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Aliases for KLHL40 Gene

Aliases for KLHL40 Gene

  • Kelch Like Family Member 40 2 3 5
  • Sarcosynapsin 2 3 4
  • Kelch Repeat And BTB Domain-Containing Protein 5 3 4
  • Kelch Repeat And BTB (POZ) Domain Containing 5 2 3
  • Nemaline Myopathy Type 8 2 3
  • KBTBD5 3 4
  • SRYP 3 4
  • Kelch-Like 40 (Drosophila) 2
  • Kelch-Like Protein 40 3
  • NEM8 3
  • SYRP 3

External Ids for KLHL40 Gene

Previous HGNC Symbols for KLHL40 Gene

  • KBTBD5

Previous GeneCards Identifiers for KLHL40 Gene

  • GC03P042727

Summaries for KLHL40 Gene

Entrez Gene Summary for KLHL40 Gene

  • This gene encodes a protein containing a BACK domain, a BTB/POZ domain, and 5 Kelch repeats, however, its exact function is not known. The gene and the multi-domain protein structure are conserved across different taxa, including primates, rodents, chicken and zebrafish. [provided by RefSeq, Dec 2012]

GeneCards Summary for KLHL40 Gene

KLHL40 (Kelch Like Family Member 40) is a Protein Coding gene. Diseases associated with KLHL40 include Nemaline Myopathy 8 and Severe Congenital Nemaline Myopathy. An important paralog of this gene is KLHL41.

UniProtKB/Swiss-Prot for KLHL40 Gene

  • Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a key regulator of skeletal muscle development (PubMed:23746549). The BCR(KLHL40) complex acts by mediating ubiquitination and degradation of TFDP1, thereby regulating the activity of the E2F:DP transcription factor complex (By similarity). Promotes stabilization of LMOD3 by acting as a negative regulator of LMOD3 ubiquitination; the molecular process by which it negatively regulates ubiquitination of LMOD3 is however unclear (By similarity).

Additional gene information for KLHL40 Gene

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for KLHL40 Gene

Genomics for KLHL40 Gene

GeneHancer (GH) Regulatory Elements for KLHL40 Gene

Promoters and enhancers for KLHL40 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
GH03J042682 Promoter/Enhancer 2 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 650.7 -0.4 -380 5 ATF1 FOXA2 ARNT INSM2 ETS1 EGR1 FOS CREM SMARCA5 ZNF362 KLHL40 SEC22C HHATL LYZL4 NKTR CCDC13 CCK KRBOX1 RN7SL567P
GH03J042695 Enhancer 0.5 FANTOM5 dbSUPER 1.9 +10.0 10048 0.6 HHATL CCDC13-AS1 CCDC13 FAM198A ZNF662 KLHL40 HHATL-AS1
GH03J042700 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE dbSUPER 0.4 +16.7 16692 2.5 ARID4B SIN3A ZNF48 SLC30A9 ZNF143 NFKBIZ ZNF202 MXD4 MIER2 REST HHATL HHATL-AS1 NKTR ZNF662 SNRK-AS1 KLHL40 CCDC13
GH03J042689 Enhancer 0.4 dbSUPER 0.4 +6.8 6762 4.7 PKNOX1 MCM2 CCDC13 CCDC13-AS1 HHATL NKTR HIGD1A KLHL40 HHATL-AS1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around KLHL40 on UCSC Golden Path with GeneCards custom track

Genomic Locations for KLHL40 Gene

Genomic Locations for KLHL40 Gene
chr3:42,685,519-42,692,544
(GRCh38/hg38)
Size:
7,026 bases
Orientation:
Plus strand
chr3:42,727,011-42,734,036
(GRCh37/hg19)
Size:
7,026 bases
Orientation:
Plus strand

Genomic View for KLHL40 Gene

Genes around KLHL40 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
KLHL40 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for KLHL40 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for KLHL40 Gene

Proteins for KLHL40 Gene

  • Protein details for KLHL40 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q2TBA0-KLH40_HUMAN
    Recommended name:
    Kelch-like protein 40
    Protein Accession:
    Q2TBA0
    Secondary Accessions:
    • Q86SI1
    • Q96MR2

    Protein attributes for KLHL40 Gene

    Size:
    621 amino acids
    Molecular mass:
    69257 Da
    Quaternary structure:
    • Component of the BCR(KLHL40) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL40 and RBX1. Interacts with LMOD3.

    Three dimensional structures from OCA and Proteopedia for KLHL40 Gene

    Alternative splice isoforms for KLHL40 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for KLHL40 Gene

Post-translational modifications for KLHL40 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for KLHL40 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for KLHL40 Gene

Domains & Families for KLHL40 Gene

Gene Families for KLHL40 Gene

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

Suggested Antigen Peptide Sequences for KLHL40 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q2TBA0

UniProtKB/Swiss-Prot:

KLH40_HUMAN :
  • Belongs to the KLHL40 family.
Family:
  • Belongs to the KLHL40 family.
genes like me logo Genes that share domains with KLHL40: view

Function for KLHL40 Gene

Molecular function for KLHL40 Gene

UniProtKB/Swiss-Prot Function:
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a key regulator of skeletal muscle development (PubMed:23746549). The BCR(KLHL40) complex acts by mediating ubiquitination and degradation of TFDP1, thereby regulating the activity of the E2F:DP transcription factor complex (By similarity). Promotes stabilization of LMOD3 by acting as a negative regulator of LMOD3 ubiquitination; the molecular process by which it negatively regulates ubiquitination of LMOD3 is however unclear (By similarity).

Phenotypes From GWAS Catalog for KLHL40 Gene

Gene Ontology (GO) - Molecular Function for KLHL40 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004842 contributes_to ubiquitin-protein transferase activity IBA --
GO:0005515 protein binding IEA --
genes like me logo Genes that share ontologies with KLHL40: view
genes like me logo Genes that share phenotypes with KLHL40: view

Human Phenotype Ontology for KLHL40 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for KLHL40 Gene

MGI Knock Outs for KLHL40:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KLHL40

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for KLHL40 Gene

Localization for KLHL40 Gene

Subcellular locations from UniProtKB/Swiss-Prot for KLHL40 Gene

Cytoplasm. Cytoplasm, myofibril, sarcomere, A band. Cytoplasm, myofibril, sarcomere, I band.

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 KLHL40 gene
Compartment Confidence
cytosol 3
nucleus 2
mitochondrion 1

Gene Ontology (GO) - Cellular Components for KLHL40 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm ISS --
GO:0031463 Cul3-RING ubiquitin ligase complex ISS --
GO:0031672 A band IBA --
GO:0031674 I band IBA --
genes like me logo Genes that share ontologies with KLHL40: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for KLHL40 Gene

Pathways & Interactions for KLHL40 Gene

SuperPathways for KLHL40 Gene

No Data Available

Gene Ontology (GO) - Biological Process for KLHL40 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007275 multicellular organism development IEA --
GO:0016567 protein ubiquitination IEA --
GO:0031397 negative regulation of protein ubiquitination IBA --
GO:0031398 positive regulation of protein ubiquitination ISS --
GO:0032435 negative regulation of proteasomal ubiquitin-dependent protein catabolic process IBA --
genes like me logo Genes that share ontologies with KLHL40: view

No data available for Pathways by source and SIGNOR curated interactions for KLHL40 Gene

Drugs & Compounds for KLHL40 Gene

No Compound Related Data Available

Transcripts for KLHL40 Gene

mRNA/cDNA for KLHL40 Gene

(1) REFSEQ mRNAs :
(6) Additional mRNA sequences :
(14) Selected AceView cDNA sequences:
(1) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for KLHL40 Gene

Kelch-like family member 40:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for KLHL40

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for KLHL40 Gene

No ASD Table

Relevant External Links for KLHL40 Gene

GeneLoc Exon Structure for
KLHL40
ECgene alternative splicing isoforms for
KLHL40

Expression for KLHL40 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for KLHL40 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for KLHL40 Gene

This gene is overexpressed in Muscle - Skeletal (x50.6).

Protein differential expression in normal tissues from HIPED for KLHL40 Gene

This gene is overexpressed in Esophagus (54.2) and Neutrophil (8.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for KLHL40 Gene



Protein tissue co-expression partners for KLHL40 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of KLHL40 Gene:

KLHL40

SOURCE GeneReport for Unigene cluster for KLHL40 Gene:

Hs.350288

mRNA Expression by UniProt/SwissProt for KLHL40 Gene:

Q2TBA0-KLH40_HUMAN
Tissue specificity: Highly expressed in fetal (19, 23 and 31 weeks of gestation) and adult skeletal muscle; expression levels tend to be higher in fetal compared to postnatal muscles (at protein level). Also expressed in fetal and adult heart.

Evidence on tissue expression from TISSUES for KLHL40 Gene

  • Heart(4.1)
  • Muscle(3.3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for KLHL40 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • digestive
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • cranial nerve
  • face
  • head
  • mouth
  • pharynx
Thorax:
  • chest wall
  • esophagus
  • lung
Abdomen:
  • stomach
Limb:
  • ankle
  • digit
  • elbow
  • finger
  • foot
  • hand
  • hip
  • knee
  • lower limb
  • shoulder
  • toe
  • upper limb
  • wrist
General:
  • peripheral nervous system
genes like me logo Genes that share expression patterns with KLHL40: view

Orthologs for KLHL40 Gene

This gene was present in the common ancestor of chordates.

Orthologs for KLHL40 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia KLHL40 34
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia KBTBD5 34 33
  • 89.57 (n)
OneToOne
dog
(Canis familiaris)
Mammalia KLHL40 34 33
  • 89.1 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Klhl40 16 34 33
  • 86.75 (n)
rat
(Rattus norvegicus)
Mammalia Klhl40 33
  • 86.06 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia KLHL40 34
  • 83 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia KLHL40 34
  • 77 (a)
OneToOne
chicken
(Gallus gallus)
Aves KLHL40 34
  • 71 (a)
OneToOne
KBTBD5 33
  • 70.77 (n)
lizard
(Anolis carolinensis)
Reptilia -- 34
  • 69 (a)
OneToMany
-- 34
  • 65 (a)
OneToMany
-- 34
  • 63 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia klhl40 33
  • 66.72 (n)
zebrafish
(Danio rerio)
Actinopterygii klhl40a 34 33
  • 61.89 (n)
OneToMany
klhl40b 34
  • 57 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 22 (a)
OneToMany
Species where no ortholog for KLHL40 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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 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 KLHL40 Gene

ENSEMBL:
Gene Tree for KLHL40 (if available)
TreeFam:
Gene Tree for KLHL40 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for KLHL40: view image

Paralogs for KLHL40 Gene

(3) SIMAP similar genes for KLHL40 Gene using alignment to 1 proteins:

  • KLH40_HUMAN
genes like me logo Genes that share paralogs with KLHL40: view

Variants for KLHL40 Gene

Sequence variations from dbSNP and Humsavar for KLHL40 Gene

SNP ID Clin Chr 03 pos Variation AA Info Type
rs123509 uncertain-significance, benign, not specified 42,691,976(+) T/C coding_sequence_variant, missense_variant
rs138075372 likely-benign, Nemaline myopathy 8 42,685,715(+) C/T coding_sequence_variant, missense_variant
rs138791086 uncertain-significance, Nemaline myopathy 8 42,688,262(+) G/A coding_sequence_variant, missense_variant
rs138852341 likely-benign, benign, not specified, Nemaline myopathy 8 42,686,065(+) C/A/T coding_sequence_variant, synonymous_variant
rs140389534 uncertain-significance, not specified, Nemaline myopathy 8 42,688,651(+) T/C coding_sequence_variant, missense_variant

Structural Variations from Database of Genomic Variants (DGV) for KLHL40 Gene

Variant ID Type Subtype PubMed ID
nsv954472 CNV deletion 24416366

Variation tolerance for KLHL40 Gene

Residual Variation Intolerance Score: 69.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.44; 54.69% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for KLHL40 Gene

Human Gene Mutation Database (HGMD)
KLHL40
SNPedia medical, phenotypic, and genealogical associations of SNPs for
KLHL40

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for KLHL40 Gene

Disorders for KLHL40 Gene

MalaCards: The human disease database

(7) MalaCards diseases for KLHL40 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
nemaline myopathy 8
  • nem8
severe congenital nemaline myopathy
  • severe congenital nm
nemaline myopathy
  • nm
locked-in syndrome
  • locked in syndrome
myopathy
  • muscular diseases
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

KLH40_HUMAN
  • Nemaline myopathy 8 (NEM8) [MIM:615348]: A severe form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. NEM8 is characterized by fetal akinesia or hypokinesia, followed by contractures, fractures, respiratory failure, and swallowing difficulties apparent at birth. Most patients die in infancy. Skeletal muscle biopsy shows numerous small nemaline bodies, often with no normal myofibrils. {ECO:0000269 PubMed:23746549, ECO:0000269 PubMed:26754003, ECO:0000269 PubMed:27528495, ECO:0000269 PubMed:27762439}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for KLHL40

genes like me logo Genes that share disorders with KLHL40: view

No data available for Genatlas for KLHL40 Gene

Publications for KLHL40 Gene

  1. Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy. (PMID: 23746549) Ravenscroft G … Laing NG (American journal of human genetics 2013) 2 3 4 58
  2. Identification of KLHL40 mutations by targeted next-generation sequencing facilitated a prenatal diagnosis in a family with three consecutive affected fetuses with fetal akinesia deformation sequence. (PMID: 27762439) Chen TH … Jong YJ (Prenatal diagnosis 2016) 3 4 58
  3. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4 58
  4. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4 58
  5. Architecture of the human interactome defines protein communities and disease networks. (PMID: 28514442) Huttlin EL … Harper JW (Nature 2017) 3 58

Products for KLHL40 Gene

Sources for KLHL40 Gene

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