• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
PTCH1 (HGNC:9585) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
patched 1
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
NBCCS, PTCH
Alias symbols
BCNS
%HI
0.48(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.08(Read more about gnomAD LOEUF score)
Cytoband
9q22.32
Genomic Coordinates
GRCh37/hg19: chr9:98205262-98279253 NCBI Ensembl UCSC
GRCh38/hg38: chr9:95442980-95516971 NCBI Ensembl UCSC
MANE Select Transcript
NM_000264.5 ENST00000331920.11 (Read more about MANE Select)
MANE Plus Clinical Transcript(s)
NM_001083603.3 ENST00000437951.6 (Read more about MANE Plus Clinical)
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}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-8192
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
07/01/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • nevoid basal cell carcinoma syndrome Monarch
HI Evidence:
  • PUBMED: PMID: 30411536
    Published in 2018, Gianferante et al. studied 18 families with nevoid basal cell carcinoma syndrome (NBCCS) originally identified for a National Cancer Institute (NCI) gene linkage study. The families underwent targeted PTCH1 testing for the NCI study, and here whole-exome sequencing (WES) and array comparative genomic hybridization (aCGH) were used to identify variants in the 7 families for whom targeted PTCH1 testing had not detected variants. Overall, pathogenic variants in PTCH1 were described in 16 of the 18 families. Of these variants, 5 were frameshifts, 3 were nonsense, 2 were in-frame deletions, 1 involved splicing, and 1 was a gross deletion. The authors did not provide coordinates for the gross deletion, so we could not verify that it included PTCH1 exclusively.
  • PUBMED: PMID: 21368767
    In 2011, Fujii et al. used PCR followed by RT-PCR to identify variants in PTCH1 in 5 unrelated Japanese patients clinically diagnosed with nevoid basal cell carcinoma syndrome (NBCCS). Analysis revealed that 2 patients had a parent with NBCCS while the other 3 patients were sporadic cases. Variants in PTCH1 were identified for all the individuals studied; Fujii et. al identified 1 splice site variant, 1 small insertion, 1 small deletion, and 2 nonsense variants. The authors also noted that each variant identified resulted in a truncated patch-1 protein or nonsense-mediated decay.
  • PUBMED: PMID: 29575684
    In 2018, Reinders et al. created a database for PTCH1. The database contains 331 previously described variants as well as 110 pathogenic or likely pathogenic variants identified using Sanger sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) in patients from either the VU University Medical Center (VUMC) or Maastricht University Medical Centre (MUMC). Of these 110 variants, 42 are frameshift, 29 are nonsense, 14 are missense, 16 are splicing errors, and 8 are either large duplications or deletions. Additionally, 80.0% of the individuals screened for these variants were either suspected or diagnosed cases of basal cell nevus syndrome (BCNS), while the remaining 20% of individuals had a family member with either a confirmed or suspected case of BCNS.
HI Evidence Comments:
Loss of function variants within this gene have been associated with nevoid basal cell carcinoma syndrome. Variants in PTCH1 have also been associated with holoprosencephaly; however, it is believed that this phenotype is caused by gain of function variants (OMIM: #610828 and PMID: 11941477).

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Published Evidence:
  • PUBMED: PMID: 18830227
    In 2009, Derwinska et al. used cytogenic analysis, array CGH, FISH analysis, sequence analysis with oligonucleotide coordinates, and PCR on a 21-month-old child displaying failure to thrive, microcephaly, and developmental delay. These analyses were also done on the child’s mother who had had 7 previous miscarriages and whom the authors described as “mildly delayed.” These analyses found that both the proband and his mother had the same variant: a duplication which included the entire PTCH1 gene as well as the noncoding first exon of the gene FANCC. The authors noted that they do not feel that the inclusion of FANCC is responsible for these phenotypes.
TS Evidence Comments:
Another, larger duplication involving PTCH1 has been reported (PMID: 21567912) in a mother and two children with developmental delay, microcephaly, and dysmorphic features. PTCH1 has been postulated to be a candidate gene for the phenotype observed in this duplication, but the potential for the other 14 genes duplicated in the region to have an effect on phenotype cannot be ruled out. Additionally, in 2018, Prontera et al. described a duplication of 9q22.32 involving PTCH1 and 7 other genes in a father and daughter with Schilbach-Rott Syndrome (SRS) (PMID: 30936464).

Genomic View

Select assembly: (NC_000009.11) (NC_000009.12)