PTCH1

Chr 9AD

patched 1

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

NCBI Gene: 5727 ENSG00000185920 UniProt: Q13635

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. [provided by RefSeq, Aug 2017]

Primary Disease Associations & Inheritance

Basal cell carcinoma, somaticMIM #605462

Basal cell nevus syndrome 1MIM #109400

Holoprosencephaly 7MIM #610828

569

ClinVar variants

Pathogenic / LP

1.00

pLI score· haploinsufficient

Active trials

Clinical Summary— PTCH1

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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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ClinVar Variants

61 Pathogenic / Likely Pathogenic· 320 VUS of 569 total submissions

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Clinical Trials

7 active or recruiting trials — potential therapeutic options may be available

Some data sources returned errors (1)

pubmed: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.07LOEUF

pLI 1.000

Z-score 7.25

OE 0.02 (0.01–0.07)

Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

1.68Z-score

OE missense 0.84 (0.79–0.89)

708 obs / 845.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.02 (0.01–0.07)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.79–0.89)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.25

0≤1.21.6

LoF obs/exp: 1 / 63.3Missense obs/exp: 708 / 845.2Syn Z: -3.76

ClinVar Variant Classifications

569 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42

Likely Pathogenic19

VUS320

Likely Benign187

Benign1

Pathogenic

Likely Pathogenic

320

VUS

187

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	30	1	11	0	42
Likely Pathogenic	11	6	2	0	19
VUS	7	292	20	1	320
Likely Benign	0	3	65	119	187
Benign	0	0	0	1	1
Total	48	302	98	121	569

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

Gene2Phenotype Curations

PTCH1-related Gorlin syndrome (basal cell nevus syndrome)

definitive

ADLoss Of FunctionAbsent Gene Product

Dev. DisordersEyeSkinCancer

G2P ↗

PTCH1-related holoprosencephaly

definitive

ADUndeterminedUncertain

Dev. Disorders

G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

PATCHED 1; PTCH1

MIM #601309 · *

Basal cell carcinoma, somatic

MIM #605462

Molecular basis of disorder known

Basal cell nevus syndrome 1

MIM #109400

Molecular basis of disorder known

Autosomal dominant

Holoprosencephaly 7

MIM #610828

Molecular basis of disorder known

Autosomal dominant

External Resources

Links to major genomics databases and tools

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GeneReview available — PTCH1

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Literature

Landmark / reviewRecent case evidence

Recent Gene-Specific Literature

Gene in title · MEDLINE · newest first

Europe PMC

Partial truncation of the C-terminal domain of PTCH1 in cancer promotes tumourigenesis by non-canonical activation of a GLI-PI3K loop.

Caballero-Ruiz B et al.·Oncogene

2026

Gastric mesenchymal tumor with PTCH1::GLI2 fusion: a distinct subset of GLI1/GLI2-altered tumors?

Nikai Y et al.·Virchows Arch

2026

Chondrosarcoma organoids reveal SHH pathway activation driven by PTCH1 and BCOR alterations.

Takami H et al.·Sci Rep

2025🔓 Open Access

CSNK1D inhibition suppresses head and neck squamous cell carcinoma progression through SHH and PTCH1 pathway.

Yang L et al.·Cell Death Dis

2025🔓 Open Access

Phase II Study of Vismodegib in Patients With SMO- or PTCH1-Mutated Tumors: Results From the National Cancer Institute Molecular Analysis for Therapy Choice Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Trial (EAY131) Subprotocol T.

Tsao AS et al.·JCO Precis Oncol

2025Cohort

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Advanced LymphomaAdvanced Malignant Solid NeoplasmBladder Carcinoma

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

ACTIVE NOT RECRUITING

NCT02465060Phase PHASE2National Cancer Institute (NCI)Started 2015-08-17

AdavosertibAfatinibAfatinib Dimaleate

Inherited Eye Disease

Clinical and Molecular Studies in Families With Inherited Eye Disease

RECRUITING

NCT02771236National Eye Institute (NEI)Started 2016-10-04

Kidney TransplantRejection

Detection of Circulating Kidney DNA in Kidney Transplant Patients Facing an Episode of Graft Rejection

RECRUITING

NCT06351488Assistance Publique - Hôpitaux de ParisStarted 2024-08-21

Spinocerebellar Ataxia