HINT1: Histidine Triad Nucleotide Binding Protein 1
A key regulator of purine metabolism and tumor suppression, implicated in inherited peripheral neuropathies and cancer.
Gene Information Card
| Symbol | HINT1 |
|---|---|
| Full Name | Histidine Triad Nucleotide Binding Protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q31.2 |
| NCBI Gene ID | 3094 ncbi.nlm.nih.gov/gene/3094 |
| Ensembl ID | ENSG00000113721 |
| UniProt ID | P49773 |
| OMIM ID | 601314 |
| HGNC ID | 4912 |
| Aliases | PKCI-1, HINT, PRKCNH1, NMAN |
Description
HINT1 (histidine triad nucleotide binding protein 1) is a member of the HIT (histidine triad) family of nucleotide hydrolases and transferases. It functions as a homodimeric purine phosphoramidase that hydrolyzes purine nucleotide phosphoramidates and may act as a tumor suppressor. HINT1 is ubiquitously expressed and plays roles in transcription regulation, apoptosis, and DNA repair. Biallelic mutations in HINT1 cause autosomal recessive axonal neuropathy with neuromyotonia (HINT1-related neuropathy).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| HINT1-related axonal neuropathy with neuromyotonia | Loss of HINT1 enzymatic activity due to biallelic mutations leads to impaired purine metabolism and altered neuromuscular junction signaling. | Multiple families; confirmed by functional studies (PMID: 22522455, 25788560) |
| Various cancers (e.g., breast, lung, colon) | Reduced HINT1 expression or loss of heterozygosity may contribute to tumor progression; HINT1 acts as a haploinsufficient tumor suppressor in mouse models. | Mouse models and human tumor expression data (PMID: 15126327, 17909063) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 14.2 | Medium |
| Heart | 12.8 | Medium |
| Liver | 11.5 | Medium |
| Skeletal Muscle | 10.1 | Medium |
| Kidney | 9.8 | Low |
| Lung | 8.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 18.3 | High expression |
| HeLa | 15.6 | High expression |
| HepG2 | 12.1 | Medium expression |
| K562 | 9.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.110G>A (p.Arg37His) | Missense | ~40% of HINT1 neuropathy alleles | Loss of enzymatic activity; impaired dimerization |
| c.148C>T (p.Arg50*) | Nonsense | ~15% of HINT1 neuropathy alleles | Premature truncation; complete loss of function |
| c.91G>T (p.Glu31*) | Nonsense | Rare | Loss of function |
| c.3G>A (p.Met1?) | Start loss | Rare | No protein production |
Mutation functional classification
Loss of Function (LOF)
Most HINT1 mutations (missense, nonsense, frameshift) result in loss of enzymatic activity, leading to autosomal recessive axonal neuropathy with neuromyotonia.
Gain of Function (GOF)
No gain-of-function mutations reported for HINT1.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is recessive.
View complete mutation data：
Gene Ontology (GO)
| • GTP binding (GO:0005525) | • hydrolase activity (GO:0016787) |
| • phosphoramidase activity (GO:0004632) | • cytoplasm (GO:0005737) |
| • nucleus (GO:0005634) | • metal ion binding (GO:0046872) |
Pathways
• Purine metabolism (Reactome: R-HSA-74217)
• Apoptosis modulation (via PKC interaction)
Protein Summary
HINT1 is a 14 kDa homodimeric protein belonging to the histidine triad (HIT) superfamily. Each monomer contains a conserved HIT motif (His-X-His-X-His-XX) that coordinates a zinc ion and is essential for catalytic activity. The enzyme hydrolyzes purine nucleotide phosphoramidates and adenosine 5'-monophosphoramidate. HINT1 interacts with several transcription factors (e.g., MITF, TFIIH) and modulates apoptosis. Loss of function leads to accumulation of toxic nucleotide metabolites and neuromuscular dysfunction.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HINT1 Knockout HEK293 Cell Line | EDJ-KQ4869 | Human | 3094 | Details Get a Quote |
| HINT1 Knockout A-549 Cell Line | EDJ-KQ27655 | Human | 3094 | Details Get a Quote |
| HINT1 Knockout HCT 116 Cell Line | EDJ-KQ27656 | Human | 3094 | Details Get a Quote |
| HINT1 Knockout HeLa Cell Line | EDJ-KQ27657 | Human | 3094 | Details Get a Quote |
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