the young type 3Open Targets
0.06Suggestive
type 2 diabetes mellitusOpen Targets
0.06Suggestive
hyperinsulinemic hypoglycemia, familial, 2Open Targets
0.06Suggestive
diabetic ketoacidosisOpen Targets
0.06Suggestive
maturity-onset diabetes of the young type 10Open Targets
0.06Suggestive
islet cell adenomatosisOpen Targets
0.06Suggestive
renal cysts and diabetes syndromeOpen Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CALML3Protein interaction100%CALML6Protein interaction100%CALML5Protein interaction100%CALM3Protein interaction100%CALML4Protein interaction100%GRIA1Protein interaction100%
Tissue Expression6 tissues
Brain
100%
Lung
10%
Liver
9%
Bone Marrow
8%
Ovary
6%
Heart
4%
Gene Interaction Network
Click a node to explore
AKAP5CALML3CALML6CALML5CALM3CALML4GRIA1
PROTEIN STRUCTURE
Preparing viewer…
PDB5NIN · 1.70 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.70LoF Tolerant
pLIⓘ
0.66Intermediate
Observed/Expected LoF0.33 [0.17–0.70]
RankingsWhere AKAP5 stands among ~20K protein-coding genes
  • #4,259of 20,598
    Most Researched111 · top quartile
  • #5,306of 17,882
    Most Constrained (LOEUF)0.70
Genes detectedAKAP5
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
AKAP5 signaling complexes: focal points and functional properties.
PMID: 25789584
Neuro Endocrinol Lett · 2015
1.00
2
A Potential Role for a Genetic Variation of AKAP5 in Human Aggression and Anger Control.
PMID: 22232585
Front Hum Neurosci · 2011
0.90
3
AKAP5 anchors PKA to enhance regulation of the HERG channel.
PMID: 32173522
Int J Biochem Cell Biol · 2020
0.80
4
AKAP5 complex facilitates purinergic modulation of vascular L-type Ca
PMID: 33082339
Nat Commun · 2020
0.70
5
Mutations in AKAP5 disrupt dendritic signaling complexes and lead to electrophysiological and behavioral phenotypes in mice.
PMID: 20428246
PLoS One · 2010
0.60