HTRA2: HtrA Serine Peptidase 2
Mitochondrial serine protease involved in apoptosis and cellular stress response
Gene Information Card
| Symbol | HTRA2 |
|---|---|
| Full Name | HtrA serine peptidase 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 2p13.1 |
| NCBI Gene ID | 27429 ncbi.nlm.nih.gov/gene/27429 |
| Ensembl ID | ENSG00000115365 |
| UniProt ID | O43464 |
| OMIM ID | 606441 |
| HGNC ID | 14376 |
| Aliases | OMI, PRSS25, PARK13 |
Description
HTRA2 (HtrA serine peptidase 2) encodes a mitochondrial serine protease that plays a key role in apoptosis by cleaving inhibitor of apoptosis proteins (IAPs) and promoting caspase activation. It also participates in mitochondrial protein quality control and cellular stress responses. Mutations in HTRA2 are associated with Parkinson disease and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Parkinson disease 13 (PARK13) | Loss-of-function mutations impair mitochondrial protease activity, leading to accumulation of damaged proteins and neuronal cell death | OMIM 606441; ClinVar |
| Colorectal cancer | Altered HTRA2 expression affects apoptosis regulation, promoting tumor cell survival | COSMIC; PubMed studies |
| Breast cancer | Dysregulation of HTRA2-mediated apoptosis contributes to chemoresistance | COSMIC; PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 15.3 | Medium |
| Liver | 8.7 | Low |
| Kidney | 10.1 | Medium |
| Testis | 18.9 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.2 | Cervical cancer cell line |
| HEK293 | 11.8 | Embryonic kidney cells |
| SH-SY5Y | 9.5 | Neuroblastoma cell line |
| MCF7 | 7.3 | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.364G>A (p.Gly122Ser) | Missense | Rare | Reduced protease activity; associated with Parkinson disease |
| c.497C>T (p.Pro166Leu) | Missense | Rare | Impaired mitochondrial localization; linked to neurodegeneration |
| c.1069G>A (p.Ala357Thr) | Missense | Rare | Decreased stability; reported in cancer |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Gly122Ser, p.Pro166Leu) reduce protease activity and mitochondrial function, leading to impaired apoptosis and neurodegeneration.
Gain of Function (GOF)
Not well documented; some cancer-associated variants may increase survival signaling.
Dominant Negative (DN)
Not reported for HTRA2.
View complete mutation data：
Gene Ontology (GO)
| • serine-type endopeptidase activity (GO:0004252) | • mitochondrion (GO:0005739) |
| • apoptotic process (GO:0006915) | • identical protein binding (GO:0042802) |
| • unfolded protein binding (GO:0051082) |
Pathways
• Apoptosis – intrinsic pathway (cleavage of XIAP)
• Mitochondrial protein quality control
• Cellular response to stress
Protein Summary
HTRA2 (Omi) is a 458-amino acid mitochondrial serine protease with an N-terminal mitochondrial targeting sequence, a central trypsin-like protease domain, and a C-terminal PDZ domain. Under normal conditions, it maintains mitochondrial proteostasis. Upon apoptotic stimuli, it is released into the cytosol where it cleaves IAPs, promoting caspase activation and cell death.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HTRA2 Knockout HEK293 Cell Line | EDJ-KQ51216 | Human | 27429 | Details Get a Quote |
| HTRA2 Knockout HeLa Cell Line | EDJ-KQ56066 | Human | 27429 | Details Get a Quote |
| HTRA2 Knockout A-549 Cell Line | EDJ-KQ64549 | Human | 27429 | Details Get a Quote |
| HTRA2 Knockout HCT 116 Cell Line | EDJ-KQ73009 | Human | 27429 | Details Get a Quote |
