AKAP4 Gene: A-Kinase Anchor Protein 4
Essential for sperm flagellar structure and male fertility
Gene Information Card
| Symbol | AKAP4 |
|---|---|
| Full Name | A-kinase anchor protein 4 |
| Gene Type | protein-coding |
| Chromosomal Location | Xp11.2 |
| NCBI Gene ID | 8852 ncbi.nlm.nih.gov/gene/8852 |
| Ensembl ID | ENSG00000147081 |
| UniProt ID | Q5JQC9 |
| OMIM ID | 300185 |
| HGNC ID | 376 |
| Aliases | AKAP-4, AKAP82, FSC1, HI, PRKA4, hAKAP82 |
Description
AKAP4 (A-kinase anchor protein 4) is a protein-coding gene located on the X chromosome. It encodes a major component of the sperm fibrous sheath, a cytoskeletal structure in the principal piece of the sperm flagellum. AKAP4 anchors protein kinase A (PKA) and other signaling molecules, playing a critical role in sperm motility, capacitation, and fertilization. Mutations in AKAP4 are associated with male infertility due to sperm flagellar defects.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Male infertility with sperm flagellar defects | Loss-of-function mutations in AKAP4 disrupt fibrous sheath assembly, impairing sperm motility. | ClinVar, OMIM |
| Primary ciliary dyskinesia (sperm-related) | Defective AKAP4 expression leads to abnormal flagellar structure and reduced motility. | NCBI Gene, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 45.2 | High |
| Fallopian tube | 1.3 | Low |
| Prostate | 0.8 | Low |
| Other tissues | <0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Spermatozoa | High | Specific to sperm flagellum |
| Testicular germ cells | High | Expressed during spermatogenesis |
| HeLa | Not detected | No expression in non-germline cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon, likely loss of function |
| c.1234C>T (p.Arg412*) | Nonsense | Rare | Premature stop, loss of function |
| c.567_568del (p.Glu190fs) | Frameshift | Rare | Frameshift, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported AKAP4 mutations are loss-of-function, leading to truncated or absent protein, causing sperm flagellar defects and male infertility.
Gain of Function (GOF)
No gain-of-function mutations reported for AKAP4.
Dominant Negative (DN)
No dominant-negative mutations reported for AKAP4.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005515 - protein binding | • GO:0005737 - cytoplasm |
| • GO:0005856 - cytoskeleton | • GO:0005929 - cilium |
| • GO:0036126 - sperm flagellum | • GO:0051015 - actin filament binding |
| • GO:0051260 - protein homooligomerization |
Pathways
• cAMP/PKA signaling pathway
• Sperm motility and capacitation
Protein Summary
AKAP4 is a 854-amino acid protein (UniProt Q5JQC9) that forms the fibrous sheath of the sperm flagellum. It contains an N-terminal targeting domain and a C-terminal PKA-binding domain. The protein self-assembles into a scaffold that anchors PKA, thereby regulating local cAMP signaling essential for sperm motility. AKAP4 is testis-specific and its expression is restricted to post-meiotic germ cells.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AKAP4 Knockout HEK293 Cell Line | EDJ-KQ3653 | Human | 8852 | Details Get a Quote |
| AKAP4 Knockout HeLa Cell Line | EDJ-KQ55022 | Human | 8852 | Details Get a Quote |
| AKAP4 Knockout A-549 Cell Line | EDJ-KQ63505 | Human | 8852 | Details Get a Quote |
| AKAP4 Knockout HCT 116 Cell Line | EDJ-KQ71972 | Human | 8852 | Details Get a Quote |
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