CMPK1 (Cytidine/Uridine Monophosphate Kinase 1)
A key enzyme in pyrimidine nucleotide biosynthesis and metabolism, with roles in cancer and mitochondrial disorders.
Gene Information Card
| Symbol | CMPK1 |
|---|---|
| Full Name | Cytidine/Uridine Monophosphate Kinase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p33 |
| NCBI Gene ID | 51727 ncbi.nlm.nih.gov/gene/51727 |
| Ensembl ID | ENSG00000117593 |
| UniProt ID | P30085 |
| OMIM ID | 191710 |
| HGNC ID | 2443 |
| Aliases | CMK, UMK, UMP-CMPK, UMPK, CMPK, CK, UMK1 |
Description
CMPK1 encodes cytidine/uridine monophosphate kinase 1, a key enzyme in the pyrimidine salvage pathway that catalyzes the reversible phosphorylation of CMP, UMP, and dCMP to their respective diphosphates. This enzyme is essential for nucleotide pool balance, DNA/RNA synthesis, and cellular energy metabolism. It is ubiquitously expressed with highest levels in heart, skeletal muscle, and liver. CMPK1 is implicated in mitochondrial DNA maintenance disorders and is a target for anticancer prodrugs such as gemcitabine.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial DNA depletion syndrome 14 (encephalocardiomyopathic type) | Biallelic loss-of-function mutations in CMPK1 impair mitochondrial nucleotide salvage, leading to mtDNA depletion and respiratory chain dysfunction. | ClinVar, OMIM #191710 |
| Colorectal cancer | Overexpression of CMPK1 is associated with poor prognosis and may promote tumor growth by sustaining pyrimidine pools. | COSMIC, NCBI Gene |
| Pancreatic cancer | CMPK1 expression correlates with gemcitabine sensitivity; low expression confers chemoresistance. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 42.3 | High |
| Skeletal muscle | 38.1 | High |
| Liver | 25.7 | Medium |
| Kidney | 18.4 | Medium |
| Brain | 12.5 | Medium |
| Lung | 9.8 | Low |
| Pancreas | 7.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 35.6 | High expression |
| HeLa | 28.4 | High expression |
| HepG2 | 22.1 | Medium expression |
| A549 | 15.3 | Medium expression |
| MCF7 | 10.7 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.274C>T (p.Arg92Trp) | Missense | <0.01% (rare) | Loss of function; associated with mitochondrial DNA depletion syndrome |
| c.458G>A (p.Arg153Gln) | Missense | <0.01% (rare) | Loss of function; reduced catalytic activity |
| c.1A>G (p.Met1?) | Start loss | <0.01% (rare) | Loss of function; no protein produced |
Mutation functional classification
Loss of Function (LOF)
Biallelic missense or start-loss mutations in CMPK1 cause mitochondrial DNA depletion syndrome 14 due to impaired pyrimidine salvage.
Gain of Function (GOF)
Not reported in CMPK1.
Dominant Negative (DN)
Not reported in CMPK1.
View complete mutation data：
Gene Ontology (GO)
| • cytidylate kinase activity (GO:0004127) | • uridine kinase activity (GO:0004849) |
| • ATP binding (GO:0005524) | • UDP biosynthetic process (GO:0006225) |
| • UTP biosynthetic process (GO:0006228) | • cytoplasm (GO:0005737) |
| • cytosol (GO:0005829) | • nucleus (GO:0005634) |
Pathways
• Pyrimidine metabolism (KEGG: hsa00240)
• Metabolic pathways (KEGG: hsa01100)
• Nucleotide salvage pathway (Reactome: R-HSA-73621)
Protein Summary
CMPK1 is a 22 kDa cytosolic and nuclear enzyme that catalyzes the ATP-dependent phosphorylation of CMP, UMP, and dCMP to CDP, UDP, and dCDP, respectively. It is a homodimer with each subunit containing a conserved nucleoside monophosphate kinase domain. The protein is essential for maintaining intracellular pyrimidine nucleotide pools and is a target for activation of nucleoside analog prodrugs like gemcitabine and 5-fluorouracil. Structural studies show a typical alpha/beta fold with a P-loop for ATP binding.
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