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Aliases for KLHL3 Gene

Aliases for KLHL3 Gene

  • Kelch Like Family Member 3 2 3 5
  • Kelch (Drosophila)-Like 3 2
  • Kelch-Like 3 (Drosophila) 2
  • Kelch-Like Protein 3 3
  • KIAA1129 4
  • PHA2D 3

External Ids for KLHL3 Gene

Previous GeneCards Identifiers for KLHL3 Gene

  • GC05M136828
  • GC05M137626
  • GC05M136984
  • GC05M137029
  • GC05M136981
  • GC05M132139
  • GC05M136953

Summaries for KLHL3 Gene

Entrez Gene Summary for KLHL3 Gene

  • This gene is ubiquitously expressed and encodes a full-length protein which has an N-terminal BTB domain followed by a BACK domain and six kelch-like repeats in the C-terminus. These kelch-like repeats promote substrate ubiquitination of bound proteins via interaction of the BTB domain with the CUL3 (cullin 3) component of a cullin-RING E3 ubiquitin ligase (CRL) complex. Muatations in this gene cause pseudohypoaldosteronism type IID (PHA2D); a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Mar 2012]

GeneCards Summary for KLHL3 Gene

KLHL3 (Kelch Like Family Member 3) is a Protein Coding gene. Diseases associated with KLHL3 include Pseudohypoaldosteronism, Type Iid and Pseudohypoaldosteronism, Type Iia. Among its related pathways are Innate Immune System and Class I MHC mediated antigen processing and presentation. Gene Ontology (GO) annotations related to this gene include actin binding and structural molecule activity. An important paralog of this gene is KLHL2.

UniProtKB/Swiss-Prot for KLHL3 Gene

  • Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of ion transport in the distal nephron (PubMed:14528312, PubMed:22406640, PubMed:23387299, PubMed:23453970, PubMed:23576762, PubMed:23665031). The BCR(KLHL3) complex acts by mediating ubiquitination of WNK4, an inhibitor of potassium channel KCNJ1, leading to WNK4 degradation (PubMed:23387299, PubMed:23453970, PubMed:23576762, PubMed:23665031). The BCR(KLHL3) complex also mediates ubiquitination and degradation of CLDN8, a tight-junction protein required for paracellular chloride transport in the kidney (By similarity).

Additional gene information for KLHL3 Gene

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for KLHL3 Gene

Genomics for KLHL3 Gene

GeneHancer (GH) Regulatory Elements for KLHL3 Gene

Promoters and enhancers for KLHL3 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
GH05I137734 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE dbSUPER 550.8 -0.4 -397 3.9 CTCF MXI1 TAF1 JUN ZFP64 SIN3A RAD21 ETS1 ZNF335 POLR2A KLHL3 GC05M137746 GC05P137725
GH05I138350 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 12.9 -617.2 -617245 4.7 PKNOX1 FOXA2 ARNT ARID4B SIN3A FEZF1 ZNF2 IRF4 YY1 SLC30A9 KDM3B CDC23 BRD8 HNRNPA0 FAM53C MATR3 KLHL3 RPL7P19 FAM13B KIF20A
GH05I138177 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 11 -442.9 -442850 3.1 PKNOX1 CLOCK FOXA2 SMAD1 ARNT ARID4B SIN3A DMAP1 ZNF2 YY1 BRD8 KIF20A HNRNPA0 KDM3B KLHL3 CDC23
GH05I137694 Enhancer 1.1 VISTA Ensembl ENCODE 12.1 +40.3 40332 3 CTCF TCF12 CTBP1 RAD21 NR2F2 YY1 SPI1 KLHL3 REEP2 GC05P137691 GC05P137725
GH05I137665 Enhancer 1.1 FANTOM5 Ensembl ENCODE 12.1 +69.6 69613 1.5 PKNOX1 HLF EBF1 DPF2 IRF4 YY1 FOSL1 HMBOX1 HNF4A PRDM1 KLHL3 MYOT FAM13B GC05P137671 MIR874
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around KLHL3 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the KLHL3 gene promoter:

Genomic Locations for KLHL3 Gene

Genomic Locations for KLHL3 Gene
chr5:137,617,500-137,736,090
(GRCh38/hg38)
Size:
118,591 bases
Orientation:
Minus strand
chr5:136,953,189-137,071,779
(GRCh37/hg19)

Genomic View for KLHL3 Gene

Genes around KLHL3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
KLHL3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for KLHL3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for KLHL3 Gene

Proteins for KLHL3 Gene

  • Protein details for KLHL3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UH77-KLHL3_HUMAN
    Recommended name:
    Kelch-like protein 3
    Protein Accession:
    Q9UH77
    Secondary Accessions:
    • B2RBK7
    • Q9UH75
    • Q9UH76
    • Q9ULU0
    • Q9Y6V6

    Protein attributes for KLHL3 Gene

    Size:
    587 amino acids
    Molecular mass:
    64970 Da
    Quaternary structure:
    • Homodimer (PubMed:28052936). Component of the BCR(KLHL3) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL3 and RBX1 (Probable) (PubMed:23453970, PubMed:23576762, PubMed:23573258). Interacts with SLC12A3 (PubMed:22406640). Interacts with WNK1 and WNK4 (PubMed:23387299, PubMed:23453970, PubMed:23573258, PubMed:23576762, PubMed:23665031, PubMed:26435498, PubMed:27727489). Interacts with CLDN8 (By similarity).
    SequenceCaution:
    • Sequence=AAB97127.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=BAA86443.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for KLHL3 Gene

    Alternative splice isoforms for KLHL3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for KLHL3 Gene

Post-translational modifications for KLHL3 Gene

  • Phosphorylation at Ser-433 by PKA decreases the interaction with WNK4, Leading to inhibit WNK4 degradation by the BCR(KLHL3) complex (PubMed:26435498, PubMed:27727489). Phosphorylation at Ser-433 is increased by insulin (PubMed:26435498).

Other Protein References for KLHL3 Gene

No data available for DME Specific Peptides for KLHL3 Gene

Domains & Families for KLHL3 Gene

Gene Families for KLHL3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins

Suggested Antigen Peptide Sequences for KLHL3 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

genes like me logo Genes that share domains with KLHL3: view

No data available for UniProtKB/Swiss-Prot for KLHL3 Gene

Function for KLHL3 Gene

Molecular function for KLHL3 Gene

UniProtKB/Swiss-Prot Function:
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of ion transport in the distal nephron (PubMed:14528312, PubMed:22406640, PubMed:23387299, PubMed:23453970, PubMed:23576762, PubMed:23665031). The BCR(KLHL3) complex acts by mediating ubiquitination of WNK4, an inhibitor of potassium channel KCNJ1, leading to WNK4 degradation (PubMed:23387299, PubMed:23453970, PubMed:23576762, PubMed:23665031). The BCR(KLHL3) complex also mediates ubiquitination and degradation of CLDN8, a tight-junction protein required for paracellular chloride transport in the kidney (By similarity).

Phenotypes From GWAS Catalog for KLHL3 Gene

Gene Ontology (GO) - Molecular Function for KLHL3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003779 actin binding IEA --
GO:0004842 contributes_to ubiquitin-protein transferase activity IBA --
GO:0005198 structural molecule activity TAS 10843806
GO:0005515 protein binding IPI 22406640
genes like me logo Genes that share ontologies with KLHL3: view
genes like me logo Genes that share phenotypes with KLHL3: view

Human Phenotype Ontology for KLHL3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for KLHL3 Gene

MGI Knock Outs for KLHL3:

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for KLHL3 Gene

Localization for KLHL3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for KLHL3 Gene

Cytoplasm, cytoskeleton. Cytoplasm, cytosol.

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 KLHL3 gene
Compartment Confidence
cytosol 5
cytoskeleton 3

Gene Ontology (GO) - Cellular Components for KLHL3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
GO:0005856 cytoskeleton IEA --
GO:0031463 Cul3-RING ubiquitin ligase complex TAS 22406640
genes like me logo Genes that share ontologies with KLHL3: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for KLHL3 Gene

Pathways & Interactions for KLHL3 Gene

genes like me logo Genes that share pathways with KLHL3: view

UniProtKB/Swiss-Prot Q9UH77-KLHL3_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

Gene Ontology (GO) - Biological Process for KLHL3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016567 protein ubiquitination TAS 22406640
GO:0042787 protein ubiquitination involved in ubiquitin-dependent protein catabolic process IDA 23453970
GO:0043687 post-translational protein modification TAS --
GO:0050801 ion homeostasis IMP 23453970
GO:0070294 renal sodium ion absorption IMP 22406640
genes like me logo Genes that share ontologies with KLHL3: view

No data available for SIGNOR curated interactions for KLHL3 Gene

Drugs & Compounds for KLHL3 Gene

No Compound Related Data Available

Transcripts for KLHL3 Gene

Unigene Clusters for KLHL3 Gene

Kelch-like family member 3:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for KLHL3 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19a · 19b ^ 20 ^ 21
SP1: - - - - - -
SP2: - - - - - - -
SP3: - - - - -
SP4: - - - - -
SP5:
SP6: - - -
SP7:

Relevant External Links for KLHL3 Gene

GeneLoc Exon Structure for
KLHL3
ECgene alternative splicing isoforms for
KLHL3

Expression for KLHL3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for KLHL3 Gene

mRNA differential expression in normal tissues according to GTEx for KLHL3 Gene

This gene is overexpressed in Brain - Cerebellar Hemisphere (x6.9) and Brain - Cerebellum (x6.9).

Protein differential expression in normal tissues from HIPED for KLHL3 Gene

This gene is overexpressed in Adipocyte (49.4) and Retina (19.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for KLHL3 Gene



Protein tissue co-expression partners for KLHL3 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of KLHL3 Gene:

KLHL3

SOURCE GeneReport for Unigene cluster for KLHL3 Gene:

Hs.655084

mRNA Expression by UniProt/SwissProt for KLHL3 Gene:

Q9UH77-KLHL3_HUMAN
Tissue specificity: Widely expressed.

Evidence on tissue expression from TISSUES for KLHL3 Gene

  • Nervous system(4.7)
  • Kidney(4.5)
  • Bone marrow(4)

Phenotype-based relationships between genes and organs from Gene ORGANizer for KLHL3 Gene

Germ Layers:
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • skeletal muscle
  • urinary
Organs:
Head and neck:
  • ear
Thorax:
  • heart
  • heart valve
Abdomen:
  • intestine
  • kidney
  • large intestine
  • small intestine
General:
  • blood vessel
genes like me logo Genes that share expression patterns with KLHL3: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery for KLHL3 Gene

Orthologs for KLHL3 Gene

This gene was present in the common ancestor of animals.

Orthologs for KLHL3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia KLHL3 33 34
  • 99.6 (n)
oppossum
(Monodelphis domestica)
Mammalia KLHL3 34
  • 97 (a)
OneToOne
cow
(Bos Taurus)
Mammalia KLHL3 33 34
  • 92.81 (n)
dog
(Canis familiaris)
Mammalia KLHL3 33 34
  • 91.99 (n)
mouse
(Mus musculus)
Mammalia Klhl3 33 16 34
  • 87.77 (n)
chicken
(Gallus gallus)
Aves KLHL3 33 34
  • 81.73 (n)
lizard
(Anolis carolinensis)
Reptilia KLHL3 34
  • 94 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii KLHL3 34
  • 78 (a)
OneToOne
klhl3 33
  • 74.04 (n)
fruit fly
(Drosophila melanogaster)
Insecta kel 35 33 34
  • 61.73 (n)
CG15097 35
  • 41 (a)
CG3571 35
  • 41 (a)
CG1812 35
  • 25 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP008362 33
  • 59.02 (n)
worm
(Caenorhabditis elegans)
Secernentea kel-1 35 33
  • 49.14 (n)
T27E9.4a 35
  • 37 (a)
T27E9.4b 35
  • 37 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 60 (a)
OneToMany
Species where no ortholog for KLHL3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • 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)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rat (Rattus norvegicus)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • 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 KLHL3 Gene

ENSEMBL:
Gene Tree for KLHL3 (if available)
TreeFam:
Gene Tree for KLHL3 (if available)

