CDHR2

Chr 5

cadherin related family member 2

Also known as: PCDH24, PCLCK, PCLKC

This gene is a member of the protocadherin family, which represents a subset of the larger cadherin superfamily. The members of the protocadherin family encode non-classical cadherins that function as calcium-dependent cell-cell adhesion molecules. This protocadherin represents a new candidate for tumor suppression. Alternatively spliced transcript variants that encode the same protein have been identified. [provided by RefSeq, Jan 2010]

0
Active trials
8
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.85
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryCDHR2
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 2.53
OE 0.65 (0.510.85)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.37Z-score
OE missense 0.96 (0.911.02)
767 obs / 796.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.65 (0.510.85)
00.351.4
Missense OE0.96 (0.911.02)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 41 / 62.6Missense obs/exp: 767 / 796.5Syn Z: -0.91
DN
0.76top 25%
GOF
0.78top 25%
LOF
0.2288th %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

CDHR2 · 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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Clinical Literature
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