AKAP10
protein-codingA-kinase anchoring protein 10, the group of A-kinase anchoring proteins
Gene summary
This gene encodes a member of the A-kinase anchor protein family. A-kinase anchor proteins bind to the regulatory subunits of protein kinase A (PKA) and confine the holoenzyme to discrete locations within the cell. The encoded protein is localized to mitochondria and interacts with both the type I and type II regulatory subunits of PKA. Polymorphisms in this gene may be associated with increased risk of arrhythmias and sudden cardiac death. [provided by RefSeq, May 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~74.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to AKAP10 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007202.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 5 | 7 | |||
| missense | 86 | 1 | 87 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 89 | 5 | 1 | 95 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_009133.2 | 15 | MANE Select | |
| Ensembl | ENSP00000225737.6 | 15 | MANE Select | |
| RefSeq | NP_001317081.1 | 14 | Standard | |
| Ensembl | ENSP00000378907.3 | 14 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| akap10 | Danio rerio | Structure: thrombocyte Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- G Protein Signaling Pathways
- Factors involved in megakaryocyte development and platelet production
- Hemostasis
Biological Process
- signal transduction
- blood coagulation
- protein localization
Molecular Function
- protein binding
- protein kinase A binding
Cellular Component
- mitochondrion
- cytosol
- plasma membrane
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000225737
- Coding exons
- 15
- Length
- 74042
- Individuals with no LoFs
- 125733
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 15
- Defined
- 125748
- p
- 0.0000596
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.35 | 263 | 332 | 0.791 | 0.0000163 | 4362 |
| Missense (PolyPhen) | 60 | 107.2 | 0.55971 | 1399 | ||
| Synonymous | -0.379 | 126 | 121 | 1.04 | 0.00000647 | 1241 |
| Loss of Function | 4.13 | 9 | 35.6 | 0.253 | 0.00000200 | 415 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000062 | 0.000062 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Differentially targeted protein that binds to type I and II regulatory subunits of protein kinase A and anchors them to the mitochondria or the plasma membrane. Although the physiological relevance between PKA and AKAPS with mitochondria is not fully understood, one idea is that BAD, a proapoptotic member, is phosphorylated and inactivated by mitochondria-anchored PKA. It cannot be excluded too that it may facilitate PKA as well as G protein signal transduction, by acting as an adapter for assembling multiprotein complexes. With its RGS domain, it could lead to the interaction to G-alpha proteins, providing a link between the signaling machinery and the downstream kinase (By similarity). {ECO:0000250}.;
- Disease
- DISEASE: Sudden cardiac death (SCD) [MIM:115080]: Unexpected rapid death due to cardiovascular collapse in a short time period, generally within one hour of initial symptoms. It is usually caused by the worsening of existing heart diseases. The sudden onset of symptoms, such as chest pain and cardiac arrhythmias, particularly ventricular tachycardia, can lead to the loss of consciousness and cardiac arrest followed by biological death. {ECO:0000269|PubMed:17485678}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Increased susceptibility to sudden cardiac death may be conferred by AKAP10 variants that are associated with markers of low vagus nerve sensitivity, e.g. fast basal heart rate and low heart rate variability.;
Recessive Scores
- pRec
- 0.131
Intolerance Scores
- LoFtool
- 0.564
- RVIS EVS
- 0.0000761
- RVIS percentile EVS
- 53.98
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- K
- Indispensability pred.
- E
- Indispensability score
- 0.956
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | Medium | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |