LOX

lysyl oxidase

Basic information

Region (hg38): 5:122063195-122078413

Links

ENSG00000113083 ∙ NCBI:4015 ∙ OMIM:153455 ∙ HGNC:6664 ∙ Uniprot:P28300 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• aortic aneurysm, familial thoracic 10 (Strong), mode of inheritance: AD
• aortic aneurysm, familial thoracic 10 (Strong), mode of inheritance: AD
• aortic aneurysm, familial thoracic 10 (Strong), mode of inheritance: AD
• aortic aneurysm, familial thoracic 10 (Moderate), mode of inheritance: AD
• familial thoracic aortic aneurysm and aortic dissection (Supportive), mode of inheritance: AD
• familial thoracic aortic aneurysm and aortic dissection (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Aortic aneurysm, familial thoracic 10	AD	Cardiovascular	Individuals can manifest with thoracic aortic aneurysm with or without dissection as well as other features, and awareness may allow preventive measures and early diagnosis and management	Cardiovascular; Musculoskeletal	26838787; 27432961

ClinVar

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

• not_provided (439 variants)
• Cardiovascular_phenotype (280 variants)
• Aortic_aneurysm,_familial_thoracic_10 (51 variants)
• not_specified (27 variants)
• LOX-related_disorder (25 variants)
• Familial_thoracic_aortic_aneurysm_and_aortic_dissection (13 variants)
• Congenital_aneurysm_of_ascending_aorta (8 variants)
• Acute_aortic_dissection (8 variants)
• Pleural_effusion (1 variants)
• Familial_aortopathy (1 variants)
• Inborn_genetic_diseases (1 variants)
• Increased_number_of_skin_folds (1 variants)
• Cutis_laxa (1 variants)
• Interphalangeal_joint_contracture_of_finger (1 variants)
• Abnormal_facial_shape (1 variants)
• Emphysema (1 variants)
• Generalized_arterial_tortuosity (1 variants)
• Connective_tissue_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LOX gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002317.7. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	1	152	1	155
missense	2	6	305	27	1	341
nonsense	11	7	1			19
start loss						0
frameshift	12	8	5			25
splice donor/acceptor (+/-2bp)	1	6	3			10
Total	26	28	315	179	2

Highest pathogenic variant AF is 0.0000409131

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LOX	protein_coding	protein_coding	ENST00000231004	7	15091

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.988	0.0123	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.652	205	233	0.880	0.0000109	2667
Missense in Polyphen		49	87.032	0.56301		1055
Synonymous	-1.61	117	96.9	1.21	0.00000454	834
Loss of Function	3.96	2	22.1	0.0905	0.00000121	227

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000363	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000329	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Responsible for the post-translational oxidative deamination of peptidyl lysine residues in precursors to fibrous collagen and elastin (PubMed:26838787). Regulator of Ras expression. May play a role in tumor suppression. Plays a role in the aortic wall architecture (By similarity). {ECO:0000250|UniProtKB:P28301, ECO:0000269|PubMed:26838787}.
• Disease: DISEASE: Aortic aneurysm, familial thoracic 10 (AAT10) [MIM:617168]: A form of thoracic aortic aneurysm, a disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance. {ECO:0000269|PubMed:26838787, ECO:0000269|PubMed:27432961}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• 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 (Consensus)

Recessive Scores

• pRec: 0.981

Intolerance Scores

• loftool: 0.253
• rvis_EVS: 0.22
• rvis_percentile_EVS: 67.92

Haploinsufficiency Scores

• pHI: 0.391
• hipred: Y
• hipred_score: 0.786
• ghis: 0.559

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.712

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lox
• 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); muscle phenotype; homeostasis/metabolism phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); 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)

Zebrafish Information Network

• Gene name: loxa
• Affected structure: primary motor neuron
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: cellular protein modification process;heart development;peptidyl-lysine oxidation;collagen fibril organization;lung development;aorta development;wound healing;response to drug;elastic fiber assembly;blood vessel morphogenesis;response to steroid hormone
• Cellular component: extracellular region;collagen trimer;extracellular space;nucleus;extracellular matrix
• Molecular function: protein-lysine 6-oxidase activity;copper ion binding;protein binding