LOXL2

lysyl oxidase like 2, the group of Scavenger receptor cysteine rich domain containing

Basic information

Region (hg38): 8:23296896-23425328

Links

ENSG00000134013 ∙ NCBI:4017 ∙ OMIM:606663 ∙ HGNC:6666 ∙ Uniprot:Q9Y4K0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LOXL2 gene.

• Inborn genetic diseases (48 variants)
• not provided (3 variants)
• not specified (1 variants)

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	2
missense			47	1	1	49
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	47	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)
8-23298846-G-C		not specified	Uncertain significance (Jan 02, 2024)
8-23298852-C-T		not specified	Uncertain significance (Oct 20, 2023)
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)
8-23302067-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)
8-23309743-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)
8-23317012-C-T		not specified	Uncertain significance (Dec 15, 2022)
8-23317020-C-T		not specified	Uncertain significance (Aug 10, 2021)
8-23317021-G-A		not specified	Uncertain significance (Feb 23, 2023)
8-23317068-A-G		not specified	Uncertain significance (Feb 03, 2022)
8-23317110-G-C		not specified	Uncertain significance (Aug 28, 2023)
8-23319902-C-A		not specified	Uncertain significance (Dec 20, 2022)
8-23319934-A-G		not specified	Uncertain significance (Jul 14, 2021)

GnomAD

Source: gnomAD

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: dbNSFP

• 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