GeneBe

LOX

protein-coding

lysyl oxidase

Gene summary

This gene encodes a member of the lysyl oxidase family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate a regulatory propeptide and the mature enzyme. The copper-dependent amine oxidase activity of this enzyme functions in the crosslinking of collagens and elastin, while the propeptide may play a role in tumor suppression. In addition, defects in this gene have been linked with predisposition to thoracic aortic aneurysms and dissections. [provided by RefSeq, Jul 2016]

MANE transcript

NM_002317.7

Inheritance

AD

ClinVar variants

P:62U:359B:209

Top phenotype

Aortic aneurysm, familial thoracic 10

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr5:122,063,195-122,078,413

External References & Databases

Ensembl (ENSG00000113083)NCBI Gene (4015)OMIM (153455)HGNC:6664GenCCUniProt (P28300)AlphaFoldClinVar (LOX)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~15.2 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

aortic aneurysm, familial thoracic 10STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014950

Submitter: PanelApp Australia

familial thoracic aortic aneurysm and aortic dissectionSTRONG

Inheritance Pattern: Unknown

Disease ID:MONDO:0019625

Submitter: ClinGen

aortic aneurysm, familial thoracic 10STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014950

Submitter: Genomics England PanelApp

aortic aneurysm, familial thoracic 10MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0014950

Submitter: Ambry Genetics

familial thoracic aortic aneurysm and aortic dissectionSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019625

Submitter: Orphanet

aortic aneurysm, familial thoracic 10STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0014950

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Aortic aneurysm, familial thoracic 10AD

Manifestation: Cardiovascular; Musculoskeletal

Intervention: Cardiovascular

Rationale: 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

Refs: 26838787; 27432961Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LOX variants in ClinVar

21 Conditions Cataloged
not providedTotal: 519
Cardiovascular phenotypeTotal: 321
Aortic aneurysm, familial thoracic 10Total: 61
not specifiedTotal: 55
LOX-related disorderTotal: 34
Familial thoracic aortic aneurysm and aortic dissectionTotal: 16
Congenital aneurysm of ascending aortaTotal: 8
Acute aortic dissectionTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002317.7. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
2
clinvar
166
clinvar
1
clinvar
 170
missense
2
clinvar
6
clinvar
345
clinvar
42
clinvar
 395
nonsense
11
clinvar
10
clinvar
2
clinvar
 23
start loss
0
frameshift
14
clinvar
9
clinvar
5
clinvar
 28
splice donor/acceptor (+/-2bp)
1
clinvar
8
clinvar
5
clinvar
 14
Total28343592081630

Highest pathogenic variant AF is 0.0000065719432

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_002317.7RefSeqNP_002308.27MANE Select
ENST00000231004.5EnsemblENSP00000231004.47MANE Select
NM_001178102.2RefSeqNP_001171573.16Standard
NM_001317073.1RefSeqNP_001304002.14Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
loxaDanio rerio

Structure: primary motor neuron

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Canonical and Non-Canonical TGF-B signaling
  • Crosslinking of collagen fibrils
  • Assembly of collagen fibrils and other multimeric structures
  • Collagen formation
  • Extracellular matrix organization

Biological Process

  • cellular protein modification process
  • heart development
  • peptidyl-lysine oxidation
  • collagen fibril organization
  • lung development

Molecular Function

  • protein-lysine 6-oxidase activity
  • copper ion binding
  • protein binding

Cellular Component

  • extracellular region
  • collagen trimer
  • extracellular space
  • nucleus
  • extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000231004
Coding exons
7
Length
15091
Individuals with no LoFs
125740
Homozygous LoFs
0
Heterozygous LoFs
8
Defined
125748
p
0.0000318
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.6522052330.8800.00001092667
Missense (PolyPhen)4987.0320.563011055
Synonymous-1.6111796.91.210.00000454834
Loss of Function3.96222.10.09050.00000121227

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000580.000058rare
Ashkenazi Jewish00.0absent
East Asian0.0000540.000054rare
Finnish00.0absent
European (Non-Finnish)0.0000360.000035rare
South Asian0.0000330.000033rare
Other00.0absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.981

Intolerance Scores

LoFtool
0.253
RVIS EVS
0.22
RVIS percentile EVS
67.92

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.712

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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