LHPP Gene: Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase
A tumor suppressor gene encoding a histidine phosphatase involved in cancer and metabolic regulation
Gene Information Card
| Symbol | LHPP |
|---|---|
| Full Name | Phospholysine phosphohistidine inorganic pyrophosphate phosphatase |
| Gene Type | Protein coding |
| Chromosomal Location | 10q26.13 |
| NCBI Gene ID | 64077 ncbi.nlm.nih.gov/gene/64077 |
| Ensembl ID | ENSG00000198924 |
| UniProt ID | Q9H008 |
| OMIM ID | 618391 |
| HGNC ID | 28858 |
| Aliases | HDHD2B, MGC26269 |
Description
LHPP encodes a histidine phosphatase that catalyzes the dephosphorylation of phospholysine and phosphohistidine residues. It acts as a tumor suppressor, particularly in hepatocellular carcinoma, by inhibiting cell proliferation and metastasis. The protein also plays a role in pyrophosphate metabolism and is implicated in neurological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | Loss of LHPP expression promotes tumor growth and metastasis via AKT/p53 signaling | PMID: 29622463, NCBI Gene |
| Bladder cancer | Reduced LHPP expression correlates with poor prognosis and increased cell invasion | PMID: 31570863, COSMIC |
| Major depressive disorder | LHPP variants associated with depression risk in genome-wide association studies | PMID: 30718914, ClinVar |
| Colorectal cancer | LHPP downregulation linked to Wnt/β-catenin pathway activation | PMID: 32467234, COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 8.3 | Medium |
| Brain | 6.1 | Low |
| Heart | 4.7 | Low |
| Lung | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line |
| HEK293 | 9.8 | Embryonic kidney cells |
| A549 | 4.1 | Lung adenocarcinoma cells |
| MCF7 | 2.5 | Breast cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.487C>T (p.Arg163Trp) | Missense | <0.01% | Loss of phosphatase activity, ClinVar |
| c.632A>G (p.Tyr211Cys) | Missense | <0.01% | Unknown significance, COSMIC |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Likely loss of function, ClinVar |
Mutation functional classification
Loss of Function (LOF)
Missense mutations in the catalytic domain (e.g., p.Arg163Trp) reduce phosphatase activity, impairing tumor suppression.
Gain of Function (GOF)
No gain-of-function mutations reported in LHPP.
Dominant Negative (DN)
No dominant-negative mutations described for LHPP.
View complete mutation data：
Gene Ontology (GO)
| • acid phosphatase activity (GO:0003993) | • cytoplasm (GO:0005737) |
| • cytosol (GO:0005829) | • phosphatase activity (GO:0016791) |
| • metal ion binding (GO:0046872) | • extracellular exosome (GO:0070062) |
Pathways
• Histidine metabolism (Reactome R-HSA-71291)
• Pyrophosphate hydrolysis (KEGG ko00760)
Protein Summary
LHPP is a 271-amino acid histidine phosphatase localized in the cytoplasm and cytosol. It hydrolyzes phospholysine and phosphohistidine, regulating protein phosphorylation status. The protein acts as a tumor suppressor by modulating AKT and p53 pathways. Its expression is reduced in multiple cancers, and loss correlates with poor prognosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LHPP Knockout HEK293 Cell Line | EDJ-KQ14068 | Human | 64077 | Details Get a Quote |
| LHPP Knockout A-549 Cell Line | EDJ-KQ43974 | Human | 64077 | Details Get a Quote |
| LHPP Knockout HCT 116 Cell Line | EDJ-KQ43975 | Human | 64077 | Details Get a Quote |
| LHPP Knockout HeLa Cell Line | EDJ-KQ43976 | Human | 64077 | Details Get a Quote |
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