PTCH1
patched 1
Basic information
Region (hg38): 9:95442979-95517057
Previous symbols: [ "NBCCS", "PTCH" ]
Links
Phenotypes
GenCC
Source:
- holoprosencephaly 7 (Definitive), mode of inheritance: AD
- nevoid basal cell carcinoma syndrome (Definitive), mode of inheritance: AD
- nevoid basal cell carcinoma syndrome (Strong), mode of inheritance: AD
- nevoid basal cell carcinoma syndrome (Supportive), mode of inheritance: AD
- holoprosencephaly (Limited), mode of inheritance: AD
- nevoid basal cell carcinoma syndrome (Strong), mode of inheritance: AD
- holoprosencephaly 7 (Limited), mode of inheritance: AD
- nevoid basal cell carcinoma syndrome (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Basal cell nevus syndrome 1 | AD | Oncologic | Individuals are at risk for a number of types of malignancies, including basal cell carcinomas and medulloblastoma , as well as (rare) malignant rare keratocyst transformation, and awareness and surveillance may allow early diagnosis and treatment (including with molecular therapies that target the Hedgehog signaling pathway), potentially reducing morbidity and mortality; Avoidance of agents such as radiation therapy is indicated | Craniofacial; Dermatologic; Endocrine; Musculoskeletal; Neurologic; Oncologic | 13851319; 8326488; 9096761; 9096762; 8981943; 11382639; 11941477; 16906569; 19439922; 19557015; 21368767; 22007994; 22565648; 22670903; 22670904; 22844361; 23677114 |
ClinVar
This is a list of variants' phenotypes submitted to
- Gorlin syndrome (3554 variants)
- Hereditary cancer-predisposing syndrome (2344 variants)
- not provided (570 variants)
- Holoprosencephaly 7 (191 variants)
- not specified (172 variants)
- Basal cell carcinoma, susceptibility to, 1 (104 variants)
- PTCH1-related condition (33 variants)
- Holoprosencephaly 7;Basal cell carcinoma, susceptibility to, 1;Gorlin syndrome (27 variants)
- Basal cell carcinoma, susceptibility to, 1;Gorlin syndrome;Holoprosencephaly 7 (25 variants)
- Inborn genetic diseases (14 variants)
- Ovarian cancer (12 variants)
- Holoprosencephaly sequence (11 variants)
- Holoprosencephaly 7;Gorlin syndrome (5 variants)
- Anophthalmia-microphthalmia syndrome (5 variants)
- Lung adenocarcinoma (4 variants)
- See cases (4 variants)
- Retinoblastoma (3 variants)
- Breast carcinoma (2 variants)
- PTCH1-Related Disorder (2 variants)
- Craniopharyngioma (2 variants)
- Medulloblastoma (2 variants)
- Basal cell carcinoma, susceptibility to, 1;Holoprosencephaly 7;Gorlin syndrome (2 variants)
- Craniosynostosis syndrome (2 variants)
- Congenital heart disease (1 variants)
- Neuroblastoma (1 variants)
- Hirschsprung disease, susceptibility to, 1 (1 variants)
- PTCH1-related disorders (1 variants)
- Holoprosencephaly 7;Gorlin syndrome;Basal cell carcinoma, susceptibility to, 1 (1 variants)
- Fraser syndrome 3 (1 variants)
- Congenital hydrocephalus (1 variants)
- Pituitary stalk interruption syndrome (1 variants)
- Irido-corneo-trabecular dysgenesis (1 variants)
- Uterine leiomyoma;Hereditary leiomyomatosis and renal cell cancer (1 variants)
- Intellectual disability;Myopia;Lens luxation (1 variants)
- Cataract;Disproportionate tall stature;Abnormal cardiovascular system morphology (1 variants)
- Postaxial polydactyly;Macrocephaly;Precocious puberty;Overgrowth (1 variants)
- Congenital omphalocele (1 variants)
- Turner syndrome (1 variants)
- Rieger anomaly;Irido-corneo-trabecular dysgenesis (1 variants)
- Autism spectrum disorder (1 variants)
- Hereditary breast ovarian cancer syndrome (1 variants)
- Rieger anomaly (1 variants)
- Germinoma (1 variants)
- Acute myeloid leukemia (1 variants)
- Gorlin syndrome;Holoprosencephaly 7 (1 variants)
- Polydactyly of a triphalangeal thumb (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PTCH1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 17 | 1016 | 16 | 1052 | ||
| missense | 10 | 30 | 1607 | 106 | 32 | 1785 |
| nonsense | 134 | 11 | 152 | |||
| start loss | 4 | |||||
| frameshift | 245 | 21 | 17 | 283 | ||
| inframe indel | 49 | 64 | ||||
| splice donor/acceptor (+/-2bp) | 41 | 30 | 77 | |||
| splice region ? | 5 | 3 | 62 | 103 | 5 | 178 |
| non coding ? | 78 | 370 | 79 | 532 | ||
| Total | 437 | 99 | 1789 | 1497 | 127 |
Highest pathogenic variant AF is 0.00000657
Variants in PTCH1
This is a list of pathogenic ClinVar variants found in the PTCH1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 9-95443052-A-G | Holoprosencephaly 7 • Gorlin syndrome | Benign/Likely benign (Jul 01, 2023) | ||
| 9-95443056-A-G | Gorlin syndrome • Holoprosencephaly 7 | Uncertain significance (Jan 13, 2018) | ||
| 9-95443121-G-A | Holoprosencephaly 7 • Gorlin syndrome | Uncertain significance (Jan 13, 2018) | ||
| 9-95443161-C-A | Gorlin syndrome • Holoprosencephaly 7 | Benign (Jan 12, 2018) | ||
| 9-95443180-A-G | Gorlin syndrome • Holoprosencephaly 7 | Uncertain significance (Jan 12, 2018) | ||
| 9-95443184-A-G | Holoprosencephaly 7 • Gorlin syndrome | Uncertain significance (Jan 12, 2018) | ||
| 9-95443236-C-T | Gorlin syndrome • Holoprosencephaly 7 | Benign (Jan 12, 2018) | ||
| 9-95443255-A-G | Gorlin syndrome • Holoprosencephaly 7 | Uncertain significance (Jan 13, 2018) | ||
| 9-95443282-C-T | Holoprosencephaly 7 • Gorlin syndrome | Uncertain significance (Jan 13, 2018) | ||
| 9-95443313-C-A | Holoprosencephaly 7 • Gorlin syndrome | Uncertain significance (Jan 13, 2018) | ||
| 9-95443363-T-C | Gorlin syndrome • Holoprosencephaly 7 | Benign (Jan 13, 2018) | ||
| 9-95443397-TACAA-T | Gorlin syndrome • Holoprosencephaly sequence | Likely benign (Jun 14, 2016) | ||
| 9-95443598-C-A | Holoprosencephaly 7 • Gorlin syndrome | Uncertain significance (Jan 13, 2018) | ||
| 9-95443656-G-T | Holoprosencephaly 7 • Gorlin syndrome | Uncertain significance (Jan 12, 2018) | ||
| 9-95443749-T-G | Holoprosencephaly 7 • Gorlin syndrome | Uncertain significance (Jan 13, 2018) | ||
| 9-95443968-T-G | Holoprosencephaly 7 • Gorlin syndrome | Uncertain significance (Jan 13, 2018) | ||
| 9-95443979-G-C | Gorlin syndrome • Holoprosencephaly 7 | Uncertain significance (Jan 12, 2018) | ||
| 9-95444104-G-GT | Gorlin syndrome • Holoprosencephaly sequence | Uncertain significance (Jun 14, 2016) | ||
| 9-95444117-T-A | Holoprosencephaly 7 • Gorlin syndrome | Conflicting classifications of pathogenicity (May 01, 2023) | ||
| 9-95444118-A-T | Gorlin syndrome • Holoprosencephaly 7 | Benign (Jan 13, 2018) | ||
| 9-95444130-A-T | Holoprosencephaly 7 • Gorlin syndrome | Uncertain significance (Jan 12, 2018) | ||
| 9-95444213-G-A | Holoprosencephaly 7 • Gorlin syndrome | Uncertain significance (Jan 12, 2018) | ||
| 9-95444218-C-T | Holoprosencephaly 7 • Gorlin syndrome | Benign (Oct 01, 2022) | ||
| 9-95444247-T-C | Gorlin syndrome • Holoprosencephaly 7 | Uncertain significance (Jan 12, 2018) | ||
| 9-95444297-C-T | Gorlin syndrome • Holoprosencephaly 7 | Uncertain significance (Jan 13, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PTCH1 | protein_coding | protein_coding | ENST00000331920 | 23 | 74078 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 4.94e-10 | 125741 | 0 | 7 | 125748 | 0.0000278 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.68 | 708 | 845 | 0.838 | 0.0000560 | 9381 |
| Missense in Polyphen | 137 | 244.15 | 0.56113 | 2695 | ||
| Synonymous | -3.76 | 453 | 362 | 1.25 | 0.0000278 | 2943 |
| Loss of Function | 7.25 | 1 | 63.3 | 0.0158 | 0.00000322 | 739 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000289 | 0.0000289 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000441 | 0.0000439 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Acts as a receptor for sonic hedgehog (SHH), indian hedgehog (IHH) and desert hedgehog (DHH). Associates with the smoothened protein (SMO) to transduce the hedgehog's proteins signal. Seems to have a tumor suppressor function, as inactivation of this protein is probably a necessary, if not sufficient step for tumorigenesis. {ECO:0000269|PubMed:21537345}.;
- Disease
- DISEASE: Basal cell nevus syndrome (BCNS) [MIM:109400]: An autosomal dominant disease characterized by nevoid basal cell carcinomas and developmental abnormalities such as rib and craniofacial alterations, polydactyly, syndactyly, and spina bifida. In addition, the patients suffer from a multitude of tumors like basal cell carcinomas, fibromas of the ovaries and heart, cysts of the skin, jaws and mesentery, as well as medulloblastomas and meningiomas. {ECO:0000269|PubMed:11231326, ECO:0000269|PubMed:15459969, ECO:0000269|PubMed:8840969, ECO:0000269|PubMed:8981943, ECO:0000269|PubMed:9620294}. Note=The disease may be caused by mutations affecting the gene represented in this entry.; DISEASE: Basal cell carcinoma (BCC) [MIM:605462]: A common malignant skin neoplasm that typically appears on hair-bearing skin, most commonly on sun-exposed areas. BCC is slow growing and rarely metastasizes, but has potentialities for local invasion and destruction. It usually develops as a flat, firm, pale area that is small, raised, pink or red, translucent, shiny, and waxy, and the area may bleed following minor injury. Tumor size can vary from a few millimeters to several centimeters in diameter. {ECO:0000269|PubMed:8658145, ECO:0000269|PubMed:9620294}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Holoprosencephaly 7 (HPE7) [MIM:610828]: A structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability. {ECO:0000269|PubMed:11941477, ECO:0000269|PubMed:17001668, ECO:0000269|PubMed:17096318}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Axon guidance - Homo sapiens (human);Basal cell carcinoma - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hedgehog signaling pathway - Homo sapiens (human);HH-Core;Hair Follicle Development- Induction (Part 1 of 3);Hedgehog ,on, state;Hedgehog ,off, state;EDA Signalling in Hair Follicle Development;Tumor suppressor activity of SMARCB1;Hedgehog Signaling Pathway;Hedgehog Signaling Pathway;Endochondral Ossification;Signaling by GPCR;Signal Transduction;sonic hedgehog receptor ptc1 regulates cell cycle;Hedgehog;Hedgehog;Class B/2 (Secretin family receptors);GPCR ligand binding;Hedgehog ,off, state;Ligand-receptor interactions;GLI proteins bind promoters of Hh responsive genes to promote transcription;Hedgehog ,on, state;Signaling by Hedgehog;Glypican 3 network;Hedgehog signaling events mediated by Gli proteins;Signaling events mediated by the Hedgehog family
(Consensus)
Recessive Scores
- pRec
- 0.787
Intolerance Scores
- loftool
- 0.000344
- rvis_EVS
- -2.73
- rvis_percentile_EVS
- 0.71
Haploinsufficiency Scores
- pHI
- 0.540
- hipred
- Y
- hipred_score
- 0.875
- ghis
- 0.636
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.972
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |
Mouse Genome Informatics
- Gene name
- Ptch1
- Phenotype
- limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; vision/eye phenotype; immune system phenotype; renal/urinary system phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; endocrine/exocrine gland phenotype; neoplasm; taste/olfaction phenotype; pigmentation phenotype; muscle phenotype; craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- ptch1
- Affected structure
- Muller cell
- Phenotype tag
- abnormal
- Phenotype quality
- physical object quality
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;branching involved in ureteric bud morphogenesis;in utero embryonic development;cell fate determination;neural tube closure;heart morphogenesis;smoothened signaling pathway;regulation of mitotic cell cycle;brain development;regulation of smoothened signaling pathway;response to mechanical stimulus;animal organ morphogenesis;dorsal/ventral pattern formation;epidermal cell fate specification;response to chlorate;positive regulation of cholesterol efflux;protein processing;spinal cord motor neuron differentiation;neural tube patterning;neural plate axis specification;embryonic limb morphogenesis;prostate gland development;response to estradiol;response to retinoic acid;regulation of protein localization;limb morphogenesis;hindlimb morphogenesis;negative regulation of multicellular organism growth;response to drug;glucose homeostasis;negative regulation of DNA-binding transcription factor activity;keratinocyte proliferation;positive regulation of epidermal cell differentiation;negative regulation of osteoblast differentiation;negative regulation of smoothened signaling pathway;positive regulation of transcription, DNA-templated;embryonic organ development;negative regulation of epithelial cell proliferation;negative regulation of cell division;pharyngeal system development;mammary gland duct morphogenesis;mammary gland epithelial cell differentiation;smoothened signaling pathway involved in dorsal/ventral neural tube patterning;cell differentiation involved in kidney development;somite development;cellular response to cholesterol;commissural neuron axon guidance;renal system development;cell proliferation involved in metanephros development;protein localization to plasma membrane;liver regeneration
- Cellular component
- nucleus;Golgi apparatus;plasma membrane;caveola;postsynaptic density;integral component of membrane;midbody;endocytic vesicle membrane;intracellular membrane-bounded organelle;dendritic growth cone;axonal growth cone;perinuclear region of cytoplasm;ciliary membrane
- Molecular function
- patched binding;smoothened binding;protein binding;hedgehog receptor activity;heparin binding;cholesterol binding;cyclin binding;protein-containing complex binding;hedgehog family protein binding