Affinage

PTCH1

Protein patched homolog 1 · UniProt Q13635

Length
1447 aa
Mass
160.5 kDa
Annotated
2026-06-10
100 papers in source corpus 16 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTCH1 is the receptor that sets the threshold of Hedgehog (Hh) pathway activity, controlling developmental patterning and acting as a tumor suppressor by restraining downstream signaling (PMID:25085974, PMID:16273213). Its membrane-embedded core is encircled by annular sterols that engage both a sterol-sensing domain (SSD) and an SSD-like domain on opposite faces of the protein, defining a route for sterol translocation across the bilayer that underlies its capacity to inhibit Smoothened (SMO) (PMID:31555730). PTCH1 physically associates with SMO and inhibits its signaling; an isoform-specific N-terminal region (exon 1B) is required for full SMO inhibition but is dispensable for the physical interaction (PMID:12203113), and the integrity of the SSD is critical, since a single missense substitution within it acts dominant-negatively to cause ectopic Hh target-gene activation and SMO stabilization (PMID:15042702). PTCH1 is itself a Gli transcriptional target acting through a single functional Gli-binding site engaged by GLI1/2/3, establishing a negative-feedback loop in which Shh- and SMO-driven activity converges on this site to upregulate Ptch1 and adapt pathway output over time (PMID:15087129, PMID:25833741); in the absence of Ptch1, the paralog Ptch2 mediates the ligand-dependent Shh response (PMID:25085974). Loss of PTCH1 function is achieved through mutational inactivation combined with epigenetic silencing of the intact allele via DNA methylation, with MeCP2 reading promoter methylation to repress PTCH1, and reactivation by methyltransferase/HDAC inhibition restores expression and prevents tumor formation (PMID:16273213, PMID:19155313, PMID:23333245). Beyond canonical signaling, PTCH1 functions as a proton-motive-force-driven multidrug efflux transporter that exports chemotherapeutics from cancer cells (PMID:30110910), and its internalization and trafficking are regulated by the co-receptor Gpr37l1 at peri-ciliary membranes (PMID:33350496).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2002 Medium

    Establishing how PTCH1 acts on SMO required determining whether physical interaction and functional inhibition are separable; multiple isoforms were shown to bind SMO yet differ in inhibitory capacity.

    Evidence Co-immunoprecipitation and luciferase reporter assays of PTCH1 isoforms in co-transfected cells

    PMID:12203113

    Open questions at the time
    • Structural basis of isoform-specific inhibition not defined
    • Did not establish the sterol-transport mechanism of inhibition
  2. 2004 High

    Defining the transcriptional logic of the Hh feedback loop, PTCH1 was shown to be induced through a single functional Gli-binding site shared by GLI1/2/3 and required for SHH/SMO-driven induction.

    Evidence Promoter-reporter assays, EMSA, and site-directed mutagenesis of Gli-binding sites

    PMID:15087129

    Open questions at the time
    • Did not address the role of the non-functional second putative Gli site
    • Tissue-specific use of the alternative promoters not resolved
  3. 2004 Medium

    Testing whether the sterol-sensing domain is functionally required, an SSD missense mutation was shown to act dominant-negatively in vivo without altering subcellular localization, distinguishing SSD-dependent function from trafficking.

    Evidence In vivo Drosophila transgenic expression with immunofluorescence and Hh target-gene analysis

    PMID:15042702

    Open questions at the time
    • Mechanism by which the SSD mutation disrupts SMO inhibition not defined
    • Relevance to vertebrate PTCH1 inferred from ortholog
  4. 2005 Medium

    Resolving how PTCH1 is inactivated in tumors retaining one allele, transcriptional silencing of the wild-type allele by promoter methylation was shown to combine with mutation of the other allele.

    Evidence Allele-specific RT-PCR and promoter methylation-reporter assays in Ptch1+/- mouse tumors

    PMID:16273213

    Open questions at the time
    • Factors directing allele-specific methylation not identified
    • Single tumor model context
  5. 2009 Medium

    Testing whether epigenetic silencing is causal and reversible in tumorigenesis, reducing Dnmt1 or treating with demethylating/HDAC inhibitors reactivated wild-type Ptch1 and prevented tumor formation.

