PTCH2

patched 2

Basic information

Region (hg38): 1:44819843-44843253

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
• 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 (757 variants)
• not provided (76 variants)
• Inborn genetic diseases (62 variants)
• Basal cell carcinoma, susceptibility to, 1 (23 variants)
• not specified (15 variants)
• PTCH2-related condition (11 variants)
• Basal cell carcinoma, susceptibility to, 1;Gorlin syndrome;Medulloblastoma (7 variants)
• Basal cell carcinoma, susceptibility to, 1;Medulloblastoma;Gorlin syndrome (2 variants)
• Breast carcinoma (2 variants)
• Medulloblastoma;Basal cell carcinoma, susceptibility to, 1;Gorlin syndrome (2 variants)
• Diffuse midline glioma, H3 K27-altered (1 variants)
• Oromandibular-limb hypogenesis spectrum (1 variants)
• Familial cancer of breast (1 variants)
• See cases (1 variants)
• Medulloblastoma (1 variants)
• PTCH2-related disease (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.

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			9	173	16	198
missense	1		381	22	5	409
nonsense			11			11
start loss						0
frameshift		1	32			33
inframe indel			4			4
splice donor/acceptor (+/-2bp)			11			11
splice region			17	23	5	45
non coding			3	76	18	97
Total	1	1	451	271	39

Variants in PTCH2

This is a list of pathogenic ClinVar variants found in the PTCH2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-44821874-A-G			Likely benign (Apr 01, 2023)
1-44822414-T-C		PTCH2-related disorder	Likely benign (Oct 25, 2019)
1-44822420-C-T		Gorlin syndrome	Uncertain significance (Nov 27, 2023)
1-44822421-A-G		Gorlin syndrome	Likely benign (Oct 02, 2021)
1-44822426-C-G		Gorlin syndrome • PTCH2-related disorder	Uncertain significance (Nov 16, 2023)
1-44822431-C-T		Gorlin syndrome	Uncertain significance (Apr 08, 2023)
1-44822436-TC-T		Gorlin syndrome	Uncertain significance (Dec 19, 2023)
1-44822437-C-T		Gorlin syndrome • not specified	Uncertain significance (Jan 21, 2022)
1-44822438-C-T		Gorlin syndrome • PTCH2-related disorder	Benign (Jan 29, 2024)
1-44822443-G-A		Breast carcinoma • Gorlin syndrome	Uncertain significance (Aug 09, 2023)
1-44822444-A-T		not specified	Uncertain significance (May 11, 2022)
1-44822447-T-G		Gorlin syndrome	Uncertain significance (Jan 27, 2024)
1-44822461-C-G		Gorlin syndrome • See cases	Uncertain significance (Dec 25, 2023)
1-44822463-A-T		Gorlin syndrome	Likely benign (Feb 24, 2020)
1-44822474-G-A		Gorlin syndrome	Uncertain significance (Nov 11, 2021)
1-44822479-C-T		Gorlin syndrome	Uncertain significance (Jan 19, 2024)
1-44822484-G-GGGCT		Gorlin syndrome	Uncertain significance (Nov 02, 2023)
1-44822498-C-A		Gorlin syndrome	Uncertain significance (Dec 28, 2023)
1-44822503-T-C		Gorlin syndrome	Uncertain significance (May 28, 2022)
1-44822509-T-C		Gorlin syndrome	Uncertain significance (Oct 23, 2018)
1-44822520-CA-C		Gorlin syndrome	Uncertain significance (Jun 17, 2022)
1-44822521-A-G		Gorlin syndrome	Uncertain significance (Nov 06, 2021)
1-44822521-AG-A		Gorlin syndrome	Uncertain significance (Sep 05, 2023)
1-44822521-A-AG		Gorlin syndrome	Uncertain significance (Dec 01, 2023)
1-44822523-G-C		Gorlin syndrome	Likely benign (Dec 09, 2023)

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