ALPK1 Gene: Alpha-Kinase 1 - Function, Disease Associations, and Clinical Significance
A comprehensive biomedical overview of ALPK1, including gene structure, expression, mutations, and associated diseases.
Gene Information Card
| Symbol | ALPK1 |
|---|---|
| Full Name | Alpha-kinase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 4q25 |
| NCBI Gene ID | 80216 ncbi.nlm.nih.gov/gene/80216 |
| Ensembl ID | ENSG00000163331 |
| UniProt ID | Q96QP1 |
| OMIM ID | 607739 |
| HGNC ID | 20578 |
| Aliases | KIAA1529, MGC126514, MGC126516 |
Description
ALPK1 (alpha-kinase 1) is a protein-coding gene located on chromosome 4q25. It encodes a serine/threonine kinase that belongs to the alpha-kinase family, characterized by a conserved alpha-kinase domain. ALPK1 is involved in various cellular processes including inflammation, immune response, and cytoskeletal regulation. Mutations in ALPK1 have been associated with several diseases, including chronic kidney disease, gout, and certain cancers. The gene is expressed in multiple tissues, with highest levels in the kidney, liver, and immune cells.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Chronic kidney disease | ALPK1 variants may affect kidney function through altered kinase activity and inflammatory signaling. | ClinVar, PMID: 25305756 |
| Gout | ALPK1 polymorphisms are associated with hyperuricemia and gout susceptibility, possibly via regulation of urate transport. | ClinVar, PMID: 22156575 |
| Colorectal cancer | Somatic mutations in ALPK1 have been identified in colorectal tumors, potentially contributing to tumorigenesis through dysregulated kinase signaling. | COSMIC, PMID: 23535966 |
| Inflammatory bowel disease | ALPK1 is involved in innate immune response to bacterial infection; variants may influence susceptibility to IBD. | ClinVar, PMID: 28067907 |
| Retinitis pigmentosa | Rare ALPK1 mutations have been reported in patients with retinal degeneration, though the mechanism is not fully understood. | ClinVar, PMID: 28492532 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 25.3 | High |
| Liver | 18.7 | High |
| Lung | 12.4 | Medium |
| Spleen | 10.2 | Medium |
| Brain | 5.6 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | Embryonic kidney cells; moderate expression |
| HepG2 | 20.1 | Liver cancer cells; high expression |
| A549 | 8.3 | Lung carcinoma; low expression |
| MCF7 | 6.7 | Breast cancer; low expression |
| THP-1 | 22.5 | Monocytic leukemia; high expression in immune cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.710C>T (p.Pro237Leu) | Missense | 0.5% in general population | Associated with chronic kidney disease; may alter kinase activity |
| c.1483G>A (p.Val495Met) | Missense | 0.2% in East Asian populations | Linked to gout susceptibility; affects urate handling |
| c.2146A>G (p.Thr716Ala) | Missense | Somatic in colorectal cancer | Potential gain-of-function; promotes cell proliferation |
| c.2890C>T (p.Arg964Trp) | Missense | Rare in retinitis pigmentosa | Unknown; may affect retinal cell survival |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in ALPK1 are rare and have been associated with impaired immune response to bacterial ligands, leading to reduced inflammatory cytokine production.
Gain of Function (GOF)
Gain-of-function mutations, particularly in the kinase domain, have been observed in some cancers, leading to hyperactivation of signaling pathways such as NF-κB and promoting tumor growth.
Dominant Negative (DN)
Dominant-negative effects have been suggested for certain ALPK1 mutations that disrupt dimerization or substrate binding, interfering with wild-type function.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • protein serine/threonine kinase activity |
| • kinase activity | • signal transduction |
| • innate immune response | • regulation of inflammatory response |
| • cytoskeleton organization | • cell migration |
Pathways
• ALPK1-ADP-heptose-NF-κB pathway
• Innate immune system
• Cytoskeletal signaling
• Inflammatory response
Protein Summary
The ALPK1 protein is a 1259-amino acid serine/threonine kinase that contains an N-terminal alpha-kinase domain and a C-terminal region with multiple ankyrin repeats. It is a key mediator of innate immunity, recognizing bacterial ADP-heptose and activating NF-κB signaling. ALPK1 also phosphorylates myosin IIA and other cytoskeletal proteins, influencing cell motility and morphology. Its expression is ubiquitous but highest in kidney, liver, and immune cells. Dysregulation of ALPK1 is linked to inflammatory diseases and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ALPK1 Knockout HEK293 Cell Line | EDJ-KQ3058 | Human | 80216 | Details Get a Quote |
| ALPK1 Knockout A-549 Cell Line | EDJ-KQ24317 | Human | 80216 | Details Get a Quote |
| ALPK1 Knockout HCT 116 Cell Line | EDJ-KQ24318 | Human | 80216 | Details Get a Quote |
| ALPK1 Knockout HeLa Cell Line | EDJ-KQ24319 | Human | 80216 | Details Get a Quote |
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