    Evidence Genetic Dnmt1 reduction and pharmacological 5-aza-dC/VPA treatment in Ptch1+/- mice with methylation and ChIP readouts

    PMID:19155313

    Open questions at the time
    • Direct methylation reader not identified in this study
    • Specificity of pharmacological reactivation for Ptch1 not isolated
  6. 2011 Medium

    Probing SMO-independent signaling, PTCH1 was shown to transduce a non-canonical DHH-driven ERK phosphorylation signal conferring SMO-inhibitor resistance in CLL cells.

    Evidence SMO inhibitor and 5E1 antibody treatment, stromal co-culture, and phospho-ERK analysis in CLL cells

    PMID:22130798

    Open questions at the time
    • Molecular link between PTCH1 and ERK not defined
    • Generality beyond trisomy-12 CLL unknown
  7. 2013 Medium

    Identifying the methylation reader that silences PTCH1, MeCP2 was shown to mediate promoter hypermethylation-associated repression during hepatic stellate cell activation.

    Evidence siRNA knockdown of MeCP2 with bisulfite/MSP, 5-aza-dC treatment, and expression analysis

    PMID:23333245

    Open questions at the time
    • Whether MeCP2 acts directly or recruits other repressors not resolved
    • Single cell-type context
  8. 2014 High

    Determining the redundancy structure of the receptor system, Ptch2 was shown to sustain the ligand-dependent Shh response in the absence of Ptch1.

    Evidence Ptch1-/- and Ptch1-/-;Ptch2-/- knockout cells, 5E1 blocking antibody, and dominant-negative constructs in chick neural tube

    PMID:25085974

    Open questions at the time
    • Stage-dependent division of labor between Ptch1 and Ptch2 not fully mapped
    • Molecular distinction between the two receptors not defined
  9. 2014 Medium

    miR-155 was shown to directly target the PTCH1 3'UTR, defining a post-transcriptional route to PTCH1 downregulation with functional consequences in endothelial progenitor cells.

    Evidence Dual-luciferase 3'UTR reporter, miR-155 perturbation, and siRNA rescue with functional cell assays

    PMID:29545091

    Open questions at the time
    • In vivo relevance of the miR-155–PTCH1 axis not established
    • Hh-pathway dependence of the phenotype not isolated
  10. 2015 Medium

    Clarifying the dynamic role of PTCH1 induction, its Gli-driven upregulation was shown to contribute to temporal adaptation of Shh output alongside Gli2 downregulation.

    Evidence Quantitative immunofluorescence of the neural tube Shh gradient with computational modeling and downstream pathway stimulation in NIH3T3 cells

    PMID:25833741

    Open questions at the time
    • Quantitative contribution of Ptch1 versus other adaptation mechanisms not separated
    • Molecular trigger linking Ptch1 levels to attenuation unspecified
  11. 2018 Medium

    Defining a signaling-independent activity, PTCH1 was shown to act as a proton-motive-force-driven multidrug efflux transporter whose inhibition sensitizes cancer cells to chemotherapy.

    Evidence Drug efflux assays, inhibitor screening, and a doxorubicin-combination xenograft model

    PMID:30110910

    Open questions at the time
    • Structural basis distinguishing efflux from sterol-transport function not defined
    • Spectrum of physiological substrates unknown
  12. 2019 High

    Providing the structural mechanism for SMO inhibition, cryo-EM of human PTCH1 bound to palmitoylated Shh revealed annular sterols engaging the SSD and SSD-like domains, defining a sterol translocation route.

    Evidence 3.4 Å cryo-EM structure with analysis of sterol interaction sites

    PMID:31555730

    Open questions at the time
    • Direction and kinetics of sterol transport not measured
    • Conformational change upon Shh binding that relieves SMO not captured
  13. 2020 Medium

    Identifying a trafficking regulator, Gpr37l1 was shown to interact with Ptch1 at peri-ciliary membranes and control its internalization, with loss elevating Ptch1, cholesterol, ciliary Smo, and Shh production.

