LACC1

Summary

LACC1 (laccase domain containing 1, HGNC:26789) is a protein-coding gene on chromosome 13q14.11, encoding Purine nucleoside phosphorylase LACC1 (Q8IV20). 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.

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.

Source: NCBI Gene 144811 — RefSeq curated summary.

At a glance

• Gene–disease (curated): juvenile arthritis due to defect in LACC1 (Strong, GenCC)
• GWAS associations: 12
• Clinical variants (ClinVar): 76 total — 5 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 29
• MANE Select transcript: NM_153218

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26789
Approved symbol	LACC1
Name	laccase domain containing 1
Location	13q14.11
Locus type	gene with protein product
Status	Approved
Aliases	FLJ38725, FAMIN
Ensembl gene	ENSG00000179630
Ensembl biotype	protein_coding
OMIM	613409
Entrez	144811

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 30 protein_coding

ENST00000325686, ENST00000425906, ENST00000441843, ENST00000851291, ENST00000851292, ENST00000851293, ENST00000851294, ENST00000851295, ENST00000851296, ENST00000851297, ENST00000851298, ENST00000851299, ENST00000851300, ENST00000851301, ENST00000851302, ENST00000851303, ENST00000851304, ENST00000851305, ENST00000920090, ENST00000962482, ENST00000962483, ENST00000962484, ENST00000962485, ENST00000962486, ENST00000962487, ENST00000962488, ENST00000962489, ENST00000962490, ENST00000962491, ENST00000962492

RefSeq mRNA: 13 — MANE Select: NM_153218 NM_001128303, NM_001350638, NM_001350639, NM_001350640, NM_001350641, NM_001350642, NM_001350643, NM_001350644, NM_001350645, NM_001350646, NM_001350647, NM_001350648, NM_153218

CCDS: CCDS9391

Canonical transcript exons

ENST00000325686 — 7 exons

Exon	Start	End
ENSE00001267793	43888757	43888982
ENSE00001267799	43883771	43883936
ENSE00001267804	43882185	43882363
ENSE00001267813	43879904	43880119
ENSE00001267824	43890114	43890274
ENSE00001267830	43880952	43881547
ENSE00001871139	43891449	43893932

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 90.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.8789 / max 521.6116, expressed in 1526 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
134918	5.7576	711
134915	5.2665	1117
134917	3.6291	1104
134912	0.5687	298
134913	0.3314	173
134914	0.2124	88
134916	0.1131	59

Top tissues by expression

251 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	90.57	gold quality
corpus callosum	UBERON:0002336	90.57	gold quality
medial globus pallidus	UBERON:0002477	88.56	gold quality
globus pallidus	UBERON:0001875	88.21	gold quality
jejunal mucosa	UBERON:0000399	87.90	gold quality
mucosa of sigmoid colon	UBERON:0004993	87.73	gold quality
ileal mucosa	UBERON:0000331	87.55	gold quality
epithelial cell of pancreas	CL:0000083	86.17	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.66	gold quality
amniotic fluid	UBERON:0000173	85.21	gold quality
rectum	UBERON:0001052	85.10	gold quality
colonic mucosa	UBERON:0000317	84.53	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.26	gold quality
substantia nigra	UBERON:0002038	83.58	gold quality
lateral globus pallidus	UBERON:0002476	83.58	gold quality
inferior vagus X ganglion	UBERON:0005363	83.21	gold quality
vermiform appendix	UBERON:0001154	83.12	gold quality
spinal cord	UBERON:0002240	83.03	gold quality
esophagus squamous epithelium	UBERON:0006920	83.03	gold quality
midbrain	UBERON:0001891	82.87	gold quality
gingival epithelium	UBERON:0001949	82.82	gold quality
epithelium of nasopharynx	UBERON:0001951	82.67	gold quality
parietal pleura	UBERON:0002400	82.47	gold quality
subthalamic nucleus	UBERON:0001906	81.77	gold quality
visceral pleura	UBERON:0002401	81.69	gold quality
gall bladder	UBERON:0002110	81.59	gold quality
gingiva	UBERON:0001828	81.56	gold quality
Ammon’s horn	UBERON:0001954	81.20	gold quality
monocyte	CL:0000576	80.97	gold quality
islet of Langerhans	UBERON:0000006	80.72	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.83
E-MTAB-5061	no	3.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

116 targeting LACC1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-126-5P	100.00	72.71	3180
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-4778-3P	99.93	70.40	1818

Literature-anchored findings (GeneRIF, showing 15)

• There is an association of a mutation in LACC1 with a monogenic form of systemic juvenile idiopathic arthritis. (PMID:25220867)
• Association between leprosy and tag SNPs at NOD2 (rs8057431) and CCDC122-LACC1 (rs4942254). (PMID:25367361)
• LACC1 common SNPs represent genetic risk factors also for JIA and ulcerative colitis. (PMID:27098602)
• The results show that a frameshift mutation in LACC1 leads to a similar juvenile arthritis phenotype as previously described. This mutations strongly supports the significance of these gene variants in the development of juvenile arthritis (PMID:27881174)
• FAMIN is a peroxisome-associated protein with primary role(s) in macrophages and other immune cells, where its metabolic functions may be modulated by PPAR signaling events (PMID:27959965)
• LACC1 is critical for amplifying PRR-induced outcomes, an effect that is attenuated by the LACC1 disease-risk variant. (PMID:28593945)
• mRNA expression levels of both HIF1A and LACC1 were upregulated in the skin lesions of individuals with leprosy. (PMID:29706348)
• Our findings confirm that LACC1 variants can be responsible for the recessive form of juvenile arthritis. (PMID:29717096)
• LACC1 Required for NOD2-Induced, ER Stress-Mediated Innate Immune Outcomes in Human Macrophages and LACC1 Risk Variants Modulate These Outcomes. (PMID:31875558)
• A novel loss-of-function mutation in LACC1 underlies hereditary juvenile arthritis with extended intra-familial phenotypic heterogeneity. (PMID:33493343)
• LACC1 deficiency links juvenile arthritis with autophagy and metabolism in macrophages. (PMID:33606008)
• [Macrophage involvement in juvenile arthritis onset: LACC1 bridges the gap?]", trans “Role des macrophages dans le developpement de l’arthrite juvenile - LACC1 fait-il le lien ? (PMID:35179464)
• LACC1 bridges NOS2 and polyamine metabolism in inflammatory macrophages. (PMID:35978195)
• LACC1: A critical involvement in macrophage immunometabolism. (PMID:37366569)
• [Monogenic variants in Laccase domain-containing 1 (LACC1) as the cause of juvenile arthritis]. (PMID:37921883)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lacc1	ENSDARG00000076914
mus_musculus	Lacc1	ENSMUSG00000044350
rattus_norvegicus	Lacc1	ENSRNOG00000022094

Protein

Protein identifiers

Purine nucleoside phosphorylase LACC1 — Q8IV20 (reviewed: Q8IV20)

Alternative names: Adenosine deaminase LACC1, Fatty acid metabolism-immunity nexus, Guanosine phosphorylase LACC1, Isocyanic acid synthase, Laccase domain-containing protein 1, S-methyl-5’-thioadenosine phosphorylase LACC1

All UniProt accessions (2): Q8IV20, A2A3Z5

UniProt curated annotations — full annotation on UniProt →

Function. 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. Also catalyzes the phosphorolysis of S-methyl-5’-thioadenosine into adenine and S-methyl-5-thio-alpha-D-ribose 1-phosphate. Also has adenosine deaminase activity. 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. Enables a purine nucleotide cycle between adenosine and inosine monophosphate and adenylosuccinate that prevents cytoplasmic acidification and balances the cytoplasmic-mitochondrial redox interface. The purine nucleotide cycle consumes aspartate and releases fumarate in a manner involving fatty acid oxidation and ATP-citrate lyase activity. 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. 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). 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. 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. Does not show laccase activity.

Subunit / interactions. Interacts with FASN. Interacts with SDHA. Interacts with ATF6, EIF2AK3 and ERN1. Interacts with autophagy regulators PRKAA1 and RACK1.

Subcellular location. Cytoplasm. Nucleus. Endoplasmic reticulum. Peroxisome.

Tissue specificity. Ubiquitously expressed, with higher expression levels in immune-related tissues such as lymph nodes and spleen. Expressed in both intestinal and peripheral myeloid-derived cells.

Post-translational modifications. Phosphorylated on tyrosine residues.

