PTCH1

Chr 9AD

patched 1

Also known as: BCNS, BCNS1, NBCCS, PTC, PTC1, PTCH, SLC65B1

The protein functions as the receptor for hedgehog ligands (sonic, indian, and desert hedgehog) and regulates hedgehog signaling by inhibiting smoothened until ligand binding causes its trafficking away from the primary cilium. Mutations cause basal cell nevus syndrome 1 and holoprosencephaly 7, both inherited in an autosomal dominant pattern. Loss-of-function mutations disrupt normal hedgehog signaling, which is critical for embryonic development and tumor suppression.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.073 OMIM phenotypes
Clinical SummaryPTCH1
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Gene-Disease Validity (ClinGen)
nevoid basal cell carcinoma syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
7 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.07LOEUF
pLI 1.000
Z-score 7.25
OE 0.02 (0.010.07)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
1.68Z-score
OE missense 0.84 (0.790.89)
708 obs / 845.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.02 (0.010.07)
00.351.4
Missense OE0.84 (0.790.89)
00.61.4
Synonymous OE1.25
01.21.6
LoF obs/exp: 1 / 63.3Missense obs/exp: 708 / 845.2Syn Z: -3.76
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePTCH1-related Gorlin syndrome (basal cell nevus syndrome)LOFAD
definitivePTCH1-related holoprosencephalyOTHERAD
DN
0.4289th %ile
GOF
0.5953th %ile
LOF
0.62top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOF1 literature citation · LOEUF 0.07
GOF1 literature citation

Literature Evidence

GOFThe gain-of-function variants of the PTCH1 gene are responsible for a mild form of HPE.PMID:30936464
LOFHaploinsufficiency of PTCH1 resulted in cerebellar overgrowth in lobules IV/V and IX of both sexes, and female-specific decreases in hippocampal size and isocortical layer thickness.PMID:32113901

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PTCH1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