ALPK3 Gene: Alpha-Kinase 3 in Cardiomyopathy and Development
Comprehensive genomic and proteomic overview of ALPK3, a cardiac alpha-kinase associated with dilated cardiomyopathy and congenital heart defects.
Gene Information Card
| Symbol | ALPK3 |
|---|---|
| Full Name | Alpha-kinase 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q25.3 |
| NCBI Gene ID | 57538 ncbi.nlm.nih.gov/gene/57538 |
| Ensembl ID | ENSG00000136383 |
| UniProt ID | Q96L96 |
| OMIM ID | 617608 |
| HGNC ID | 20887 |
| Aliases | MAK, KIAA1330, cardiomyopathy-associated protein 3 |
Description
ALPK3 (alpha-kinase 3) encodes a member of the alpha-kinase family, characterized by a catalytic domain distinct from conventional protein kinases. The protein is predominantly expressed in cardiac and skeletal muscle and plays a critical role in sarcomere assembly, cardiac development, and maintenance of myocardial structure. Biallelic loss-of-function mutations in ALPK3 cause autosomal recessive dilated cardiomyopathy (DCM) with or without congenital heart defects, while heterozygous variants may predispose to adult-onset DCM.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dilated cardiomyopathy 1MM (CMD1MM) | Biallelic loss-of-function mutations disrupt sarcomere integrity and cardiac contractility, leading to DCM. | ClinVar, OMIM #617608 |
| Congenital heart defects (e.g., ventricular septal defect) | ALPK3 deficiency impairs embryonic cardiac morphogenesis, often co-occurring with DCM. | OMIM, NCBI Gene |
| Hypertrophic cardiomyopathy (HCM) | Rare missense variants may alter kinase activity, contributing to HCM phenotype. | ClinVar, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 45.2 | High |
| Skeletal muscle | 38.7 | High |
| Testis | 12.1 | Medium |
| Brain | 3.5 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (iPSC-derived) | 52.8 | High expression; essential for sarcomere organization |
| Skeletal muscle myoblasts | 41.3 | High; involved in myotube formation |
| HEK293 | 2.1 | Low; not endogenous |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.334C>T (p.Arg112Ter) | Nonsense | Rare | Loss of function; truncation leads to DCM |
| c.1234_1235del (p.Lys412GlufsTer3) | Frameshift deletion | Rare | Loss of function; associated with severe early-onset DCM |
| c.2155G>A (p.Gly719Arg) | Missense | Unknown | Likely damaging; reported in HCM cases |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function (nonsense, frameshift, splice-site) causes autosomal recessive dilated cardiomyopathy with or without congenital heart defects.
Gain of Function (GOF)
Not established; no activating mutations reported in ALPK3.
Dominant Negative (DN)
Possible for some missense variants in heterozygous state, but evidence limited.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004672 – protein kinase activity | • GO:0005524 – ATP binding |
| • GO:0005856 – cytoskeleton | • GO:0030017 – sarcomere |
| • GO:0007517 – muscle organ development | • GO:0086003 – cardiac muscle cell contraction |
Pathways
• Cardiac muscle contraction (KEGG: hsa04260)
• Sarcomere assembly and maintenance (Reactome: R-HSA-390522)
Protein Summary
ALPK3 is a 1,480-amino-acid alpha-kinase with an N-terminal kinase domain and a C-terminal region containing multiple ankyrin repeats. It localizes to the sarcomere Z-disc and M-band, where it phosphorylates substrates involved in myofibril assembly and stability. The protein is essential for normal cardiac development and function; its deficiency leads to sarcomere disorganization, impaired contractility, and cardiomyopathy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ALPK3 Knockout HEK293 Cell Line | EDJ-KQ2035 | Human | 57538 | Details Get a Quote |
| ALPK3 Knockout HeLa Cell Line | EDJ-KQ56861 | Human | 57538 | Details Get a Quote |
| ALPK3 Knockout A-549 Cell Line | EDJ-KQ65375 | Human | 57538 | Details Get a Quote |
| ALPK3 Knockout HCT 116 Cell Line | EDJ-KQ73814 | Human | 57538 | Details Get a Quote |
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