Patched domain-containing protein 1 (PTCHD1)

Patched domain-containing protein 1 (PTCHD1) is an 888-amino acid, 12-pass transmembrane protein expressed predominantly in the brain, particularly in regions critical for cognition such as the cerebellum, cortex, and temporal lobe[1][2][3][4][6]. PTCHD1 contains a sterol-sensing domain and a distinctive C-terminal PDZ-binding motif, positioning it within the "patched domain-containing" protein family, closely related to but functionally distinct from canonical Hedgehog pathway receptors such as PTCH1[1][2][3][4]. While structurally similar to receptors involved in the Hedgehog (Hh) signaling pathway, PTCHD1 does not directly bind Sonic Hedgehog ligand; instead, it interacts with various postsynaptic proteins, including scaffolding molecules (PSD95, SAP102) and components of retromer complexes (e.g., VPS35), indicating a role in synaptic signaling and trafficking[3][6]. PTCHD1 mutations or deletions are strongly linked to neurodevelopmental conditions, most notably autism spectrum disorder and X-linked intellectual disability, with a broad spectrum of clinical phenotypes including developmental delays, behavioral disturbances, and psychiatric symptoms[1][2][4][7]. There are currently no known drugs that directly target PTCHD1 or established biomarkers for patient selection, and its role in disease is primarily through genetic contribution rather than pharmacologic intervention[1][2][4][7].

Other names

SLC65C1FLJ30296AUTSX4CXDELp22.11DELXP22.11MGC149798