PTCH1

Summary

PTCH1 (patched 1, HGNC:9585) is a protein-coding gene on chromosome 9q22.32, encoding Protein patched homolog 1 (Q13635). Acts as a receptor for sonic hedgehog (SHH), indian hedgehog (IHH) and desert hedgehog (DHH). In precision oncology, PTCH1 LOH confers sensitivity to Vismodegib in Medulloblastoma (CIViC Level B); 2 further curated variant–drug associations are listed below. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the patched family of proteins and a component of the hedgehog signaling pathway. Hedgehog signaling is important in embryonic development and tumorigenesis. The encoded protein is the receptor for the secreted hedgehog ligands, which include sonic hedgehog, indian hedgehog and desert hedgehog. Following binding by one of the hedgehog ligands, the encoded protein is trafficked away from the primary cilium, relieving inhibition of the G-protein-coupled receptor smoothened, which results in activation of downstream signaling. Mutations of this gene have been associated with basal cell nevus syndrome and holoprosencephaly.

Source: NCBI Gene 5727 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nevoid basal cell carcinoma syndrome (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 97
• Clinical variants (ClinVar): 5,047 total — 479 pathogenic, 116 likely-pathogenic
• Phenotypes (HPO): 232
• Druggable target: yes
• Precision-oncology evidence (CIViC): 3 curated variant–drug associations
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 11 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000264

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9585
Approved symbol	PTCH1
Name	patched 1
Location	9q22.32
Locus type	gene with protein product
Status	Approved
Aliases	BCNS, SLC65B1
Ensembl gene	ENSG00000185920
Ensembl biotype	protein_coding
OMIM	601309
Entrez	5727

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 14 protein_coding, 6 protein_coding_CDS_not_defined, 5 retained_intron, 4 nonsense_mediated_decay

ENST00000331920, ENST00000375271, ENST00000375290, ENST00000429896, ENST00000430669, ENST00000437951, ENST00000468211, ENST00000488809, ENST00000546744, ENST00000546820, ENST00000547615, ENST00000547672, ENST00000548379, ENST00000548420, ENST00000548945, ENST00000549678, ENST00000550136, ENST00000550914, ENST00000551425, ENST00000551623, ENST00000551630, ENST00000551845, ENST00000553011, ENST00000553256, ENST00000687744, ENST00000690194, ENST00000692981, ENST00000693534, ENST00000711046

RefSeq mRNA: 9 — MANE Select: NM_000264 NM_000264, NM_001083602, NM_001083603, NM_001083604, NM_001083605, NM_001083606, NM_001083607, NM_001354918, NM_001354919

CCDS: CCDS43851, CCDS47995, CCDS47996, CCDS6714, CCDS87661

Canonical transcript exons

ENST00000331920 — 24 exons

Exon	Start	End
ENSE00001466612	95442980	95446391
ENSE00001603786	95449841	95449940
ENSE00001630740	95508161	95509266
ENSE00001657782	95478055	95478186
ENSE00001683149	95476759	95476857
ENSE00001694942	95477547	95477702
ENSE00001754264	95476034	95476159
ENSE00001796032	95479000	95479147
ENSE00002168565	95479969	95480090
ENSE00002729294	95453478	95453620
ENSE00003470024	95467116	95467425
ENSE00003473841	95481949	95482040
ENSE00003479218	95461856	95461998
ENSE00003485014	95459600	95459783
ENSE00003503243	95468751	95469153
ENSE00003511832	95506407	95506599
ENSE00003537919	95469813	95469931
ENSE00003545716	95446911	95447451
ENSE00003560352	95449069	95449323
ENSE00003565694	95456276	95456413
ENSE00003576708	95485685	95485874
ENSE00003593424	95480390	95480588
ENSE00003634275	95482134	95482203
ENSE00003644051	95458013	95458293

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 99.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.6128 / max 396.4850, expressed in 1237 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101567	3.3324	484
101568	2.0253	598
101566	1.1378	327
101570	0.9646	197
101562	0.5752	337
101576	0.5720	192
101564	0.4733	252
101569	0.2514	121
101563	0.2358	111
101565	0.2220	91

Top tissues by expression

292 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.27	gold quality
dorsal root ganglion	UBERON:0000044	98.41	gold quality
trigeminal ganglion	UBERON:0001675	98.02	gold quality
sural nerve	UBERON:0015488	97.68	gold quality
pylorus	UBERON:0001166	95.62	gold quality
sperm	CL:0000019	95.29	gold quality
male germ cell	CL:0000015	94.33	gold quality
pigmented layer of retina	UBERON:0001782	93.76	gold quality
cardia of stomach	UBERON:0001162	93.67	gold quality
medial globus pallidus	UBERON:0002477	93.11	gold quality
endometrium	UBERON:0001295	93.02	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	92.92	gold quality
globus pallidus	UBERON:0001875	92.67	gold quality
colonic epithelium	UBERON:0000397	92.58	gold quality
caput epididymis	UBERON:0004358	92.16	gold quality
cerebellum	UBERON:0002037	92.11	gold quality
cerebellar cortex	UBERON:0002129	91.88	gold quality
cerebellar hemisphere	UBERON:0002245	91.86	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.72	gold quality
tibial nerve	UBERON:0001323	91.63	gold quality
endothelial cell	CL:0000115	90.92	gold quality
lateral globus pallidus	UBERON:0002476	90.51	gold quality
adult organism	UBERON:0007023	89.67	gold quality
seminal vesicle	UBERON:0000998	89.51	gold quality
visceral pleura	UBERON:0002401	88.46	gold quality
mucosa of sigmoid colon	UBERON:0004993	88.43	gold quality
jejunal mucosa	UBERON:0000399	88.24	gold quality
urethra	UBERON:0000057	88.17	gold quality
Brodmann (1909) area 23	UBERON:0013554	87.94	gold quality
substantia nigra pars compacta	UBERON:0001965	87.77	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	101.46
E-GEOD-134144	yes	39.31
E-CURD-46	yes	7.80
E-HCAD-11	yes	7.09
E-ANND-3	yes	7.07

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, CTNNB1, GLI1, GLI2, GLI3, MEIS1, MSX1, NR1H3, RUNX2, SMARCB1, SOX4, SPOP, ZKSCAN7, ZNF354C, ZNF431

miRNA regulators (miRDB)

175 targeting PTCH1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-3617-3P	99.98	67.86	918
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4666A-3P	99.96	71.71	3434

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• No germline PTCH mutations have been identified in 8 subjects with Birt-Hogg-Dube syndrome, suggesting that PTCH should be excluded as a candidate gene for BHD. (PMID:11836379)
• Mutations for basal cell carcinoma (BCC), were screened in 15 cases of sporadic BCCs that developed in sun-exposed skin region in a Korean population (PMID:12007715)
• results suggest that the Ptc tumour suppressor functions normally as a transmembrane molecular transporter, which acts indirectly to inhibit Smo activity (PMID:12192414)
• Patched expression in human astrocytic tumors inversely correlates with histological malignancy (PMID:12241103)
• odontogenic keratocysts arise with heterozygous mutations of the gene (PMID:12407090)
• The patched polymorphism Pro1315Leu (C3944T) may modulate the association between use of oral contraceptives and breast cancer risk (PMID:12516098)
• Nineteen novel mutations and five new polymorphisms were identified (PMID:12925203)
• mutations are probably related not only to basal cell nevus-associated odontogenic keratocysts but also to sporadic odontgenic keratocysts (PMID:15308259)
• thirteen novel mutations identified in the mutational screening of nevoid basal cell carcinoma syndrome patients in Italy (PMID:15459969)
• cDNA microarray analysis performed on cell lines derived from ovarian dermoid cysts did not show any significant alteration in the expression of the analyzed target genes of PTCH signaling. (PMID:15492847)
• Papillary carcinomas with high RET/PTC1 expression showed an association trend for large tumor size. (PMID:15502856)
• No phenotype-genotype relationships were found in the Japanese nevoid basal cell carcinoma syndrome patients (PMID:15565302)
• Data show that in both human and mouse a novel Patched homolog 1 first exon (1C) is expressed. (PMID:15581634)
• ptc1 mutations and truncation are responsible for the majority of basal cell carcinoma (BCC) cases. (PMID:15592520)
• 9 new mutations wew found: c.1436T>G p.L479R; c.1138G>T p.E380X; c.323_324ins2; c.2011_2012dup; c.2535_2536dup; c.2577_2583del, c.3000_3005del; c.3050_3051del; & c.6552A>T. (PMID:15712338)
• Seven isoforms of human PTCH mRNA were identified. (PMID:15780749)
• Elevated expression of hedgehog target genes human patched gene 1 (PTCH1) or Gli1 occurs in 63 of the 99 primary gastric cancers. (PMID:15905200)
• analysis of missense mutations in the PTCH gene which may be responsible for Nevoid Basal Cell Carcinoma Syndrome (PMID:16088933)
• possible relationship between the CGG8 allele in PTCH1 and the risk for ameloblastoma (PMID:16109989)
• Isoforms - novel exon, exon 12b, was specifically expressed in the brain and heart, especially in the cerebellum. Also, disease-associated aberrant splicings found in two patients with nevoid basal cell carcinoma syndrome. (PMID:16203740)
• Patched-expressing cells have been identified among endodermally lineage-restricted, murine embryonic stem cells as well as in livers of fetal and adult Ptc-lacZ mice. (PMID:16322088)
• analysis of PTCH mutations in nevoid basal cell carcinoma syndrome [review] (PMID:16419085)
• Our data show that MC1R and PTCH variants are associated with basal cell carcinoma (BCC) risk in the French population. (PMID:16645598)
• Germline mutations on PTCH can cause isolated odontogenic cyst, and this PTCH gene responsible for nevoid basal cell carcinoma syndrome plays an important role in the formation of odontogenic cyst. (PMID:16675912)
• alteration of both p53 and PTCH genes is likely to play a role in radiation-induced basal cell carcinogenesis (PMID:16777989)
• novel insertion mutation in exon 6 of the PTCH gene was identified in a Korean family with naevoid basal cell carcinoma syndrome (PMID:16780502)
• aberrant expressions of PTCH and Smo were common in pancreatic carcinoma tissues & were associated with low-level differentiation of tumor tissue & hyperglycemia; this indicated that these molecules played a fundamental role in pancreas tumorigenesis (PMID:16804411)
• the upstream part of the Hedgehog pathway involving Hedgehog interaction with Patched, regulation of Smoothened by Patched, and Smoothened enrichment at the plasma membrane is highly conserved between Drosophila and humans (PMID:16867986)
• defects are associated with the pathogenesis of syndromic as well as a subset of non-syndromic keratocysts (PMID:16931872)
• Patched-1 containing exon 12b is a dominant negative isoform and is expressed in medulloblastomas (PMID:16934747)
• Mutation screening identified a novel nonsense mutation in PTCH (c.1136C > G; p.Ser383X), the gene associated with Gorlin syndrome. (PMID:17258529)
• Reduced expression of PTCH is associated with breast cancer (PMID:17295047)
• Shh-Ptch1-Gli1 signaling pathway may play a role in the progression of colorectal tumor. (PMID:17461467)
• Patched gene is epigenetically regulated in ovarian dermoids and fibromas, but not in basocellular carcinomas. (PMID:17487419)
• PTCH mutations are not mainly involved in the pathogenesis of sporadic trichoblastomas (PMID:17597182)
• a (UV-) mutated PTCH gene is important for sporadic BCC formation independent of clinical phenotype and the IVS16-80G/C and/or IVS17+21G/A SNP site might be important for tumorigenesis in certain BCC patients (PMID:17597822)
• A patient with nevoid basal-cell carcinoma syndrome and West syndrome. The patient had a heterozygous mutation (insertion of TGGC) in the PTCH gene. (PMID:17950424)
• prevalence of PTCH and p53 mutations for basal cell carcinoma is 63% and 46% in psoralen /UVA associated cancer (PMID:18059486)
• A novel PTCH1 mutation in a patient of nevoid basal cell carcinoma syndrome. (PMID:18068337)
• there was no evidence of methylation in the PTCH1-1B promoter in the MB cases examined, nor was there methylation in the control cerebellum samples. (PMID:18068533)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptch1	ENSDARG00000016404
danio_rerio		ENSDARG00000095859
mus_musculus	Ptch1	ENSMUSG00000021466
rattus_norvegicus	Ptch1	ENSRNOG00000019354
drosophila_melanogaster	ptc	FBGN0003892
drosophila_melanogaster	disp	FBGN0029088
drosophila_melanogaster	Ptr	FBGN0262867
caenorhabditis_elegans		WBGENE00004208
caenorhabditis_elegans		WBGENE00004211
caenorhabditis_elegans	ptr-17	WBGENE00004231

Paralogs (10): NPC1L1 (ENSG00000015520), SCAP (ENSG00000114650), PTCH2 (ENSG00000117425), DISP2 (ENSG00000140323), NPC1 (ENSG00000141458), DISP1 (ENSG00000154309), PTCHD1 (ENSG00000165186), PTCHD3 (ENSG00000182077), DISP3 (ENSG00000204624), PTCHD4 (ENSG00000244694)

Protein

Protein identifiers

Protein patched homolog 1 — Q13635 (reviewed: Q13635)

All UniProt accessions (10): A0A0C4DGI4, A0A0C4DGJ5, A0A8I5KPP5, Q13635, F8VPA3, F8VQS6, F8VXL8, H0Y3B8, H0YHK0, H3BLX7

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Interacts with SNX17. Interacts with IHH. Interacts with G-protein coupled receptor GPR37L1.

Subcellular location. Cell membrane.

Tissue specificity. In the adult, expressed in brain, lung, liver, heart, placenta, skeletal muscle, pancreas and kidney. Expressed in tumor cells but not in normal skin.

Post-translational modifications. Glycosylation is necessary for SHH binding. In the absence of Hh ligands, ubiquitination by ITCH at Lys-1426 promotes endocytosis and both proteasomal and lysosomal degradation.

Disease relevance. Basal cell nevus syndrome 1 (BCNS1) [MIM:109400] A form of basal cell nevus syndrome, a 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 fibromas of the ovaries and heart, cysts of the skin, jaws and mesentery, as well as medulloblastomas and meningiomas. BCNS1 inheritance is autosomal dominant. The disease may be caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry. Holoprosencephaly 7 (HPE7) [MIM:610828] A form of holoprosencephaly, a structural anomaly of the brain in which the developing forebrain fails to correctly separate into right and left hemispheres. It is a genetically and clinically heterogeneous disorder with a wide spectrum of severity, ranging from alobar holoprosencephaly with severe facial abnormalities, such as cyclopia and proboscis, to mild forms that include lobar or microform holoprosencephaly, without cerebral malformations and with mild craniofacial defects. HPE7 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the patched family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q13635-1	L, 1B	yes
Q13635-2	L’, 1Ckid
Q13635-3	M, 1C
Q13635-4	S, 1A, 1CdeltaE2

RefSeq proteins (9): NP_000255, NP_001077071, NP_001077072, NP_001077073, NP_001077074, NP_001077075, NP_001077076, NP_001341847, NP_001341848 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000731	SSD	Domain
IPR004766	TM_rcpt_patched	Family
IPR053958	HMGCR/SNAP/NPC1-like_SSD	Domain

Pfam: PF12349

UniProt features (181 total): helix 57, strand 32, sequence variant 28, topological domain 13, turn 13, transmembrane region 12, glycosylation site 6, sequence conflict 6, region of interest 3, compositionally biased region 3, splice variant 3, modified residue 2, chain 1, domain 1, cross-link 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
6RTW	X-RAY DIFFRACTION	1.9
6RTX	X-RAY DIFFRACTION	1.95
6RTY	X-RAY DIFFRACTION	2.1
6RVC	X-RAY DIFFRACTION	2.2
6RMG	ELECTRON MICROSCOPY	3.4
6E1H	ELECTRON MICROSCOPY	3.5
6OEU	ELECTRON MICROSCOPY	3.5
6RVD	ELECTRON MICROSCOPY	3.5
6DMY	ELECTRON MICROSCOPY	3.6
6N7H	ELECTRON MICROSCOPY	3.6
9MS8	ELECTRON MICROSCOPY	3.73
6OEV	ELECTRON MICROSCOPY	3.8
6DMB	ELECTRON MICROSCOPY	3.9
6DMO	ELECTRON MICROSCOPY	4.1
6N7K	ELECTRON MICROSCOPY	6.5
6N7G	ELECTRON MICROSCOPY	6.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13635-F1	74.36	0.43

Antibody-complex structures (SAbDab): 4 — 6RTW, 6RTY, 6RVC, 9MS8

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 1195, 1197, 1426

Glycosylation sites (6): 141, 312, 349, 414, 875, 1000

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-373080	Class B/2 (Secretin family receptors)
R-HSA-5610787	Hedgehog ‘off’ state
R-HSA-5632681	Ligand-receptor interactions
R-HSA-5632684	Hedgehog ‘on’ state
R-HSA-5635838	Activation of SMO
R-HSA-5635851	GLI proteins bind promoters of Hh responsive genes to promote transcription

MSigDB gene sets: 1060 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, RNGTGGGC_UNKNOWN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MAMMARY_GLAND_MORPHOGENESIS, FREAC2_01, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_AXIS_SPECIFICATION, GOBP_GLAND_MORPHOGENESIS

GO Biological Process (65): negative regulation of transcription by RNA polymerase II (GO:0000122), branching involved in ureteric bud morphogenesis (GO:0001658), in utero embryonic development (GO:0001701), cell fate determination (GO:0001709), neural tube closure (GO:0001843), heart morphogenesis (GO:0003007), signal transduction (GO:0007165), spermatid development (GO:0007286), regulation of mitotic cell cycle (GO:0007346), brain development (GO:0007420), regulation of smoothened signaling pathway (GO:0008589), response to xenobiotic stimulus (GO:0009410), response to mechanical stimulus (GO:0009612), animal organ morphogenesis (GO:0009887), dorsal/ventral pattern formation (GO:0009953), epidermal cell fate specification (GO:0009957), response to chlorate (GO:0010157), negative regulation of keratinocyte proliferation (GO:0010839), positive regulation of cholesterol efflux (GO:0010875), protein processing (GO:0016485), spinal cord motor neuron differentiation (GO:0021522), neural tube patterning (GO:0021532), dorsal/ventral neural tube patterning (GO:0021904), neural plate axis specification (GO:0021997), embryonic limb morphogenesis (GO:0030326), prostate gland development (GO:0030850), response to estradiol (GO:0032355), response to retinoic acid (GO:0032526), regulation of protein localization (GO:0032880), limb morphogenesis (GO:0035108), hindlimb morphogenesis (GO:0035137), negative regulation of multicellular organism growth (GO:0040015), glucose homeostasis (GO:0042593), response to alkaloid (GO:0043279), keratinocyte proliferation (GO:0043616), positive regulation of epidermal cell differentiation (GO:0045606), negative regulation of osteoblast differentiation (GO:0045668), negative regulation of smoothened signaling pathway (GO:0045879), positive regulation of DNA-templated transcription (GO:0045893), embryonic organ development (GO:0048568)

