AKAP5
protein-codingA-kinase anchoring protein 5, the group of A-kinase anchoring proteins
Gene summary
The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. The encoded protein binds to the RII-beta regulatory subunit of PKA, and also to protein kinase C and the phosphatase calcineurin. It is predominantly expressed in cerebral cortex and may anchor the PKA protein at postsynaptic densities (PSD) and be involved in the regulation of postsynaptic events. It is also expressed in T lymphocytes and may function to inhibit interleukin-2 transcription by disrupting calcineurin-dependent dephosphorylation of NFAT. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.0 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 AKAP5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004857.3. 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 | 1 | 1 | ||||
| missense | 58 | 3 | 2 | 63 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 58 | 3 | 3 | 64 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004848.3 | 1 | MANE Select | |
| Ensembl | ENSP00000378207.3 | 1 | MANE Select | |
| Ensembl | ENSP00000315615.5 | 1 | Standard | |
| Ensembl | ENSP00000811747.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- G Protein Signaling Pathways
- Developmental Biology
- Metabolism
- Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
- Regulation of insulin secretion
Biological Process
- protein targeting
- signal transduction
- adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
- negative regulation of adenylate cyclase activity
- chemical synaptic transmission
Molecular Function
- protein binding
- calmodulin binding
- adenylate cyclase binding
- SH3 domain binding
- protein phosphatase 2B binding
Cellular Component
- cytosol
- plasma membrane
- cytoplasmic side of plasma membrane
- postsynaptic density
- dendrite membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000394718
- Coding exons
- 1
- Length
- 9005
- Individuals with no LoFs
- 125679
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125681
- p
- 0.00000796
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.17 | 164 | 212 | 0.773 | 0.00000992 | 2811 |
| Missense (PolyPhen) | 28 | 42.15 | 0.6643 | 633 | ||
| Synonymous | 0.787 | 66 | 74.6 | 0.884 | 0.00000338 | 817 |
| Loss of Function | 2.68 | 2 | 12.1 | 0.166 | 5.08e-7 | 188 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May anchor the PKA protein to cytoskeletal and/or organelle-associated proteins, targeting the signal carried by cAMP to specific intracellular effectors. Association with to the beta2-adrenergic receptor (beta2-AR) not only regulates beta2-AR signaling pathway, but also the activation by PKA by switching off the beta2-AR signaling cascade.;
Intolerance Scores
- RVIS EVS
- 0.73
- RVIS percentile EVS
- 86.08
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.312
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |