This gene encodes a member of the lysyl oxidase gene family. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyses the first step in the formation of crosslinks in collagens and elastin. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient ... See more...

Aliases for LOXL4 Gene

Aliases for LOXL4 Gene

  • Lysyl Oxidase Like 4 2 3 5
  • Lysyl Oxidase-Related Protein C 3 4
  • Lysyl Oxidase-Like Protein 4 3 4
  • Lysyl Oxidase Homolog 4 3 4
  • LOXC 3 4
  • Lysyl Oxidase-Like 4 Pseudogene 3
  • Lysyl Oxidase Related C 3
  • Lysyl Oxidase-Like 4 2
  • EC 1.4.3.- 4
  • EC 1.4.3 52

External Ids for LOXL4 Gene

Previous GeneCards Identifiers for LOXL4 Gene

  • GC10M098900
  • GC10M099241
  • GC10M100138
  • GC10M099672
  • GC10M099997
  • GC10M093632

Summaries for LOXL4 Gene

Entrez Gene Summary for LOXL4 Gene

  • This gene encodes a member of the lysyl oxidase gene family. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyses the first step in the formation of crosslinks in collagens and elastin. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family. [provided by RefSeq, Jul 2008]

GeneCards Summary for LOXL4 Gene

LOXL4 (Lysyl Oxidase Like 4) is a Protein Coding gene. Diseases associated with LOXL4 include Pelvic Organ Prolapse and Retinal Microaneurysm. Among its related pathways are Simplified Interaction Map Between LOXL4 and Oxidative Stress Pathway and Degradation of the extracellular matrix. Gene Ontology (GO) annotations related to this gene include copper ion binding and oxidoreductase activity, acting on the CH-NH2 group of donors, oxygen as acceptor. An important paralog of this gene is LOXL3.

UniProtKB/Swiss-Prot Summary for LOXL4 Gene

Gene Wiki entry for LOXL4 Gene

Additional gene information for LOXL4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for LOXL4 Gene

Genomics for LOXL4 Gene

GeneHancer (GH) Regulatory Elements for LOXL4 Gene

Promoters and enhancers for LOXL4 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
GH10J098267 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 523.1 -0.6 -647 3.4 EP300 FOXK2 POLR2G NCOR1 JUND ZIC2 KDM6A TCF7 FOXA1 ZBTB25 LOXL4 lnc-R3HCC1L-2 ENSG00000230928 HSALNG0080006
GH10J098266 Promoter 0.7 Ensembl 500.7 +1.5 1549 0.6 POLR2A ZFHX2 PKNOX1 ZNF189 ZMYM3 GLIS1 ZFP3 EGR2 ESR1 LOXL4 lnc-R3HCC1L-2 ENSG00000230928
GH10J097421 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 31.5 +842.7 842667 7.2 ZBTB40 ZNF217 CTCF ZSCAN5C NRF1 MYC POLR2G SP1 RBAK PHF8 PGAM1 LOC644215 RRP12 EXOSC1 MMS19 NPM1P26 R3HCC1L RPL13AP5 LCOR TM9SF3
GH10J098132 Promoter/Enhancer 1.7 Ensembl ENCODE CraniofacialAtlas 29 +133.6 133613 3.5 EP300 ZBTB40 ZNF217 SIN3A NRF1 TCF12 USF1 POLR2G SP1 RBAK R3HCC1L LOXL4 HPS1 EXOSC1 MMS19 MARVELD1 HSALNG0079995
GH10J097326 Promoter/Enhancer 1.9 Ensembl ENCODE CraniofacialAtlas dbSUPER 21.1 +935.5 935540 11.9 EP300 FOXK2 ZNF217 ZSCAN5C SIN3A TCF12 NRF1 MYC POLR2G SP1 ENSG00000225850 EXOSC1 R3HCC1L NPM1P26 MARVELD1 LOXL4 RPL13AP5 TM9SF3 SLIT1 ARHGAP19
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around LOXL4 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for LOXL4

Top Transcription factor binding sites by QIAGEN in the LOXL4 gene promoter:
  • Evi-1
  • GR
  • GR-alpha
  • ITF-2
  • NF-AT
  • NF-AT1
  • NF-kappaB
  • RelA
  • STAT3
  • Tal-1beta

Genomic Locations for LOXL4 Gene

Genomic Locations for LOXL4 Gene
chr10:98,247,686-98,268,250
(GRCh38/hg38)
Size:
20,565 bases
Orientation:
Minus strand
chr10:100,007,443-100,028,007
(GRCh37/hg19)
Size:
20,565 bases
Orientation:
Minus strand

Genomic View for LOXL4 Gene

Genes around LOXL4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
LOXL4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for LOXL4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for LOXL4 Gene

Proteins for LOXL4 Gene

  • Protein details for LOXL4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96JB6-LOXL4_HUMAN
    Recommended name:
    Lysyl oxidase homolog 4
    Protein Accession:
    Q96JB6
    Secondary Accessions:
    • Q5W0B3
    • Q96DY1
    • Q96PC0
    • Q9H6T5

    Protein attributes for LOXL4 Gene

    Size:
    756 amino acids
    Molecular mass:
    84483 Da
    Cofactor:
    Name=Cu cation; Xref=ChEBI:CHEBI:23378;
    Cofactor:
    Name=lysine tyrosylquinone residue; Xref=ChEBI:CHEBI:20489;
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=AAH07522.1; Type=Erroneous initiation; Evidence={ECO:0000305};

neXtProt entry for LOXL4 Gene

Selected DME Specific Peptides for LOXL4 Gene

Q96JB6:
  • GEGRVEVL
  • YRHDIDCQWVDITDV
  • IHLSEVRC
  • ESDFSNN
  • RRLLRFS
  • GEGPIWLDN
  • CHRHYHS
  • EVFTHYDLL

Post-translational modifications for LOXL4 Gene

  • The lysine tyrosylquinone cross-link (LTQ) is generated by condensation of the epsilon-amino group of a lysine with a topaquinone produced by oxidation of tyrosine.
  • Glycosylation at Asn198 and Asn629
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • LOXL4_HUMAN (1482)

Other Protein References for LOXL4 Gene

Domains & Families for LOXL4 Gene

Gene Families for LOXL4 Gene

Protein Domains for LOXL4 Gene

Blocks:
  • Speract/scavenger receptor
  • Lysyl oxidase
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for LOXL4 Gene

GenScript: Design optimal peptide antigens:
  • Lysyl oxidase-related protein C (LOXL4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q96JB6

UniProtKB/Swiss-Prot:

LOXL4_HUMAN :
  • Belongs to the lysyl oxidase family.
Family:
  • Belongs to the lysyl oxidase family.
genes like me logo Genes that share domains with LOXL4: view

Function for LOXL4 Gene

Molecular function for LOXL4 Gene

UniProtKB/Swiss-Prot Function:
May modulate the formation of a collagenous extracellular matrix.

Enzyme Numbers (IUBMB) for LOXL4 Gene

Phenotypes From GWAS Catalog for LOXL4 Gene

Gene Ontology (GO) - Molecular Function for LOXL4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004720 protein-lysine 6-oxidase activity IBA 21873635
GO:0005044 scavenger receptor activity IEA --
GO:0005507 copper ion binding IEA --
GO:0005515 protein binding IPI 16189514
GO:0016491 oxidoreductase activity IEA --
genes like me logo Genes that share ontologies with LOXL4: view
genes like me logo Genes that share phenotypes with LOXL4: view

Animal Model Products

  • Taconic Biosciences Mouse Models for LOXL4

CRISPR Products

miRNA for LOXL4 Gene

miRTarBase miRNAs that target LOXL4

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LOXL4

Clone Products

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for LOXL4 Gene

Localization for LOXL4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for LOXL4 Gene

Secreted, extracellular space.

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 LOXL4 gene
Compartment Confidence
extracellular 4
plasma membrane 2
cytoskeleton 1
mitochondrion 1
nucleus 1
endoplasmic reticulum 1
cytosol 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for LOXL4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IBA 21873635
GO:0016020 membrane IEA --
GO:0043235 receptor complex IDA 23382219
GO:0070062 extracellular exosome HDA 19199708
genes like me logo Genes that share ontologies with LOXL4: view

Pathways & Interactions for LOXL4 Gene

genes like me logo Genes that share pathways with LOXL4: view

Gene Ontology (GO) - Biological Process for LOXL4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006897 endocytosis IEA --
GO:0018057 peptidyl-lysine oxidation IBA 21873635
GO:0030199 collagen fibril organization IBA 21873635
GO:0055114 oxidation-reduction process IEA --
genes like me logo Genes that share ontologies with LOXL4: view

No data available for SIGNOR curated interactions for LOXL4 Gene

Drugs & Compounds for LOXL4 Gene

(2) Drugs for LOXL4 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Copper Approved, Investigational Pharma 236

(1) Additional Compounds for LOXL4 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with LOXL4: view

Transcripts for LOXL4 Gene

mRNA/cDNA for LOXL4 Gene

1 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
1 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 LOXL4

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for LOXL4 Gene

ExUns: 1 ^ 2a · 2b · 2c ^ 3 ^ 4a · 4b ^ 5a · 5b ^ 6 ^ 7 ^ 8 ^ 9a · 9b · 9c ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18
SP1: -
SP2: - - - -
SP3:
SP4: - - - -
SP5: -

Relevant External Links for LOXL4 Gene

GeneLoc Exon Structure for
LOXL4

Expression for LOXL4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for LOXL4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for LOXL4 Gene

This gene is overexpressed in Islet of Langerhans (36.2) and Bone marrow mesenchymal stem cell (18.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for LOXL4 Gene



Protein tissue co-expression partners for LOXL4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for LOXL4

SOURCE GeneReport for Unigene cluster for LOXL4 Gene:

Hs.306814

mRNA Expression by UniProt/SwissProt for LOXL4 Gene:

Q96JB6-LOXL4_HUMAN
Tissue specificity: Expressed in many tissues, the highest levels among the tissues studied being in the skeletal muscle, testis and pancreas. Expressed in cartilage.

Evidence on tissue expression from TISSUES for LOXL4 Gene

  • Eye(4.2)
  • Lung(2.4)
  • Skin(2.4)
genes like me logo Genes that share expression patterns with LOXL4: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for LOXL4 Gene

Orthologs for LOXL4 Gene

This gene was present in the common ancestor of animals.

Orthologs for LOXL4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia LOXL4 31 30
  • 99.69 (n)
OneToOne
dog
(Canis familiaris)
Mammalia LOXL4 31 30
  • 88.83 (n)
OneToOne
cow
(Bos Taurus)
Mammalia LOXL4 31 30
  • 88.53 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Loxl4 30
  • 85.54 (n)
mouse
(Mus musculus)
Mammalia Loxl4 17 31 30
  • 85.36 (n)
oppossum
(Monodelphis domestica)
Mammalia LOXL4 31
  • 80 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia LOXL4 31
  • 63 (a)
OneToOne
chicken
(Gallus gallus)
Aves LOXL4 31 30
  • 71.99 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia LOXL4 31
  • 66 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia loxl4 30
  • 65.42 (n)
zebrafish
(Danio rerio)
Actinopterygii loxl4 31 30
  • 62.54 (n)
OneToMany
LOXL4 (2 of 2) 31
  • 59 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta lox 32
  • 42 (a)
lox2 32
  • 40 (a)
Species where no ortholog for LOXL4 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)
  • 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 LOXL4 Gene

ENSEMBL:
Gene Tree for LOXL4 (if available)
TreeFam:
Gene Tree for LOXL4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for LOXL4: view image

Paralogs for LOXL4 Gene

(2) SIMAP similar genes for LOXL4 Gene using alignment to 1 proteins:

  • LOXL4_HUMAN

Pseudogenes.org Pseudogenes for LOXL4 Gene

genes like me logo Genes that share paralogs with LOXL4: view

Variants for LOXL4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for LOXL4 Gene

SNP ID Clinical significance and condition Chr 10 pos Variation AA Info Type
rs11189525 - p.Pro372Thr
rs1983864 - p.Asp405Ala
rs33995374 - p.Arg154Gln

Additional dbSNP identifiers (rs#s) for LOXL4 Gene

Structural Variations from Database of Genomic Variants (DGV) for LOXL4 Gene

Variant ID Type Subtype PubMed ID
esv2676146 CNV deletion 23128226
esv2739962 CNV deletion 23290073
esv3261051 CNV deletion 24192839
esv3546734 CNV deletion 23714750
esv3624332 CNV loss 21293372
nsv1069959 CNV deletion 25765185
nsv1152838 CNV deletion 26484159
nsv831954 CNV loss 17160897

Variation tolerance for LOXL4 Gene

Residual Variation Intolerance Score: 94.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 13.15; 95.15% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for LOXL4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
LOXL4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for LOXL4 Gene

Disorders for LOXL4 Gene

MalaCards: The human disease database

(5) MalaCards diseases for LOXL4 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
pelvic organ prolapse
  • pelvic organ prolapse, susceptibility to
retinal microaneurysm
  • microaneurysm
squamous cell carcinoma, head and neck
  • hnscc
urofacial syndrome 1
  • ufs1
scoliosis
- elite association - COSMIC cancer census association via MalaCards
Search LOXL4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for LOXL4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with LOXL4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for LOXL4 Gene

Publications for LOXL4 Gene

  1. Systematic screening of lysyl oxidase-like (LOXL) family genes demonstrates that LOXL2 is a susceptibility gene to intracranial aneurysms. (PMID: 17287949) Akagawa H … Inoue I (Human genetics 2007) 3 23 41 54
  2. Molecular cloning and biological activity of a novel lysyl oxidase-related gene expressed in cartilage. (PMID: 11292829) Ito H … Nakamura T (The Journal of biological chemistry 2001) 2 3 4 54
  3. A novel human lysyl oxidase-like gene (LOXL4) on chromosome 10q24 has an altered scavenger receptor cysteine rich domain. (PMID: 11691588) Asuncion L … Csiszar K (Matrix biology : journal of the International Society for Matrix Biology 2001) 3 4 23 54
  4. Cloning and characterization of a fifth human lysyl oxidase isoenzyme: the third member of the lysyl oxidase-related subfamily with four scavenger receptor cysteine-rich domains. (PMID: 11691589) Mäki JM … Kivirikko KI (Matrix biology : journal of the International Society for Matrix Biology 2001) 3 4 23 54
  5. Lysyl oxidase-like 4 is alternatively spliced in an anatomic site-specific manner in tumors involving the serosal cavities. (PMID: 19015874) Sebban S … Reich R (Virchows Archiv : an international journal of pathology 2009) 3 23 54

Products for LOXL4 Gene

Sources for LOXL4 Gene