LOXL1

Chr 15

lysyl oxidase like 1

Also known as: LOL, LOXL

NCBI Gene: 4016 ENSG00000129038 UniProt: Q08397

This gene encodes a member of the lysyl oxidase family of proteins. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyzes the first step in the formation of crosslinks in collagen and elastin. The encoded preproprotein is proteolytically processed to generate the mature enzyme. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family. Mutations in this gene are associated with exfoliation syndrome. [provided by RefSeq, Jan 2016]

Research

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtExfoliation syndrome

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.38

LOEUF

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.38LOEUF

pLI 0.887

Z-score 3.56

OE 0.15 (0.07–0.38)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.13Z-score

OE missense 0.81 (0.72–0.90)

217 obs / 268.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.15 (0.07–0.38)

0≤0.351.4

Missense OE?0.81 (0.72–0.90)

0≤0.61.4

Synonymous OE?0.77

0≤1.21.6

LoF obs/exp: 3 / 20.3Missense obs/exp: 217 / 268.9Syn Z: 1.93

Background carrier burden — how many people carry a rare variant somewhere in LOXL1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 88

836 rare PASS variants

Rare truncating (LoF)

1 in 2,100

94 rare PASS variants

Rare synonymous (reference)

1 in 150

420 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LOXL1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 1,900
South Asian	~43k	1 in 62	1 in 2,800
Remaining (unassigned)	~30k	1 in 74	1 in 3,000
European (Finnish)	~27k	1 in 270	≈ 1 in 5,900
Admixed American	~22k	1 in 54	1 in 1,600
African / African American	~21k	1 in 63	1 in 3,400
East Asian	~20k	1 in 82	1 in 1,400
Ashkenazi Jewish	~13k	1 in 230	≈ 1 in 12,000
Middle Eastern	~2,884	1 in 80	≈ 1 in 700

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 7 coding exons well covered in gnomAD exomes; exons 1, 7 marginal. Genomes: all 7.? see exons ↓