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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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AKAP1
A-kinase anchoring protein 1
Chromosome 17 · 17q22
NCBI Gene: 8165Ensembl: ENSG00000121057.14HGNC: HGNC:367UniProt: A0A140VK05
119PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Apoptosis
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
RNA bindingmitochondrionmembraneprotein bindingneurodegenerative diseasealcohol drinkingNephropathynephritis
✦AI Summary

AKAP1 is a mitochondrial outer membrane-anchoring protein that coordinates compartmentalized PKA signaling to regulate diverse cellular processes. Functionally, AKAP1 binds regulatory subunits of PKA and recruits them to the mitochondrial surface, enabling spatially-localized phosphorylation events 1. Beyond its canonical scaffolding role, AKAP1 recruits electron transport chain mRNA to the outer membrane for localized translation, with loss of AKAP1 reducing ETC protein levels 2. In metabolism, AKAP1 phosphorylates and inactivates GPAT1 via PKA signaling to suppress lysophosphatidic acid synthesis, protecting against diet-induced liver steatosis 3. AKAP1 also regulates mitochondrial dynamics by maintaining Drp1 phosphorylation at inhibitory sites, preventing excessive fission 4, and controls mtDNA replication by phosphorylating Larp1, reducing TFAM expression 5. Clinically, AKAP1 dysfunction associates with multiple pathologies: upregulation impairs mtDNA replication and podocyte injury in diabetic kidney disease 5; suppression by miR-199a-5p aggravates renal ischemia-reperfusion injury 4; and dysregulation contributes to intervertebral disc degeneration 1. Additionally, AKAP1 phosphorylates GRP75 at mitochondria-associated ER membranes to protect cancer cells against ferroptosis 6. These findings position AKAP1 as a versatile signaling hub with therapeutic potential across metabolic, degenerative, and cancer-related diseases.

Sources cited
1
AKAP1 recruits mRNAs of short ETC component proteins to the outer mitochondrial membrane for translation, independent of translation, and AKAP1 loss reduces ETC levels
PMID: 40876456
2
AKAP1 phosphorylates and inactivates GPAT1 via PKA signaling to suppress LPA synthesis and protect against diet-induced hepatic steatosis and steatohepatitis
PMID: 40341440
3
AKAP1 recruits PKC and mediates Larp1 phosphorylation to reduce TFAM expression and mtDNA replication under hyperglycemic conditions in diabetic kidney disease
PMID: 35844803
4
miR-199a-5p targets and reduces AKAP1, disrupting Drp1-s637 phosphorylation and promoting mitochondrial fission that aggravates renal ischemia-reperfusion injury
PMID: 39265082
5
AKAP1 maintains PKA RIIα interaction and Drp1-S656 phosphorylation to prevent mitochondrial fragmentation; TRIB3 elevation disrupts this interaction in intervertebral disc degeneration
PMID: 40848982
6
AKAP1-anchored PKA phosphorylates GRP75 at S148 in mitochondria-associated ER membranes, sequestering GRP75 to promote Nrf2 activation and ferroptosis protection in cancer cells
PMID: 39537840
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.52Moderate
alcohol drinkingOpen Targets
0.33Weak
NephropathyOpen Targets
0.31Weak
nephritisOpen Targets
0.30Weak
lower urinary tract calculusOpen Targets
0.29Weak
diabetic ketoacidosisOpen Targets
0.25Weak
prostate cancerOpen Targets
0.11Weak
breast ductal adenocarcinomaOpen Targets
0.11Weak
Familial prostate cancerOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.09Suggestive
non-small cell lung carcinomaOpen Targets
0.09Suggestive
androgenetic alopeciaOpen Targets
0.08Suggestive
hair colorOpen Targets
0.08Suggestive
obesityOpen Targets
0.08Suggestive
coronary artery diseaseOpen Targets
0.07Suggestive
skin agingOpen Targets
0.07Suggestive
glaucomaOpen Targets
0.06Suggestive
spondylolisthesisOpen Targets
0.06Suggestive
alopeciaOpen Targets
0.06Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SLC8A3Protein interaction100%CFAP91Protein interaction98%MYCBPAPProtein interaction98%PRKACAProtein interaction97%PRKACBProtein interaction97%PRKACGProtein interaction97%
Tissue Expression6 tissues
Heart
100%
Liver
42%
Brain
20%
Ovary
16%
Lung
16%
Bone Marrow
8%
Gene Interaction Network
Click a node to explore
AKAP1SLC8A3CFAP91MYCBPAPPRKACAPRKACBPRKACG
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q92667
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.53Moderately Constrained
pLIⓘ
0.67Intermediate
Observed/Expected LoF0.39 [0.30–0.53]
RankingsWhere AKAP1 stands among ~20K protein-coding genes
  • #3,952of 20,598
    Most Researched119 · top quartile
  • #3,275of 17,882
    Most Constrained (LOEUF)0.53 · top quartile
Genes detectedAKAP1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
AKAP1 contributes to impaired mtDNA replication and mitochondrial dysfunction in podocytes of diabetic kidney disease.
PMID: 35844803
Int J Biol Sci · 2022
1.00
2
Proximity-specific ribosome profiling reveals the logic of localized mitochondrial translation.
PMID: 40876456
Cell · 2025
0.90
3
Hepatic AKAP1 deficiency exacerbates diet-induced MASLD by enhancing GPAT1-mediated lysophosphatidic acid synthesis.
PMID: 40341440
Nat Commun · 2025
0.80
4
HNF4A and HNF1A exhibit tissue specific target gene regulation in pancreatic beta cells and hepatocytes.
PMID: 38909044
Nat Commun · 2024
0.70
5
AKAP1/PKA-mediated GRP75 phosphorylation at mitochondria-associated endoplasmic reticulum membranes protects cancer cells against ferroptosis.
PMID: 39537840
Cell Death Differ · 2025
0.60