Free for academic non-profit institutions. Other users need a Commercial license

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 Arthrogryposis, Distal, Type 3. Among its related pathways are Immune System and Class I MHC mediated antigen processing and presentation. 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. The BCR(KLHL3) complex acts by mediating ubiquitination of WNK4, an inhibitor of potassium channel KCNJ1, leading to WNK4 degradation.

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

Genomics for KLHL3 Gene

Regulatory Elements for KLHL3 Gene

Enhancers for KLHL3 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH05F137694 1.4 VISTA Ensembl ENCODE 12.1 +40.4 40370 3.0 CTCF TAL1 RAD21 ZFP69B ARID1B NFE2 NR2F6 SPI1 KLHL3 REEP2 GC05P137691 GC05P137725
GH05F137665 1.1 FANTOM5 Ensembl ENCODE 12.1 +69.4 69422 1.9 PKNOX1 STAT1 HLF HMBOX1 PRDM1 SPI1 KLHL3 MYOT FAM13B GC05P137671 MIR874
GH05F137833 1.5 FANTOM5 Ensembl ENCODE 8 -100.1 -100126 5.9 PKNOX1 SIN3A FEZF1 GATA2 FOS SP3 YY2 TSHZ1 ZNF264 MAFF MYOT HNRNPA0 CDC23 KDM3B RNU6-1148P KLHL3 PKD2L2 GC05M137818 NPY6R
GH05F137620 1 Ensembl ENCODE 10.8 +113.9 113860 2.7 SOX5 USF1 NFYC USF2 CEBPB CEBPG YY1 RAD51 ATF3 NFYB SPOCK1 MIR874 KLHL3 NME5 EGR1 GC05M137619 PIR48538 GC05M137622
GH05F137629 0.9 Ensembl ENCODE 11.5 +106.1 106090 0.8 CTCF ZNF654 PKNOX1 TRIM22 REST ZIC2 ZNF2 RAD21 RFX5 ZNF366 KLHL3 SPOCK1 RNU6-1148P REEP2 GFRA3 GC05M137619 MIR874
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around KLHL3 on UCSC Golden Path with GeneCards custom track

Promoters for KLHL3 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00001291149 790 1801 CTCF ZFP64 RAD21 ZFHX2 ZBTB48 POLR2A SMC3 NFE2 ZBTB20 NFE2L2

Genomic Location for KLHL3 Gene

137,617,500 bp from pter
137,736,090 bp from pter
118,591 bases
Minus strand

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

    Protein attributes for KLHL3 Gene

    587 amino acids
    Molecular mass:
    64970 Da
    Quaternary structure:
    • Component of the BCR(KLHL3) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL3 and RBX1 (Probable). Interacts with SLC12A3. Interacts with WNK1 and WNK4.
    • 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


neXtProt entry for KLHL3 Gene

Post-translational modifications for KLHL3 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

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

Suggested Antigen Peptide Sequences for KLHL3 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry



  • Contains 1 BACK (BTB/Kelch associated) domain.
  • Contains 6 Kelch repeats.
  • Contains 1 BACK (BTB/Kelch associated) domain.
  • Contains 1 BTB (POZ) domain.
  • Contains 6 Kelch repeats.
genes like me logo Genes that share domains with KLHL3: view

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. The BCR(KLHL3) complex acts by mediating ubiquitination of WNK4, an inhibitor of potassium channel KCNJ1, leading to WNK4 degradation.

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:

Animal Model Products

Inhibitory RNA Products

Flow Cytometry 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

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 IEA,IDA 22406640
GO:0005856 cytoskeleton IEA --
GO:0031463 Cul3-RING ubiquitin ligase complex IEA,TAS 22406640
genes like me logo Genes that share ontologies with KLHL3: view

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 IEA,TAS 22406640
GO:0042787 protein ubiquitination involved in ubiquitin-dependent protein catabolic process IDA 23453970
GO:0050801 ion homeostasis IEA,IMP 23453970
GO:0070294 renal sodium ion absorption IMP 22406640
GO:0070936 protein K48-linked ubiquitination IDA 23576762
genes like me logo Genes that share ontologies with KLHL3: view

No data available for SIGNOR curated interactions for KLHL3 Gene

Transcripts for KLHL3 Gene

Unigene Clusters for KLHL3 Gene

Kelch-like family member 3:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry 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: - - - - -
SP6: - - -