GO Molecular Function (9): patched binding (GO:0005113), smoothened binding (GO:0005119), hedgehog receptor activity (GO:0008158), heparin binding (GO:0008201), cholesterol binding (GO:0015485), cyclin binding (GO:0030332), protein-containing complex binding (GO:0044877), hedgehog family protein binding (GO:0097108), protein binding (GO:0005515)

GO Cellular Component (13): plasma membrane (GO:0005886), caveola (GO:0005901), midbody (GO:0030496), endocytic vesicle membrane (GO:0030666), dendritic growth cone (GO:0044294), axonal growth cone (GO:0044295), apical part of cell (GO:0045177), postsynaptic membrane (GO:0045211), perinuclear region of cytoplasm (GO:0048471), ciliary membrane (GO:0060170), Golgi apparatus (GO:0005794), cilium (GO:0005929), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Hedgehog ‘on’ state	3
Signaling by Hedgehog	2
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
animal organ development	2
protein binding	2
binding	2
bounding membrane of organelle	2
growth cone	2
cytoplasm	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
branching morphogenesis of an epithelial tube	1
ureteric bud morphogenesis	1
chordate embryonic development	1
cell fate commitment	1
cellular developmental process	1
primary neural tube formation	1
tube closure	1
heart development	1
animal organ morphogenesis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
germ cell development	1
spermatid differentiation	1
mitotic cell cycle	1
regulation of cell cycle	1
central nervous system development	1
head development	1
smoothened signaling pathway	1
regulation of signal transduction	1
response to chemical	1
response to external stimulus	1
response to abiotic stimulus	1
anatomical structure morphogenesis	1
regionalization	1
cell fate specification	1
epidermal cell differentiation	1
response to oxygen-containing compound	1

Protein interactions and networks

STRING

2945 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTCH1	SMO	Q99835	999
PTCH1	IHH	Q14623	999
PTCH1	SHH	Q15465	999
PTCH1	DHH	O43323	998
PTCH1	GAS1	P54826	983
PTCH1	CDON	Q4KMG0	978
PTCH1	GLI1	P08151	975
PTCH1	SUFU	Q9UMX1	975
PTCH1	GLI2	P10070	967
PTCH1	GLI3	P10071	955
PTCH1	HHIP	Q96QV1	954
PTCH1	BOC	Q9BWV1	926
PTCH1	RET	P07949	915
PTCH1	CCNB1	P14635	909
PTCH1	NCOA4	Q13772	901

IntAct

24 interactions, top by confidence:

A	B	Type	Score
GRK2	PTCH1	psi-mi:“MI:0407”(direct interaction)	0.600
GRK2	PTCH1	psi-mi:“MI:0915”(physical association)	0.600
PTCH1	Cdon	psi-mi:“MI:0915”(physical association)	0.520
PTCH1	GRK2	psi-mi:“MI:0915”(physical association)	0.500
PTCH1	CCNB1	psi-mi:“MI:0915”(physical association)	0.500
PTCH1	CCNB1	psi-mi:“MI:0914”(association)	0.500
SHH	PTCH1	psi-mi:“MI:0407”(direct interaction)	0.440
PPIA	PTCH1	psi-mi:“MI:0407”(direct interaction)	0.440
YAP1	PTCH1	psi-mi:“MI:0407”(direct interaction)	0.440
PTCH1	SMO	psi-mi:“MI:0914”(association)	0.430
HHIP	PTCH1	psi-mi:“MI:0915”(physical association)	0.400
CDON	PTCH1	psi-mi:“MI:0915”(physical association)	0.400
PTCH1	CDON	psi-mi:“MI:0915”(physical association)	0.400
PTCH1	PLXNB2	psi-mi:“MI:0914”(association)	0.350
PTCH1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
PTCH1	Cav1	psi-mi:“MI:0914”(association)	0.270

BioGRID (399): CNTNAP3 (Affinity Capture-MS), B4GALT7 (Affinity Capture-MS), CACNA2D2 (Affinity Capture-MS), IMPAD1 (Affinity Capture-MS), SEMA6A (Affinity Capture-MS), PLXNA1 (Affinity Capture-MS), TMEM132A (Affinity Capture-MS), PAM (Affinity Capture-MS), HLA-C (Affinity Capture-MS), HLA-A (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), TMEM160 (Affinity Capture-MS), PLXNB2 (Affinity Capture-MS), NDST2 (Affinity Capture-MS), TPST2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5PUP4, A2AFS3, M0R7X9, O70472, O75882, O95803, P01134, P26012, P52799, P52848, P69849, Q02353, Q05204, Q0VCJ8, Q12841, Q13635, Q15155, Q3UHN9, Q3ZBS2, Q58D84, Q5EA46, Q5JPE7, Q5R9Y1, Q5U4X8, Q5VV63, Q5ZJB7, Q5ZMH6, Q61115, Q62356, Q62632, Q6A051, Q6GQK9, Q6GQT9, Q6P988, Q6UXG2, Q7Z5A7, Q86TD4, Q90693, Q91WE9, Q96CW9

Diamond homologs: A0A125YWU9, H2L0G5, Q09614, Q13635, Q61115, Q90693, Q98864, Q9Y6C5, O35595, O42334, O42335, P18502, Q0EEE2, Q09311, Q9XWL9, P97260, A3KFU9, B9U3F2, Q3KNS1, Q9P2K9

SIGNOR signaling

22 interactions.

A	Effect	B	Mechanism
CASP3	“down-regulates activity”	PTCH1	cleavage
PTCH1	“down-regulates activity”	SMO	binding
SHH	“down-regulates activity”	PTCH1	binding
GLI3	“up-regulates quantity by expression”	PTCH1	“transcriptional regulation”
“Yellow AB”	down-regulates	PTCH1	“chemical inhibition”
GLI1	“up-regulates quantity by expression”	PTCH1	“transcriptional regulation”
CASP3	down-regulates	PTCH1	cleavage
PTCH1	up-regulates	CCNB1	binding
“Caspase 3 complex”	down-regulates	PTCH1	cleavage
“Caspase 3 complex”	“down-regulates activity”	PTCH1	cleavage
GPC6	“up-regulates activity”	PTCH1	binding
LRP2	“up-regulates quantity”	PTCH1	binding
IHH	“down-regulates activity”	PTCH1	binding
PTCH1	“form complex”	CDON/BOC/PTCH1	binding
GLI2	“up-regulates quantity by expression”	PTCH1	“transcriptional regulation”
SLITRK5	“down-regulates activity”	PTCH1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 12 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
neuroblast proliferation	5	183.2×	1e-08

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 11 cancer types — ANGS, BCC, CHOL, ESCA, MBL, NPC, OS, PAST, PLMESO, SKIN, WDTC.

Clinical variants and AI predictions

ClinVar

5047 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	479
Likely pathogenic	116
Uncertain significance	2109
Likely benign	1585
Benign	101

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1020298	NM_000264.5(PTCH1):c.1524TGGTGT[1] (p.509GV[1])	Pathogenic
1068532	NM_000264.5(PTCH1):c.654+1G>A	Pathogenic
1068897	NM_000264.5(PTCH1):c.3030del (p.Asn1011fs)	Pathogenic
1068949	NC_000009.12:g.95449841dup	Pathogenic
1069018	NM_000264.5(PTCH1):c.1480dup (p.Ser494fs)	Pathogenic
1069312	NC_000009.12:g.95482041_95482042insGCTCTCCCTCTCCCTCTCCCTCTCCCTCTCCCTCTCCCTCCCCCTCCCTCTCCCTCTCCCTCTCCCTCTACCTCCACGGTCNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAGATATTCTATTATC	Pathogenic
1069426	NM_000264.5(PTCH1):c.1603-1G>A	Pathogenic
1069671	NC_000009.11:g.(?98229392)(98232219_?)del	Pathogenic
1069761	NM_000264.5(PTCH1):c.1068-2A>G	Pathogenic
1069765	NM_000264.5(PTCH1):c.554_584+1dup	Pathogenic
1069985	NM_000264.5(PTCH1):c.376G>T (p.Glu126Ter)	Pathogenic
1070415	NM_000264.5(PTCH1):c.3058C>T (p.Gln1020Ter)	Pathogenic
1070583	NM_000264.5(PTCH1):c.1303dup (p.Ser435fs)	Pathogenic
1071198	NM_000264.5(PTCH1):c.3027_3030del (p.Ser1008_Tyr1009insTer)	Pathogenic
1071334	NM_000264.5(PTCH1):c.1338C>A (p.Tyr446Ter)	Pathogenic
1071486	NM_000264.5(PTCH1):c.351dup (p.Ala118fs)	Pathogenic
1071610	NM_000264.5(PTCH1):c.202-1G>C	Pathogenic
1071736	NM_000264.5(PTCH1):c.639del (p.Gly214fs)	Pathogenic
1071934	NM_000264.5(PTCH1):c.834G>A (p.Trp278Ter)	Pathogenic
1071963	NC_000009.11:g.(?98204264)(98271831_?)del	Pathogenic
1071964	NC_000009.11:g.(?98247957)(98248166_?)del	Pathogenic
1072031	NM_000264.5(PTCH1):c.3441_3444del (p.Phe1147fs)	Pathogenic
1072169	NM_000264.5(PTCH1):c.2684dup (p.Pro896fs)	Pathogenic
1072215	NM_000264.5(PTCH1):c.591G>A (p.Trp197Ter)	Pathogenic
1072436	NM_000264.5(PTCH1):c.3139del (p.Leu1047fs)	Pathogenic
1072439	NM_000264.5(PTCH1):c.1253del (p.Lys418fs)	Pathogenic
1072730	NM_000264.5(PTCH1):c.1237C>T (p.Gln413Ter)	Pathogenic
1072732	NM_000264.5(PTCH1):c.1538ATG[1] (p.Asp514del)	Pathogenic
1072733	NM_000264.5(PTCH1):c.1525G>C (p.Gly509Arg)	Pathogenic
1072894	NM_000264.5(PTCH1):c.912C>A (p.Cys304Ter)	Pathogenic

SpliceAI

3601 predictions. Top by Δscore:

Variant	Effect	Δscore
9:95449063:ACTT:A	donor_loss	1.0000
9:95449065:TTA:T	donor_loss	1.0000
9:95449066:TA:T	donor_loss	1.0000
9:95449067:A:AC	donor_gain	1.0000
9:95449067:ACAGT:A	donor_loss	1.0000
9:95449068:C:CT	donor_gain	1.0000
9:95449068:CA:C	donor_gain	1.0000
9:95449068:CAG:C	donor_gain	1.0000
9:95449068:CAGT:C	donor_gain	1.0000
9:95449068:CAGTG:C	donor_gain	1.0000
9:95449321:CAC:C	acceptor_gain	1.0000
9:95453473:CTTA:C	donor_loss	1.0000
9:95453474:TTACC:T	donor_loss	1.0000
9:95453475:TAC:T	donor_loss	1.0000
9:95453476:ACC:A	donor_loss	1.0000
9:95453617:AGGCC:A	acceptor_loss	1.0000
9:95453618:GGCCT:G	acceptor_loss	1.0000
9:95453619:GCCTG:G	acceptor_loss	1.0000
9:95453620:CCTG:C	acceptor_gain	1.0000
9:95453620:CCTGT:C	acceptor_loss	1.0000
9:95453621:C:CA	acceptor_loss	1.0000
9:95453622:T:A	acceptor_loss	1.0000
9:95453623:G:C	acceptor_gain	1.0000
9:95453623:G:GC	acceptor_gain	1.0000
9:95456272:ATACC:A	donor_loss	1.0000
9:95456273:TA:T	donor_loss	1.0000
9:95456274:A:AC	donor_gain	1.0000
9:95456274:A:AG	donor_loss	1.0000
9:95456275:C:CC	donor_gain	1.0000
9:95456410:TCAC:T	acceptor_gain	1.0000

