This gene encodes a type I transmembrane protein and member of the immunoglobulin superfamily of cell adhesion molecules. The encoded protein localizes to adherens junctions in pancreatic beta cells and regulates insulin secretion. Autoantibodies against the encoded protein have been detected in serum from patients with type 1 diabetes. This gene may also play a role in glomeru... See more...

Aliases for KIRREL2 Gene

Aliases for KIRREL2 Gene

  • Kirre Like Nephrin Family Adhesion Molecule 2 2 3 5
  • NEPH3 2 3 4
  • Kin Of Irregular Chiasm-Like Protein 2 3 4
  • Kin Of IRRE-Like Protein 2 3 4
  • Nephrin-Like Protein 3 3 4
  • FILTRIN 2 3
  • NLG1 2 3
  • Kin Of IRRE Like 2 (Drosophila) 2
  • Nephrin-Like Gene 1 3
  • Kin Of IRRE Like 2 3
  • DKFZp564A1164 2
  • MGC15718 2
  • KIRREL2 5

External Ids for KIRREL2 Gene

Previous GeneCards Identifiers for KIRREL2 Gene

  • GC00U991236
  • GC19P041023
  • GC19P041039
  • GC19P041038
  • GC19P036347
  • GC19P032853
  • GC19P035855
  • GC19P037037
  • GC19P037199
  • GC19P037297
  • GC19P037731
  • GC19P035856
  • GC19P036016
  • GC19P036178
  • GC19P036256
  • GC19P036423
  • GC19P036584
  • GC19P036750
  • GC19P036896

Summaries for KIRREL2 Gene

Entrez Gene Summary for KIRREL2 Gene

  • This gene encodes a type I transmembrane protein and member of the immunoglobulin superfamily of cell adhesion molecules. The encoded protein localizes to adherens junctions in pancreatic beta cells and regulates insulin secretion. Autoantibodies against the encoded protein have been detected in serum from patients with type 1 diabetes. This gene may also play a role in glomerular development and decreased expression of this gene has been observed in human glomerular diseases. This gene and the related opposite-strand gene nephrin (GeneID: 527362) are regulated by a bidirectional promoter. [provided by RefSeq, Jul 2016]

GeneCards Summary for KIRREL2 Gene

KIRREL2 (Kirre Like Nephrin Family Adhesion Molecule 2) is a Protein Coding gene. Diseases associated with KIRREL2 include Hemophagocytic Lymphohistiocytosis, Familial, 3 and Familial Nephrotic Syndrome. Among its related pathways are Cell junction organization and Primary Focal Segmental Glomerulosclerosis FSGS. An important paralog of this gene is KIRREL1.

UniProtKB/Swiss-Prot Summary for KIRREL2 Gene

Gene Wiki entry for KIRREL2 Gene

Additional gene information for KIRREL2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for KIRREL2 Gene

Genomics for KIRREL2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for KIRREL2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH19J035855 Promoter/Enhancer 1.5 EPDnew Ensembl ENCODE 600.7 +4.8 4757 2 LEF1 IKZF1 MTA2 ZSCAN4 DPF2 SOX6 TCF12 ZNF148 EP300 SP2 KIRREL2 ZNF567 ZNF260 ZNF345 ZNF790 ZNF146 ZNF850 TMEM147-AS1 ZNF565 ZFP14
GH19J035851 Promoter/Enhancer 0.9 EPDnew ENCODE 600.7 -0.3 -281 0.2 CREB1 CTCF ZBTB33 TEAD4 ZNF629 ZFX ZBTB48 POLR2A CREM ZNF143 KIRREL2 piR-52475-009 lnc-PRODH2-4 NPHS1 PRODH2
GH19J035912 Promoter/Enhancer 1.3 FANTOM5 Ensembl ENCODE 11.2 +62.4 62353 1 IKZF2 TRIM22 PKNOX1 DPF2 RELB RUNX3 FOS BCL11A NBN HDGF TYROBP APLP1 NPHS1 KIRREL2 NFKBID SDHAF1 HCST FFAR2 IGFLR1 U2AF1L4
GH19J035766 Enhancer 1.2 Ensembl ENCODE CraniofacialAtlas dbSUPER 11.3 -83.8 -83784 2.5 RXRB POLR2A ZNF600 KLF9 SP2 ZBTB10 ZNF316 MAFF MAFK MAFG ARHGAP33 PRODH2 LINC01529 KIRREL2 NPHS1 UPK1A ENSG00000267049 piR-48759-157 PROSER3
GH19J035693 Enhancer 1.2 Ensembl ENCODE 10.7 -157.8 -157805 0.9 ARHGAP35 SP1 GATAD2A CTCF ZNF629 ZNF512 IKZF1 ZNF692 RCOR2 TARDBP lnc-IGFLR1-2 TMEM147-AS1 ZNF567 HAUS5 ZNF599 KMT2B PROSER3 ZNF792 RBM42 U2AF1L4
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around KIRREL2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for KIRREL2

Top Transcription factor binding sites by QIAGEN in the KIRREL2 gene promoter:
  • c-Myb
  • E2F
  • E2F-1
  • E2F-2
  • E2F-3a
  • E2F-4
  • E2F-5
  • En-1
  • p53

Genomic Locations for KIRREL2 Gene

Genomic Locations for KIRREL2 Gene
chr19:35,851,635-35,867,146
(GRCh38/hg38)
Size:
15,512 bases
Orientation:
Plus strand
chr19:36,346,763-36,358,048
(GRCh37/hg19)
Size:
11,286 bases
Orientation:
Plus strand

Genomic View for KIRREL2 Gene

Genes around KIRREL2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
KIRREL2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for KIRREL2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for KIRREL2 Gene

Proteins for KIRREL2 Gene

  • Protein details for KIRREL2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q6UWL6-KIRR2_HUMAN
    Recommended name:
    Kin of IRRE-like protein 2
    Protein Accession:
    Q6UWL6
    Secondary Accessions:
    • C9JHF1
    • C9JJ76
    • F1T0I2
    • Q6P1R1
    • Q7Z5P1
    • Q7Z5P2
    • Q96IQ8
    • Q9H0T1

    Protein attributes for KIRREL2 Gene

    Size:
    708 amino acids
    Molecular mass:
    75092 Da
    Quaternary structure:
    • Homodimer. Interacts with NPHS2/podocin (via the C-terminus). Interacts with NPHS1 (via the Ig-like domains). Interacts with FYN.
    SequenceCaution:
    • Sequence=AAH64925.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};

    Alternative splice isoforms for KIRREL2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for KIRREL2 Gene

Post-translational modifications for KIRREL2 Gene

  • N-glycosylated.
  • The extracellular domain is cleaved leading to the generation of a soluble fragment and a membrane-bound C-terminal fragment, which is further cleaved by gamma-secretase.
  • Glycosylation at Asn143, Asn301, and Asn484
  • Modification sites at PhosphoSitePlus

Antibody Products

  • Abcam antibodies for KIRREL2
  • Boster Bio Antibodies for KIRREL2

No data available for DME Specific Peptides for KIRREL2 Gene

Domains & Families for KIRREL2 Gene

Gene Families for KIRREL2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for KIRREL2 Gene

InterPro:
Blocks:
  • Immunoglobulin subtype
  • CD80-like C2-set immunoglobulin
ProtoNet:

Suggested Antigen Peptide Sequences for KIRREL2 Gene

GenScript: Design optimal peptide antigens:
  • Kin of IRRE-like protein 2 (F1T0I2_HUMAN)
  • Nephrin-like protein 3 (KIRR2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q6UWL6

UniProtKB/Swiss-Prot:

KIRR2_HUMAN :
  • Belongs to the immunoglobulin superfamily.
Family:
  • Belongs to the immunoglobulin superfamily.
genes like me logo Genes that share domains with KIRREL2: view

Function for KIRREL2 Gene

Molecular function for KIRREL2 Gene

UniProtKB/Swiss-Prot Function:
May regulate basal insulin secretion.

Phenotypes From GWAS Catalog for KIRREL2 Gene

Gene Ontology (GO) - Molecular Function for KIRREL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 25416956
GO:0042802 identical protein binding IEA,ISS --
genes like me logo Genes that share ontologies with KIRREL2: view
genes like me logo Genes that share phenotypes with KIRREL2: view

Animal Models for KIRREL2 Gene

MGI Knock Outs for KIRREL2:

Animal Model Products

  • Taconic Biosciences Mouse Models for KIRREL2

CRISPR Products

miRNA for KIRREL2 Gene

miRTarBase miRNAs that target KIRREL2

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KIRREL2

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for KIRREL2 Gene

Localization for KIRREL2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for KIRREL2 Gene

Cell membrane. Single-pass type I membrane protein. Note=Localized along the sites of the cell contacts. Colocalizes with E-Cadherin and beta-catenin. {ECO:0000250 UniProtKB:Q7TSU7}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for KIRREL2 gene
Compartment Confidence
plasma membrane 5
extracellular 2
cytoskeleton 1
mitochondrion 1
nucleus 1
endoplasmic reticulum 1
lysosome 0
golgi apparatus 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Centriolar satellite (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for KIRREL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0005911 cell-cell junction IEA,ISS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA,NAS 12837264
GO:0036057 slit diaphragm IEA --
genes like me logo Genes that share ontologies with KIRREL2: view

Pathways & Interactions for KIRREL2 Gene

genes like me logo Genes that share pathways with KIRREL2: view

Pathways by source for KIRREL2 Gene

1 BioSystems pathway for KIRREL2 Gene
2 Reactome pathways for KIRREL2 Gene

Gene Ontology (GO) - Biological Process for KIRREL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001933 negative regulation of protein phosphorylation IEA --
GO:0007155 cell adhesion NAS 12837264
GO:0098609 cell-cell adhesion IEA --
genes like me logo Genes that share ontologies with KIRREL2: view

No data available for SIGNOR curated interactions for KIRREL2 Gene

Drugs & Compounds for KIRREL2 Gene

No Compound Related Data Available

Transcripts for KIRREL2 Gene

mRNA/cDNA for KIRREL2 Gene

5 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KIRREL2

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for KIRREL2 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17a · 17b
SP1:
SP2:
SP3:
SP4: -

Relevant External Links for KIRREL2 Gene

GeneLoc Exon Structure for
KIRREL2

Expression for KIRREL2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for KIRREL2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for KIRREL2 Gene

This gene is overexpressed in Pancreas (x44.8).