Disease relevance. Juvenile arthritis (JUVAR) [MIM:618795] A rare, familial form of juvenile arthritis characterized by autosomal recessive inheritance and onset in early childhood of symmetric, chronic joint inflammation. It causes joint swelling, pain, stiffness and restricted joint movement. JUVAR has high clinical variability. Some patients exhibit systemic symptoms, including quotidian fever, erythematous rash, generalized lymphadenopathy, hepatomegaly, and/or splenomegaly. Others display polyarthritis without systemic inflammation. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 Zn(2+) ion per subunit.

Induction. Up-regulated by phorbol 12-myristate 13-acetate (PMA). Down-regulated by PPAR ligands. Up-regulated upon pattern recognition receptor (PRR) stimulation. Up-regulated upon CSF1- and CSF2-induced differentiation of macrophages.

Similarity. Belongs to the purine nucleoside phosphorylase YfiH/LACC1 family.

RefSeq proteins (13): NP_001121775, NP_001337567, NP_001337568, NP_001337569, NP_001337570, NP_001337571, NP_001337572, NP_001337573, NP_001337574, NP_001337575, NP_001337576, NP_001337577, NP_694950* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003730	Cu_polyphenol_OxRdtase	Family
IPR011324	Cytotoxic_necrot_fac-like_cat	Homologous_superfamily
IPR038371	Cu_polyphenol_OxRdtase_sf	Homologous_superfamily

Pfam: PF02578

Catalyzed reactions (Rhea), 6 shown:

• S-methyl-5’-thioadenosine + phosphate = 5-(methylsulfanyl)-alpha-D-ribose 1-phosphate + adenine (RHEA:11852)
• guanosine + phosphate = alpha-D-ribose 1-phosphate + guanine (RHEA:13233)
• adenosine + H2O + H(+) = inosine + NH4(+) (RHEA:24408)
• adenosine + phosphate = alpha-D-ribose 1-phosphate + adenine (RHEA:27642)
• inosine + phosphate = alpha-D-ribose 1-phosphate + hypoxanthine (RHEA:27646)
• L-citrulline + H(+) = isocyanate + L-ornithine (RHEA:83407)

UniProt features (16 total): sequence variant 6, mutagenesis site 5, binding site 3, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IV20-F1	88.62	0.75

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 250; 284; 301

Post-translational modifications (1): 247

Mutagenesis-validated functional residues (5):

Position	Phenotype
52	does not affect ability to promote pattern recognition receptor (prr)-induced cytokines in macrophages; when associated
89	does not affect ability to promote pattern recognition receptor (prr)-induced cytokines in macrophages; when associated
247	decreased acetylation; does not affect ability to promote pattern recognition receptor (prr)-induced cytokines in macrop
249–250	impaired ability to promote pattern recognition receptor (prr)-induced cytokines in macrophages.
265	does not affect ability to promote pattern recognition receptor (prr)-induced cytokines in macrophages; when associated

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 251 (showing top): GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_NUCLEOTIDE_BINDING_DOMAIN_LEUCINE_RICH_REPEAT_CONTAINING_RECEPTOR_SIGNALING_PATHWAY, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_CYTOKINE_PRODUCTION, RIGGI_EWING_SARCOMA_PROGENITOR_DN, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_REGULATION_OF_PH, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS

GO Biological Process (10): pattern recognition receptor signaling pathway (GO:0002221), positive regulation of cytokine production involved in immune response (GO:0002720), inflammatory response (GO:0006954), obsolete regulation of cellular pH (GO:0030641), innate immune response (GO:0045087), regulation of inflammatory response (GO:0050727), nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070431), regulation of purine nucleotide metabolic process (GO:1900542), immune system process (GO:0002376), regulation of defense response (GO:0031347)

GO Molecular Function (9): adenosine deaminase activity (GO:0004000), purine-nucleoside phosphorylase activity (GO:0004731), copper ion binding (GO:0005507), S-methyl-5-thioadenosine phosphorylase activity (GO:0017061), guanosine phosphorylase activity (GO:0047975), protein binding (GO:0005515), transferase activity (GO:0016740), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), peroxisome (GO:0005777), endoplasmic reticulum (GO:0005783), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response	2
purine-nucleoside phosphorylase activity	2
catalytic activity	2
intracellular membrane-bounded organelle	2
innate immune response-activating signaling pathway	1
positive regulation of cytokine production	1
cytokine production involved in immune response	1
positive regulation of production of molecular mediator of immune response	1
regulation of cytokine production involved in immune response	1
immune response	1
defense response to symbiont	1
inflammatory response	1
regulation of defense response	1
regulation of response to external stimulus	1
nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway	1
regulation of nucleotide metabolic process	1
purine nucleotide metabolic process	1
biological_process	1
regulation of response to stress	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amidines	1
deaminase activity	1
pentosyltransferase activity	1
transition metal ion binding	1
binding	1
cation binding	1
microbody	1
cytoplasm	1
endomembrane system	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

