AKAP8
A-kinase anchoring protein 8, the group of A-kinase anchoring proteins
Basic information
Region (hg38): 19:15353385-15379815
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (133 variants)
- not_provided (27 variants)
- Long_QT_syndrome (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the AKAP8 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005858.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 15 | |||||
| missense | 120 | 16 | 141 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 120 | 24 | 12 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| AKAP8 | protein_coding | protein_coding | ENST00000269701 | 14 | 26414 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.664 | 0.336 | 125736 | 0 | 12 | 125748 | 0.0000477 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.0000295 | 453 | 453 | 1.00 | 0.0000303 | 4557 |
| Missense in Polyphen | 130 | 145.81 | 0.89158 | 1518 | ||
| Synonymous | -1.29 | 211 | 188 | 1.12 | 0.0000147 | 1314 |
| Loss of Function | 4.04 | 6 | 29.8 | 0.201 | 0.00000135 | 338 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000163 | 0.000152 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000231 | 0.000217 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000267 | 0.0000264 |
| Middle Eastern | 0.000231 | 0.000217 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.000173 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Anchoring protein that mediates the subcellular compartmentation of cAMP-dependent protein kinase (PKA type II) (PubMed:9473338). Acts as an anchor for a PKA-signaling complex onto mitotic chromosomes, which is required for maintenance of chromosomes in a condensed form throughout mitosis. Recruits condensin complex subunit NCAPD2 to chromosomes required for chromatin condensation; the function appears to be independent from PKA-anchoring (PubMed:10601332, PubMed:10791967, PubMed:11964380). May help to deliver cyclin D/E to CDK4 to facilitate cell cycle progression (PubMed:14641107). Required for cell cycle G2/M transition and histone deacetylation during mitosis. In mitotic cells recruits HDAC3 to the vicinity of chromatin leading to deacetylation and subsequent phosphorylation at 'Ser-10' of histone H3; in this function may act redundantly with AKAP8L (PubMed:16980585). Involved in nuclear retention of RPS6KA1 upon ERK activation thus inducing cell proliferation (PubMed:22130794). May be involved in regulation of DNA replication by acting as scaffold for MCM2 (PubMed:12740381). Enhances HMT activity of the KMT2 family MLL4/WBP7 complex and is involved in transcriptional regulation. In a teratocarcinoma cell line is involved in retinoic acid-mediated induction of developmental genes implicating H3 'Lys-4' methylation (PubMed:23995757). May be involved in recruitment of active CASP3 to the nucleus in apoptotic cells (PubMed:16227597). May act as a carrier protein of GJA1 for its transport to the nucleus (PubMed:26880274). Seems to involved in modulation of rDNA transcription. Preferentially binds GC-rich DNA in vitro and associates to GC-rich ribosomal RNA promoters (PubMed:26683827). Involved in modulation of Toll-like receptor signaling. Required for the cAMP-dependent suppression of TNF-alpha in early stages of LPS-induced macrophage activation; the function probably implicates targeting of PKA to NFKB1 (By similarity). {ECO:0000250|UniProtKB:Q63014, ECO:0000250|UniProtKB:Q9DBR0, ECO:0000269|PubMed:10601332, ECO:0000269|PubMed:10791967, ECO:0000269|PubMed:11964380, ECO:0000269|PubMed:16980585, ECO:0000269|PubMed:22130794, ECO:0000269|PubMed:26683827, ECO:0000269|PubMed:26880274, ECO:0000305|PubMed:14641107, ECO:0000305|PubMed:9473338}.;
- Pathway
- miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in squamous cell - TarBase;G Protein Signaling Pathways;akap95 role in mitosis and chromosome dynamics;TNFalpha
(Consensus)
Recessive Scores
- pRec
- 0.271
Intolerance Scores
- loftool
- 0.583
- rvis_EVS
- 0.5
- rvis_percentile_EVS
- 79.66
Haploinsufficiency Scores
- pHI
- 0.111
- hipred
- Y
- hipred_score
- 0.658
- ghis
- 0.512
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.962
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Akap8
- Phenotype
- craniofacial phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; digestive/alimentary phenotype; respiratory system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype;
Gene ontology
- Biological process
- mitotic cell cycle;mitotic chromosome condensation;signal transduction;protein transport;positive regulation of histone deacetylation;negative regulation of tumor necrosis factor production;regulation of histone phosphorylation;cell cycle G2/M phase transition;innate immune response;cellular response to lipopolysaccharide;cellular response to prostaglandin E stimulus
- Cellular component
- condensed chromosome;female pronucleus;nucleus;nucleoplasm;nucleolus;mitochondrion;Golgi apparatus;membrane;nuclear matrix
- Molecular function
- double-stranded DNA binding;RNA binding;protein binding;zinc ion binding;protein kinase A regulatory subunit binding;histone deacetylase binding;NF-kappaB binding