GUK1: Guanylate Kinase 1
A key enzyme in nucleotide metabolism and cellular energy homeostasis
Gene Information Card
| Symbol | GUK1 |
|---|---|
| Full Name | Guanylate Kinase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q42.13 |
| NCBI Gene ID | 2987 ncbi.nlm.nih.gov/gene/2987 |
| Ensembl ID | ENSG00000143727 |
| UniProt ID | Q16774 |
| OMIM ID | 139270 |
| HGNC ID | 4691 |
| Aliases | GMK, GUK, GUK1A, GUK1B |
Description
GUK1 encodes guanylate kinase 1, a cytosolic enzyme that catalyzes the reversible phosphorylation of GMP to GDP using ATP as a phosphate donor. This reaction is essential for nucleotide salvage, cGMP metabolism, and maintaining cellular guanine nucleotide pools. The enzyme is ubiquitously expressed and plays a role in cell proliferation and signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Somatic mutations and altered expression may disrupt nucleotide pool balance, affecting DNA replication and repair. | COSMIC database reports mutations in colorectal, lung, and breast cancers. |
| Hemolytic anemia (rare) | Deficiency in GUK1 activity may impair erythrocyte nucleotide metabolism, leading to reduced ATP levels. | ClinVar and OMIM list rare variants associated with hemolytic anemia. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 10.8 | Medium |
| Heart | 8.3 | Medium |
| Brain | 6.1 | Low |
| Skeletal Muscle | 15.2 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.7 | High expression in embryonic kidney cells |
| HeLa | 11.2 | Moderate expression in cervical cancer cells |
| HepG2 | 13.0 | High expression in liver cancer cells |
| K562 | 9.5 | Moderate expression in leukemia cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.274C>T (p.Arg92Cys) | Missense | 0.01% (gnomAD) | Reduced catalytic activity in vitro |
| c.389G>A (p.Arg130His) | Missense | 0.005% | Potential loss of function; reported in ClinVar |
| c.1A>G (p.Met1Val) | Start loss | <0.001% | Likely loss of function; associated with hemolytic anemia |
Mutation functional classification
Loss of Function (LOF)
Missense and start-loss variants reduce or abolish enzymatic activity, impairing GMP phosphorylation.
Gain of Function (GOF)
No gain-of-function mutations have been reported for GUK1.
Dominant Negative (DN)
No dominant-negative effects have been described for GUK1.
View complete mutation data：
Gene Ontology (GO)
| • guanylate kinase activity (GO:0004385) | • ATP binding (GO:0005524) |
| • purine nucleotide metabolic process (GO:0006163) | • cytoplasm (GO:0005737) |
| • cytosol (GO:0005829) |
Pathways
• Purine metabolism (KEGG: hsa00230)
• Pyrimidine metabolism (KEGG: hsa00240)
• cGMP-PKG signaling pathway (Reactome: R-HSA-418594)
Protein Summary
Guanylate kinase 1 (GUK1) is a 21.9 kDa monomeric enzyme that catalyzes the ATP-dependent phosphorylation of GMP to GDP. It belongs to the guanylate kinase family and contains a conserved ATP-binding domain. The protein is widely expressed and localizes to the cytosol. Structural studies show a typical alpha/beta fold with a central beta-sheet flanked by alpha-helices.
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