CRB2 crumbs cell polarity complex component 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CRB2provided by HGNC
Official Full Name: crumbs cell polarity complex component 2provided by HGNC
Primary source: HGNC:HGNC:18688
See related: Ensembl:ENSG00000148204 MIM:609720; AllianceGenome:HGNC:18688
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FSGS9; VMCKD
Summary: This gene encodes a member of a family of proteins that are components of the Crumbs cell polarity complex. In mammals, members of this family are thought to play a role in many cellular processes in early embryonic development. A similar protein in Drosophila determines apicobasal polarity in embryonic epithelial cells. Mutations in this gene are associated with focal segmental glomerulosclerosis 9, and with ventriculomegaly with cystic kidney disease. [provided by RefSeq, Aug 2016]
Expression: Broad expression in brain (RPKM 3.7), kidney (RPKM 3.4) and 23 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 9q33.3

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (123354065..123380326)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (135551766..135578059)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (126118476..126142605)

Chromosome 9 - NC_000009.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Human CRB1 and CRB2 form homo- and heteromeric protein complexes in the retina.
Title: Human CRB1 and CRB2 form homo- and heteromeric protein complexes in the retina.
Bi-allelic variations in CRB2, encoding the crumbs cell polarity complex component 2, lead to non-communicating hydrocephalus due to atresia of the aqueduct of sylvius and central canal of the medulla.
Title: Bi-allelic variations in CRB2, encoding the crumbs cell polarity complex component 2, lead to non-communicating hydrocephalus due to atresia of the aqueduct of sylvius and central canal of the medulla.
Exome Sequencing Revealed a Novel Splice Site Variant in the CRB2 Gene Underlying Nephrotic Syndrome.
Title: Exome Sequencing Revealed a Novel Splice Site Variant in the CRB2 Gene Underlying Nephrotic Syndrome.
Loss of surface transport is a main cellular pathomechanism of CRB2 variants causing podocytopathies.
Title: Loss of surface transport is a main cellular pathomechanism of CRB2 variants causing podocytopathies.
CRB2 enhances malignancy of glioblastoma via activation of the NF-kappaB pathway.
Title: CRB2 enhances malignancy of glioblastoma via activation of the NF-κB pathway.
Podocyte-specific Crb2 knockout mice develop focal segmental glomerulosclerosis.
Title: Podocyte-specific Crb2 knockout mice develop focal segmental glomerulosclerosis.
Data show that crumbs homolog 2 protein (CRB2) protein precedes the expression of crumbs homologue 1 protein (CRB1) in the developing retina.
Title: Human iPSC-Derived Retinas Recapitulate the Fetal CRB1 CRB2 Complex Formation and Demonstrate that Photoreceptors and Müller Glia Are Targets of AAV5.
Thus, we conclude that CRB2 p.R1249G mutation causes retinitis pigmentosa (RP) via accelerating epithelial-mesenchymal transition (EMT), dysfunction and loss of retinal pigment epithelium cells, and establish CRB2 as a novel Crumbs family member associated with non-syndromic RP.
Title: CRB2 mutation causes autosomal recessive retinitis pigmentosa.
CRB2 may play an important role in the mechanistic pathway of developing podocytes through tyrosine phosphorylation by associating with mTORC1 activation.
Title: Association of crumbs homolog-2 with mTORC1 in developing podocyte.
Case Report: steroid-resistant nephrotic syndrome caused by a novel Crumbs homolog 2 mutation.
Title: Long-term clinicopathologic observation in a case of steroid-resistant nephrotic syndrome caused by a novel Crumbs homolog 2 mutation.

Submit: New GeneRIF Correction See all GeneRIFs (23)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Focal segmental glomerulosclerosis 9 MedGen: C4015555 OMIM: 616220 GeneReviews: Not available	Compare labs
Ventriculomegaly-cystic kidney disease MedGen: C1857423 OMIM: 219730 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH94250 (e-PCR)
- UniSTS:86802