AlphaMissense

9455 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:95453492:G:C	F1145L	1.000
9:95453492:G:T	F1145L	1.000
9:95453493:A:C	F1145C	1.000
9:95453494:A:G	F1145L	1.000
9:95467146:A:G	W844R	1.000
9:95467146:A:T	W844R	1.000
9:95469869:G:C	S597R	1.000
9:95469869:G:T	S597R	1.000
9:95469871:T:G	S597R	1.000
9:95476140:A:G	L541P	1.000
9:95476150:C:A	G538W	1.000
9:95476811:A:G	L517P	1.000
9:95476813:A:C	F516L	1.000
9:95476813:A:T	F516L	1.000
9:95476815:A:G	F516L	1.000
9:95477594:C:G	G486R	1.000
9:95477596:A:G	L485P	1.000
9:95477632:C:T	G473D	1.000
9:95477633:C:G	G473R	1.000
9:95477642:C:G	G470R	1.000
9:95477642:C:T	G470R	1.000
9:95479020:A:G	W399R	1.000
9:95479020:A:T	W399R	1.000
9:95479054:C:A	W387C	1.000
9:95479054:C:G	W387C	1.000
9:95479056:A:G	W387R	1.000
9:95479056:A:T	W387R	1.000
9:95506416:A:G	W129R	1.000
9:95506416:A:T	W129R	1.000
9:95506418:A:G	L128P	1.000

dbSNP variants (sampled 300 via entrez): RS1000033761 (9:95502628 T>C), RS1000066632 (9:95494280 G>A), RS1000099875 (9:95509662 A>G), RS1000105444 (9:95502382 T>C), RS1000111689 (9:95505797 G>A), RS1000252307 (9:95447519 A>C,G), RS1000253959 (9:95452463 G>A), RS1000279933 (9:95459096 G>A,C), RS1000413965 (9:95490729 G>A,C), RS1000475698 (9:95450992 G>C), RS1000510415 (9:95463918 A>G), RS1000512103 (9:95453804 C>T), RS1000585082 (9:95448574 G>A), RS1000614118 (9:95460403 C>G,T), RS1000620150 (9:95497615 T>A)

Disease associations

OMIM: gene MIM:601309 | disease phenotypes: MIM:109400, MIM:605462, MIM:610828, MIM:604229, MIM:174500, MIM:142623, MIM:167000, MIM:160700, MIM:236600, MIM:617667, MIM:150699, MIM:150800, MIM:116200, MIM:118220, MIM:123100, MIM:236100

GenCC curated gene-disease

Disease	Classification	Inheritance
holoprosencephaly 7	Definitive	Autosomal dominant
nevoid basal cell carcinoma syndrome	Definitive	Autosomal dominant
basal cell nevus syndrome 1	Definitive	Autosomal dominant
exstrophy-epispadias complex	Strong	Autosomal dominant
holoprosencephaly	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
nevoid basal cell carcinoma syndrome	Definitive	AD

Mondo (34): nevoid basal cell carcinoma syndrome (MONDO:0007187), basal cell carcinoma, susceptibility to, 1 (MONDO:0011556), hereditary neoplastic syndrome (MONDO:0015356), holoprosencephaly 7 (MONDO:0012562), basal cell nevus syndrome 1 (MONDO:0958174), Peters anomaly (MONDO:0011414), Rieger anomaly (MONDO:0019628), polydactyly of a triphalangeal thumb (MONDO:0008270), retinoblastoma (MONDO:0008380), Hirschsprung disease, susceptibility to, 1 (MONDO:0007723), microform holoprosencephaly (MONDO:0017219), congenital heart disease (MONDO:0005453), ovarian cancer (MONDO:0008170), intellectual disability (MONDO:0001071), myopia (MONDO:0001384)

Orphanet (24): Inherited cancer-predisposing syndrome (Orphanet:140162), Gorlin syndrome (Orphanet:377), Holoprosencephaly (Orphanet:2162), Peters anomaly (Orphanet:708), Rieger anomaly (Orphanet:91483), Microphthalmia-anophthalmia-coloboma (Orphanet:98555), Patterson-Stevenson-Fontaine syndrome (Orphanet:2439), Triphalangeal thumb-polysyndactyly syndrome (Orphanet:2950), Polydactyly of a triphalangeal thumb (Orphanet:93336), Retinoblastoma (Orphanet:790), Hirschsprung disease (Orphanet:388), Microform holoprosencephaly (Orphanet:280200), Rare ovarian cancer (Orphanet:213500), Congenital hydrocephalus (Orphanet:2185), Turner syndrome (Orphanet:881)

HPO phenotypes

232 total (30 of 232 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000062	Ambiguous genitalia
HP:0000098	Tall stature
HP:0000104	Renal agenesis
HP:0000119	Abnormality of the genitourinary system
HP:0000160	Narrow mouth
HP:0000161	Median cleft upper lip
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000202	Orofacial cleft
HP:0000204	Cleft upper lip
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000242	Parietal bossing
HP:0000243	Trigonocephaly
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000267	Cranial asymmetry
HP:0000280	Coarse facial features
HP:0000283	Broad face
HP:0000286	Epicanthus
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000343	Long philtrum
HP:0000369	Low-set ears
HP:0000400	Macrotia

GWAS associations

97 associations (top):

Study	Trait	p-value
GCST000174_7	Height	4.000000e-11
GCST000542_5	Pulmonary function	5.000000e-07
GCST000628_1	Chemerin levels	4.000000e-06
GCST001784_53	Pulmonary function (smoking interaction)	8.000000e-12
GCST002646_7	Infant length	2.000000e-10
GCST002647_2	Height	5.000000e-30
GCST002647_30	Height	4.000000e-34
GCST002702_87	Height	2.000000e-07
GCST003388_1	Bone mineral density (spine)	1.000000e-11
GCST003389_3	Bone mineral density (hip)	2.000000e-06
GCST003996_48	Monobrow	1.000000e-13
GCST004063_89	Waist circumference adjusted for body mass index	9.000000e-07
GCST004063_90	Waist circumference adjusted for body mass index	4.000000e-12
GCST004063_91	Waist circumference adjusted for body mass index	5.000000e-08
GCST004067_132	Hip circumference adjusted for BMI	2.000000e-08
GCST004067_199	Hip circumference adjusted for BMI	2.000000e-09
GCST004067_88	Hip circumference adjusted for BMI	7.000000e-15
GCST004166_44	Nonsyndromic cleft lip with cleft palate	5.000000e-10
GCST004500_114	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	6.000000e-08
GCST004500_71	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	6.000000e-06
GCST004501_126	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	9.000000e-08
GCST004504_92	Waist circumference adjusted for BMI in non-smokers	2.000000e-07
GCST004562_108	Waist circumference adjusted for body mass index	8.000000e-09
GCST004562_140	Waist circumference adjusted for body mass index	3.000000e-10
GCST004562_231	Waist circumference adjusted for body mass index	3.000000e-08
GCST004562_35	Waist circumference adjusted for body mass index	7.000000e-11
GCST004562_55	Waist circumference adjusted for body mass index	1.000000e-06
GCST004563_117	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	1.000000e-09
GCST004563_121	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	5.000000e-10
GCST004563_13	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	3.000000e-06

