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Aliases for KLHL12 Gene

Aliases for KLHL12 Gene

  • Kelch Like Family Member 12 2 3 5
  • CUL3-Interacting Protein 1 3 4
  • DKIR Homolog 3 4
  • C3IP1 3 4
  • Kelch-Like 12 (Drosophila) 2
  • Kelch-Like Protein C3IP1 3
  • Kelch-Like Protein 12 3
  • HDKIR 4
  • DKIR 3

External Ids for KLHL12 Gene

Previous GeneCards Identifiers for KLHL12 Gene

  • GC01M200149
  • GC01M199591
  • GC01M201126
  • GC01M174025

Summaries for KLHL12 Gene

Entrez Gene Summary for KLHL12 Gene

  • This gene encodes a member of the KLHL (Kelch-like) family of proteins. This protein has been identified as an autoantigen in the autoimmune disease Sjogren's syndrome and as a potential biomarker in primary biliary cirrhosis. This protein may act as a substrate adaptor of the Cullin-3 ubiquitin ligase complex to promote substrate-specific ubiquitylation. Ubiquitylation by this complex has been shown to regulate the Wnt signaling pathway as well as COPII vesicle coat size. A pseudogene has been identified on chromosome 22. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

GeneCards Summary for KLHL12 Gene

KLHL12 (Kelch Like Family Member 12) is a Protein Coding gene. Diseases associated with KLHL12 include Primary Biliary Cirrhosis. Among its related pathways are Signaling by Wnt and CDK-mediated phosphorylation and removal of Cdc6. An important paralog of this gene is KLHL20.

UniProtKB/Swiss-Prot for KLHL12 Gene

  • Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a negative regulator of Wnt signaling pathway and ER-Golgi transport (PubMed:22358839, PubMed:27565346). The BCR(KLHL12) complex is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B) (PubMed:22358839, PubMed:27565346). The BCR(KLHL12) complex is also involved in neural crest specification: in response to cytosolic calcium increase, interacts with the heterodimer formed with PEF1 and PDCD6/ALG-2, leading to bridge together the BCR(KLHL12) complex and SEC31 (SEC31A or SEC31B), promoting monoubiquitination of SEC31 and subsequent collagen export (PubMed:27716508). As part of the BCR(KLHL12) complex, also acts as a negative regulator of the Wnt signaling pathway by mediating ubiquitination and subsequent proteolysis of DVL3 (PubMed:16547521). The BCR(KLHL12) complex also mediates polyubiquitination of DRD4 and PEF1, without leading to degradation of these proteins (PubMed:18303015, PubMed:20100572, PubMed:27716508).

Gene Wiki entry for KLHL12 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for KLHL12 Gene

Genomics for KLHL12 Gene

Regulatory Elements for KLHL12 Gene

Enhancers for KLHL12 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
GH01G202963 1.7 FANTOM5 ENCODE dbSUPER 13.4 -38.0 -38011 6.6 HDGF PKNOX1 CREB3L1 ARNT ARID4B SIN3A YBX1 ZBTB7B ZNF766 ZNF143 CYB5R1 BTG2 KLHL12 LOC100506747 ADIPOR1 KDM5B PCAT6 LOC148709 LOC730222 RABIF
GH01G203005 1.2 ENCODE 11.7 -78.4 -78366 3.2 CREB3L1 ZFP64 DMAP1 YY1 SP3 NFYC TBX21 MEF2D GLIS1 NR2C1 LOC100506747 KLHL12 CYB5R1 KDM5B PCAT6 RPS27P8 RPS20P8
GH01G202952 1.1 Ensembl ENCODE dbSUPER 11.8 -24.4 -24434 1.8 MAX FOSL1 ZNF316 NFIC ZBTB48 ZNF24 FOS HNF4A ZBTB33 KLHL12 KDM5B PCAT6 ADIPOR1 CYB5R1 GC01P202952
GH01G202926 1.2 ENCODE 10.6 +1.6 1580 1.9 MLX CREB3L1 ZFP64 YBX1 DMAP1 YY1 SLC30A9 ZNF143 ZNF263 SP3 RNPEP ENSG00000273478 ELF3-AS1 ZBED6 HNRNPA1P59 PRELP LOC100506672 KLHL12 SNRPE ADIPOR1
GH01G202887 1.1 ENCODE 9.8 +39.8 39809 2.1 HDGF HNRNPUL1 PKNOX1 FOXA2 CREB3L1 ARNT AGO1 ZFP64 SIN3A ARID4B KLHL12 RABIF PIR34155
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around KLHL12 on UCSC Golden Path with GeneCards custom track

Promoters for KLHL12 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000018359 1444 1600 MLX CREB3L1 ZFP64 YBX1 DMAP1 YY1 SLC30A9 ZNF143 ZNF263 SP3

Genomic Location for KLHL12 Gene

Chromosome:
1
Start:
202,891,096 bp from pter
End:
202,928,644 bp from pter
Size:
37,549 bases
Orientation:
Minus strand

Genomic View for KLHL12 Gene

Genes around KLHL12 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
KLHL12 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for KLHL12 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for KLHL12 Gene

Proteins for KLHL12 Gene

  • Protein details for KLHL12 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q53G59-KLH12_HUMAN
    Recommended name:
    Kelch-like protein 12
    Protein Accession:
    Q53G59
    Secondary Accessions:
    • A6NEN8
    • B7Z7B8
    • Q9HBX5

    Protein attributes for KLHL12 Gene

    Size:
    568 amino acids
    Molecular mass:
    63277 Da
    Quaternary structure:
    • Component of the BCR(KLHL12) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL12 and RBX1 (PubMed:22358839). This complex interacts with DVL3 upon activation of the Wnt signaling pathway by WNT3A (PubMed:16547521). Interacts with DRD4, KLHL2 and SEC31A (PubMed:15383316,PubMed:18303015, PubMed:22358839). Interacts with PEF1 and PDCD6/ALG-2; interaction takes place in response to cytosolic calcium increase and leads to bridge together the BCR(KLHL12) complex and SEC31 (SEC31A or SEC31B) (PubMed:27716508).

    Three dimensional structures from OCA and Proteopedia for KLHL12 Gene

    Alternative splice isoforms for KLHL12 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for KLHL12 Gene

Post-translational modifications for KLHL12 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for KLHL12 Gene

Domains & Families for KLHL12 Gene

Gene Families for KLHL12 Gene

Graphical View of Domain Structure for InterPro Entry

Q53G59

UniProtKB/Swiss-Prot:

KLH12_HUMAN :
  • The BTB domain is required for interaction with CUL3.
Domain:
  • The BTB domain is required for interaction with CUL3.
genes like me logo Genes that share domains with KLHL12: view

Function for KLHL12 Gene

Molecular function for KLHL12 Gene

UniProtKB/Swiss-Prot Function:
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a negative regulator of Wnt signaling pathway and ER-Golgi transport (PubMed:22358839, PubMed:27565346). The BCR(KLHL12) complex is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B) (PubMed:22358839, PubMed:27565346). The BCR(KLHL12) complex is also involved in neural crest specification: in response to cytosolic calcium increase, interacts with the heterodimer formed with PEF1 and PDCD6/ALG-2, leading to bridge together the BCR(KLHL12) complex and SEC31 (SEC31A or SEC31B), promoting monoubiquitination of SEC31 and subsequent collagen export (PubMed:27716508). As part of the BCR(KLHL12) complex, also acts as a negative regulator of the Wnt signaling pathway by mediating ubiquitination and subsequent proteolysis of DVL3 (PubMed:16547521). The BCR(KLHL12) complex also mediates polyubiquitination of DRD4 and PEF1, without leading to degradation of these proteins (PubMed:18303015, PubMed:20100572, PubMed:27716508).

Gene Ontology (GO) - Molecular Function for KLHL12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004842 contributes_to ubiquitin-protein transferase activity IBA --
GO:0005515 protein binding IPI 16189514
GO:0042802 identical protein binding IPI 16189514
genes like me logo Genes that share ontologies with KLHL12: view
genes like me logo Genes that share phenotypes with KLHL12: view

Animal Model Products

CRISPR Products

miRNA for KLHL12 Gene

miRTarBase miRNAs that target KLHL12

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for KLHL12 Gene

Localization for KLHL12 Gene

Subcellular locations from UniProtKB/Swiss-Prot for KLHL12 Gene

Cytoplasmic vesicle, COPII-coated vesicle.

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 KLHL12 gene
Compartment Confidence
cytosol 5
cytoskeleton 4
nucleus 2
golgi apparatus 2
endoplasmic reticulum 1

Gene Ontology (GO) - Cellular Components for KLHL12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane IEA --
GO:0005815 microtubule organizing center IDA --
GO:0005829 cytosol TAS --
GO:0030127 COPII vesicle coat IDA 27716508
GO:0030134 ER to Golgi transport vesicle IEA,IDA 22358839
genes like me logo Genes that share ontologies with KLHL12: view

Pathways & Interactions for KLHL12 Gene

genes like me logo Genes that share pathways with KLHL12: view

Pathways by source for KLHL12 Gene

UniProtKB/Swiss-Prot Q53G59-KLH12_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

Gene Ontology (GO) - Biological Process for KLHL12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006513 protein monoubiquitination IDA 22358839
GO:0006810 transport IEA --
GO:0006888 ER to Golgi vesicle-mediated transport IMP,IDA 27716508
GO:0014029 neural crest formation IMP 27716508
GO:0014032 neural crest cell development IMP 27716508
genes like me logo Genes that share ontologies with KLHL12: view

No data available for SIGNOR curated interactions for KLHL12 Gene

Transcripts for KLHL12 Gene

Unigene Clusters for KLHL12 Gene

Kelch-like family member 12:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for KLHL12 Gene

No ASD Table

Relevant External Links for KLHL12 Gene

GeneLoc Exon Structure for
KLHL12
ECgene alternative splicing isoforms for
KLHL12

Expression for KLHL12 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for KLHL12 Gene

Protein differential expression in normal tissues from HIPED for KLHL12 Gene

This gene is overexpressed in Neutrophil (56.5) and Fetal ovary (8.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for KLHL12 Gene



NURSA nuclear receptor signaling pathways regulating expression of KLHL12 Gene:

KLHL12

SOURCE GeneReport for Unigene cluster for KLHL12 Gene:

Hs.706793

mRNA Expression by UniProt/SwissProt for KLHL12 Gene:

Q53G59-KLH12_HUMAN
Tissue specificity: Ubiquitously expressed. Highly expressed in testis and at lower levels in the submandibular salivary gland.

