LACC1

Chr 13q14.11

laccase domain multifunctional purine nucleosidase 1

Aliases:: FLJ38725, FAMIN
MANE:: ENST00000325686.7

OMIM: 613409 ↗NCBI: 144811 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

LACC1 · Q8IV20

v62025-08-01

Predicted Aligned Error matrix for LACC1 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

88.8/ 100

Confident

430 residues

Confidence breakdown

Very high(≥ 90)76%
Confident(70–90)11%
Low(50–70)5%
Very low(< 50)8%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Primary immunodeficiency or monogenic inflammatory bowel disease
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

juvenile idiopathic arthritis
0.64
juvenile arthritis due to defect in LACC1
0.59
Crohn disease
0.54
leprosy
0.51
systemic-onset juvenile idiopathic arthritis
0.37
psoriasis
0.31
ulcerative colitis
0.28
sclerosing cholangitis
0.28
ankylosing spondylitis
0.28
Behcet disease
0.26

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Purine nucleoside phosphorylase LACC1

Purine nucleoside enzyme that catalyzes the phosphorolysis of adenosine, guanosine and inosine nucleosides, yielding D-ribose 1-phosphate and the respective free bases, adenine, guanine and hypoxanthine (PubMed:31978345). Also catalyzes the phosphorolysis of S-methyl-5'-thioadenosine into adenine and S-methyl-5-thio-alpha-D-ribose 1-phosphate (PubMed:31978345). Also has adenosine deaminase activity (PubMed:31978345). Acts as a regulator of innate immunity in macrophages by modulating the purine nucleotide metabolism, thereby regulating the metabolic function and bioenergetic state of macrophages (PubMed:31978345). Enables a purine nucleotide cycle between adenosine and inosine monophosphate and adenylosuccinate that prevents cytoplasmic acidification and balances the cytoplasmic-mitochondrial redox interface (PubMed:31978345). The purine nucleotide cycle consumes aspartate and releases fumarate in a manner involving fatty acid oxidation and ATP-citrate lyase activity (PubMed:31978345). Participates in pattern recognition receptor (PRR)-induced cytokines in macrophages: associates with the NOD2-signaling complex and promotes optimal NOD2-induced signaling, cytokine secretion and bacterial clearance (PubMed:28593945, PubMed:31875558). Localizes to the endoplasmic reticulum upon PRR stimulation of macrophages and associates with endoplasmic reticulum-stress sensors, promoting the endoplasmic reticulum unfolded protein response (UPR) (PubMed:31875558). Component of L-arginine metabolism in activated macrophages supporting anti-inflammatory and antibacterial macrophage effector functions. Cleaves L-citrulline, a product of L-arginine metabolized via NOS2, to yield isocyanate, a reactive carbonyl species-like cytotoxin, and L-ornithine, a precursor in polyamine biosynthesis. Through L-ornithine controls cellular polyamine pools likely triggering polyamine-mediated proinflammatory cytokine suppression and autophagy stimulation (PubMed:35978195). Directly interacts with components of autophagy machinery to regulate macrophage metabolism and bacterial phagocytosis. Acts downstream of the energy sensor AMP-activated protein kinase (AMPK) to promote autophagy associated to lipid droplets generation providing fatty acids for mitochondrial respiration (PubMed:33606008). Does not show laccase activity (PubMed:27959965, PubMed:31978345)