EFO canonical traits (26, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0004713	FEV/FVC ratio
EFO:0004573	chemerin measurement
EFO:0006785	infant body height
EFO:0007701	spine bone mineral density
EFO:0007702	hip bone mineral density
EFO:0007906	synophrys measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0003959	cleft lip
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0004344	birth weight
EFO:0009270	heel bone mineral density
EFO:0007660	neuroticism measurement
EFO:0009589	worry measurement
EFO:0009599	feeling emotionally hurt measurement
EFO:0008579	risk-taking behaviour
EFO:0004312	vital capacity
EFO:0009603	stroke outcome severity measurement
EFO:0005939	parental genotype effect measurement
EFO:0004771	visual cortical surface area measurement
EFO:0004346	neuroimaging measurement
EFO:0009863	anxiety measurement
EFO:0004980	appendicular lean mass
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (21)

Descriptor	Name	Tree numbers
D001478	Basal Cell Nevus Syndrome	C04.182.089.530.690.150; C04.557.470.200.165.150; C04.557.470.565.165.150; C04.700.175; C05.116.099.105; C05.500.470.690.150; C07.320.450.670.130; C16.131.077.130; C16.320.700.175
D002280	Carcinoma, Basal Cell	C04.557.470.200.165; C04.557.470.565.165
D002386	Cataract	C11.510.245
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
D003397	Craniopharyngioma	C04.557.465.625.200; C04.557.580.625.200
D003398	Craniosynostoses	C05.116.099.370.894.232; C05.660.207.240; C05.660.906.364; C16.131.621.207.240; C16.131.621.906.364
D018237	Germinoma	C04.557.465.330
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D016142	Holoprosencephaly	C05.660.207.410; C10.500.034.875; C16.131.077.410; C16.131.260.380; C16.131.621.207.410; C16.131.666.034.875; C16.320.180.380
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009216	Myopia	C11.744.636
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D012175	Retinoblastoma	C04.557.465.625.600.725; C04.557.470.670.725; C04.557.580.625.600.725; C04.588.364.818.760; C11.270.862; C11.319.475.760; C11.768.717.760
D012208	Rhabdomyosarcoma	C04.557.450.590.550.660; C04.557.450.795.550.660
D012873	Skin Diseases, Genetic	C16.320.850; C17.800.827
D014424	Turner Syndrome	C12.050.351.875.253.309.872; C12.050.351.875.253.795.750; C12.200.706.316.309.872; C12.200.706.316.795.750; C12.800.316.309.872; C12.800.316.795.750; C14.240.400.980; C14.280.400.980; C16.131.240.400.970; C16.131.260.830.835.750; C16.131.939.316.309.872; C16.131.939.316.795.750; C16.320.180.830.835.750; C19.391.119.309.872; C19.391.119.795.750
C535516	Hereditary leiomyomatosis and renal cell cancer (supp.)
C563660	Holoprosencephaly 7 (supp.)
C537884	Peters anomaly (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169150 (SINGLE PROTEIN)

Clinical evidence (CIViC)

Drug × variant × indication: 3 predictive associations from 3 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
PTCH1 LOH	Vismodegib	Medulloblastoma	Sensitivity/Response	CIViC B	EID749
PTCH1 Mutation	Vismodegib	Cancer	Sensitivity/Response	CIViC B	EID5978
PTCH1 Mutation	Sonidegib	Medulloblastoma	Sensitivity/Response	CIViC B	EID748

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

70 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment, decreases expression, affects expression	6
trichostatin A	affects cotreatment, decreases expression	4
Resveratrol	decreases expression, increases expression	3
Vorinostat	affects cotreatment, decreases expression	3
Fluorouracil	affects localization, affects cotreatment, increases expression, decreases expression, decreases reaction	3
arsenite	increases methylation, increases expression	2
entinostat	decreases expression, affects cotreatment	2
bisphenol S	increases methylation, decreases methylation, increases expression, affects cotreatment	2
Decitabine	decreases reaction, affects expression, affects methylation, decreases expression	2
Arsenic Trioxide	decreases expression	2
Fulvestrant	affects cotreatment, increases methylation, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Cadmium	decreases expression, increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Quercetin	decreases expression, increases expression, decreases reaction	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
cyclopamine	decreases expression, decreases reaction	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
mono-(2-ethylhexyl)phthalate	affects cotreatment, increases expression, decreases expression, decreases reaction	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	increases expression	1
nickel monoxide	decreases reaction, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
goralatide	affects cotreatment, decreases expression, decreases reaction	1
polyhexamethyleneguanidine	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
triptonide	increases expression	1
CGP 52608	affects binding, increases reaction	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5128478	Binding	Inhibition of Ptch1 in human adrenocortical carcinoma cells assessed as fold increase doxorubicin cytotoxicity	Inhibition of the drug efflux activity of Ptch1 as a promising strategy to overcome chemotherapy resistance in cancer cells. — Eur J Med Chem

Cellosaurus cell lines

51 cell lines: 30 cancer cell line, 15 induced pluripotent stem cell, 2 spontaneously immortalized cell line, 2 telomerase immortalized cell line, 1 finite cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1327	KE-37	Cancer cell line	Male
CVCL_1360	KYSE-50	Cancer cell line	Male
CVCL_1714	SUP-T1	Cancer cell line	Male
CVCL_1E03	BC7	Cancer cell line	Male
CVCL_1H35	Sup-T1 Nef-ER 31	Cancer cell line	Male
CVCL_2197	SKW-3	Cancer cell line	Male
CVCL_4V58	SKW3/Clo	Cancer cell line	Male
CVCL_A8HE	SCMCi001-A-1	Induced pluripotent stem cell	Female
CVCL_A9NU	Sup-T1 CCR5+ H6	Cancer cell line	Male
CVCL_A9NV	Sup-T1 CCR5+ L23	Cancer cell line	Male

