CRB2

Chr 9AR

crumbs cell polarity complex component 2

Also known as: FSGS9, VMCKD

The protein is an apical polarity component of the Crumbs complex that regulates epithelial-to-mesenchymal transition during gastrulation and maintains retinal neuroepithelium organization and cortical development. Autosomal recessive mutations cause focal segmental glomerulosclerosis 9 and ventriculomegaly with cystic kidney disease, affecting the kidney, brain ventricular system, and potentially retinal development. The gene shows very low constraint against loss-of-function variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.892 OMIM phenotypes
Clinical SummaryCRB2
🧬
Gene-Disease Validity (ClinGen)
focal segmental glomerulosclerosis 9 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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
0.89LOEUF
pLI 0.000
Z-score 2.16
OE 0.65 (0.480.89)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.11Z-score
OE missense 0.89 (0.830.94)
662 obs / 747.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.65 (0.480.89)
00.351.4
Missense OE0.89 (0.830.94)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 29 / 44.5Missense obs/exp: 662 / 747.1Syn Z: -0.25
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedCRB2-related retinitis pigmentosaOTHERAR
definitiveCRB2-related ventriculomegaly with cystic kidney diseaseLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6162th %ile
GOF
0.7126th %ile
LOF
0.3066th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CRB2 · 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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