This gene encodes a member of a small, conserved family of proteins with similar structure, including a string of extracellular leucine-rich repeats. A related protein was shown to be involved in B-cell development. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2012] See more...

Aliases for LRRC8E Gene

Aliases for LRRC8E Gene

  • Leucine Rich Repeat Containing 8 VRAC Subunit E 2 3 5
  • Leucine Rich Repeat Containing 8 Family Member E 2 3
  • Volume-Regulated Anion Channel Subunit LRRC8E 3 4
  • Leucine-Rich Repeat-Containing Protein 8E 3 4
  • FLJ23420 2
  • LRRC8E 5

External Ids for LRRC8E Gene

Previous GeneCards Identifiers for LRRC8E Gene

  • GC19P007860
  • GC19P007953
  • GC19P007623

Summaries for LRRC8E Gene

Entrez Gene Summary for LRRC8E Gene

  • This gene encodes a member of a small, conserved family of proteins with similar structure, including a string of extracellular leucine-rich repeats. A related protein was shown to be involved in B-cell development. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2012]

GeneCards Summary for LRRC8E Gene

LRRC8E (Leucine Rich Repeat Containing 8 VRAC Subunit E) is a Protein Coding gene. Diseases associated with LRRC8E include Steroid-Induced Glaucoma and Hereditary Lymphedema I. An important paralog of this gene is LRRC8C.

UniProtKB/Swiss-Prot Summary for LRRC8E Gene

  • Non-essential component of the volume-regulated anion channel (VRAC, also named VSOAC channel), an anion channel required to maintain a constant cell volume in response to extracellular or intracellular osmotic changes (PubMed:24790029, PubMed:26824658, PubMed:28193731). The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (PubMed:24790029, PubMed:26824658). Mediates efflux of amino acids, such as aspartate, in response to osmotic stress (PubMed:28193731). Channel activity requires LRRC8A plus at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition (PubMed:24790029, PubMed:26824658, PubMed:28193731).

Gene Wiki entry for LRRC8E Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for LRRC8E Gene

Genomics for LRRC8E Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for LRRC8E 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
GH19J007887 Promoter/Enhancer 1.6 EPDnew Ensembl ENCODE 261.1 +0.2 154 1.5 MYC IKZF1 ZNF600 KLF9 ZNF223 ZNF10 ZIC2 NONO SMAD5 CHD2 LRRC8E RF00001-143 RNA5SP463 piR-56497-074 ENSG00000269300 EVI5L MAP2K7
GH19J007889 Promoter 0.4 Ensembl 260.4 +1.2 1196 0.2 ZNF121 LRRC8E piR-56497-074 MAP2K7
GH19J007888 Enhancer 0.3 Ensembl 250.7 -1.3 -1304 0.4 GABPB1 ZBTB33 RF00001-143 LRRC8E RNA5SP463 PRR36
GH19J007829 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 10 -58.0 -58004 3 SP1 MYC IKZF1 JUND ZNF580 ATF2 KLF9 ZIC2 YY1 CTCF EVI5L ELAVL1 HNRNPM PRR36 LRRC8E lnc-PRR36-4
GH19J007902 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 8.9 +15.6 15562 3.1 SP1 MYC IKZF1 SSRP1 JUND ATF2 POLR2A CEBPA NFIC ZIC2 MAP2K7 ENSG00000214248 HSALNG0123687 ZNF558 HNRNPM ELAVL1 XAB2 ZNF414 ENSG00000269300 ZNF557
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around LRRC8E on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for LRRC8E

Top Transcription factor binding sites by QIAGEN in the LRRC8E gene promoter:
  • AP-1
  • c-Fos
  • c-Jun
  • E2F
  • E2F-1
  • E2F-3a
  • E47
  • GR
  • GR-alpha

Genomic Locations for LRRC8E Gene

Latest Assembly
chr19:7,888,505-7,902,021
(GRCh38/hg38)
Size:
13,517 bases
Orientation:
Plus strand

Previous Assembly
chr19:7,953,395-7,966,901
(GRCh37/hg19 by Entrez Gene)
Size:
13,507 bases
Orientation:
Plus strand

chr19:7,953,390-7,966,901
(GRCh37/hg19 by Ensembl)
Size:
13,512 bases
Orientation:
Plus strand

Genomic View for LRRC8E Gene

Genes around LRRC8E on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
LRRC8E Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for LRRC8E Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for LRRC8E Gene

Proteins for LRRC8E Gene

  • Protein details for LRRC8E Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q6NSJ5-LRC8E_HUMAN
    Recommended name:
    Volume-regulated anion channel subunit LRRC8E
    Protein Accession:
    Q6NSJ5
    Secondary Accessions:
    • B3KR78
    • Q2YDY3
    • Q7L236
    • Q8N3B0
    • Q9H5H8

    Protein attributes for LRRC8E Gene

    Size:
    796 amino acids
    Molecular mass:
    90247 Da
    Quaternary structure:
    • Heterohexamer (Probable). Oligomerizes with other LRRC8 proteins (LRRC8A, LRRC8C, LRRC8D and/or LRRC8B) to form a heterohexamer (PubMed:24790029, PubMed:26824658, PubMed:28193731). Detected in a channel complex that contains LRRC8A, LRRC8C and LRRC8E (PubMed:28193731). In vivo, the subunit composition may depend primarily on expression levels, and heterooligomeric channels containing various proportions of the different LRRC8 proteins may coexist (Probable).
    SequenceCaution:
    • Sequence=BAB15648.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAB15648.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence.; Evidence={ECO:0000305};

neXtProt entry for LRRC8E Gene

Post-translational modifications for LRRC8E Gene

  • Glycosylation at Asn63 and Asn302
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for LRRC8E Gene

Domains & Families for LRRC8E Gene

Gene Families for LRRC8E Gene

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

Protein Domains for LRRC8E Gene

Suggested Antigen Peptide Sequences for LRRC8E Gene

GenScript: Design optimal peptide antigens:
  • Leucine-rich repeat-containing protein 8E (LRC8E_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q6NSJ5

UniProtKB/Swiss-Prot:

LRC8E_HUMAN :
  • Belongs to the LRRC8 family.
Family:
  • Belongs to the LRRC8 family.
genes like me logo Genes that share domains with LRRC8E: view

Function for LRRC8E Gene

Molecular function for LRRC8E Gene

UniProtKB/Swiss-Prot Function:
Non-essential component of the volume-regulated anion channel (VRAC, also named VSOAC channel), an anion channel required to maintain a constant cell volume in response to extracellular or intracellular osmotic changes (PubMed:24790029, PubMed:26824658, PubMed:28193731). The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (PubMed:24790029, PubMed:26824658). Mediates efflux of amino acids, such as aspartate, in response to osmotic stress (PubMed:28193731). Channel activity requires LRRC8A plus at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition (PubMed:24790029, PubMed:26824658, PubMed:28193731).

Phenotypes From GWAS Catalog for LRRC8E Gene

Gene Ontology (GO) - Molecular Function for LRRC8E Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005225 contributes_to volume-sensitive anion channel activity IMP 28193731
GO:0005515 protein binding IPI 21516116
genes like me logo Genes that share ontologies with LRRC8E: view
genes like me logo Genes that share phenotypes with LRRC8E: view

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LRRC8E

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for LRRC8E Gene

Localization for LRRC8E Gene

Subcellular locations from UniProtKB/Swiss-Prot for LRRC8E Gene

Cell membrane. Multi-pass membrane protein. Endoplasmic reticulum membrane. Note=In the absence of LRRC8A, resides primarily in a cytoplasmic compartment, probably the endoplasmic reticulum. Requires LRRC8A for expression at the cell membrane. {ECO:0000269 PubMed:24790029}.

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 LRRC8E gene
Compartment Confidence
plasma membrane 5
extracellular 1
cytoskeleton 1
endoplasmic reticulum 1
cytosol 1
mitochondrion 0
peroxisome 0
nucleus 0
golgi apparatus 0

Gene Ontology (GO) - Cellular Components for LRRC8E Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA 24790029
GO:0005783 endoplasmic reticulum IEA --
GO:0005789 endoplasmic reticulum membrane IEA --
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane IMP 26824658
genes like me logo Genes that share ontologies with LRRC8E: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for LRRC8E Gene

Pathways & Interactions for LRRC8E Gene

PathCards logo

SuperPathways for LRRC8E Gene

No Data Available

Gene Ontology (GO) - Biological Process for LRRC8E Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006811 ion transport IEA --
GO:0015698 inorganic anion transport IEA --
GO:0015810 aspartate transmembrane transport IMP 28193731
GO:0055085 transmembrane transport TAS --
GO:0071470 cellular response to osmotic stress IMP 28193731
genes like me logo Genes that share ontologies with LRRC8E: view

No data available for Pathways by source and SIGNOR curated interactions for LRRC8E Gene

Drugs & Compounds for LRRC8E Gene

No Compound Related Data Available

Transcripts for LRRC8E Gene

mRNA/cDNA for LRRC8E Gene

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

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LRRC8E

Alternative Splicing Database (ASD) splice patterns (SP) for LRRC8E Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b ^ 3 ^ 4a · 4b · 4c · 4d
SP1: -
SP2: - -
SP3:
SP4: - - -

Relevant External Links for LRRC8E Gene

GeneLoc Exon Structure for
LRRC8E

Expression for LRRC8E Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for LRRC8E Gene

mRNA differential expression in normal tissues according to GTEx for LRRC8E Gene

This gene is overexpressed in Minor Salivary Gland (x5.5), Adrenal Gland (x5.2), Skin - Sun Exposed (Lower leg) (x5.0), Esophagus - Mucosa (x4.4), and Skin - Not Sun Exposed (Suprapubic) (x4.2).

Protein differential expression in normal tissues from HIPED for LRRC8E Gene

This gene is overexpressed in Pancreas (29.6), Urine (26.5), and Heart (7.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for LRRC8E Gene



Protein tissue co-expression partners for LRRC8E Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for LRRC8E

SOURCE GeneReport for Unigene cluster for LRRC8E Gene:

Hs.501511

Evidence on tissue expression from TISSUES for LRRC8E Gene

  • Lung(4.3)
  • Kidney(4.1)
genes like me logo Genes that share expression patterns with LRRC8E: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for LRRC8E Gene

Orthologs for LRRC8E Gene

This gene was present in the common ancestor of chordates.

Orthologs for LRRC8E Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia LRRC8E 29 30
  • 99.37 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia LRRC8E 29 30
  • 88.82 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia LRRC8E 30
  • 88 (a)
OneToOne
Cow
(Bos Taurus)
Mammalia LRRC8E 29 30
  • 86.73 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Lrrc8e 29
  • 84.03 (n)
Mouse
(Mus musculus)
Mammalia Lrrc8e 29 16 30
  • 83.4 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia LRRC8E 30
  • 65 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia lrrc8e 29
  • 64.06 (n)
Str.6450 29
African clawed frog
(Xenopus laevis)
Amphibia Xl.7346 29
Zebrafish
(Danio rerio)
Actinopterygii LRRC8E 30
  • 59 (a)
OneToOne
Species where no ortholog for LRRC8E was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • Fruit Fly (Drosophila melanogaster)
  • 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)
  • Platypus (Ornithorhynchus anatinus)
  • 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)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for LRRC8E Gene

ENSEMBL:
Gene Tree for LRRC8E (if available)
TreeFam:
Gene Tree for LRRC8E (if available)
Aminode:
Evolutionary constrained regions (ECRs) for LRRC8E: view image
Alliance of Genome Resources:
Additional Orthologs for LRRC8E

Paralogs for LRRC8E Gene

(7) SIMAP similar genes for LRRC8E Gene using alignment to 5 proteins:

  • LRC8E_HUMAN
  • M0QZ48_HUMAN
  • M0R2D8_HUMAN
  • M0R2K8_HUMAN
  • M0R3C1_HUMAN
genes like me logo Genes that share paralogs with LRRC8E: view

Variants for LRRC8E Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for LRRC8E Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
rs139734410 Benign: not provided 7,899,974(+) C/A
NM_025061.6(LRRC8E):c.1452C>A (p.Asp484Glu)
MISSENSE
rs146655359 Benign: not provided 7,900,374(+) C/T
NM_025061.6(LRRC8E):c.1852C>T (p.Arg618Cys)
MISSENSE
rs36038711 Benign: not provided 7,899,819(+) G/Ap.Val433Ile
NM_025061.6(LRRC8E):c.1297G>A (p.Val433Ile)
MISSENSE
rs796052173 Likely Benign: Long QT syndrome 7,900,299(+) G/A
NM_025061.6(LRRC8E):c.1777G>A (p.Gly593Arg)
MISSENSE
rs2042919 -- p.Glu181Gly

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for LRRC8E Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for LRRC8E Gene

Variant ID Type Subtype PubMed ID
esv3643596 CNV loss 21293372
nsv828418 CNV gain 20364138
nsv828419 CNV gain 20364138
nsv833733 CNV gain 17160897
nsv953961 CNV deletion 24416366

Variation tolerance for LRRC8E Gene

Residual Variation Intolerance Score: 81.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.62; 65.45% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for LRRC8E Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
LRRC8E
Leiden Open Variation Database (LOVD)
LRRC8E

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for LRRC8E Gene

Disorders for LRRC8E Gene

MalaCards: The human disease database

(5) MalaCards diseases for LRRC8E Gene - From: COP

Disorder Aliases PubMed IDs
steroid-induced glaucoma
  • corticosteroid-induced glaucoma
hereditary lymphedema i
  • congenital primary lymphedema
hereditary lymphedema
  • milroy disease
immunodeficiency 13
  • imd13
agammaglobulinemia, x-linked
  • xla
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for LRRC8E

genes like me logo Genes that share disorders with LRRC8E: view

No data available for UniProtKB/Swiss-Prot and Genatlas for LRRC8E Gene

Publications for LRRC8E Gene

  1. Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC. (PMID: 24790029) Voss FK … Jentsch TJ (Science (New York, N.Y.) 2014) 2 3 4
  2. Selective transport of neurotransmitters and modulators by distinct volume-regulated LRRC8 anion channels. (PMID: 28193731) Lutter D … Jentsch TJ (Journal of cell science 2017) 3 4
  3. LRRC8 Proteins Form Volume-Regulated Anion Channels that Sense Ionic Strength. (PMID: 26824658) Syeda R … Patapoutian A (Cell 2016) 3 4
  4. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4
  5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4

Products for LRRC8E Gene

Sources for LRRC8E Gene