Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

PTCH1

contributors: mct/npt - updated : 21-10-2018

HGNC name	patched homolog 1 (Drosophila)
HGNC id	9585

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	DEL9Q22 chromosome 9q22.3 microdeletion syndrome HPE7 holoprosencephaly NBCCS2 nevoid basal cell carcinoma syndrome
Location	9q22.32      Physical location : 98.205.265 - 98.279.247
Synonym name	patched homolog (Drosophila)
	PTCH protein +12b
	PTCH protein +4'
	PTCH protein -10
	patched homolog 1 splice variant 1C
Synonym symbol(s)	BCNS, PTC, PTC1, PTCH, NBCCS, FLJ26746, FLJ42602, HPE7, TSG9D, PTCH11

DNA

TYPE	functioning gene
STRUCTURE	74.00 kb     24 Exon(s)

regulatory sequence	Promoter
	alternative promoter
motif	repetitive sequence   triplet
text structure	six first exons (1a, 1a', 1b,1c,1c', 1d, 1e )
	CGG triplet repeat located 4 bp upstream of the first methionine codon, in the 5' UTR
	only one of two putative Gli-binding sites identified in the promoter region is functional, and the transactivating Gli proteins, GLI1, GLI2 and GLI3, bind and enhance transcription through this site
	three ZNF431 binding sites in the promoter

MAPPING

cloned

Y

linked

N

status

confirmed

Map

see NBCCS

RNA

TRANSCRIPTS	type	messenger

text	regulated by three independent promoters generating transcripts with alternative first exons an alternative exon, exon 12b, located between exon 12 and 13 having an in-frame stop codon, the mRNA isoform containing this exon (Patched12b) encodes a truncated patched-1 protein

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001083603 24 splicing 7911 NP_001077072 - 1446 colon, testis - exon 1a variant a prime or PTCHl2 PTCH1B - splicing - - - specifically upregulated in nodular BCCs - inhibiting SMO activity. NM_000264 24 splicing 7957 NP_000255 160.5 1447 colon, testis, brain, ovary - exon 1b, variant 1b or PTCHl methylated in some cases of medulloblastoma NM_001083604 24 splicing 7675 NP_001077073 - 1295 - - exon 1c, variant 1c or PTCHs N-terminally truncated lacking the first transmembrane domain exon 1c transcription is upregulated by HH signaling, but the resulting PTCH1-1C protein has a lower capacity for pathway inhibition than PTCH1-1B NM_001083605 24 splicing 7658 NP_001077074 - 1295 - - exon 1c', variant c prime or PTCHs N-terminally truncated lacking the first transmembrane domain NM_001083607 24 splicing 7831 NP_001077076 - 1295 - - exon 1e, variant 1e or PTCHs N-terminally truncated lacking the first transmembrane domain NM_001083602 24 splicing 8065 NP_001077071 - 1381 - - exon 1a', variant a' ou PTCH2 NM_001083606 24 splicing 7757 NP_001077075 - 1295 widely - exon 1d, variant 1d or PTCHs PTCH +12b - splicing 879 - 106 expressed in some of the medulloblastoma tissues and cell lines - exon 1-5, exon 10 and exon 12b specfically expressed in brain and heart, especially in cerebellum having a dominant negative effect on PATCH1 important role in the pathogenesis of medulloblastoma as well as brain development

EXPRESSION

Type

widely

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine large intestine colon   highly Hearing/Equilibrium ear       highly Nervous brain hindbrain cerebellum     Rattus norvegicus Fetal   brain hindbrain cerebellum     Rattus norvegicus Adult   brain limbic system hippocampus   highly Rattus norvegicus Adult   brain limbic system hippocampus   highly Rattus norvegicus Fetal Respiratory lung       moderately Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Rattus norvegicus Nervous Purkinje cell Rattus norvegicus Reproductive spermatocyte Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, pregnancy

Text	ventral neural tube, somites, limb bud, placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N and C cytoplasmic termini
	twelve membrane spanning segments, five of them (TM2 to TM6) forming a sterol sensing domain(SSD)
	a proline-rich motif in the C terminal region
	two large hydrophilic extracellular loops
	two functional GLI-binding sequences

conjugated

GlycoP

HOMOLOGY

interspecies

homolog to Drosophila segment polarity gene patched (PTC)