Clinical trials (associated diseases)

211 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04760028	PHASE4	COMPLETED	Study on the Influencing Factors of Electroencephalogram Parameters Under Anesthesia
NCT00336531	PHASE4	COMPLETED	Efficacy of Prophylactic Itraconazole in High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation
NCT02319486	PHASE4	COMPLETED	CEV With/Without Periocular Carboplatin Chemotherapy for Extraocular Retinoblastoma
NCT02933333	PHASE4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT02343562	PHASE4	UNKNOWN	Probiotics for Prophylaxis of Postoperative Hirschsprungs Associated Enterocolitis
NCT07186647	PHASE4	COMPLETED	Laparoscopic-Assisted Transanal Pull-Through for Hirschsprung Disease in Pediatric:Short and Intermediate Outcomes of Two Different Techniques
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT00049959	PHASE3	TERMINATED	Two Studies to Determine if Verteporfin PDT is Effective & Safe in Treating Multiple Basal Cell Carcinoma of the Skin.
NCT03703310	PHASE3	COMPLETED	Study of Patidegib Topical Gel, 2%, for the Reduction of Disease Burden of Persistently Developing Basal Cell Carcinomas (BCCs) in Subjects With Basal Cell Nevus Syndrome (Gorlin Syndrome)
NCT04308395	PHASE3	TERMINATED	Extension Study of Patidegib Topical Gel, 2% in Subjects With Gorlin Syndrome (Basal Cell Nevus Syndrome)
NCT06050122	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Patidegib Gel 2% for Preventing Basal Cell Carcinomas on the Face of Adults With Gorlin Syndrome
NCT00186888	PHASE3	COMPLETED	Study of Treatment for Patients With Cancer of the Eye -Retinoblastoma
NCT01906814	PHASE3	UNKNOWN	Adjuvant Chemotherapy for High-risk Retinoblastoma After Enucleation
NCT01987596	PHASE3	TERMINATED	Study of Fixed vs. Flexible Filgrastim to Accelerate Bone Marrow Recovery After Chemotherapy in Children With Cancer
NCT02137928	PHASE3	UNKNOWN	Carboplatin Periocular Injection for Retinoblastoma
NCT04799002	PHASE3	RECRUITING	Topotecan and Melphalan for Retinoblastoma
NCT05080010	PHASE3	RECRUITING	Adjuvant Chemotherapy for High-risk Postenucleation Retinoblastoma
NCT04904081	PHASE3	UNKNOWN	Feasibility of Use of Indocyanine Green in Pediatric Colorectal Surgery
NCT00957229	PHASE2	COMPLETED	To Determine The Efficacy and Safety of GDC-0449 in Patients With Basal Cell Nevus Syndrome (BCNS)
NCT01350115	PHASE2	COMPLETED	Efficacy, Safety and Pharmacokinetics of Oral LDE225 in Treatment of Patients With Nevoid Basal Cell Carcinoma Syndrome (NBCCS)
NCT01556009	PHASE2	COMPLETED	Trial Comparing the Effects of Intermittent Vismodegib vs. PDT in Patients With Multiple Basal Cell Carcinomas
NCT02017964	PHASE2	COMPLETED	Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed, Non-metastatic Desmoplastic Medulloblastoma
NCT02303041	PHASE2	TERMINATED	Pilot Study of Sonidegib and Buparlisib in Treating Patients With Advanced or Metastatic Basal Cell Carcinoma
NCT02762084	PHASE2	COMPLETED	Trial of Patidegib Gel 2%, 4%, and Vehicle to Decrease the Number of Surgically Eligible Basal Cell Carcinomas in Gorlin Syndrome Patients
NCT03767439	PHASE2	WITHDRAWN	Nivolumab With Vismodegib in Patients With Basal Cell Nevus Syndrome
NCT04416516	PHASE2	COMPLETED	Safety and Efficacy of ASN-002 Combined With a Hedgehog Pathway Inhibitor
NCT00002515	PHASE2	COMPLETED	Combination Chemotherapy Followed by Bone Marrow Transplantation in Treating Patients With Rare Cancer
NCT00002675	PHASE2	COMPLETED	Chemotherapy in Treating Patients With Retinoblastoma
NCT00002794	PHASE2	COMPLETED	Carboplatin Plus Vincristine in Treating Children With Retinoblastoma
NCT00003173	PHASE2	COMPLETED	High-Dose Thiotepa Plus Peripheral Stem Cell Transplantation in Treating Patients With Refractory Solid Tumors
NCT00003273	PHASE2	WITHDRAWN	Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Children With Newly Diagnosed Brain Tumor
NCT00004006	PHASE2	COMPLETED	Combination Chemotherapy, Radiation Therapy, and Bone Marrow Transplantation in Treating Patients With Retinoblastoma
NCT00006102	PHASE2	COMPLETED	Rebeccamycin Analogue in Treating Children With Solid Tumors or Non-Hodgkin’s Lymphoma
NCT00024258	PHASE2	COMPLETED	Arsenic Trioxide in Treating Patients With Advanced Neuroblastoma or Other Childhood Solid Tumors
NCT00110110	PHASE2	UNKNOWN	Combination Chemotherapy and Cyclosporine Followed by Focal Therapy for Bilateral Retinoblastoma
NCT00179920	PHASE2	COMPLETED	Chemotherapy Treatment for Children With Intraocular Germ-Line Retinoblastoma
NCT00432445	PHASE2	TERMINATED	Proton Beam Radiation Therapy for Intraocular and Periocular Retinoblastoma
NCT00445965	PHASE2	COMPLETED	Iodine I 131 Monoclonal Antibody 3F8 in Treating Patients With Central Nervous System Cancer or Leptomeningeal Cancer
NCT00831844	PHASE2	COMPLETED	Cixutumumab in Treating Patients With Relapsed or Refractory Solid Tumors
NCT01151748	PHASE2	WITHDRAWN	Intra-arterial Chemotherapy for Advanced Intraocular Retinoblastoma