LOXL2
lysyl oxidase like 2, the group of Scavenger receptor cysteine rich domain containing
Basic information
Region (hg38): 8:23296897-23425328
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the LOXL2 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | |||||
| missense | 60 | 62 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 1 | |||||
| Total | 0 | 0 | 60 | 2 | 3 |
Variants in LOXL2
This is a list of pathogenic ClinVar variants found in the LOXL2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 8-23298067-T-G | not specified | Uncertain significance (Nov 18, 2022) | ||
| 8-23298101-G-A | not specified | Uncertain significance (Apr 09, 2024) | ||
| 8-23298111-T-C | not specified | Uncertain significance (Apr 08, 2024) | ||
| 8-23298838-A-G | not specified | Uncertain significance (Jun 13, 2024) | ||
| 8-23298846-G-C | not specified | Uncertain significance (Jan 02, 2024) | ||
| 8-23298852-C-T | not specified | Uncertain significance (Oct 20, 2023) | ||
| 8-23298863-G-A | not specified | Uncertain significance (May 10, 2024) | ||
| 8-23298877-C-T | not specified | Uncertain significance (Apr 30, 2024) | ||
| 8-23298878-G-A | not specified | Uncertain significance (Dec 20, 2022) | ||
| 8-23298895-A-T | not specified | Uncertain significance (Dec 20, 2023) | ||
| 8-23298922-A-G | not specified | Uncertain significance (Jun 03, 2022) | ||
| 8-23302050-G-T | not specified | Uncertain significance (Jun 16, 2024) | ||
| 8-23302067-A-G | not specified | Uncertain significance (Oct 05, 2021) | ||
| 8-23302083-T-C | not specified | Uncertain significance (Aug 22, 2023) | ||
| 8-23302174-G-T | not specified | Likely benign (Nov 09, 2017) | ||
| 8-23309693-C-T | not specified | Uncertain significance (Nov 30, 2022) | ||
| 8-23309710-G-A | not specified | Uncertain significance (Nov 15, 2021) | ||
| 8-23309713-C-T | not specified | Uncertain significance (Feb 15, 2023) | ||
| 8-23309714-G-A | not specified | Uncertain significance (Apr 15, 2024) | ||
| 8-23309743-T-C | not specified | Uncertain significance (Apr 24, 2023) | ||
| 8-23309767-C-T | not specified | Uncertain significance (May 26, 2022) | ||
| 8-23309791-T-A | not specified | Uncertain significance (Aug 21, 2023) | ||
| 8-23309795-C-T | not specified | Uncertain significance (Sep 07, 2022) | ||
| 8-23309875-T-G | not specified | Uncertain significance (Apr 10, 2023) | ||
| 8-23316961-C-T | not specified | Uncertain significance (Dec 03, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| LOXL2 | protein_coding | protein_coding | ENST00000389131 | 13 | 128140 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 3.38e-7 | 1.00 | 125701 | 0 | 47 | 125748 | 0.000187 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.225 | 483 | 497 | 0.972 | 0.0000320 | 5108 |
| Missense in Polyphen | 189 | 213.98 | 0.88324 | 2086 | ||
| Synonymous | -0.218 | 213 | 209 | 1.02 | 0.0000153 | 1446 |
| Loss of Function | 3.34 | 18 | 41.1 | 0.438 | 0.00000209 | 429 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000475 | 0.000474 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000662 | 0.000653 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000150 | 0.000149 |
| Middle Eastern | 0.000662 | 0.000653 |
| South Asian | 0.000166 | 0.000163 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Mediates the post-translational oxidative deamination of lysine residues on target proteins leading to the formation of deaminated lysine (allysine) (PubMed:27735137). Acts as a transcription corepressor and specifically mediates deamination of trimethylated 'Lys-4' of histone H3 (H3K4me3), a specific tag for epigenetic transcriptional activation (PubMed:27735137). Shows no activity against histone H3 when it is trimethylated on 'Lys-9' (H3K9me3) or 'Lys-27' (H3K27me3) or when 'Lys-4' is monomethylated (H3K4me1) or dimethylated (H3K4me2) (PubMed:27735137). Also mediates deamination of methylated TAF10, a member of the transcription factor IID (TFIID) complex, which induces release of TAF10 from promoters, leading to inhibition of TFIID-dependent transcription (PubMed:25959397). LOXL2-mediated deamination of TAF10 results in transcriptional repression of genes required for embryonic stem cell pluripotency including POU5F1/OCT4, NANOG, KLF4 and SOX2 (By similarity). Involved in epithelial to mesenchymal transition (EMT) via interaction with SNAI1 and participates in repression of E-cadherin CDH1, probably by mediating deamination of histone H3 (PubMed:16096638, PubMed:27735137, PubMed:24414204). During EMT, involved with SNAI1 in negatively regulating pericentromeric heterochromatin transcription (PubMed:24239292). SNAI1 recruits LOXL2 to pericentromeric regions to oxidize histone H3 and repress transcription which leads to release of heterochromatin component CBX5/HP1A, enabling chromatin reorganization and acquisition of mesenchymal traits (PubMed:24239292). Interacts with the endoplasmic reticulum protein HSPA5 which activates the IRE1-XBP1 pathway of the unfolded protein response, leading to expression of several transcription factors involved in EMT and subsequent EMT induction (PubMed:28332555). Involved in E-cadherin repression following hypoxia, a hallmark of EMT believed to amplify tumor aggressiveness, suggesting that it may play a role in tumor progression (PubMed:20026874). When secreted into the extracellular matrix, promotes cross-linking of extracellular matrix proteins by mediating oxidative deamination of peptidyl lysine residues in precursors to fibrous collagen and elastin (PubMed:20306300). Acts as a regulator of sprouting angiogenesis, probably via collagen IV scaffolding (PubMed:21835952). Acts as a regulator of chondrocyte differentiation, probably by regulating expression of factors that control chondrocyte differentiation (By similarity). {ECO:0000250|UniProtKB:P58022, ECO:0000269|PubMed:16096638, ECO:0000269|PubMed:20026874, ECO:0000269|PubMed:20306300, ECO:0000269|PubMed:21835952, ECO:0000269|PubMed:24239292, ECO:0000269|PubMed:24414204, ECO:0000269|PubMed:25959397, ECO:0000269|PubMed:27735137}.;
- Pathway
- Canonical and Non-Canonical TGF-B signaling;Crosslinking of collagen fibrils;Assembly of collagen fibrils and other multimeric structures;Collagen formation;Extracellular matrix organization;De novo fatty acid biosynthesis
(Consensus)
Recessive Scores
- pRec
- 0.0999
Intolerance Scores
- loftool
- 0.770
- rvis_EVS
- -1.59
- rvis_percentile_EVS
- 3.11
Haploinsufficiency Scores
- pHI
- 0.117
- hipred
- N
- hipred_score
- 0.364
- ghis
- 0.596
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.458
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Loxl2
- Phenotype
- liver/biliary system phenotype; neoplasm; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; immune system phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- loxl2a
- Affected structure
- angiogenic sprout
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;response to hypoxia;epithelial to mesenchymal transition;endothelial cell proliferation;sprouting angiogenesis;cellular protein modification process;receptor-mediated endocytosis;cell adhesion;aging;positive regulation of epithelial to mesenchymal transition;peptidyl-lysine oxidation;electron transport chain;collagen fibril organization;positive regulation of chondrocyte differentiation;endothelial cell migration;negative regulation of transcription, DNA-templated;response to copper ion;heterochromatin organization;negative regulation of stem cell population maintenance
- Cellular component
- chromatin;basement membrane;extracellular space;nucleus;nucleoplasm;endoplasmic reticulum;membrane;collagen-containing extracellular matrix
- Molecular function
- protein-lysine 6-oxidase activity;scavenger receptor activity;copper ion binding;calcium ion binding;protein binding;electron transfer activity;oligosaccharide binding