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Aliases for KLHL3 Gene

Aliases for KLHL3 Gene

  • Kelch Like Family Member 3 2 3 5
  • Kelch-Like Family Member 3 3
  • Kelch (Drosophila)-Like 3 2
  • Kelch-Like 3 (Drosophila) 2
  • 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. GO annotations related to this gene include actin binding and structural molecule activity. An important paralog of this gene is KLHL5.

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 Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

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

ENSRs around KLHL3 on UCSC Golden Path with GeneCards custom track

Genomic Location for KLHL3 Gene

Chromosome:
5
Start:
137,617,500 bp from pter
End:
137,736,090 bp from pter
Size:
118,591 bases
Orientation:
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:
    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:
    • 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.
    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

Proteomics data for KLHL3 Gene at MOPED

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

Q9UH77

UniProtKB/Swiss-Prot:

KLHL3_HUMAN :
  • Contains 1 BACK (BTB/Kelch associated) domain.
  • Contains 6 Kelch repeats.
Domain:
  • Contains 1 BACK (BTB/Kelch associated) domain.
  • Contains 1 BTB (POZ) domain.
Similarity:
  • 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
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 Model Products

No data available for Enzyme Numbers (IUBMB) , Animal Models , 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
Jensen Localization Image for KLHL3 Gene 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:0005829 cytosol IDA 22406640
genes like me logo Genes that share ontologies with KLHL3: view

Pathways & Interactions for KLHL3 Gene

SuperPathways for KLHL3 Gene

No Data Available

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:0050801 ion homeostasis IEA,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 Pathways by source and 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:

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 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



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.
genes like me logo Genes that share expression patterns with KLHL3: view

Protein tissue co-expression partners for KLHL3 Gene

- Elite partner

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
cow
(Bos Taurus)
Mammalia KLHL3 35
  • 92.81 (n)
  • 98.8 (a)
KLHL3 36
  • 98 (a)
OneToOne
dog
(Canis familiaris)
Mammalia KLHL3 35
  • 91.99 (n)
  • 98.47 (a)
KLHL3 36
  • 96 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Klhl3 35
  • 87.77 (n)
  • 97.27 (a)
Klhl3 16
Klhl3 36
  • 89 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia KLHL3 35
  • 99.6 (n)
  • 99.83 (a)
KLHL3 36
  • 100 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia KLHL3 36
  • 97 (a)
OneToOne
chicken
(Gallus gallus)
Aves KLHL3 35
  • 81.73 (n)
  • 94.66 (a)
KLHL3 36
  • 93 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia KLHL3 36
  • 94 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii klhl3 35
  • 74.04 (n)
  • 81.53 (a)
KLHL3 36
  • 78 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta CG15097 37
  • 41 (a)
CG1812 37
  • 25 (a)
CG3571 37
  • 41 (a)
kel 37
  • 60 (a)
kel 35
  • 61.73 (n)
  • 61.01 (a)
kel 36
  • 50 (a)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP008362 35
  • 59.02 (n)
  • 60 (a)
worm
(Caenorhabditis elegans)
Secernentea kel-1 37
  • 42 (a)
T27E9.4a 37
  • 37 (a)
T27E9.4b 37
  • 37 (a)
kel-1 35
  • 49.14 (n)
  • 45.28 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 60 (a)
OneToMany
Species with no ortholog for KLHL3:
  • 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

Pseudogenes.org Pseudogenes for KLHL3 Gene

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

Variants for KLHL3 Gene

Sequence variations from dbSNP and Humsavar for KLHL3 Gene

SNP ID Clin Chr 05 pos Sequence Context AA Info Type
VAR_067501 Pseudohypoaldosteronism 2D (PHA2D)
rs199469624 Pseudohypoaldosteronism 2D (PHA2D) 137,709,759(-) GTGCG(A/G/T)TGTTC reference, missense
VAR_067503 Pseudohypoaldosteronism 2D (PHA2D)
VAR_067504 Pseudohypoaldosteronism 2D (PHA2D)
VAR_067505 Pseudohypoaldosteronism 2D (PHA2D)

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

Variant ID Type Subtype PubMed ID
nsv830499 CNV Loss 17160897
esv2673264 CNV Deletion 23128226
nsv830500 CNV Loss 17160897
nsv509089 CNV Insertion 20534489
esv272140 CNV Insertion 20981092
esv989099 CNV Insertion 20482838
esv1505834 CNV Insertion 17803354
nsv5022 CNV Loss 18451855
esv2653233 CNV Deletion 19546169
esv2042994 CNV Deletion 18987734
nsv513264 CNV Loss 21212237
esv2886 CNV Deletion 18987735
esv2730815 CNV Deletion 23290073
esv988201 CNV Deletion 20482838
esv1408200 CNV Deletion 17803354
nsv328717 CNV Loss 16902084
esv7996 CNV Loss 19470904

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

HapMap Linkage Disequilibrium report
KLHL3
Human Gene Mutation Database (HGMD)
KLHL3

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

Disorders for KLHL3 Gene

MalaCards: The human disease database

(6) 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
pseudohypoaldosteronism, type iia
  • pseudohypoaldosteronism type iia
pseudohypoaldosteronism
metabolic acidosis
familial hypertension
  • genetic hypertension
- 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}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for KLHL3

Genetic Association Database (GAD)
KLHL3
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
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 M.M. (Genomics 2000) 2 3 4 67
  2. KLHL3 regulates paracellular chloride transport in the kidney by ubiquitination of claudin-8. (PMID: 25831548) Gong Y. … Hou J. (Proc. Natl. Acad. Sci. U.S.A. 2015) 3
  3. Hypercalciuria in familial hyperkalemia and hypertension with KLHL3 mutations. (PMID: 25925082) Mayan H. … Hanukoglu A. (Nephron 2015) 3
  4. Hypertension-causing Mutations in Cullin3 Protein Impair RhoA Protein Ubiquitination and Augment the Association with Substrate Adaptors. (PMID: 26100637) Ibeawuchi S.R. … Sigmund C.D. (J. Biol. Chem. 2015) 3
  5. Characterisation of the Cullin-3 mutation that causes a severe form of familial hypertension and hyperkalaemia. (PMID: 26286618) Schumacher F.R. … Kurz T. (EMBO Mol Med 2015) 3

Products for KLHL3 Gene

Sources for KLHL3 Gene

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