CRB2

crumbs cell polarity complex component 2, the group of Crumbs complex

Basic information

Region (hg38): 9:123356170-123380324

Links

ENSG00000148204 ∙ NCBI:286204 ∙ OMIM:609720 ∙ HGNC:18688 ∙ Uniprot:Q5IJ48 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ventriculomegaly-cystic kidney disease (Definitive), mode of inheritance: AR
• ventriculomegaly-cystic kidney disease (Strong), mode of inheritance: AR
• familial idiopathic steroid-resistant nephrotic syndrome (Supportive), mode of inheritance: AD
• ventriculomegaly-cystic kidney disease (Supportive), mode of inheritance: AR
• focal segmental glomerulosclerosis 9 (Strong), mode of inheritance: AR
• focal segmental glomerulosclerosis 9 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Focal segmental glomerulosclerosis 9; Ventriculomegaly with cystic kidney disease	AR	Renal	The condition can involve steroid-resistant nephrotic syndrome, and early diagnosis may allow early and more specific management	Neurologic; Renal	25557779; 25557780

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CRB2 gene.

• not provided (13 variants)
• Inborn genetic diseases (1 variants)
• Ventriculomegaly-cystic kidney disease (1 variants)
• CRB2-related disorder (1 variants)
• Focal segmental glomerulosclerosis 9 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CRB2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	161	16	182
missense		5	237	38	7	287
nonsense	6	2				8
start loss			1			1
frameshift	7	3	2			12
inframe indel			3			3
splice donor/acceptor (+/-2bp)	1	1				2
splice region			5	7	2	14
non coding			1	47	46	94
Total	14	11	249	246	69

Highest pathogenic variant AF is 0.0000591

Variants in CRB2

This is a list of pathogenic ClinVar variants found in the CRB2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-123356192-G-T			Benign (Jan 25, 2019)
9-123356238-AGCAGAGC-A		Ventriculomegaly-cystic kidney disease	Benign (Jul 30, 2021)
9-123356261-A-G			Uncertain significance (Jul 23, 2021)
9-123356265-C-T		Inborn genetic diseases • CRB2-related disorder	Benign/Likely benign (Jan 24, 2024)
9-123356272-C-T			Likely benign (Mar 03, 2022)
9-123356274-G-A			Uncertain significance (Nov 10, 2020)
9-123356289-A-AC			Uncertain significance (Sep 16, 2018)
9-123356298-C-T		Focal segmental glomerulosclerosis 9 • CRB2-related disorder • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jun 04, 2024)
9-123356303-G-GCCTCTGT		Focal segmental glomerulosclerosis 9	Likely pathogenic (May 16, 2019)
9-123356314-G-T			Likely benign (May 12, 2018)
9-123356318-C-T			Uncertain significance (Jun 06, 2022)
9-123356321-C-T			Benign (Jan 31, 2024)
9-123356337-C-A		Inborn genetic diseases	Uncertain significance (Oct 26, 2021)
9-123356343-C-A			Uncertain significance (Jan 04, 2021)
9-123356345-C-T		Inborn genetic diseases	Uncertain significance (May 26, 2024)
9-123356370-T-C			Likely benign (May 26, 2023)
9-123356373-C-T			Likely benign (Dec 31, 2021)
9-123356520-G-A			Likely benign (Feb 23, 2020)
9-123356538-G-A			Likely benign (Apr 04, 2020)
9-123356641-G-C			Benign (Feb 14, 2020)
9-123362696-T-C			Benign (Nov 10, 2018)
9-123362868-C-T		Inborn genetic diseases	Uncertain significance (Apr 05, 2023)
9-123362869-G-A			Likely benign (Oct 17, 2022)
9-123362872-G-C			Likely benign (Jul 19, 2022)
9-123362873-C-T			Uncertain significance (Nov 30, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CRB2	protein_coding	protein_coding	ENST00000373631	13	24155

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.49e-14	0.917	125666	0	81	125747	0.000322

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.11	662	747	0.886	0.0000482	7989
Missense in Polyphen		67	82.694	0.81022		830
Synonymous	-0.252	353	347	1.02	0.0000250	2811
Loss of Function	2.16	29	44.5	0.651	0.00000237	470

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000354	0.000352
Ashkenazi Jewish	0.000105	0.0000992
East Asian	0.000382	0.000381
Finnish	0.00	0.00
European (Non-Finnish)	0.000363	0.000352
Middle Eastern	0.000382	0.000381
South Asian	0.000626	0.000621
Other	0.000504	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Apical polarity protein that plays a central role during the epithelial-to-mesenchymal transition (EMT) at gastrulation, when newly specified mesodermal cells move inside the embryo. Acts by promoting cell ingression, the process by which cells leave the epithelial epiblast and move inside the embryo to form a new tissue layer. The anisotropic distribution of CRB2 and MYH10/myosin-IIB at cell edges define which cells will ingress: cells with high apical CRB2 are probably extruded from the epiblast by neighboring cells with high levels of apical MYH10/myosin-IIB. Also required for maintenance of the apical polarity complex during development of the cortex. {ECO:0000250|UniProtKB:Q80YA8}.
• Disease: DISEASE: Focal segmental glomerulosclerosis 9 (FSGS9) [MIM:616220]: A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation. {ECO:0000269|PubMed:25557779}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Ventriculomegaly with cystic kidney disease (VMCKD) [MIM:219730]: A severe autosomal recessive developmental disorder manifesting in utero. It is characterized by cerebral ventriculomegaly, echogenic kidneys, microscopic renal tubular cysts and findings of congenital nephrosis. {ECO:0000269|PubMed:25557780}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Hippo signaling pathway - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.121

Intolerance Scores

• loftool: 0.103
• rvis_EVS: 0.1
• rvis_percentile_EVS: 61.28

Haploinsufficiency Scores

• pHI: 0.140
• hipred: Y
• hipred_score: 0.584
• ghis: 0.484

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.807

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Crb2
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; embryo phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); pigmentation phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; vision/eye phenotype

Zebrafish Information Network

• Gene name: crb2a
• Affected structure: cardiac muscle cell
• Phenotype tag: abnormal
• Phenotype quality: structure

Gene ontology

• Biological process: mesoderm formation;somitogenesis;heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules;regulation of gastrulation;positive regulation of epithelial to mesenchymal transition;negative regulation of endopeptidase activity;notochord formation;positive regulation of BMP signaling pathway;establishment or maintenance of epithelial cell apical/basal polarity;maintenance of epithelial cell apical/basal polarity;ingression involved in gastrulation with mouth forming second;cardiovascular system development
• Cellular component: plasma membrane;integral component of membrane;apical plasma membrane;protein-containing complex;membrane raft;extracellular exosome
• Molecular function: calcium ion binding;aspartic-type endopeptidase inhibitor activity;protein-containing complex binding