Evidence on tissue expression from TISSUES for KLHL12 Gene

  • Thyroid gland(4.2)
  • Nervous system(3.7)
genes like me logo Genes that share expression patterns with KLHL12: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for KLHL12 Gene

Orthologs for KLHL12 Gene

This gene was present in the common ancestor of chordates.

Orthologs for KLHL12 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia KLHL12 34 35
  • 99.47 (n)
oppossum
(Monodelphis domestica)
Mammalia KLHL12 35
  • 98 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia KLHL12 35
  • 95 (a)
OneToOne
dog
(Canis familiaris)
Mammalia KLHL12 34 35
  • 93.43 (n)
rat
(Rattus norvegicus)
Mammalia Klhl12 34
  • 91.43 (n)
mouse
(Mus musculus)
Mammalia Klhl12 34 16 35
  • 91 (n)
cow
(Bos Taurus)
Mammalia KLHL12 34 35
  • 88.15 (n)
chicken
(Gallus gallus)
Aves KLHL12 35
  • 84 (a)
OneToOne
LOC101748977 34
  • 77.76 (n)
lizard
(Anolis carolinensis)
Reptilia KLHL12 35
  • 96 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia klhl12 34
  • 77.45 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.32296 34
zebrafish
(Danio rerio)
Actinopterygii klhl12 34 35
  • 75.77 (n)
wufi60g03 34
Species where no ortholog for KLHL12 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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)
  • 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)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (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 KLHL12 Gene

ENSEMBL:
Gene Tree for KLHL12 (if available)
TreeFam:
Gene Tree for KLHL12 (if available)

Paralogs for KLHL12 Gene

Paralogs for KLHL12 Gene

Pseudogenes.org Pseudogenes for KLHL12 Gene

genes like me logo Genes that share paralogs with KLHL12: view

Variants for KLHL12 Gene

Sequence variations from dbSNP and Humsavar for KLHL12 Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type
rs1000031395 -- 202,898,320(+) AAGCA(C/T)CTAGG intron-variant
rs1000236243 -- 202,923,488(+) TGACT(A/G)AGCAT intron-variant
rs1000531286 -- 202,897,990(+) GTCTT(C/T)TTCTC intron-variant
rs1000681649 -- 202,924,627(+) AAAAA(A/G)GGAGA intron-variant
rs1000721342 -- 202,909,413(+) ATTTT(C/T)ACATA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for KLHL12 Gene

Variant ID Type Subtype PubMed ID
nsv832359 CNV loss 17160897
nsv946589 CNV duplication 23825009
nsv946590 CNV duplication 23825009

Variation tolerance for KLHL12 Gene

Residual Variation Intolerance Score: 11.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.23; 24.58% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for KLHL12 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
KLHL12

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for KLHL12 Gene

Disorders for KLHL12 Gene

MalaCards: The human disease database

(1) MalaCards diseases for KLHL12 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
primary biliary cirrhosis
  • biliary liver cirrhosis
- elite association - COSMIC cancer census association via MalaCards

Relevant External Links for KLHL12

Genetic Association Database (GAD)
KLHL12
Human Genome Epidemiology (HuGE) Navigator
KLHL12
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
KLHL12
genes like me logo Genes that share disorders with KLHL12: view

No data available for UniProtKB/Swiss-Prot and Genatlas for KLHL12 Gene

Publications for KLHL12 Gene

  1. The KLHL12-cullin-3 ubiquitin ligase negatively regulates the Wnt- beta-catenin pathway by targeting Dishevelled for degradation. (PMID: 16547521) Angers S. … Moon R.T. (Nat. Cell Biol. 2006) 2 3 4 64
  2. Regulation of the CUL3 ubiquitin ligase by a calcium-dependent co- adaptor. (PMID: 27716508) McGourty C.A. … Rape M. (Cell 2016) 3 4 64
  3. A regulator of secretory vesicle size, Kelch-like protein 12, facilitates the secretion of apolipoprotein B100 and very-low-density lipoproteins--brief report. (PMID: 24334870) Butkinaree C. … Fisher E.A. (Arterioscler. Thromb. Vasc. Biol. 2014) 2 3 64
  4. Structural basis for Cul3 assembly with the BTB-Kelch family of E3 ubiquitin ligases. (PMID: 23349464) Canning P. … Bullock A.N. (J. Biol. Chem. 2013) 3 4 64
  5. Ubiquitin-dependent regulation of COPII coat size and function. (PMID: 22358839) Jin L. … Rape M. (Nature 2012) 3 4 64

Products for KLHL12 Gene

Sources for KLHL12 Gene

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