Relevant External Links for KLHL3 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for KLHL3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and 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:


SOURCE GeneReport for Unigene cluster for KLHL3 Gene:


mRNA Expression by UniProt/SwissProt for KLHL3 Gene:

Tissue specificity: Widely expressed.
genes like me logo Genes that share expression patterns with KLHL3: view

Primer Products

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
(Pan troglodytes)
Mammalia KLHL3 34 35
  • 99.6 (n)
(Monodelphis domestica)
Mammalia KLHL3 35
  • 97 (a)
(Bos Taurus)
Mammalia KLHL3 34 35
  • 92.81 (n)
(Canis familiaris)
Mammalia KLHL3 34 35
  • 91.99 (n)
(Mus musculus)
Mammalia Klhl3 34 16 35
  • 87.77 (n)
(Gallus gallus)
Aves KLHL3 34 35
  • 81.73 (n)
(Anolis carolinensis)
Reptilia KLHL3 35
  • 94 (a)
(Danio rerio)
Actinopterygii KLHL3 35
  • 78 (a)
klhl3 34
  • 74.04 (n)
fruit fly
(Drosophila melanogaster)
Insecta kel 36 34 35
  • 61.73 (n)
CG15097 36
  • 41 (a)
CG3571 36
  • 41 (a)
CG1812 36
  • 25 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP008362 34
  • 59.02 (n)
(Caenorhabditis elegans)
Secernentea kel-1 36 34
  • 49.14 (n)
T27E9.4a 36
  • 37 (a)
T27E9.4b 36
  • 37 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 60 (a)
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

Gene Tree for KLHL3 (if available)
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 Sequence Context AA Info Type
rs199469623 Pseudohypoaldosteronism 2D (PHA2D) [MIM:614495], Pathogenic 137,709,761(-) CTGTG(A/C/T)GATGT reference, missense
rs199469624 Pseudohypoaldosteronism 2D (PHA2D) [MIM:614495], Pathogenic 137,709,759(-) GTGCG(A/G/T)TGTTC reference, missense
rs199469625 Pseudohypoaldosteronism 2D (PHA2D) [MIM:614495], Pathogenic 137,698,396(-) GTCTG(A/C)GAGTA reference, missense
rs199469626 Pseudohypoaldosteronism 2D (PHA2D) [MIM:614495], Pathogenic 137,692,320(-) CACCT(G/T)CACTG reference, missense
rs199469627 Pseudohypoaldosteronism 2D (PHA2D) [MIM:614495], Pathogenic 137,639,955(-) CGGCC(A/G)GGCAC reference, missense

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

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

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)

Relevant External Links for KLHL3 Gene

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

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

Disorders for KLHL3 Gene

MalaCards: The human disease database

(8) MalaCards diseases for KLHL3 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
pseudohypoaldosteronism, type iid
  • pseudohypoaldosteronism type iid
arthrogryposis, distal, type 3
  • gordon syndrome
pseudohypoaldosteronism, type iia
  • pseudohypoaldosteronism type 2a
pseudohypoaldosteronism, type iie
  • pseudohypoaldosteronism, type iid
- elite association - COSMIC cancer census association via MalaCards
Search KLHL3 in MalaCards View complete list of genes associated with diseases


  • 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}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for KLHL3

Genetic Association Database (GAD)
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
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 M.M. (Genomics 2000) 2 3 4 64
  2. Impaired KLHL3-mediated ubiquitination of WNK4 causes human hypertension. (PMID: 23453970) Wakabayashi M. … Uchida S. (Cell Rep 2013) 3 4 64
  3. Disease-causing mutations in KLHL3 impair its effect on WNK4 degradation. (PMID: 23665031) Wu G. … Peng J.B. (FEBS Lett. 2013) 3 4 64
  4. Kelch-like 3 and Cullin 3 regulate electrolyte homeostasis via ubiquitination and degradation of WNK4. (PMID: 23576762) Shibata S. … Lifton R.P. (Proc. Natl. Acad. Sci. U.S.A. 2013) 3 4 64
  5. Crystal structure of KLHL3 in complex with Cullin3. (PMID: 23573258) Ji A.X. … PrivAc G.G. (PLoS ONE 2013) 3 4 64

Products for KLHL3 Gene

Sources for KLHL3 Gene

Loading form....