PTCH2: Patched 2 Gene in Hedgehog Signaling and Cancer
Comprehensive genomic and clinical resource for PTCH2, a tumor suppressor gene implicated in basal cell carcinoma and medulloblastoma.
Gene Information Card
| Symbol | PTCH2 |
|---|---|
| Full Name | Patched 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p34.1 |
| NCBI Gene ID | 8643 ncbi.nlm.nih.gov/gene/8643 |
| Ensembl ID | ENSG00000117479 |
| UniProt ID | Q9Y6C5 |
| OMIM ID | 603673 |
| HGNC ID | 9586 |
| Aliases | PTC2, PTC-2, patched homolog 2 |
Description
PTCH2 (Patched 2) is a tumor suppressor gene that encodes a transmembrane receptor for the Hedgehog (Hh) signaling pathway. It negatively regulates the pathway by inhibiting Smoothened (SMO) in the absence of Hh ligands. PTCH2 is homologous to PTCH1 but has distinct expression patterns and functions. Loss-of-function mutations in PTCH2 are associated with increased susceptibility to basal cell carcinoma and medulloblastoma, and it is implicated in Gorlin syndrome (nevoid basal cell carcinoma syndrome) in some cases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Basal cell carcinoma | Loss-of-function mutations in PTCH2 lead to constitutive activation of Hedgehog signaling, promoting tumorigenesis. | PMID: 11536076; COSMIC |
| Medulloblastoma | PTCH2 mutations contribute to Hedgehog-driven medulloblastoma, particularly in the SHH subtype. | PMID: 12118247; ClinVar |
| Gorlin syndrome (nevoid basal cell carcinoma syndrome) | Rare germline PTCH2 mutations can phenocopy PTCH1-related Gorlin syndrome. | OMIM #603673; PMID: 16905682 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | Medium |
| Cerebellum | 8.3 | Medium |
| Lung | 5.1 | Low |
| Kidney | 4.2 | Low |
| Liver | 2.8 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | 15.2 | High expression in skin-derived cells |
| DAOY (medulloblastoma) | 9.8 | Moderate expression |
| A549 (lung carcinoma) | 6.4 | Low expression |
| HEK293 (embryonic kidney) | 3.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2564G>A (p.Arg855His) | Missense | 0.2% in BCC | Loss of function; reduced inhibition of SMO |
| c.1234C>T (p.Arg412*) | Nonsense | 0.1% in medulloblastoma | Truncation; complete loss of function |
| c.1789_1790del (p.Leu597fs) | Frameshift | 0.05% in Gorlin-like syndrome | Loss of function; premature stop codon |
Mutation functional classification
Loss of Function (LOF)
Most PTCH2 mutations are loss-of-function, leading to unchecked Hedgehog signaling and tumor growth.
Gain of Function (GOF)
No gain-of-function mutations have been reported for PTCH2.
Dominant Negative (DN)
Some missense mutations may act in a dominant-negative manner by interfering with wild-type PTCH2 function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • patched binding (GO:0005113) | • signal transduction (GO:0007165) |
| • integral component of membrane (GO:0016021) | • smoothened signaling pathway (GO:0007224) |
| • positive regulation of transcription by RNA polymerase II (GO:0045944) |
Pathways
• Hedgehog signaling pathway (KEGG: hsa04340)
• Developmental biology (Reactome: R-HSA-1266738)
Protein Summary
PTCH2 is a 12-pass transmembrane protein that functions as a receptor for Sonic Hedgehog (SHH) and Indian Hedgehog (IHH). It forms a receptor complex with SMO and inhibits SMO activity in the absence of ligand. Upon Hh binding, PTCH2 internalizes and allows SMO to activate downstream transcription factors (GLI1-3). PTCH2 is structurally similar to PTCH1 but has a shorter C-terminal domain and different tissue distribution. It is expressed in skin, cerebellum, and lung, and its loss contributes to Hedgehog pathway hyperactivation in cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PTCH2 Knockout HEK293 Cell Line | EDJ-KQ911 | Human | 8643 | Details Get a Quote |
| PTCH2 Knockout HeLa Cell Line | EDJ-KQ54967 | Human | 8643 | Details Get a Quote |
| PTCH2 Knockout A-549 Cell Line | EDJ-KQ63449 | Human | 8643 | Details Get a Quote |
| PTCH2 Knockout HCT 116 Cell Line | EDJ-KQ71917 | Human | 8643 | Details Get a Quote |