    Evidence Gpr37l1-null astrocyte cultures with localization, cholesterol, Shh, and proliferation readouts

    PMID:33350496

    Open questions at the time
    • Molecular mechanism of Gpr37l1-driven internalization not defined
    • Generality beyond cerebellar astrocytes unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the sterol-transport activity captured structurally is mechanistically coupled to SMO inhibition, ciliary trafficking, and the multidrug efflux function within a single protein remains unresolved.
  • No dynamic measurement linking sterol transport to SMO repression
  • Relationship between efflux transport and sterol-sensing functions undefined
  • Mechanism of non-canonical PTCH1→ERK signaling unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2 GO:0001618 virus receptor activity 1 GO:0005215 transporter activity 1 GO:0008289 lipid binding 1
Localization
GO:0005886 plasma membrane 2 GO:0005929 cilium 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-1643685 Disease 3 R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 2
Partners
GLI1GLI2GLI3GPR37L1SHHSMO

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2019 Cryo-EM structure of human PTCH1 bound to a palmitoylated Sonic hedgehog ligand (ShhNC24II) at 3.4 Å resolution reveals that the membrane-embedded region of PTCH1 is surrounded by 10 sterol molecules at the inner and outer lipid bilayer; these annular sterols interact with both the sterol-sensing domain (SSD) and the SSD-like domain (SSDL) on opposite sides of PTCH1, suggesting a route for sterol translocation across the lipid bilayer. Cryo-EM structure determination (3.4 Å resolution) with structural analysis of sterol binding sites Science advances High 31555730
2004 PTCH1 is transcriptionally regulated by three independent promoters generating transcripts with alternative first exons. Only one of two putative Gli-binding sites in the promoter region is functional; GLI1, GLI2, and GLI3 bind and activate transcription through this single site. Upstream pathway components SHH and SMO operate exclusively through this functional Gli-binding site, as mutation of it abolishes enhanced transcription induced by Gli proteins, SHH, or SMO. Promoter-reporter assays, electrophoretic mobility shift assay (EMSA), site-directed mutagenesis of Gli-binding sites, transfection with truncated GLI3 Gene High 15087129
2002 PTCH1 encodes multiple isoforms arising from alternative first exons (exon 1, 1A, 1B). All PTCH1 isoforms interact with SMOH in co-transfected cells and can inhibit SHH activity. However, only the PTCH1B isoform fully inhibits SMOH signaling, while other isoforms cannot; the N-terminal region encoded by exon 1B is required for complete SMOH inhibition but not for physical interaction with SMOH. Co-immunoprecipitation (doubly transfected cells), functional luciferase reporter assays (SHH and SMO inhibition), RT-PCR of tissue expression Oncogene Medium 12203113
2004 A missense mutation in the sterol-sensing domain of patched (G509V, equivalent in Drosophila ptc) acts as a dominant negative in vivo in Drosophila: ectopic expression causes ectopic activation of Hedgehog target genes and ectopic membrane stabilization of Smoothened. Unlike a C-terminal truncation dominant-negative (which localizes to plasma membrane), G509V shows vesicular localization identical to wild-type, indicating that dominant-negative function can result from disruption of different aspects of Patched protein behavior. A different mutation at the same residue (G509R) did not show dominant-negative activity. In vivo Drosophila transgenic expression, immunofluorescence localization, genetic analysis of Hh target gene activation Developmental dynamics Medium 15042702
2015 In the vertebrate neural tube, Ptch1 transcriptional upregulation (via Shh-induced Gli activity) contributes to adaptation/attenuation of Shh pathway output over time, alongside Gli2 protein downregulation and differential stability of Gli isoforms. Adaptation continues when the pathway is stimulated downstream of Ptch1, indicating that Ptch1 upregulation is one of multiple mechanisms controlling intracellular Shh signaling dynamics. Quantitative immunofluorescence of Shh gradient in mouse neural tube, computational modeling, Gli2 protein expression analysis, pathway stimulation downstream of Ptch1 in NIH3T3 cells Nature communications Medium 25833741
2014 In Ptch1-/- cells, Shh signaling remains ligand-dependent: the Shh-blocking antibody 5E1 inhibits the response in Ptch1-/- cells, and Ptch1-/-;Ptch2-/- double knockout cells cannot further activate the Shh response beyond Ptch1-/- alone. Expression of a dominant-negative Ptch2 (but not dominant-negative Ptch1) in the developing chick neural tube activates the Shh response, demonstrating that Ptch2 mediates the Shh response in the absence of Ptch1 at early developmental stages. Genetic knockout cells (Ptch1-/-, Ptch1-/-;Ptch2-/-), Shh-blocking antibody (5E1), dominant-negative constructs in chick neural tube in ovo electroporation, migration assays Development High 25085974
2018 PTCH1 functions as a multidrug efflux transporter that pumps chemotherapeutic agents such as doxorubicin out of cancer cells using the proton motive force (reversed pH gradient in cancer cells), unlike ABC transporters which use ATP hydrolysis. Inhibition of Ptch1 drug efflux activity enhances cytotoxicity of chemotherapeutics in cancer cell lines overexpressing Ptch1, and in vivo combination with doxorubicin prevented xenografted adrenocortical carcinoma tumor development. Drug efflux assays in cancer cell lines, chemical library screening for Ptch1 inhibitors, in vivo xenograft mouse model with doxorubicin combination treatment Cells Medium 30110910
