HIPK1 Gene - Homeodomain-Interacting Protein Kinase 1
A serine/threonine kinase involved in transcriptional regulation, apoptosis, and cancer signaling
Gene Information Card
| Symbol | HIPK1 |
|---|---|
| Full Name | Homeodomain-Interacting Protein Kinase 1 |
| Gene Type | Protein-coding |
| Chromosomal Location | 1p13.2 |
| NCBI Gene ID | 204851 ncbi.nlm.nih.gov/gene/204851 |
| Ensembl ID | ENSG00000163349 |
| UniProt ID | Q86Z02 |
| OMIM ID | 608003 |
| HGNC ID | 19012 |
| Aliases | Myak, Nbak2, Hipk1a, Hipk1b |
Description
HIPK1 (Homeodomain-Interacting Protein Kinase 1) encodes a serine/threonine kinase that belongs to the HIPK family. The protein interacts with homeodomain transcription factors and acts as a corepressor or coactivator of transcription. It is involved in diverse cellular processes including apoptosis, cell proliferation, DNA damage response, and development. HIPK1 is also implicated in tumorigenesis and neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | HIPK1 overexpression promotes cell proliferation and invasion via activation of NF-κB and Wnt/β-catenin pathways. | PMID: 23455477; COSMIC |
| Colorectal Cancer | HIPK1 is frequently amplified and contributes to tumor growth by regulating p53 and apoptosis. | PMID: 25605248; COSMIC |
| Acute Myeloid Leukemia | HIPK1 fusion with NUP98 (NUP98-HIPK1) drives leukemogenesis through aberrant transcriptional activation. | PMID: 17053056; COSMIC |
| Neuroblastoma | HIPK1 expression correlates with poor prognosis and MYCN amplification. | PMID: 21947009 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Liver | 6.1 | Low |
| Lung | 9.7 | Low |
| Kidney | 7.4 | Low |
| Testis | 15.2 | Medium |
| Spleen | 5.8 | Low |
| Pancreas | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 14.0 | Embryonic kidney; moderate expression |
| HeLa | 11.5 | Cervical carcinoma; moderate expression |
| MCF7 | 9.8 | Breast cancer; moderate expression |
| A549 | 7.2 | Lung cancer; low expression |
| K562 | 6.5 | Leukemia; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Trp) | Missense | 0.02% (gnomAD) | Unknown; predicted damaging by SIFT |
| c.567_568insA (p.Glu190fs) | Frameshift | <0.01% | Loss of function |
| NUP98-HIPK1 fusion | Gene fusion | Rare in AML | Oncogenic; constitutive kinase activity |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the kinase domain or C-terminal regulatory region are predicted to cause loss of kinase activity and impaired transcriptional regulation.
Gain of Function (GOF)
NUP98-HIPK1 fusion results in constitutive kinase activity and aberrant transcriptional activation, contributing to leukemogenesis.
Dominant Negative (DN)
Missense mutations in the kinase domain (e.g., p.Lys221Arg) may act as dominant-negative by competing with wild-type HIPK1 for substrates without catalytic activity.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway (Reactome: R-HSA-195721)
• p53 signaling pathway (KEGG: hsa04115)
• Apoptosis (KEGG: hsa04210)
• TNF signaling pathway (KEGG: hsa04668)
• Transcriptional regulation by HIPK1 (Reactome: R-HSA-6804757)
Protein Summary
HIPK1 is a 1,258-amino-acid serine/threonine kinase with an N-terminal kinase domain, a central interaction domain, and a C-terminal autoinhibitory region. It localizes to the nucleus and cytoplasm, and phosphorylates transcription factors such as p53, c-Myb, and homeodomain proteins. HIPK1 also functions as a scaffold in signaling complexes, modulating apoptosis, cell cycle, and DNA repair. Its activity is regulated by autophosphorylation and ubiquitin-mediated degradation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HIPK1 Knockout HEK293 Cell Line | EDJ-KQ3288 | Human | 204851 | Details Get a Quote |
| HIPK1 Knockout A-549 Cell Line | EDJ-KQ26205 | Human | 204851 | Details Get a Quote |
| HIPK1 Knockout HCT 116 Cell Line | EDJ-KQ26206 | Human | 204851 | Details Get a Quote |
| HIPK1 Knockout HeLa Cell Line | EDJ-KQ26207 | Human | 204851 | Details Get a Quote |
