LOXL1
protein-codinglysyl oxidase like 1
Gene summary
This gene encodes a member of the lysyl oxidase family of proteins. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyzes the first step in the formation of crosslinks in collagen and elastin. The encoded preproprotein is proteolytically processed to generate the mature enzyme. 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. Mutations in this gene are associated with exfoliation syndrome. [provided by RefSeq, Jan 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~26.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LOXL1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005576.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 2 | 2 | 5 | ||
| missense | 77 | 2 | 3 | 82 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 79 | 4 | 5 | 88 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005567.2 | 7 | MANE Select | |
| Ensembl | ENSP00000261921.7 | 7 | MANE Select | |
| Ensembl | ENSP00000457827.1 | 3 | Standard | |
| Ensembl | ENSP00000526690.1 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| loxl1 | Danio rerio | Structure: somite Quality: morphology abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Canonical and Non-Canonical TGF-B signaling
- Crosslinking of collagen fibrils
- Assembly of collagen fibrils and other multimeric structures
- Collagen formation
- Extracellular matrix organization
Biological Process
- peptidyl-lysine oxidation
- protein deamination
- response to lipopolysaccharide
- aorta development
- oxidation-reduction process
Molecular Function
- protein-lysine 6-oxidase activity
- copper ion binding
Cellular Component
- acrosomal vesicle
- extracellular region
- basement membrane
- extracellular space
- collagen-containing extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261921
- Coding exons
- 7
- Length
- 26149
- Individuals with no LoFs
- 125715
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125720
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.13 | 217 | 269 | 0.807 | 0.0000148 | 3603 |
| Missense (PolyPhen) | 103 | 145.82 | 0.70633 | 1748 | ||
| Synonymous | 1.93 | 92 | 119 | 0.775 | 0.00000685 | 1196 |
| Loss of Function | 3.56 | 3 | 20.3 | 0.148 | 8.77e-7 | 260 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000030 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000055 | 0.000046 | rare |
| European (Non-Finnish) | 0.000019 | 0.000018 | rare |
| South Asian | 0.000036 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Active on elastin and collagen substrates. {ECO:0000250}.;
- Disease
- DISEASE: Exfoliation syndrome (XFS) [MIM:177650]: A disorder characterized by accumulation of abnormal fibrillar deposits in the anterior segment of the eye. In addition to being a cause of glaucoma and glaucomatous optic neuropathy, exfoliation syndrome has also been associated with lens zonule weakness, cataract formation, and systemic vascular complications due to deposition of exfoliation material in extraocular tissues. {ECO:0000269|PubMed:18037624, ECO:0000269|PubMed:19343041}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Susceptibility to exfoliation syndrome is conferred by a risk haplotype that includes two LOXL1 coding non-synonymous SNPs (Arg141Leu and Gly153Asp) and one intronic SNP. Arg141Leu and Gly153Asp are sufficient to confer disease susceptibility in some populations.;
Recessive Scores
- pRec
- 0.295
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.980
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |