The protein encoded by this gene is a ubiquitin ligase substrate receptor and is regulated by autoubiquitination. Variations in the translation initiation codon of this gene have been found, which result in an N-terminally truncated but more stable protein due to loss of the autoubiquitination function. The more stable mutant protein causes an increased ubiquitin and degradatio... See more...

Aliases for KLHL24 Gene

Aliases for KLHL24 Gene

  • Kelch Like Family Member 24 2 3 5
  • DRE1 2 3 4
  • Kelch-Like Protein 24 3 4
  • KRIP6 3 4
  • Kainate Receptor Interacting Protein For GluR6 3
  • Kainate Receptor-Interacting Protein For GluR6 4
  • Kelch-Like 24 (Drosophila) 2
  • Kelch-Like 24 3
  • Protein DRE1 4
  • FLJ20059 2
  • KLHL24 5
  • EBSSH 3

External Ids for KLHL24 Gene

Previous GeneCards Identifiers for KLHL24 Gene

  • GC03P184837
  • GC03P183353
  • GC03P180759

Summaries for KLHL24 Gene

Entrez Gene Summary for KLHL24 Gene

  • The protein encoded by this gene is a ubiquitin ligase substrate receptor and is regulated by autoubiquitination. Variations in the translation initiation codon of this gene have been found, which result in an N-terminally truncated but more stable protein due to loss of the autoubiquitination function. The more stable mutant protein causes an increased ubiquitin and degradation of keratin 14, which leads to skin fragility and the potentially life-threatening disease epidermolysis bullosa. The encoded protein is also involved in the regulation of kainate receptors. [provided by RefSeq, Mar 2017]

GeneCards Summary for KLHL24 Gene

KLHL24 (Kelch Like Family Member 24) is a Protein Coding gene. Diseases associated with KLHL24 include Epidermolysis Bullosa Simplex, Generalized, With Scarring And Hair Loss and Epidermolysis Bullosa Simplex, Generalized. An important paralog of this gene is KLHL6.

UniProtKB/Swiss-Prot Summary for KLHL24 Gene

  • Necessary to maintain the balance between intermediate filament stability and degradation, a process that is essential for skin integrity (PubMed:27889062). As part of the BCR(KLHL24) E3 ubiquitin ligase complex, mediates ubiquitination of KRT14 and controls its levels during keratinocytes differentiation (PubMed:27798626). Specifically reduces kainate receptor-mediated currents in hippocampal neurons, most probably by modulating channel properties (By similarity).

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for KLHL24 Gene

Genomics for KLHL24 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for KLHL24 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around KLHL24 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for KLHL24

Top Transcription factor binding sites by QIAGEN in the KLHL24 gene promoter:
  • AML1a
  • CBF(2)
  • ER-alpha
  • GATA-1
  • GATA-3
  • NF-1
  • POU2F1
  • POU2F1a
  • PPAR-gamma1
  • PPAR-gamma2

Genomic Locations for KLHL24 Gene

Genomic Locations for KLHL24 Gene
chr3:183,635,610-183,684,519
(GRCh38/hg38)
Size:
48,910 bases
Orientation:
Plus strand
chr3:183,353,356-183,402,307
(GRCh37/hg19)
Size:
48,952 bases
Orientation:
Plus strand

Genomic View for KLHL24 Gene

Genes around KLHL24 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
KLHL24 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for KLHL24 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for KLHL24 Gene

Proteins for KLHL24 Gene

  • Protein details for KLHL24 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q6TFL4-KLH24_HUMAN
    Recommended name:
    Kelch-like protein 24
    Protein Accession:
    Q6TFL4
    Secondary Accessions:
    • A5PLN8
    • Q9H620
    • Q9NXT9

    Protein attributes for KLHL24 Gene

    Size:
    600 amino acids
    Molecular mass:
    68361 Da
    Quaternary structure:
    • Forms homodimers. Interacts with GRIK2 (By similarity). Component of the BCR(KLHL24) E3 ubiquitin ligase complex, composed of CUL3, RBX1 and KLHL24. Interacts with CUL3. Interacts with KRT14 (PubMed:27798626).
    SequenceCaution:
    • Sequence=BAA90921.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=BAB15447.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};

    Alternative splice isoforms for KLHL24 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for KLHL24 Gene

Post-translational modifications for KLHL24 Gene

  • Autoubiquitinated. Autoubiquitination leads to proteasomal degradation and is necessary to control KLHL24 levels.
  • Ubiquitination at Lys181 and Lys441
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for KLHL24 Gene

Domains & Families for KLHL24 Gene

Gene Families for KLHL24 Gene

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

Protein Domains for KLHL24 Gene

InterPro:
Blocks:
  • BTB/POZ domain
  • BTB/Kelch-associated
ProtoNet:

Suggested Antigen Peptide Sequences for KLHL24 Gene

GenScript: Design optimal peptide antigens:
  • Protein DRE1 (KLH24_HUMAN)
genes like me logo Genes that share domains with KLHL24: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for KLHL24 Gene

Function for KLHL24 Gene

Molecular function for KLHL24 Gene

UniProtKB/Swiss-Prot Function:
Necessary to maintain the balance between intermediate filament stability and degradation, a process that is essential for skin integrity (PubMed:27889062). As part of the BCR(KLHL24) E3 ubiquitin ligase complex, mediates ubiquitination of KRT14 and controls its levels during keratinocytes differentiation (PubMed:27798626). Specifically reduces kainate receptor-mediated currents in hippocampal neurons, most probably by modulating channel properties (By similarity).

Phenotypes From GWAS Catalog for KLHL24 Gene

Gene Ontology (GO) - Molecular Function for KLHL24 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 27798626
genes like me logo Genes that share ontologies with KLHL24: view
genes like me logo Genes that share phenotypes with KLHL24: view

Human Phenotype Ontology for KLHL24 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KLHL24

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for KLHL24 Gene

Localization for KLHL24 Gene

Subcellular locations from UniProtKB/Swiss-Prot for KLHL24 Gene

Perikaryon. Cell projection, axon. Cytoplasm. Cell junction, desmosome. Cell junction, adherens junction.

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 KLHL24 gene
Compartment Confidence
nucleus 3
cytosol 3
plasma membrane 1
extracellular 1
cytoskeleton 1
endoplasmic reticulum 1

Gene Ontology (GO) - Cellular Components for KLHL24 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA,IDA 27889062
GO:0005912 adherens junction IEA,IDA 27889062
GO:0030054 cell junction IEA --
GO:0030057 desmosome IEA,IDA 27889062
GO:0030424 axon IEA --
genes like me logo Genes that share ontologies with KLHL24: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for KLHL24 Gene

Pathways & Interactions for KLHL24 Gene

PathCards logo

SuperPathways for KLHL24 Gene

No Data Available

Gene Ontology (GO) - Biological Process for KLHL24 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016567 protein ubiquitination IDA 27798626
GO:0045109 intermediate filament organization IMP 27889062
GO:0051865 protein autoubiquitination IMP 27798626
GO:2000312 regulation of kainate selective glutamate receptor activity IEA --
genes like me logo Genes that share ontologies with KLHL24: view

No data available for Pathways by source and SIGNOR curated interactions for KLHL24 Gene

Drugs & Compounds for KLHL24 Gene

No Compound Related Data Available

Transcripts for KLHL24 Gene

mRNA/cDNA for KLHL24 Gene

17 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
15 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KLHL24

Alternative Splicing Database (ASD) splice patterns (SP) for KLHL24 Gene

ExUns: 1a · 1b · 1c · 1d · 1e ^ 2a · 2b · 2c ^ 3 ^ 4 ^ 5 ^ 6a · 6b · 6c · 6d · 6e · 6f · 6g · 6h · 6i ^ 7 ^ 8a · 8b ^ 9 ^ 10 ^ 11
SP1: - - - - -
SP2: - - - - - - - - -
SP3: - - -
SP4: - - - - - -
SP5: - - - -
SP6: - - - -
SP7: - - - - - - -
SP8: - - - - -
SP9: - - - - - - - - - - - - - - -
SP10: -
SP11: - - - - - -
SP12: - - - - - - - -
SP13: - - - - - - -
SP14: -

Relevant External Links for KLHL24 Gene

GeneLoc Exon Structure for
KLHL24

Expression for KLHL24 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for KLHL24 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for KLHL24 Gene

This gene is overexpressed in Muscle - Skeletal (x4.1).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for KLHL24

SOURCE GeneReport for Unigene cluster for KLHL24 Gene:

Hs.407709

mRNA Expression by UniProt/SwissProt for KLHL24 Gene:

Q6TFL4-KLH24_HUMAN
Tissue specificity: Expressed in the skin (PubMed:27889062, PubMed:27798626). Found in keratinocytes, dermal fibroblasts, and melanocytes (PubMed:27889062). Basal-layer keratinocytes have lower KLHL24 expression than suprabasal keratinocytes (PubMed:27798626).

Evidence on tissue expression from TISSUES for KLHL24 Gene

  • Intestine(4.3)
  • Skin(3.7)
  • Nervous system(3)
  • Muscle(2.2)
  • Heart(2.1)
genes like me logo Genes that share expression patterns with KLHL24: view

No data available for Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for KLHL24 Gene

Orthologs for KLHL24 Gene

This gene was present in the common ancestor of chordates.

Orthologs for KLHL24 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia KLHL24 30 31
  • 99.72 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia KLHL24 31
  • 97 (a)
OneToOne
Dog
(Canis familiaris)
Mammalia KLHL24 30 31
  • 95.44 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia KLHL24 30 31
  • 95.28 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia KLHL24 31
  • 94 (a)
OneToOne
Mouse
(Mus musculus)
Mammalia Klhl24 30 17 31
  • 91.94 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Klhl24 30
  • 91.22 (n)
Chicken
(Gallus gallus)
Aves KLHL24 31
  • 97 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia KLHL24 31
  • 95 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia klhl24 30
  • 78.78 (n)
Zebrafish
(Danio rerio)
Actinopterygii klhl24b 31
  • 85 (a)
OneToMany
klhl24a 30 31
  • 70.07 (n)
OneToMany
zgc63606 30
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 51 (a)
OneToMany
Species where no ortholog for KLHL24 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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 Vase (Ciona intestinalis)
  • 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 KLHL24 Gene

ENSEMBL:
Gene Tree for KLHL24 (if available)
TreeFam:
Gene Tree for KLHL24 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for KLHL24: view image

Paralogs for KLHL24 Gene

(34) SIMAP similar genes for KLHL24 Gene using alignment to 9 proteins:

  • KLH24_HUMAN
  • C9J0A6_HUMAN
  • C9J2N4_HUMAN
  • C9J3M5_HUMAN
  • C9JCK3_HUMAN
  • C9JMQ9_HUMAN
  • C9JN72_HUMAN
  • C9JQ67_HUMAN
  • C9JXR5_HUMAN
genes like me logo Genes that share paralogs with KLHL24: view

Variants for KLHL24 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for KLHL24 Gene

SNP ID Clinical significance and condition Chr 03 pos Variation AA Info Type
rs1057515580 Pathogenic: Epidermolysis bullosa simplex, Koebner type; Epidermolysis bullosa simplex, generalized, with scarring and hair loss 183,650,358(+) T/C INITIATIOR_CODON_VARIANT,MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT,FIVE_PRIME_UTR_VARIANT
rs779398932 Uncertain Significance: not provided 183,650,798(+) A/G MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT,FIVE_PRIME_UTR_VARIANT
rs886037956 Pathogenic: Epidermolysis bullosa simplex, Koebner type; Epidermolysis bullosa simplex, generalized, with scarring and hair loss; not provided. Pathogenic: not provided 183,650,357(+) A/GA/T INITIATIOR_CODON_VARIANT,MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT,FIVE_PRIME_UTR_VARIANT
rs886037957 Pathogenic: Epidermolysis bullosa simplex, Koebner type; Epidermolysis bullosa simplex, generalized, with scarring and hair loss. Pathogenic: Epidermolysis bullosa simplex, Koebner type; Epidermolysis bullosa simplex, generalized, with scarring and hair loss 183,650,359(+) G/AG/T INITIATIOR_CODON_VARIANT,MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT,FIVE_PRIME_UTR_VARIANT

Additional dbSNP identifiers (rs#s) for KLHL24 Gene

Structural Variations from Database of Genomic Variants (DGV) for KLHL24 Gene

Variant ID Type Subtype PubMed ID
esv1329997 CNV insertion 17803354
esv2660932 CNV deletion 23128226
esv27076 CNV loss 19812545
esv3598924 CNV gain 21293372
esv3598930 CNV loss 21293372
nsv1116017 CNV insertion 24896259
nsv1136787 CNV deletion 24896259

Variation tolerance for KLHL24 Gene

Residual Variation Intolerance Score: 13.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.38; 71.01% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for KLHL24 Gene

Human Gene Mutation Database (HGMD)
KLHL24
SNPedia medical, phenotypic, and genealogical associations of SNPs for
KLHL24

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for KLHL24 Gene

Disorders for KLHL24 Gene

MalaCards: The human disease database

(10) MalaCards diseases for KLHL24 Gene - From: OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

KLH24_HUMAN
  • Epidermolysis bullosa simplex, generalized, with scarring and hair loss (EBSSH) [MIM:617294]: A form of epidermolysis bullosa, a group of mechano-bullous disorders characterized by structural skin fragility, recurrent blister formation and erosion of the skin and mucous membranes occurring spontaneously or after mild trauma. Epidermolysis bullosa simplex is characterized by intraepidermal tissue separation that occurs within the basal keratinocytes at the bottom layer of epidermis. EBSSH is an autosomal dominant epidermolysis bullosa simplex, presenting at birth with extensive skin defects on the extremities, leaving behind hypopigmentation and atrophy with a whirled pattern. Cutaneous fragility and generalized blistering persist during childhood and decrease in adulthood. Adult patients have dyspigmentation and atrophy of the skin, scars, follicular atrophoderma, sparse body hair, progressive diffuse alopecia of the scalp, diffuse palmoplantar keratoderma, and nail changes. {ECO:0000269 PubMed:27798626, ECO:0000269 PubMed:27889062}. Note=The disease is caused by mutations affecting the gene represented in this entry. Gain-of-function mutations that lead to excessive ubiquitination and degradation of KRT14 result in compromised mechanical integrity of basal keratinocytes. Under this pathological condition, trivial mechanical stress can induce blister formation at the basal layer of skin. {ECO:0000269 PubMed:27798626}.
genes like me logo Genes that share disorders with KLHL24: view

No data available for Genatlas for KLHL24 Gene

Publications for KLHL24 Gene

  1. Stabilizing mutations of KLHL24 ubiquitin ligase cause loss of keratin 14 and human skin fragility. (PMID: 27798626) Lin Z … Tan X (Nature genetics 2016) 3 4
  2. Monoallelic Mutations in the Translation Initiation Codon of KLHL24 Cause Skin Fragility. (PMID: 27889062) He Y … Has C (American journal of human genetics 2016) 3 4
  3. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4
  4. A reference map of the human binary protein interactome. (PMID: 32296183) Luck K … Calderwood MA (Nature 2020) 3
  5. Cardiomyopathy with lethal arrhythmias associated with inactivation of KLHL24. (PMID: 30715372) Hedberg-Oldfors C … Jamshidi Y (Human molecular genetics 2019) 3

Products for KLHL24 Gene

Sources for KLHL24 Gene