SPEG (Striated Muscle Enriched Protein Kinase)
A critical regulator of cardiac and skeletal muscle function, associated with dilated cardiomyopathy and centronuclear myopathy.
Gene Information Card
| Symbol | SPEG |
|---|---|
| Full Name | Striated Muscle Enriched Protein Kinase |
| Gene Type | Protein coding |
| Chromosomal Location | 2q35 |
| NCBI Gene ID | 10290 ncbi.nlm.nih.gov/gene/10290 |
| Ensembl ID | ENSG00000115977 |
| UniProt ID | Q15772 |
| OMIM ID | 615950 |
| HGNC ID | 11203 |
| Aliases | APEG1, BPEG, SPEGalpha, SPEGbeta |
Description
SPEG (Striated Muscle Enriched Protein Kinase) encodes a protein kinase that is predominantly expressed in cardiac and skeletal muscle. It plays a crucial role in myofibril organization, calcium handling, and muscle contraction. Mutations in SPEG are associated with dilated cardiomyopathy (DCM) and centronuclear myopathy (CNM). The gene produces multiple isoforms through alternative splicing, including SPEGalpha and SPEGbeta.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dilated Cardiomyopathy (DCM) | Loss-of-function mutations impair myofibril integrity and calcium homeostasis, leading to ventricular dilation and systolic dysfunction. | ClinVar, OMIM |
| Centronuclear Myopathy (CNM) | Recessive mutations disrupt muscle fiber maturation and nuclear positioning, causing congenital muscle weakness. | OMIM, PubMed |
| Left Ventricular Noncompaction (LVNC) | SPEG variants may contribute to abnormal myocardial trabeculation, though mechanism is less defined. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 45.2 | High |
| Skeletal Muscle | 38.7 | High |
| Esophagus | 6.1 | Low |
| Thyroid | 4.8 | Low |
| Testis | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (iPSC-derived) | 52.3 | High expression in differentiated cardiac cells |
| Skeletal muscle myotubes | 41.5 | High expression in mature muscle fibers |
| HeLa | 0.8 | Very low expression |
| HEK293 | 0.5 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | Rare | Loss of function, truncation of kinase domain |
| c.2567_2568del (p.Leu856fs) | Frameshift | Rare | Loss of function, premature termination |
| c.3452G>A (p.Arg1151Gln) | Missense | Rare | Impaired kinase activity, associated with DCM |
| c.4567C>T (p.Arg1523Trp) | Missense | Rare | Reduced protein stability, linked to CNM |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and splice-site mutations that lead to truncated or absent SPEG protein, resulting in dilated cardiomyopathy and centronuclear myopathy.
Gain of Function (GOF)
Not reported for SPEG; no activating mutations have been described.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type SPEG function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Cardiac muscle contraction (KEGG: hsa04260)
• cGMP-PKG signaling pathway (KEGG: hsa04022)
• Calcium signaling pathway (KEGG: hsa04020)
Protein Summary
SPEG is a large multidomain protein kinase (approximately 300 kDa) containing two serine/threonine kinase domains, multiple immunoglobulin-like domains, and a fibronectin type III domain. It localizes to the Z-disc and sarcoplasmic reticulum in striated muscle, where it phosphorylates key targets involved in excitation-contraction coupling and myofibril stability. SPEG interacts with junctophilin-2 (JPH2) and regulates calcium release from the sarcoplasmic reticulum. Loss of SPEG leads to disrupted calcium handling, myofibrillar disarray, and progressive muscle weakness.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPEG Knockout HEK293 Cell Line | EDJ-KQ6997 | Human | 10290 | Details Get a Quote |
| SPEGNB Knockout HEK293 Cell Line | EDJ-KQ15480 | Human | 100996693 | Details Get a Quote |
| SPEG Knockout A-549 Cell Line | EDJ-KQ31726 | Human | 10290 | Details Get a Quote |
| SPEG Knockout HCT 116 Cell Line | EDJ-KQ31727 | Human | 10290 | Details Get a Quote |
| SPEG Knockout HeLa Cell Line | EDJ-KQ31728 | Human | 10290 | Details Get a Quote |
