LOXL4
protein-codinglysyl oxidase like 4, the group of Scavenger receptor cysteine rich domain containing
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~20.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0018230
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LOXL4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032211.7. 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 | 3 | 3 | ||||
| missense | 155 | 4 | 159 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 160 | 4 | 0 | 164 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_115587.6 | 14 | MANE Select | |
| Ensembl | ENSP00000260702.3 | 14 | MANE Select | |
| Ensembl | ENSP00000575937.1 | 14 | Standard | |
| Ensembl | ENSP00000575938.1 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Simplified Interaction Map Between LOXL4 and Oxidative Stress Pathway
- Canonical and Non-Canonical TGF-B signaling
- Crosslinking of collagen fibrils
- Assembly of collagen fibrils and other multimeric structures
- Collagen formation
Biological Process
- receptor-mediated endocytosis
- peptidyl-lysine oxidation
- collagen fibril organization
Molecular Function
- protein-lysine 6-oxidase activity
- scavenger receptor activity
- copper ion binding
- protein binding
Cellular Component
- extracellular space
- membrane
- receptor complex
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000260702
- Coding exons
- 14
- Length
- 20561
- Individuals with no LoFs
- 125491
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 256
- Defined
- 125748
- p
- 0.00102
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.158 | 471 | 481 | 0.980 | 0.0000308 | 4914 |
| Missense (PolyPhen) | 196 | 196.97 | 0.99505 | 1922 | ||
| Synonymous | 0.889 | 174 | 190 | 0.918 | 0.0000116 | 1508 |
| Loss of Function | 0.929 | 33 | 39.3 | 0.840 | 0.00000178 | 407 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00068 | 0.00068 | rare |
| Latino/Admixed American | 0.00041 | 0.00040 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00044 | 0.00044 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.00060 | 0.00060 | rare |
| South Asian | 0.0049 | 0.0049 | notable |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May modulate the formation of a collagenous extracellular matrix.;
Recessive Scores
- pRec
- 0.165
Intolerance Scores
- LoFtool
- 0.924
- RVIS EVS
- -0.37
- RVIS percentile EVS
- 28.29
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.808
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | High | Medium | High |
| Cancer | High | High | High |