Protein differential expression in normal tissues from HIPED for KIRREL2 Gene

This gene is overexpressed in Adipocyte (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for KIRREL2 Gene



Protein tissue co-expression partners for KIRREL2 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for KIRREL2

SOURCE GeneReport for Unigene cluster for KIRREL2 Gene:

Hs.145729

mRNA Expression by UniProt/SwissProt for KIRREL2 Gene:

Q6UWL6-KIRR2_HUMAN
Tissue specificity: Highly expressed in beta-cells of the pancreatic islets.

Evidence on tissue expression from TISSUES for KIRREL2 Gene

  • Nervous system(4.5)
  • Eye(4.4)
  • Kidney(2.3)
  • Pancreas(2.1)
  • Lung(2)
genes like me logo Genes that share expression patterns with KIRREL2: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for KIRREL2 Gene

Orthologs for KIRREL2 Gene

This gene was present in the common ancestor of animals.

Orthologs for KIRREL2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia KIRREL2 30 31
  • 99.23 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia KIRREL2 30 31
  • 88.68 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia KIRREL2 30 31
  • 87.52 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Kirrel2 30
  • 84.05 (n)
Mouse
(Mus musculus)
Mammalia Kirrel2 30 17 31
  • 84 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 75 (a)
ManyToMany
Oppossum
(Monodelphis domestica)
Mammalia KIRREL2 31
  • 66 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia -- 31
  • 39 (a)
ManyToMany
Zebrafish
(Danio rerio)
Actinopterygii kirrel3l 31
  • 37 (a)
ManyToMany
Fruit Fly
(Drosophila melanogaster)
Insecta rst 31
  • 20 (a)
ManyToMany
kirre 31
  • 18 (a)
ManyToMany
Worm
(Caenorhabditis elegans)
Secernentea syg-1 31
  • 22 (a)
OneToMany
Species where no ortholog for KIRREL2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)

Evolution for KIRREL2 Gene

ENSEMBL:
Gene Tree for KIRREL2 (if available)
TreeFam:
Gene Tree for KIRREL2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for KIRREL2: view image

Paralogs for KIRREL2 Gene

Paralogs for KIRREL2 Gene

(2) SIMAP similar genes for KIRREL2 Gene using alignment to 3 proteins:

  • KIRR2_HUMAN
  • K7EJS8_HUMAN
  • V9GXZ7_HUMAN
genes like me logo Genes that share paralogs with KIRREL2: view

Variants for KIRREL2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for KIRREL2 Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
732252 Conflicting Interpretations: Congenital nephrotic syndrome; not provided 35,851,824(+) G/A MISSENSE_VARIANT
762363 Likely Benign: not provided 35,851,665(+) C/T SYNONYMOUS_VARIANT
777469 Benign: not provided 35,859,572(+) G/A MISSENSE_VARIANT
798426 Likely Benign: not provided 35,851,647(+) G/A SYNONYMOUS_VARIANT
847759 Likely Pathogenic: not provided 35,851,778(+) A/G SPLICE_DONOR_VARIANT

Additional dbSNP identifiers (rs#s) for KIRREL2 Gene

Structural Variations from Database of Genomic Variants (DGV) for KIRREL2 Gene

Variant ID Type Subtype PubMed ID
dgv51n68 CNV loss 17160897
nsv953286 CNV deletion 24416366

Variation tolerance for KIRREL2 Gene

Residual Variation Intolerance Score: 93.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.52; 85.95% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for KIRREL2 Gene

Human Gene Mutation Database (HGMD)
KIRREL2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
KIRREL2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for KIRREL2 Gene

Disorders for KIRREL2 Gene

MalaCards: The human disease database

(3) MalaCards diseases for KIRREL2 Gene - From: DISEASES and GeneCards

- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for KIRREL2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with KIRREL2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for KIRREL2 Gene

Publications for KIRREL2 Gene

  1. Kirrel2, a novel immunoglobulin superfamily gene expressed primarily in beta cells of the pancreatic islets. (PMID: 12837264) Sun C … Carulli JP (Genomics 2003) 2 3 4 23
  2. Filtrin is a novel member of nephrin-like proteins. (PMID: 12504092) Ihalmo P … Holthöfer H (Biochemical and biophysical research communications 2003) 2 3 23
  3. Full-length transcriptome analysis of human retina-derived cell lines ARPE-19 and Y79 using the vector-capping method. (PMID: 21697133) Oshikawa M … Kato S (Investigative ophthalmology & visual science 2011) 3 4
  4. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 41
  5. Regulation of Neph3 gene in podocytes--key roles of transcription factors NF-kappaB and Sp1. (PMID: 19703278) Ristola M … Holthöfer H (BMC molecular biology 2009) 3 23

Products for KIRREL2 Gene

  • Signalway Proteins for KIRREL2

Sources for KIRREL2 Gene