Alt. symbols: C13orf31 | FLJ38725 | FAMIN

Approved name: laccase domain containing 1
Alt. names: chromosome 13 open reading frame 31, laccase (multicopper oxidoreductase) domain containing 1 | fatty acid metabolism–immunity nexus

Location: 13q14.11: 43879284 - 43893932 (+)
Gene type: protein_coding, 3 transcripts.

Scores: LoFtool: | pLI: 0.00000464 | LOEUF: 1.076

HGNC: 26789

NCBI: 144811, RefSeq: NG_053160.1

Ensembl: ENSG00000179630.11

LRG_ | Status: none

OMIM: 613409

Expression | ProteinAtlas

LACC1 encodes FAMIN, a purine nucleoside enzyme that modulates purine nucleotide metabolism to regulate the metabolic function and bioenergetic state of macrophages (PMID: 31978345). It catalyzes the phosphorolysis of adenosine, guanosine and inosine nucleosides into D-ribose 1-phosphate and the respective free bases, adenine, guanine and hypoxanthine. It also catalyzes the phosphorolysis of S-methyl-5'-thioadenosine into adenine and S-methyl-5-thio-alpha-D-ribose 1-phosphate and has adenosine deaminase activity. It drives a purine nucleotide cycle that consumes aspartate and releases fumarate in a manner dependent upon fatty acid oxidation and ATP-citrate lyase activity, preventing cytoplasmic acidification and balancing the cytoplasmic-mitochondrial redox interface. It also participates in pattern recognition receptor (PRR)-induced macrophage activation, associating with the NOD2 signaling complex to promote optimal NOD2-induced signaling, cytokine secretion and bacterial clearance (PMID: 28593945, 31875558). Upon PRR stimulation of macrophages, it localizes to the endoplasmic reticulum (ER) and associates with sensors of ER stress to promote the unfolded protein response (UPR).

Biallelic mutations in LACC1, encoding the laccase domain-containing 1 (LACC1) oxidoreductase or FAMIN, are associated with a monogenic form of poly- or oligo-articular juvenile arthritis [OMIM: 618795] characterized by early childhood onset of symmetric arthritis in multiple large and/or small joints, often along with systemic symptoms such as quotidian fever, erythematous rash or recurrent painful erysipelas-like plaques, serositis, tenosynovitis, generalized lymphadenopathy, and hepato- and/o r spleno-megaly (PMID: 25220867, 27881174, 29717096, 30872671). Labs show markedly increased inflammatory markers and patients may also have leukocytosis, thrombocytosis, and autoantibodies such as ANA (antinuclear antibody) but usually undetectable or weak RF (rheumatoid factor) and no ENA (extractable nuclear antigen) positivity. Of note, FAMIN associates with fatty acid synthase on peroxisomes to promote fatty-acid oxidation, and the NOD2-signaling complex to induce mitochondrial production of reactive oxygen species, cytokine secretion and bacterial clearance by macrophages (PMID: 28593945, 31875558). [Load More]