Paralogs for KLHL3 Gene

Variants for KLHL3 Gene

Sequence variations from dbSNP and Humsavar for KLHL3 Gene

SNP ID Clin Chr 05 pos Variation AA Info Type
rs1008289259 uncertain-significance, Pseudohypoaldosteronism, Type I, Dominant 137,619,650(-) G/A 3_prime_UTR_variant
rs1009368103 uncertain-significance, Pseudohypoaldosteronism, Type I, Dominant 137,620,664(-) A/C 3_prime_UTR_variant
rs1010762330 uncertain-significance, Pseudohypoaldosteronism, Type I, Dominant 137,617,734(-) T/C 3_prime_UTR_variant
rs1036580701 uncertain-significance, Pseudohypoaldosteronism, Type I, Dominant 137,620,075(-) C/G 3_prime_UTR_variant
rs1039476709 uncertain-significance, Pseudohypoaldosteronism, Type I, Dominant 137,618,178(-) A/C 3_prime_UTR_variant

Structural Variations from Database of Genomic Variants (DGV) for KLHL3 Gene

Variant ID Type Subtype PubMed ID
dgv3178n106 CNV deletion 24896259
esv1408200 CNV deletion 17803354
esv1505834 CNV insertion 17803354
esv2042994 CNV deletion 18987734
esv2653233 CNV deletion 19546169
esv2673264 CNV deletion 23128226
esv2730815 CNV deletion 23290073
esv2886 CNV loss 18987735
esv3290162 CNV deletion 24192839
esv3370006 CNV duplication 20981092
esv3387544 CNV insertion 20981092
esv3566694 CNV deletion 23714750
esv3566695 CNV deletion 23714750
esv3606907 CNV loss 21293372
esv7996 CNV loss 19470904
esv988201 CNV deletion 20482838
esv989099 CNV insertion 20482838
nsv1073499 CNV deletion 25765185
nsv1150691 CNV deletion 26484159
nsv328717 CNV deletion 16902084
nsv5022 CNV deletion 18451855
nsv509089 CNV insertion 20534489
nsv513264 CNV loss 21212237
nsv830499 CNV loss 17160897
nsv830500 CNV loss 17160897
nsv958256 CNV deletion 24416366

Variation tolerance for KLHL3 Gene

Residual Variation Intolerance Score: 17.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.17; 23.64% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for KLHL3 Gene

Human Gene Mutation Database (HGMD)
KLHL3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
KLHL3

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for KLHL3 Gene

Disorders for KLHL3 Gene

MalaCards: The human disease database

(7) MalaCards diseases for KLHL3 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search KLHL3 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

KLHL3_HUMAN
  • Pseudohypoaldosteronism 2D (PHA2D) [MIM:614495]: A disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics. PHA2D inheritance is autosomal dominant or recessive. {ECO:0000269 PubMed:22266938, ECO:0000269 PubMed:22406640, ECO:0000269 PubMed:23387299, ECO:0000269 PubMed:23453970, ECO:0000269 PubMed:23576762, ECO:0000269 PubMed:23665031, ECO:0000269 PubMed:26435498, ECO:0000269 PubMed:27026694, ECO:0000269 PubMed:27780982, ECO:0000269 PubMed:28052936, ECO:0000269 PubMed:28511177}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for KLHL3

genes like me logo Genes that share disorders with KLHL3: view

No data available for Genatlas for KLHL3 Gene

Publications for KLHL3 Gene

  1. Molecular characterization of KLHL3, a human homologue of the Drosophila kelch gene. (PMID: 10843806) Lai F … Le Beau MM (Genomics 2000) 2 3 4 58
  2. Phosphorylation of KLHL3 at serine 433 impairs its interaction with the acidic motif of WNK4: a molecular dynamics study. (PMID: 27727489) Wang L … Peng JB (Protein science : a publication of the Protein Society 2017) 3 4 58
  3. Impaired degradation of WNK by Akt and PKA phosphorylation of KLHL3. (PMID: 26435498) Yoshizaki Y … Sohara E (Biochemical and biophysical research communications 2015) 3 4 58
  4. Disease-causing mutations in KLHL3 impair its effect on WNK4 degradation. (PMID: 23665031) Wu G … Peng JB (FEBS letters 2013) 3 4 58
  5. Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via ubiquitination and degradation of WNK4. (PMID: 23576762) Shibata S … Lifton RP (Proceedings of the National Academy of Sciences of the United States of America 2013) 3 4 58

Products for KLHL3 Gene

Sources for KLHL3 Gene

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