2005 In heterozygous Ptch1 knockout mouse tumors, the wild-type Ptch1 allele is transcriptionally silenced (via promoter methylation sensitivity), while the mutant allele is predominantly expressed. This mutant Ptch1-derived protein is incapable of pathway inhibition. Transcriptional silencing of one Ptch1 allele followed by mutation of the other (or vice versa) constitutes a mechanism of PTCH1/Ptch1 tumor suppressor inactivation that explains retention of one allele in many tumors. Allele-specific RT-PCR in Ptch1+/- mouse tumors, promoter methylation-reporter assays, functional pathway inhibition assays International journal of oncology Medium 16273213
2009 In heterozygous Ptch1 knockout mice, epigenetic silencing of the intact (wild-type) Ptch1 allele via DNA methylation contributes to tumor formation. Reducing Dnmt1 activity significantly reduced tumor incidence. Combined treatment with the DNA methyltransferase inhibitor 5-aza-dC and the HDAC inhibitor valproic acid reactivated wild-type Ptch1 expression (associated with reduced Ptch1 promoter methylation and histone hyperacetylation) and efficiently prevented medulloblastoma and rhabdomyosarcoma formation. Genetic reduction of Dnmt1 in Ptch1+/- mice, pharmacological treatment (5-aza-dC + VPA) in vivo, promoter methylation analysis, chromatin immunoprecipitation (histone acetylation) Cancer research Medium 19155313
2013 MeCP2 (methyl-CpG-binding protein 2) mediates silencing of PTCH1 via DNA methylation in hepatic stellate cells. Hypermethylation of the PTCH1 promoter is associated with HSC activation and liver fibrogenesis. siRNA knockdown of MeCP2 increased PTCH1 mRNA and protein expression in hepatic myofibroblasts, and 5-aza-dC treatment prevented loss of PTCH1 expression during HSC activation. siRNA knockdown of MeCP2, bisulfite sequencing/MSP of PTCH1 promoter, 5-aza-dC treatment, RT-PCR and Western blot Cellular signalling Medium 23333245
2017 MeCP2 reduces PTCH1 expression in fibroblast-like synoviocytes of adjuvant arthritis rats through promoter hypermethylation. Knockdown of MeCP2 by siRNA increased PTCH1 expression, which in turn inhibited Hedgehog signaling (decreased Gli1 and Shh) and reduced secretion of inflammatory cytokines IL-6 and TNF-α. siRNA knockdown of MeCP2, methylation-specific PCR, RT-PCR, Western blot, cytokine measurement (ELISA) Inflammation Medium 28573530
2014 PTCH53 (PTCHD4), a p53 target gene homologous to PTCH1, is transcriptionally activated by p53 in response to DNA damage and can repress Hedgehog pathway activation by inhibiting canonical signaling by the GPCR SMO, delineating a novel inducible pathway by which p53 represses Hh signals. (Note: this is about PTCH53/PTCHD4, not PTCH1 itself, but the paper defines functional relationship of PTCH1 homology.) Luciferase reporter assays, quantitative RT-PCR in TP53-mutant cell lines and human tumors, SMO inhibition assays The Journal of biological chemistry Low 25296753
2020 The G protein-coupled receptor Gpr37l1 interacts with Ptch1 at peri-ciliary membranes in cerebellar astrocytes. In Gpr37l1-/- astrocytes, Ptch1 protein expression and internalization are markedly increased, intracellular cholesterol content rises, ciliary localization of Smo increases, and Shh production is markedly elevated, along with increased astrocyte proliferation. These findings indicate that Gpr37l1 specifically regulates Ptch1 internalization/trafficking, with consequent effects on Shh production and downstream proliferative signaling. Gpr37l1 null mutant mouse cerebellar primary astrocyte cultures, immunofluorescence of Ptch1 and Smo localization, cholesterol measurement, Shh production quantification, proliferation assays Journal of neuroscience research Medium 33350496
2011 In CLL cells with trisomy 12, constitutive Hedgehog pathway activation is driven by autocrine Desert Hedgehog (DHH) ligand secretion, which activates pathway signaling through PTCH1. BM stromal cell-derived DHH activates a non-canonical ERK phosphorylation pathway directly downstream of the PTCH1 receptor without involvement of SMO, conferring resistance to SMO inhibitors; this could be overcome by the HH-blocking antibody 5E1 or combination of SMO and ERK inhibitors. SMO inhibitor treatment of CLL cells, HH-blocking antibody (5E1), co-culture experiments with DHH-expressing BM stromal cells, phospho-ERK Western blot, GLI1/PTCH1 transcript quantification Blood Medium 22130798
2020 PTCH1 promotes anchorage-independent (spheroid) growth, migration, and invasion of non-small cell lung cancer cells, associated with expression of MMP7 and SOX2. shRNA-mediated PTCH1 knockdown reduced spherical colony formation, migration, and invasion in vitro, and decreased bone destruction and osteoclastogenesis in a mouse bone metastasis model in vivo. Lentiviral shRNA knockdown of PTCH1, spheroid colony formation assay, migration/invasion assays, mouse bone metastasis model, Western blot (MMP7, SOX2) Bone Medium 33359005
2018 miR-155 directly targets the 3'UTR of PTCH1 mRNA (validated by dual-luciferase reporter assay) and downregulates PTCH1 mRNA and protein expression. miR-155-mediated PTCH1 downregulation worsens high glucose-induced endothelial progenitor cell dysfunction (reduced viability, migration, tube formation, NO production; increased apoptosis and ROS); silencing PTCH1 by siRNA abrogated the protective effect of anti-miR-155. Dual-luciferase reporter assay, miR-155 overexpression/inhibition, PTCH1 siRNA knockdown, cell viability, migration, tube formation, NO, apoptosis, and ROS assays Experimental cell research Medium 29545091

