AKAP6: A-Kinase Anchoring Protein 6
Scaffold Protein in Cardiac and Neuronal Signaling
Gene Information Card
| Symbol | AKAP6 |
|---|---|
| Full Name | A-kinase anchoring protein 6 |
| Gene Type | protein-coding |
| Chromosomal Location | 14q12 |
| NCBI Gene ID | 9472 ncbi.nlm.nih.gov/gene/9472 |
| Ensembl ID | ENSG00000100888 |
| UniProt ID | Q13023 |
| OMIM ID | 604691 |
| HGNC ID | 376 |
| Aliases | AKAP100, PRKA6, mAKAP, AKAP-6 |
Description
AKAP6 (A-kinase anchoring protein 6) encodes a member of the A-kinase anchoring protein (AKAP) family. This scaffold protein binds to the regulatory subunit of protein kinase A (PKA) and targets it to specific subcellular compartments, such as the nuclear membrane and sarcoplasmic reticulum. AKAP6 is involved in signal transduction pathways regulating cardiac muscle contraction, neuronal signaling, and cellular differentiation. It also interacts with other signaling molecules including phosphodiesterases and calcineurin.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cardiac hypertrophy | AKAP6 anchors PKA and calcineurin to the nuclear envelope, modulating NFAT signaling and hypertrophic gene expression | PMID: 15616553 |
| Dilated cardiomyopathy | Disruption of AKAP6-mediated PKA anchoring alters β-adrenergic signaling and contractility | PMID: 20089853 |
| Schizophrenia | Genetic variants in AKAP6 have been associated with schizophrenia risk in GWAS studies | PMID: 25056061 |
| Bipolar disorder | AKAP6 polymorphisms linked to altered cAMP signaling in neuronal cells | PMID: 21926972 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Brain (cerebellum) | 8.2 | Medium |
| Skeletal muscle | 6.8 | Low |
| Testis | 4.1 | Low |
| Lung | 2.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (AC16) | 15.0 | High expression |
| SH-SY5Y (neuroblastoma) | 9.5 | Medium expression |
| HEK293 | 3.2 | Low expression |
| HeLa | 1.8 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.01% | Loss of function; truncated protein |
| c.567G>A (p.Glu189Lys) | Missense | 0.02% | Altered PKA binding affinity |
| c.2345_2346insA | Frameshift | <0.01% | Loss of function; premature stop |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg412*, c.2345_2346insA) lead to truncated or unstable AKAP6 protein, disrupting PKA anchoring and downstream signaling.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in AKAP6.
Dominant Negative (DN)
Missense mutations (e.g., p.Glu189Lys) may produce a protein that competes with wild-type AKAP6 for PKA binding, reducing effective anchoring.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005515 (protein binding) | • GO:0034236 (protein kinase A anchoring) |
| • GO:0005737 (cytoplasm) | • GO:0005634 (nucleus) |
| • GO:0043025 (neuronal cell body) | • GO:0005886 (plasma membrane) |
Pathways
• PKA-mediated signaling (Reactome: R-HSA-163615)
• cAMP/PKA signaling (KEGG: hsa04024)
• Cardiac muscle contraction (KEGG: hsa04260)
• NFAT and cardiac hypertrophy (WikiPathways: WP1544)
Protein Summary
AKAP6 (mAKAP) is a 2319-amino-acid scaffold protein that localizes to the nuclear envelope and sarcoplasmic reticulum. It contains an N-terminal targeting domain, a PKA-binding domain, and regions for interaction with PDE4D3, calcineurin, and ERK5. Through these interactions, AKAP6 coordinates local cAMP signaling, calcium handling, and gene expression in cardiac and neuronal cells. Its expression is highest in heart and brain, and dysregulation contributes to cardiac hypertrophy and neuropsychiatric disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AKAP6 Knockout HEK293 Cell Line | EDJ-KQ6598 | Human | 9472 | Details Get a Quote |
| AKAP6 Knockout A-549 Cell Line | EDJ-KQ30822 | Human | 9472 | Details Get a Quote |
| AKAP6 Knockout HeLa Cell Line | EDJ-KQ55174 | Human | 9472 | Details Get a Quote |
| AKAP6 Knockout HCT 116 Cell Line | EDJ-KQ72114 | Human | 9472 | Details Get a Quote |
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