HIPK2 Gene: Homeodomain-Interacting Protein Kinase 2
Key regulator of DNA damage response, apoptosis, and tumor suppression
Gene Information Card
| Symbol | HIPK2 |
|---|---|
| Full Name | Homeodomain-Interacting Protein Kinase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q34 |
| NCBI Gene ID | 28996 ncbi.nlm.nih.gov/gene/28996 |
| Ensembl ID | ENSG00000164362 |
| UniProt ID | Q9H2X6 |
| OMIM ID | 606868 |
| HGNC ID | 14402 |
| Aliases | PRO0473, STK-17B, hHIPk2 |
Description
HIPK2 (Homeodomain-Interacting Protein Kinase 2) is a serine/threonine kinase that phosphorylates homeodomain transcription factors and plays a critical role in DNA damage response, apoptosis, and cell cycle regulation. It acts as a co-repressor for several transcription factors and is involved in p53-mediated apoptosis. HIPK2 is considered a tumor suppressor gene, and its dysregulation is implicated in various cancers and fibrotic diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Loss of HIPK2 expression reduces p53-mediated apoptosis, promoting tumorigenesis | PMID: 19029980; COSMIC |
| Breast cancer | HIPK2 downregulation correlates with poor prognosis and resistance to chemotherapy | PMID: 21725308; ClinVar |
| Renal cell carcinoma | HIPK2 inactivation via promoter methylation leads to increased cell proliferation | PMID: 23108493; COSMIC |
| Liver fibrosis | HIPK2 promotes hepatic stellate cell apoptosis; loss exacerbates fibrosis | PMID: 23395172; OMIM |
| Acute myeloid leukemia | HIPK2 mutations (e.g., missense) associated with altered kinase activity | PMID: 25207736; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 8.2 | Medium |
| Heart | 6.5 | Medium |
| Liver | 5.1 | Low |
| Kidney | 7.3 | Medium |
| Lung | 4.8 | Low |
| Colon | 9.1 | Medium |
| Breast | 6.0 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 12.4 | High expression; commonly used for functional studies |
| HeLa | 8.7 | Medium expression; cervical cancer line |
| MCF7 | 5.2 | Low expression; breast cancer line |
| HCT116 | 10.1 | High expression; colorectal cancer line |
| A549 | 6.8 | Medium expression; lung cancer line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1342C>T (p.Arg448Trp) | Missense | 0.2% (COSMIC) | Reduced kinase activity; loss of pro-apoptotic function |
| c.1873G>A (p.Glu625Lys) | Missense | 0.1% (COSMIC) | Altered substrate binding; potential gain-of-function |
| c.2215_2216del (p.Glu739fs) | Frameshift | <0.1% (COSMIC) | Truncated protein; loss of function |
| c.1A>G (p.Met1Val) | Start loss | <0.1% (ClinVar) | No protein expression; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most HIPK2 mutations in cancer are loss-of-function, reducing kinase activity or protein stability, impairing p53-mediated apoptosis and DNA repair.
Gain of Function (GOF)
Rare; some missense variants (e.g., p.Glu625Lys) may alter substrate specificity, potentially promoting oncogenic signaling.
Dominant Negative (DN)
Not well documented; truncated forms could theoretically interfere with wild-type HIPK2 dimerization.
View complete mutation data：
Gene Ontology (GO)
Pathways
• p53 signaling pathway (KEGG: hsa04115)
• Apoptosis (KEGG: hsa04210)
• DNA damage response (Reactome: R-HSA-5693606)
• HIPK2-mediated phosphorylation of p53 (Reactome: R-HSA-6804757)
Protein Summary
HIPK2 is a 1198-amino acid serine/threonine kinase with an N-terminal kinase domain, a homeodomain-interacting region, and a C-terminal autoinhibitory domain. It localizes to nuclear speckles and phosphorylates key substrates including p53 (at Ser46), CtBP1, and PML. HIPK2 activity is tightly regulated by sumoylation, ubiquitination, and subcellular localization. Its tumor suppressor role is mediated through induction of apoptosis in response to genotoxic stress.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HIPK2 Knockout HEK293 Cell Line | EDJ-KQ3146 | Human | 28996 | Details Get a Quote |
| HIPK2 Knockout A-549 Cell Line | EDJ-KQ24538 | Human | 28996 | Details Get a Quote |
| HIPK2 Knockout HCT 116 Cell Line | EDJ-KQ24539 | Human | 28996 | Details Get a Quote |
| HIPK2 Knockout HeLa Cell Line | EDJ-KQ24540 | Human | 28996 | Details Get a Quote |
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