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Sporadic medulloblastomas contain PTCH mutations. Cancer research 456 9041183
2005 Somatic mutations in the PTCH, SMOH, SUFUH and TP53 genes in sporadic basal cell carcinomas. The British journal of dermatology 313 15656799
2011 Consensus statement from the first international colloquium on basal cell nevus syndrome (BCNS). American journal of medical genetics. Part A 174 21834049
1996 Mutations in the human homologue of Drosophila patched (PTCH) in basal cell carcinomas and the Gorlin syndrome: different in vivo mechanisms of PTCH inactivation. Cancer research 170 8840960
2000 PTCH gene mutations in odontogenic keratocysts. Journal of dental research 165 10890722
2000 Analysis of PTCH/SMO/SHH pathway genes in medulloblastoma. Genes, chromosomes & cancer 154 10564585
2004 Expression of the PTCH1 tumor suppressor gene is regulated by alternative promoters and a single functional Gli-binding site. Gene 148 15087129
2006 PTCH mutations: distribution and analyses. Human mutation 127 16419085
2000 Evidence that haploinsufficiency of Ptch leads to medulloblastoma in mice. Genes, chromosomes & cancer 121 10738305
2015 Ptch1 and Gli regulate Shh signalling dynamics via multiple mechanisms. Nature communications 120 25833741
1995 Epithelial cell proliferation in odontogenic keratocysts: a comparative immunocytochemical study of Ki67 in simple, recurrent and basal cell naevus syndrome (BCNS)-associated lesions. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 104 7542341
2004 Basal cell carcinoma and its development: insights from radiation-induced tumors in Ptch1-deficient mice. Cancer research 103 14871823
2008 Cooperation between the Hic1 and Ptch1 tumor suppressors in medulloblastoma. Genes & development 98 18347096
2004 Molecular neuro-oncology and development of targeted therapeutic strategies for brain tumors. Part 2: PI3K/Akt/PTEN, mTOR, SHH/PTCH and angiogenesis. Expert review of anticancer therapy 96 14748662
2009 Antitumor effects of a combined 5-aza-2'deoxycytidine and valproic acid treatment on rhabdomyosarcoma and medulloblastoma in Ptch mutant mice. Cancer research 92 19155313
2008 A missense mutation in PTCH2 underlies dominantly inherited NBCCS in a Chinese family. Journal of medical genetics 89 18285427
2007 Unmasking of epigenetically silenced genes reveals DNA promoter methylation and reduced expression of PTCH in breast cancer. Breast cancer research and treatment 87 17295047
1993 Further localization of the gene for nevoid basal cell carcinoma syndrome (NBCCS) in 15 Australasian families: linkage and loss of heterozygosity. American journal of human genetics 80 8352281
2002 Mutations of the p53 and PTCH gene in basal cell carcinomas: UV mutation signature and strand bias. Journal of dermatological science 78 12007715
1998 PTCH gene mutations in invasive transitional cell carcinoma of the bladder. Oncogene 77 9764827
2010 Mechanisms of inactivation of PTCH1 gene in nevoid basal cell carcinoma syndrome: modification of the two-hit hypothesis. Clinical cancer research : an official journal of the American Association for Cancer Research 65 20068110
2019 Structural basis of sterol recognition by human hedgehog receptor PTCH1. Science advances 62 31555730
2001 Role of PTCH and p53 genes in early-onset basal cell carcinoma. The American journal of pathology 62 11159175
2002 Alternative first exons of PTCH1 are differentially regulated in vivo and may confer different functions to the PTCH1 protein. Oncogene 60 12203113
1999 The patched/hedgehog/smoothened signalling pathway in human breast cancer: no evidence for H133Y SHH, PTCH and SMO mutations. European journal of cancer (Oxford, England : 1990) 59 10505029
2016 Sequence variants in the PTCH1 gene associate with spine bone mineral density and osteoporotic fractures. Nature communications 58 26733130
