PTCH2

Chr 1

patched 2

Also known as: PTC2, SLC65B2

This gene encodes a transmembrane receptor of the patched gene family. The encoded protein may function as a tumor suppressor in the hedgehog signaling pathway. Alterations in this gene have been associated with nevoid basal cell carcinoma syndrome, basal cell carcinoma, medulloblastoma, and susceptibility to congenital macrostomia. Alternatively spliced transcript variants have been described.[provided by RefSeq, Oct 2009]

OMIMResearchGenerating clinical summary…
LOFmechanismLOEUF 0.852 OMIM phenotypes
Clinical SummaryPTCH2
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Gene-Disease Validity (ClinGen)
nevoid basal cell carcinoma syndrome · ADLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.85LOEUF
pLI 0.000
Z-score 2.43
OE 0.64 (0.480.85)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.78Z-score
OE missense 0.92 (0.860.98)
638 obs / 696.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.64 (0.480.85)
00.351.4
Missense OE?0.92 (0.860.98)
00.61.4
Synonymous OE?1.00
01.21.6
LoF obs/exp: 33 / 51.9Missense obs/exp: 638 / 696.3Syn Z: 0.04
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedPTCH2-related Gorlin syndromeLOFAD

This gene — mechanism propensity

DN
0.7132th %ile
GOF
0.74top 25%
LOF
0.2680th %ile

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

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PTCH2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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