AKAP8L
protein-codingA-kinase anchoring protein 8 like
Gene summary
Enables histone deacetylase binding activity and lamin binding activity. Involved in several processes, including cell cycle G2/M phase transition; mitotic chromosome condensation; and regulation of mRNA export from nucleus. Located in chromatin; cytoplasm; and nuclear lumen. Part of ribonucleoprotein complex. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~39.1 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 AKAP8L variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014371.4. 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 | 1 | 1 | 2 | |||
| missense | 104 | 1 | 105 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 107 | 2 | 1 | 110 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055186.3 | 14 | MANE Select | |
| Ensembl | ENSP00000380557.3 | 14 | MANE Select | |
| RefSeq | NP_001278407.1 | 14 | Standard | |
| Ensembl | ENSP00000470906.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Epstein-Barr virus infection - Homo sapiens (human)
Biological Process
- mRNA processing
- mitotic chromosome condensation
- RNA splicing
- regulation of mRNA export from nucleus
- positive regulation of histone deacetylation
Molecular Function
- DNA binding
- RNA binding
- protein binding
- lamin binding
- DEAD/H-box RNA helicase binding
Cellular Component
- chromatin
- nucleus
- cytoplasm
- nuclear matrix
- PML body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000397410
- Coding exons
- 14
- Length
- 39094
- Individuals with no LoFs
- 124626
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 19
- Defined
- 124645
- p
- 0.0000762
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.03 | 335 | 393 | 0.853 | 0.0000243 | 4247 |
| Missense (PolyPhen) | 74 | 118.37 | 0.62518 | 1354 | ||
| Synonymous | 0.278 | 146 | 150 | 0.971 | 0.00000998 | 1191 |
| Loss of Function | 4.04 | 10 | 36.2 | 0.276 | 0.00000190 | 405 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00019 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000053 | 0.000046 | rare |
| European (Non-Finnish) | 0.000073 | 0.000071 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00017 | 0.00017 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Could play a role in constitutive transport element (CTE)-mediated gene expression by association with DHX9. Increases CTE-dependent nuclear unspliced mRNA export (PubMed:10748171, PubMed:11402034). Proposed to target PRKACA to the nucleus but does not seem to be implicated in the binding of regulatory subunit II of PKA (PubMed:10761695, PubMed:11884601). May be involved in nuclear envelope breakdown and chromatin condensation. May be involved in anchoring nuclear membranes to chromatin in interphase and in releasing membranes from chromating at mitosis (PubMed:11034899). May regulate the initiation phase of DNA replication when associated with TMPO isoform Beta (PubMed:12538639). 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 seems to act redundantly with AKAP8 (PubMed:16980585). May be involved in regulation of pre-mRNA splicing (PubMed:17594903). {ECO:0000269|PubMed:10748171, ECO:0000269|PubMed:11034899, ECO:0000269|PubMed:11402034, ECO:0000269|PubMed:11884601, ECO:0000269|PubMed:12538639, ECO:0000269|PubMed:16980585, ECO:0000305|PubMed:10761695}.; FUNCTION: (Microbial infection) Can synergize with DHX9 to activate the CTE-mediated gene expression of type D retroviruses. {ECO:0000269|PubMed:11402034}.;
Intolerance Scores
- LoFtool
- 0.227
- RVIS EVS
- -0.34
- RVIS percentile EVS
- 30.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.979
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |