AKAP4
protein-codingA-kinase anchoring protein 4, 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 is localized to the sperm flagellum and may be involved in the regulation of sperm motility. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [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 ~10.2 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 AKAP4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003886.3. 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 | 3 | 4 | 7 | |||
| missense | 83 | 9 | 92 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 87 | 13 | 0 | 100 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003877.2 | 6 | MANE Select | |
| Ensembl | ENSP00000351327.2 | 6 | MANE Select | |
| RefSeq | NP_647450.1 | 5 | Standard | |
| Ensembl | ENSP00000365232.3 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- G Protein Signaling Pathways
Biological Process
- signal transduction
- transmembrane receptor protein serine/threonine kinase signaling pathway
- single fertilization
- flagellated sperm motility
- motile cilium assembly
Molecular Function
- protein binding
- protein kinase A binding
Cellular Component
- nucleus
- cytoplasm
- cytoskeleton
- cAMP-dependent protein kinase complex
- Z disc
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000358526
- Coding exons
- 6
- Length
- 10259
- Individuals with no LoFs
- 124167
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 1
- Defined
- 124169
- p
- 0.00000805
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.784 | 270 | 309 | 0.875 | 0.0000219 | 5701 |
| Missense (PolyPhen) | 65 | 104.83 | 0.62005 | 2221 | ||
| Synonymous | -0.204 | 120 | 117 | 1.02 | 0.00000874 | 1589 |
| Loss of Function | 3.86 | 1 | 19.3 | 0.0518 | 0.00000129 | 397 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000038 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.000054 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Major structural component of sperm fibrous sheath. Plays a role in sperm motility. {ECO:0000269|PubMed:9822690}.;
Recessive Scores
- pRec
- 0.127
Intolerance Scores
- LoFtool
- 0.100
- RVIS EVS
- 0.67
- RVIS percentile EVS
- 84.61
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.444
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |