PTCH2

patched 2

Basic information

Region (hg38): 1:44819154-44843253

Links

ENSG00000117425

∙ NCBI:8643 ∙ OMIM:603673 ∙ HGNC:9586 ∙ Uniprot:Q9Y6C5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

nevoid basal cell carcinoma syndrome (Limited), mode of inheritance: Unknown
nevoid basal cell carcinoma syndrome (Moderate), mode of inheritance: AD
nevoid basal cell carcinoma syndrome (Supportive), mode of inheritance: AD
commissural facial cleft (Supportive), mode of inheritance: AD
nevoid basal cell carcinoma syndrome (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Basal cell nevus syndrome	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 keratocysttransformation, 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	Dermatologic; Musculoskeletal; Oncologic	18285427; 22670903; 22670904; 23479190

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PTCH2 gene.

Gorlin_syndrome (930 variants)
not_specified (175 variants)
Basal_cell_carcinoma,_susceptibility_to,_1 (87 variants)
not_provided (84 variants)
PTCH2-related_disorder (73 variants)
Medulloblastoma (64 variants)
Basal_cell_nevus_syndrome_1 (31 variants)
Oromandibular-limb_hypogenesis_spectrum (2 variants)
Breast_carcinoma (2 variants)
Duplication_of_the_pituitary_gland (1 variants)
See_cases (1 variants)
Basal_cell_carcinoma,_somatic (1 variants)
Diffuse_midline_glioma,_H3_K27-altered (1 variants)
Familial_cancer_of_breast (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PTCH2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003738.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	235 clinvar	13 clinvar	253
missense	1 clinvar	1 clinvar	508 clinvar	37 clinvar	3 clinvar	550
nonsense			13 clinvar			13
start loss						0
frameshift		3 clinvar	37 clinvar			40
splice donor/acceptor (+/-2bp)			17 clinvar			17
Total	1	4	580	272	16

Highest pathogenic variant AF is 0.000006197945

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PTCH2	protein_coding	protein_coding	ENST00000372192	22	23220

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.41e-16	0.964	125478	1	269	125748	0.00107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.785	638	696	0.916	0.0000445	7665
Missense in Polyphen		166	195.86	0.84756		2196
Synonymous	0.0356	304	305	0.997	0.0000198	2642
Loss of Function	2.43	33	51.9	0.635	0.00000238	561

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00133	0.00133
Ashkenazi Jewish	0.000201	0.000198
East Asian	0.00381	0.00376
Finnish	0.000233	0.000231
European (Non-Finnish)	0.00114	0.00113
Middle Eastern	0.00381	0.00376
South Asian	0.000654	0.000653
Other	0.000985	0.000978

dbNSFP

Source: dbNSFP

Function: FUNCTION: May have a role in epidermal development. May act as a receptor for Sonic hedgehog (SHH).;
Disease: DISEASE: Medulloblastoma (MDB) [MIM:155255]: Malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children. {ECO:0000269|PubMed:9931336}. Note=The disease is 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:9931336}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Basal cell carcinoma - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hedgehog signaling pathway - Homo sapiens (human);HH-Core;Hedgehog ,on, state;Hedgehog Signaling Pathway;Hedgehog Signaling Pathway;Signaling by GPCR;Signal Transduction;Hedgehog;Hedgehog;Class B/2 (Secretin family receptors);GPCR ligand binding;GLI proteins bind promoters of Hh responsive genes to promote transcription;Hedgehog ,on, state;Signaling by Hedgehog;Signaling events mediated by the Hedgehog family (Consensus)

Recessive Scores

pRec: 0.198

Intolerance Scores

loftool: 0.0291
rvis_EVS: -1.52
rvis_percentile_EVS: 3.47

Haploinsufficiency Scores

pHI: 0.685
hipred: N
hipred_score: 0.367
ghis: 0.547

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.961

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Ptch2
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); muscle phenotype; hematopoietic 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); normal phenotype; neoplasm; digestive/alimentary phenotype; immune system phenotype;

Zebrafish Information Network

Gene name: ptch2
Affected structure: retinal ganglion cell
Phenotype tag: abnormal
Phenotype quality: mislocalised

Gene ontology

Biological process: cell fate determination;smoothened signaling pathway;epidermal cell fate specification;hair cycle;skin development;positive regulation of epidermal cell differentiation;negative regulation of smoothened signaling pathway
Cellular component: plasma membrane;integral component of membrane
Molecular function: smoothened binding;hedgehog receptor activity;hedgehog family protein binding