HTRA1
Chr 10ADARHtrA serine peptidase 1
Also known as: ARMD7, CADASIL2, CARASIL, CARASIL2, HtrA, L56, ORF480, PRSS11
This serine protease regulates extracellular matrix proteins, insulin-like growth factor availability, and TGF-beta signaling pathways. Mutations cause cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL-like syndrome), which can follow either autosomal dominant or autosomal recessive inheritance patterns. The gene shows low constraint against loss-of-function variants, consistent with both recessive disease and the observation that some individuals may tolerate heterozygous mutations.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative, gain-of-function and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
HTRA1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools