HTRA2

Chr 2AR

HtrA serine peptidase 2

Also known as: MGCA8, OMI, PARK13, PRSS25

NCBI Gene: 27429 ENSG00000115317 UniProt: O43464 OMIM: 606441

The protein is a mitochondrial serine protease that promotes apoptosis by cleaving inhibitor proteins and relieving their suppression of caspases. Mutations cause autosomal recessive Parkinson disease 13 and 3-methylglutaconic aciduria type VIII. The gene shows low constraint against loss-of-function variants (pLI 0.004, LOEUF 0.756), which is consistent with recessive inheritance where heterozygous carriers are typically unaffected.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a serine protease. The protein has been localized in the endoplasmic reticulum and interacts with an alternatively spliced form of mitogen-activated protein kinase 14. The protein has also been localized to the mitochondria with release to the cytosol following apoptotic stimulus. The protein is thought to induce apoptosis by binding the apoptosis inhibitory protein baculoviral IAP repeat-containing 4. Nuclear localization of this protein has also been observed. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Parkinson disease 13}MIM #610297

3-methylglutaconic aciduria, type VIIIMIM #617248

Clinical highlights

Gene-disease validity (ClinGen)

3-methylglutaconic aciduria type 8 · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.76

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — HTRA2