Homologene

FAMILY

patched family

CATEGORY

signaling , receptor

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,cytoskeleton,microtubule
text	localization to primary cilia

basic FUNCTION	repressing SMO activity in the absence of SHH
	involved in endocytosis and vesicle transport
	playing a role in the development of basal cell cancer
	regulates hedgehog signaling at the primary cilium, inhibiting the Hh pathway by excluding SMOH and also allows cilia to function as chemosensors for the detection of extracellular SHH
	PTCH1 and SMO are present in the processes and growth cones of immature neurons
	key regulator of embryonic development, acting through the sonic hedgehog (SHH) signaling pathway
	also acts as a lineage-dependent oncogene
	essential role for ligand-dependent feedback inhibition of vertebrate HH signaling governed collectively by PTCH1, PTCH2 and HHIP
	PTCH1 and PTCH2 co-operate in regulating cellular responses to SHH
	PTCH1/PTCH2 mediate likely secretion of a SMO-inhibitory cholesterol precursor
	PTCH1 and the integral membrane protein 2A (ITM2A) inhibit autophagy by reducing autolysosome formation

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

development

text	embryonic patterning

PATHWAY

metabolism

signaling

signal transduction

GLI1 and PTCH1 are both components and transcriptional targets of the SHH pathway

a component

INTERACTION

DNA

RNA

small molecule

protein	receptor for SHH signaling proteins (negative regulator of the HH-signaling pathway by repressing downstream signaling by the coreceptor smoothened (SMOH))
	regulator of HH (role of splicing variation and promoter choice for HH signaling regulation)
	interacting with SCUBE2
	Sertoli cells coordinate DHH-dependent spermatogenesis events via PTCH1 and SMO prior to the first meiotic division and in postmeiotic (haploid) cells, particularly during the first half of spermiogenesis
	GPC5 binds to both Hh and PTCH1 through its glycosaminoglycan chains)
	direct transcriptional target of ZNF431
	PTCH1 intracellular domain (ICD7) interacted with most components of the CUL2 (CUL2)-based E3 ligase complex, including ELOC, ELOB, ZYG11B, and CUL2 itself
	PTCH1 is a novel CHL1-binding protein and CHL1 interacts with the first extracellular loop of PTCH1 via its extracellular domain
	HH reciprocally controls trafficking of SMO and PTC through the SMURF family of E3 ubiquitin ligases
	inactivation of PTCH1 by HH likely allows a transmembrane sterol to access this seven-transmembrane site (potentially through a hydrophobic tunnel), which drives the activation of SMO

cell & other

REGULATION

activated by

hedgehog proteins (transcriptional activation mediated via the HH-signaling pathway is dependent on the single functional Gli-binding site)

inhibited by

SHH by binding to it at the cilium and inducing its internalization, degradationor movements to other regions of the plasma membrane

Other

regulated by GLI transcription factor

ASSOCIATED DISORDERS

corresponding disease(s)

NBCCS2 , HPE7 , DEL9Q22 , DEL9Q223

related resource

PTCH Mutation Database

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral somatic mutation       in desmoplastic medulloblastoma and in basal cells carcinoma tumoral       loss of function in medulloblastoma and skin tumors tumoral somatic mutation       in basal cell carcinoma (BCC) of the skin tumoral   LOH     in ovarian tumors, benign or malignant, sporadic basal cell carcinoma, small cell lung carcinoma, lymph node metastasis of primary breast cancer tumoral   deletion     in papillary thyroid carcinoma, in trichoepithelioma, sebaceous nevus, non-melanoma skin cancer, basal cell carcinoma tumoral germinal mutation       in bladder carcinoma tumoral somatic mutation       in keratocystic odontogenic tumors constitutional   amplification     duplication in a family with microcephaly and mild developmental delay tumoral   LOH     in nonsyndromic or sporadic cardiac fibroma tumoral     --other   aberrant methylation of the PTCH1 promoter may be an early, initiating event of colon carcinogenesis constitutional       loss of function concomitant loss of PTCH1 and PTCH2 activity inhibits epidermal lineage specification and differentiation

Susceptibility

to basal cells carcinoma

Variant & Polymorphism SNP , insertion/deletion , other	increasing the risk of basal cells carcinoma

Candidate gene	in a mouse model, APP-dependent up-regulation of Ptch1 underlies proliferation impairment of neural precursors in Down syndrome (;
	for Wilms tumor in del 9q22 patients
Marker	alterations of FANCC and PTCH1 could be used as molecular marker for early diagnosis and prognosis of head and neck squamous cell carcinoma (HNSCC)
Therapy target

ANIMAL & CELL MODELS

	inhibition of Shh signaling pathway exacerbated rat ischemic damage caused by permanent middle cerebral artery occlusion, which may be correlated with down-regulated expression of Gli1, Ptch1 and Sod1
	inactivation of Ptch1 in mice leads to formation of gastrointestinal stromal tumor-like tumors that express Pdgfr&
	945;, but not Kit