2014 Underestimated PTCH1 mutation rate in sporadic keratocystic odontogenic tumors. Oral oncology 58 25458233
2013 DNA methylation and MeCP2 regulation of PTCH1 expression during rats hepatic fibrosis. Cellular signalling 55 23333245
2006 MC1R and PTCH gene polymorphism in French patients with basal cell carcinomas. The Journal of investigative dermatology 54 16645598
2010 PTCH1, a receptor of Hedgehog signaling pathway, is correlated with metastatic potential of colorectal cancer. Upsala journal of medical sciences 52 20230186
2008 PTCH1 and SMO gene alterations in keratocystic odontogenic tumors. Journal of dental research 52 18502968
2006 Contributions of PTCH gene variants to isolated cleft lip and palate. The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association 51 16405370
2001 PTCH mutations in squamous cell carcinoma of the skin. The Journal of investigative dermatology 50 11286632
1997 Patched (ptch)-associated preferential expression of smoothened (smoh) in human basal cell carcinoma of the skin. Cancer research 50 9354432
2013 PTCH1 gene mutations in Keratocystic odontogenic tumors: a study of 43 Chinese patients and a systematic review. PloS one 49 24204797
2019 Mutation of the PTCH1 gene predicts recurrence of breast cancer. Scientific reports 48 31704974
2006 PTCH mutations and deletions in patients with typical nevoid basal cell carcinoma syndrome and in patients with a suspected genetic predisposition to basal cell carcinoma: a French study. British journal of cancer 48 16909134
2019 Long noncoding RNA LINC-PINT regulates laryngeal carcinoma cell stemness and chemoresistance through miR-425-5p/PTCH1/SHH axis. Journal of cellular physiology 46 31131448
2009 The immunoprofile of odontogenic keratocyst (keratocystic odontogenic tumor) that includes expression of PTCH, SMO, GLI-1 and bcl-2 is similar to ameloblastoma but different from odontogenic cysts. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 46 19473442
2006 PTCH mutations in sporadic and Gorlin-syndrome-related odontogenic keratocysts. Journal of dental research 46 16931872
2014 Ptch2 mediates the Shh response in Ptch1-/- cells. Development (Cambridge, England) 40 25085974
2011 Trisomy 12 and elevated GLI1 and PTCH1 transcript levels are biomarkers for Hedgehog-inhibitor responsiveness in CLL. Blood 40 22130798
2005 Detecting tissue-specific alternative splicing and disease-associated aberrant splicing of the PTCH gene with exon junction microarrays. Human molecular genetics 40 16203740
2014 Ptch2 shares overlapping functions with Ptch1 in Smo regulation and limb development. Developmental biology 39 25448692
2002 Immunolocalization of PTCH protein in odontogenic cysts and tumors. Journal of dental research 39 12407090
2001 PTCH gene altered in dentigerous cysts. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 37 11555162
2017 MeCP2 Regulates PTCH1 Expression Through DNA Methylation in Rheumatoid Arthritis. Inflammation 35 28573530
2015 Melittin induces PTCH1 expression by down-regulating MeCP2 in human hepatocellular carcinoma SMMC-7721 cells. Toxicology and applied pharmacology 35 26189965
2009 Time-point and dosage of gene inactivation determine the tumor spectrum in conditional Ptch knockouts. Carcinogenesis 35 19321799
2018 MiR-155 targets PTCH1 to mediate endothelial progenitor cell dysfunction caused by high glucose. Experimental cell research 34 29545091
2018 Targeting the Multidrug Transporter Ptch1 Potentiates Chemotherapy Efficiency. Cells 32 30110910
2014 A PTCH1 homolog transcriptionally activated by p53 suppresses Hedgehog signaling. The Journal of biological chemistry 31 25296753
2013 Mutations in the hedgehog pathway genes SMO and PTCH1 in human gastric tumors. PloS one 31 23349881
2011 Multiple (familial) trichoepitheliomas: a clinicopathological and molecular biological study, including CYLD and PTCH gene analysis, of a series of 16 patients. The American Journal of dermatopathology 31 21389835
2013 "PTCH"-ing it together: a basal cell nevus syndrome review. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.] 29 23725561
2020 Biallelic PTCH1 Inactivation Is a Dominant Genomic Change in Sporadic Keratocystic Odontogenic Tumors. The American journal of surgical pathology 27 31725470
2023 GLI1-Altered Mesenchymal Tumors With ACTB or PTCH1 Fusion: A Molecular and Clinicopathologic Analysis. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 26 37992966
2006 Germline mutations of the PTCH gene in families with odontogenic keratocysts and nevoid basal cell carcinoma syndrome. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 26 16675912
2001 Clonal composition of human adamantinomatous craniopharyngiomas and somatic mutation analyses of the patched (PTCH), Gsalpha and Gi2alpha genes. Neuroscience letters 26 11524144
2018 New mutations and an updated database for the patched-1 (PTCH1) gene. Molecular genetics & genomic medicine 24 29575684
2017 Co-expression analysis revealed PTCH1-3'UTR promoted cell migration and invasion by activating miR-101-3p/SLC39A6 axis in non-small cell lung cancer: implicating the novel function of PTCH1. Oncotarget 24 29435142
2012 Ptch1 overexpression drives skin carcinogenesis and developmental defects in K14Ptch(FVB) mice. The Journal of investigative dermatology 24 23223138
2009 Involvement of p16 and PTCH in pathogenesis of melanoma and basal cell carcinoma. International journal of oncology 24 19287961
2007 UV fingerprints predominate in the PTCH mutation spectra of basal cell carcinomas independent of clinical phenotype. The Journal of investigative dermatology 24 17597822
2005 PTCH codon 1315 polymorphism and risk for nonmelanoma skin cancer. The British journal of dermatology 24 15888139
2005 A model for PTCH1/Ptch1-associated tumors comprising mutational inactivation and gene silencing. International journal of oncology 24 16273213
2012 Aberrant methylation of the PTCH1 gene promoter region in aberrant crypt foci. International journal of cancer 23 22945423
2024 PTCH1-mutant human cerebellar organoids exhibit altered neural development and recapitulate early medulloblastoma tumorigenesis. Disease models & mechanisms 22 38411252
2023 BBOX1-AS1 Activates Hedgehog Signaling Pathway to Facilitate the Proliferation and Stemness of Esophageal Squamous Cell Carcinoma Cells via miR-506-5p/EIF5A/PTCH1 Axis. Current molecular pharmacology 22 36717994
2023 Ginsenoside Rb1 for overcoming cisplatin-insensitivity of A549/DDP cells in vitro and vivo through the dual-inhibition on two efflux pumps of ABCB1 and PTCH1. Phytomedicine : international journal of phytotherapy and phytopharmacology 22 37087793
2020 Ptch2/Gas1 and Ptch1/Boc differentially regulate Hedgehog signalling in murine primordial germ cell migration. Nature communications 22 32332736
2020 Upregulation of miRNA-9-5p Promotes Angiogenesis after Traumatic Brain Injury by Inhibiting Ptch-1. Neuroscience 22 32502567
2008 PTCH germline mutations in Chinese nevoid basal cell carcinoma syndrome patients. Oral diseases 21 18302678
2005 Is loss of heterozygosity at 9q22.3 (PTCH gene) and 19p13.3 (STK11 gene) involved in the pathogenesis of ovarian stromal tumors? Human pathology 21 16084949
2021 N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) mitigates the liver fibrosis via WTAP/m6A/Ptch1 axis through Hedgehog pathway. Gene 20 34921949
2007 PTCH mutations are not mainly involved in the pathogenesis of sporadic trichoblastomas. Human pathology 19 17597182