RH79586 (e-PCR)
- UniSTS:88125

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables aspartic-type endopeptidase inhibitor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in circulatory system development	ISS Inferred from Sequence or Structural Similarity more info
involved_in establishment of cell polarity	ISS Inferred from Sequence or Structural Similarity more info
involved_in establishment or maintenance of epithelial cell apical/basal polarity	IBA Inferred from Biological aspect of Ancestor more info
involved_in establishment or maintenance of epithelial cell apical/basal polarity	NAS Non-traceable Author Statement more info	PubMed
involved_in heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules	IBA Inferred from Biological aspect of Ancestor more info
involved_in ingression involved in gastrulation with mouth forming second	ISS Inferred from Sequence or Structural Similarity more info
involved_in maintenance of epithelial cell apical/basal polarity	ISS Inferred from Sequence or Structural Similarity more info
involved_in mesoderm formation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of endopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in notochord formation	ISS Inferred from Sequence or Structural Similarity more info
involved_in photoreceptor cell maintenance	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of BMP signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of epithelial to mesenchymal transition	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of gastrulation	ISS Inferred from Sequence or Structural Similarity more info
involved_in retina homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in retinal cone cell development	ISS Inferred from Sequence or Structural Similarity more info
involved_in somitogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in visual perception	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in apical junction complex	NAS Non-traceable Author Statement more info	PubMed
located_in apical plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in apical plasma membrane	NAS Non-traceable Author Statement more info	PubMed
located_in apicolateral plasma membrane	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
part_of protein-containing complex	IBA Inferred from Biological aspect of Ancestor more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
part_of subapical complex	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: protein crumbs homolog 2

Names: crumbs 2, cell polarity complex component; crumbs family member 2; crumbs-like protein 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_051311.1 RefSeqGene

Range

7133..29689

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_173689.7 → NP_775960.4 protein crumbs homolog 2 precursor

See identical proteins and their annotated locations for NP_775960.4

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the supported protein.

Source sequence(s)

AK124819, AL365504, AL445489, AY720432, DA240339

Consensus CDS

CCDS6852.2

UniProtKB/Swiss-Prot

A2A3N4, Q0QD46, Q5IJ48, Q5JS41, Q5JS43, Q6ZTA9, Q6ZWI6

Related

ENSP00000362734.3, ENST00000373631.8

Conserved Domains (5) summary

cd00054
Location:321 → 356

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

cd00110
Location:653 → 773

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...

pfam00008
Location:1060 → 1090

EGF; EGF-like domain

pfam02210
Location:465 → 588

Laminin_G_2; Laminin G domain

cl22861
Location:900 → 1024

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...

RNA

NR_104603.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks several exons in the 5' region but includes an alternate 5' terminal exon, and it also includes an alternate 3' terminal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AK126775, AL445489, AY720432, CX871675

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000009.12 Reference GRCh38.p14 Primary Assembly

Range

123354065..123380326

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011518558.4 → XP_011516860.1 protein crumbs homolog 2 isoform X4

See identical proteins and their annotated locations for XP_011516860.1

Conserved Domains (5) summary

cd00054
Location:256 → 291

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

cd00110
Location:588 → 708

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...

pfam00008
Location:995 → 1025

EGF; EGF-like domain

pfam02210
Location:400 → 523

Laminin_G_2; Laminin G domain

cl22861
Location:835 → 959

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...
XM_011518557.4 → XP_011516859.1 protein crumbs homolog 2 isoform X4

See identical proteins and their annotated locations for XP_011516859.1

Conserved Domains (5) summary

cd00054
Location:256 → 291

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

cd00110
Location:588 → 708

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...

pfam00008
Location:995 → 1025

EGF; EGF-like domain

pfam02210
Location:400 → 523

Laminin_G_2; Laminin G domain

cl22861
Location:835 → 959

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...
XM_011518556.4 → XP_011516858.1 protein crumbs homolog 2 isoform X1

Conserved Domains (5) summary

cd00054
Location:321 → 356

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

cd00110
Location:653 → 773

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...

pfam00008
Location:1051 → 1081

EGF; EGF-like domain

pfam02210
Location:465 → 588

Laminin_G_2; Laminin G domain

cl22861
Location:891 → 1015

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...
XM_047423244.1 → XP_047279200.1 protein crumbs homolog 2 isoform X2
XM_047423245.1 → XP_047279201.1 protein crumbs homolog 2 isoform X3
XM_005251934.4 → XP_005251991.1 protein crumbs homolog 2 isoform X5

UniProtKB/Swiss-Prot

Q5IJ48

Related

ENSP00000435279.1, ENST00000460253.1

Conserved Domains (5) summary

cd00054
Location:26 → 61

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

cd00110
Location:321 → 441

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...

pfam00008
Location:479 → 509

EGF; EGF-like domain

pfam02210
Location:133 → 256

Laminin_G_2; Laminin G domain

cl22861
Location:568 → 692

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...