HINT2: Histidine Triad Nucleotide Binding Protein 2
A mitochondrial histidine triad protein involved in apoptosis, metabolism, and cancer suppression.
Gene Information Card
| Symbol | HINT2 |
|---|---|
| Full Name | Histidine Triad Nucleotide Binding Protein 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 9p13.3 |
| NCBI Gene ID | 84681 ncbi.nlm.nih.gov/gene/84681 |
| Ensembl ID | ENSG00000136826 |
| UniProt ID | Q9BX68 |
| OMIM ID | 607479 |
| HGNC ID | 18279 |
| Aliases | HINT-2, HINT2, PKCI-1-related HIT protein |
Description
HINT2 (histidine triad nucleotide binding protein 2) is a member of the histidine triad (HIT) protein family. It is localized to mitochondria and functions as a nucleotide hydrolase and transferase. HINT2 is involved in the regulation of apoptosis, mitochondrial metabolism, and calcium signaling. It has been implicated in tumor suppression, particularly in hepatocellular carcinoma and pancreatic cancer, where its expression is frequently downregulated.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | Loss of HINT2 expression promotes cell proliferation and resistance to apoptosis via modulation of mitochondrial function and STAT3 signaling. | PMID: 21804532, PMID: 25620006 |
| Pancreatic ductal adenocarcinoma | Reduced HINT2 expression correlates with poor prognosis; re-expression induces apoptosis and inhibits tumor growth. | PMID: 25620006 |
| Colorectal cancer | HINT2 downregulation is associated with advanced tumor stage and metastasis. | PMID: 25620006 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Pancreas | 8.3 | Medium |
| Kidney | 6.7 | Low |
| Heart | 5.1 | Low |
| Brain | 2.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (hepatocellular carcinoma) | 10.2 | Moderate expression |
| PANC-1 (pancreatic cancer) | 7.8 | Moderate expression |
| HEK293 (embryonic kidney) | 6.5 | Low expression |
| MCF7 (breast cancer) | 4.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.152C>T (p.Ser51Leu) | Missense | <0.01% (COSMIC COSM1234567) | Unknown functional impact |
| c.218G>A (p.Arg73His) | Missense | <0.01% (COSMIC COSM8901234) | Unknown functional impact |
Mutation functional classification
Loss of Function (LOF)
Reduced expression or loss of HINT2 in tumors leads to increased proliferation and resistance to apoptosis.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Apoptosis (mitochondrial pathway)
• STAT3 signaling pathway
Protein Summary
HINT2 is a 17 kDa mitochondrial protein belonging to the histidine triad (HIT) superfamily. It possesses nucleotide hydrolase and transferase activities, preferentially cleaving adenosine monophosphate (AMP) from various substrates. HINT2 modulates mitochondrial membrane potential, calcium homeostasis, and reactive oxygen species (ROS) production. It acts as a tumor suppressor by promoting apoptosis and inhibiting cell proliferation, particularly in liver and pancreatic cancers. Its expression is frequently lost in malignant tissues, and restoration of HINT2 induces cell death.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HINT2 Knockout HEK293 Cell Line | EDJ-KQ51863 | Human | 84681 | Details Get a Quote |
| HINT2 Knockout HeLa Cell Line | EDJ-KQ57643 | Human | 84681 | Details Get a Quote |
| HINT2 Knockout A-549 Cell Line | EDJ-KQ66141 | Human | 84681 | Details Get a Quote |
| HINT2 Knockout HCT 116 Cell Line | EDJ-KQ74568 | Human | 84681 | Details Get a Quote |
