CDHR2

Chr 5

cadherin related family member 2

CDHR2 encodes a protocadherin that functions as a calcium-dependent cell adhesion molecule, forming complexes with CDHR5 to control microvillus packing and brush border formation in epithelial cells. Mutations cause autosomal recessive cone-rod dystrophy and retinal dystrophy, affecting photoreceptor function and leading to progressive vision loss. This gene is not highly constrained against loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.85
Clinical SummaryCDHR2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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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.

3D Protein StructureAlphaFold

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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