2004 Functional analysis in Drosophila indicates that the NBCCS/PTCH1 mutation G509V results in activation of smoothened through a dominant-negative mechanism. Developmental dynamics : an official publication of the American Association of Anatomists 19 15042702
2021 PTCH1 mutation promotes antitumor immunity and the response to immune checkpoint inhibitors in colorectal cancer patients. Cancer immunology, immunotherapy : CII 18 34028566
2019 Functionally Distinctive Ptch Receptors Establish Multimodal Hedgehog Signaling in the Tooth Epithelial Stem Cell Niche. Stem cells (Dayton, Ohio) 18 31145830
2019 Loss of the PTCH1 tumor suppressor defines a new subset of plexiform fibromyxoma. Journal of translational medicine 18 31362756
2016 Shh/Ptch and EGF/ErbB cooperatively regulate branching morphogenesis of fetal mouse submandibular glands. Developmental biology 18 26930157
2004 Germline mutations of the PTCH gene in Japanese patients with nevoid basal cell carcinoma syndrome. Archives of dermatological research 18 15565302
2017 Nevoid basal cell carcinoma syndrome caused by splicing mutations in the PTCH1 gene. Familial cancer 17 27561271
2010 MMP-13 expression in keratocyst odontogenic tumour associated with NBCCS and sporadic keratocysts. Oral diseases 17 20561220
2009 Genetic and clinicopathologic aspects of Gorlin-Goltz syndrome (NBCCS): presentation of two case reports and literature review. Minerva stomatologica 17 19234436
2008 PTCH1 isoforms in odontogenic keratocysts. Oral oncology 17 18674957
2004 Spectrum of PTCH mutations in Italian nevoid basal cell-carcinoma syndrome patients: identification of thirteen novel alleles. Human mutation 17 15459969
2018 Genome-wide identification, phylogeny, evolution, and expression patterns of MtN3/saliva/SWEET genes and functional analysis of BcNS in Brassica rapa. BMC genomics 16 29499648
2013 Altered expression of PTCH and HHIP in gastric cancer through their gene promoter methylation: novel targets for gastric cancer. Molecular medicine reports 16 23440386
2012 Loss of heterozygosity of the PTCH gene in ameloblastoma. Human pathology 16 22221699
2006 Mutation in exon 7 of PTCH deregulates SHH/PTCH/SMO signaling: possible linkage to WNT. International journal of molecular medicine 16 16596257
2006 Aberrant expression of PTCH (patched gene) and Smo (smoothened gene) in human pancreatic cancerous tissues and its association with hyperglycemia. Pancreas 16 16804411
2019 Nevoid Basal Cell Carcinoma Syndrome: PTCH1 Mutation Profile and Expression of Genes Involved in the Hedgehog Pathway in Argentinian Patients. Cells 15 30754660
2017 Naproxen Inhibits UVB-induced Basal Cell and Squamous Cell Carcinoma Development in Ptch1+/- /SKH-1 Hairless Mice. Photochemistry and photobiology 15 28329421
2020 Gpr37l1/prosaposin receptor regulates Ptch1 trafficking, Shh production, and cell proliferation in cerebellar primary astrocytes. Journal of neuroscience research 14 33350496
2018 PTCH1 Germline Mutations and the Basaloid Follicular Hamartoma Values in the Tumor Spectrum of Basal Cell Carcinoma Syndrome (NBCCS). Anticancer research 14 29277811
2006 Molecular basis of basal cell carcinogenesis in the atomic-bomb survivor population: p53 and PTCH gene alterations. Carcinogenesis 14 16777989
2022 Long Non-coding RNA SNHG16 Facilitates Esophageal Cancer Cell Proliferation and Self-renewal through the microRNA-802/PTCH1 Axis. Current medicinal chemistry 13 35579168
2020 PTCH1 regulates anchorage-independent growth and bone invasion of non-small cell lung cancer cells. Bone 13 33359005
1995 The prevalence of cervical and thoracic congenital skeletal abnormalities in basal cell naevus syndrome; a review of cervical and chest radiographs in 80 patients with BCNS. The British journal of radiology 13 7627481

Missed literature

Know a paper Affinage missed for PTCH1? Flag it for the maintainers and the community.

No submissions yet.