LOXL3

lysyl oxidase like 3, the group of Scavenger receptor cysteine rich domain containing

Basic information

Region (hg38): 2:74532258-74555690

Links

ENSG00000115318 ∙ NCBI:84695 ∙ OMIM:607163 ∙ HGNC:13869 ∙ Uniprot:P58215 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Stickler syndrome (Moderate), mode of inheritance: AR
• autosomal recessive Stickler syndrome (Supportive), mode of inheritance: AR
• myopia 28, autosomal recessive (Limited), mode of inheritance: AR
• myopia 28, autosomal recessive (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myopia 28, autosomal recessive	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	26957899; 33456446

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LOXL3 gene.

• not provided (3 variants)
• 3-methylglutaconic aciduria type 8 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LOXL3 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			3	110	2	115
missense			190	7	6	203
nonsense			9			9
start loss						0
frameshift	1		8			9
inframe indel			1			1
splice donor/acceptor (+/-2bp)			2			2
splice region			3	10		13
non coding	2		25	73	8	108
Total	3	0	238	190	16

Highest pathogenic variant AF is 0.0000132

Variants in LOXL3

This is a list of pathogenic ClinVar variants found in the LOXL3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-74532596-T-C			Benign (Jul 15, 2018)
2-74532600-G-A			Likely benign (Apr 06, 2022)
2-74532607-G-A			Likely benign (Aug 08, 2022)
2-74532609-G-A			Likely benign (Oct 26, 2022)
2-74532611-A-C			Likely benign (Aug 01, 2023)
2-74532634-A-G		Parkinson disease 13, autosomal dominant, susceptibility to	Conflicting classifications of pathogenicity (Nov 17, 2023)
2-74532641-C-T			Pathogenic (Aug 09, 2022)
2-74532658-C-T		Parkinson disease 13, autosomal dominant, susceptibility to • HTRA2-related disorder	Likely benign (Jan 29, 2024)
2-74532659-G-A			Uncertain significance (May 04, 2022)
2-74532659-G-T		Autism	Uncertain significance (-)
2-74532661-T-C			Likely benign (Sep 03, 2023)
2-74532675-T-A		Leigh syndrome	Uncertain significance (Oct 03, 2023)
2-74532685-T-C		HTRA2-related disorder	Likely benign (Nov 14, 2022)
2-74532686-A-T			Uncertain significance (Jan 27, 2022)
2-74532694-C-T			Likely benign (Jan 18, 2024)
2-74532698-G-A		Parkinson disease 13, autosomal dominant, susceptibility to	Benign/Likely benign (Aug 01, 2024)
2-74532713-C-T		Inborn genetic diseases	Uncertain significance (Jan 26, 2024)
2-74532714-G-A		3-methylglutaconic aciduria type 8	Pathogenic (Oct 04, 2022)
2-74532725-G-C			Likely benign (Nov 22, 2023)
2-74532726-G-T			Likely benign (Feb 21, 2022)
2-74532729-G-A			Likely benign (Jun 20, 2023)
2-74532730-C-T			Likely benign (Nov 13, 2023)
2-74532732-G-T			Likely benign (Feb 16, 2023)
2-74532803-T-C			Likely benign (Dec 07, 2023)
2-74532805-C-A			Likely benign (Aug 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LOXL3	protein_coding	protein_coding	ENST00000264094	13	23277

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.66e-13	0.964	125635	0	113	125748	0.000449

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.56	375	471	0.797	0.0000282	4898
Missense in Polyphen		162	222.65	0.72759		2303
Synonymous	1.53	159	185	0.857	0.0000110	1503
Loss of Function	2.29	27	43.3	0.624	0.00000244	403

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00112	0.00111
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000874	0.000816
Finnish	0.0000466	0.0000462
European (Non-Finnish)	0.000551	0.000545
Middle Eastern	0.000874	0.000816
South Asian	0.0000980	0.0000980
Other	0.000491	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Protein-lysine 6-oxidase that mediates the oxidation of peptidyl lysine residues to allysine in target proteins (PubMed:17018530, PubMed:28065600). Catalyzes the post- translational oxidative deamination of peptidyl lysine residues in precursors of elastin and different types of collagens, a prerequisite in the formation of cross-links between collagens and elastin (PubMed:17018530). Required for somite boundary formation by catalyzing oxidation of fibronectin (FN1), enhancing integrin signaling in myofibers and their adhesion to the myotendinous junction (MTJ) (By similarity). Acts as a regulator of inflammatory response by inhibiting differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg): acts by interacting with STAT3 in the nucleus and catalyzing both deacetylation and oxidation of lysine residues on STAT3, leading to disrupt STAT3 dimerization and inhibit STAT3 transcription activity (PubMed:28065600). Oxidation of lysine residues to allysine on STAT3 preferentially takes place on lysine residues that are acetylated (PubMed:28065600). Also able to catalyze deacetylation of lysine residues on STAT3 (PubMed:28065600). {ECO:0000250|UniProtKB:Q9Z175, ECO:0000269|PubMed:17018530, ECO:0000269|PubMed:28065600}.; FUNCTION: Isoform 2: Shows protein-lysine 6-oxidase activity toward elastin and different types of collagens, with the highest activity toward collagen type IV (PubMed:17018530). {ECO:0000269|PubMed:17018530}.
• Disease: DISEASE: Note=Defects in LOXL3 are found in a family with an autosomal recessive form of Stickler syndrome, an inherited disorder that associates ocular signs with more or less complete forms of Pierre Robin sequence and sensorineural deafness (PubMed:25663169). Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate) (PubMed:25663169). The degree of hearing loss varies among affected individuals and may become more severe over time (PubMed:25663169). Syndrome expressivity is variable (PubMed:25663169). Ocular disorders include non-progressive myopia with associated chorioretinal degeneration (PubMed:25663169). Defects in LOXL3 are found in another family with early-onset high myopia (PubMed:26957899). The disease may be caused by mutations affecting the gene represented in this entry (PubMed:25663169, PubMed:26957899). {ECO:0000269|PubMed:25663169, ECO:0000269|PubMed:26957899}.
• Pathway: TYROBP Causal Network;Crosslinking of collagen fibrils;Assembly of collagen fibrils and other multimeric structures;Collagen formation;Extracellular matrix organization (Consensus)

Recessive Scores

• pRec: 0.161

Intolerance Scores

• loftool: 0.897
• rvis_EVS: 0
• rvis_percentile_EVS: 54.07

Haploinsufficiency Scores

• pHI: 0.370
• hipred: Y
• hipred_score: 0.623
• ghis: 0.541

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.340

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Loxl3
• Phenotype: craniofacial phenotype; growth/size/body region phenotype; digestive/alimentary phenotype; skeleton phenotype; respiratory system phenotype; 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)

Zebrafish Information Network

• Gene name: loxl3b
• Affected structure: ceratobranchial cartilage
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: epithelial to mesenchymal transition;receptor-mediated endocytosis;inflammatory response;peptidyl-lysine oxidation;spinal cord development;collagen fibril organization;lung development;negative regulation of transcription, DNA-templated;roof of mouth development;somite development;fibronectin fibril organization;negative regulation of T-helper 17 cell lineage commitment;positive regulation of integrin-mediated signaling pathway
• Cellular component: extracellular region;extracellular space;nucleus;cytoplasm;membrane
• Molecular function: fibronectin binding;protein-lysine 6-oxidase activity;scavenger receptor activity;copper ion binding;protein binding