LACC1

Chr 13

laccase domain multifunctional purine nucleosidase 1

Also known as: C13orf31, FAMIN, JUVAR

NCBI Gene: 144811 ENSG00000179630 UniProt: Q8IV20

This gene encodes a purine nucleoside enzyme that regulates innate immunity in macrophages by modulating purine nucleotide metabolism, promoting optimal NOD2-induced signaling, cytokine secretion, and bacterial clearance. Mutations cause autosomal recessive juvenile arthritis, along with other inflammatory conditions including early-onset Crohn's disease and systemic juvenile idiopathic arthritis. The gene shows low constraint against loss-of-function variants (pLI near 0), consistent with its recessive inheritance pattern.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an oxidoreductase that promotes fatty-acid oxidation, with concomitant inflammasome activation, mitochondrial and NADPH-oxidase-dependent reactive oxygen species production, and bactericidal activity of macrophages. The encoded protein forms a complex with fatty acid synthase on peroxisomes and is thought to be modulated by peroxisome proliferator-activated receptor signaling events. Naturally occurring mutations in this gene are associated with inflammatory bowel disease, Behcet's disease, leprosy, ulcerative colitis, early-onset Crohn's disease, and systemic juvenile idiopathic arthritis. [provided by RefSeq, Apr 2017]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtJuvenile arthritis

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.08

LOEUF

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

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.08LOEUF

pLI 0.000

Z-score 1.35

OE 0.63 (0.39–1.08)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.64Z-score

OE missense 0.69 (0.61–0.79)

157 obs / 226.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.63 (0.39–1.08)

0≤0.351.4

Missense OE?0.69 (0.61–0.79)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 10 / 15.8Missense obs/exp: 157 / 226.5Syn Z: 0.23

Background carrier burden — how many people carry a rare variant somewhere in LACC1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 230

456 rare PASS variants

Rare truncating (LoF)

1 in 2,700

54 rare PASS variants

Rare synonymous (reference)

1 in 410

171 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LACC1. 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 350	1 in 2,300
South Asian	~43k	1 in 190	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 160	1 in 1,600
European (Finnish)	~27k	1 in 570	1 in 1,200
Admixed American	~22k	1 in 180	≈ 1 in 11,000
African / African American	~21k	1 in 95	1 in 1,500
East Asian	~20k	1 in 310	≈ 1 in 4,900
Ashkenazi Jewish	~13k	1 in 500	1 in 720
Middle Eastern	~2,884	1 in 100	none seen

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): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