764 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LACC1	CCDC122	Q5T0U0	945
LACC1	TNFSF15	O95150	725
LACC1	RIPK2	O43353	714
LACC1	NOD2	Q9HC29	695
LACC1	SPRYD7	Q5W111	631
LACC1	PXDNL	A1KZ92	605
LACC1	PXDN	Q92626	604
LACC1	LRRK2	Q5S007	601
LACC1	KIR2DL1	P43626	588
LACC1	VIL1	P09327	543
LACC1	TYR	P14679	541
LACC1	PRODH	O43272	507
LACC1	LTA4H	P09960	499
LACC1	TNP1	P09430	497
LACC1	SLC11A1	P49279	487

IntAct

43 interactions, top by confidence:

A	B	Type	Score
RAC1	RAP1GDS1	psi-mi:“MI:0914”(association)	0.800
SNX8	POR	psi-mi:“MI:0914”(association)	0.640
OSER1	LACC1	psi-mi:“MI:0914”(association)	0.620
OSER1	LACC1	psi-mi:“MI:0915”(physical association)	0.620
ORC4	LACC1	psi-mi:“MI:0915”(physical association)	0.590
LACC1	FASN	psi-mi:“MI:0915”(physical association)	0.540
LACC1	FASN	psi-mi:“MI:2364”(proximity)	0.540
TPT1	CST7	psi-mi:“MI:0914”(association)	0.530
LACC1	DUSP14	psi-mi:“MI:0914”(association)	0.530
LACC1	CKS2	psi-mi:“MI:0914”(association)	0.530
LACC1	PAP2	psi-mi:“MI:0915”(physical association)	0.500
LACC1	ABCD3	psi-mi:“MI:0403”(colocalization)	0.380
LACC1	ABCD3	psi-mi:“MI:2364”(proximity)	0.380
LACC1	CAT	psi-mi:“MI:0403”(colocalization)	0.380
LACC1	CAT	psi-mi:“MI:2364”(proximity)	0.380
LACC1	FLJ10842	psi-mi:“MI:0914”(association)	0.350
PALM2AKAP2	ANK2	psi-mi:“MI:0914”(association)	0.350
DNAJB2	UBB	psi-mi:“MI:0914”(association)	0.350

BioGRID (97): LACC1 (Affinity Capture-MS), LACC1 (Affinity Capture-MS), LACC1 (Affinity Capture-MS), SIN3A (Affinity Capture-MS), NUFIP2 (Affinity Capture-MS), ARID4B (Affinity Capture-MS), GPATCH8 (Affinity Capture-MS), BRMS1L (Affinity Capture-MS), OSER1 (Affinity Capture-MS), HEPHL1 (Affinity Capture-MS), TSNAX (Affinity Capture-MS), SERPINB5 (Affinity Capture-MS), PPP2CA (Affinity Capture-MS), SUDS3 (Affinity Capture-MS), PKP3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0K9RDW0, A6H7I3, A8MR21, A8MS41, A9JRL3, B8BDK0, C3VEQ2, F4I933, F4KFT7, O35099, O35710, O80560, O81360, O81916, O82387, P79942, P93236, Q0J0B2, Q0WKY2, Q43093, Q5VTE6, Q5Z856, Q66GQ6, Q6TAS3, Q84W55, Q8BZT9, Q8H4D4, Q8IV20, Q8K1C0, Q8LPN3, Q8VYP9, Q8W4K1, Q8W4R8, Q944I4, Q99683, Q9C5W3, Q9C671, Q9ET55, Q9FEB5, Q9FGC7

Diamond homologs: A0A384KG77, O31726, O51423, P33644, P44552, P45497, P67257, P84138, P94338, P9WKD4, P9WKD5, Q1EIR0, Q49WW9, Q4L5N8, Q5HGP4, Q5HQ05, Q6GA25, Q6GHP8, Q7A617, Q8CSX5, Q8IV20, Q8NX32, Q99US8, Q9PET8, Q9RT03, Q9ZHA4, P33664, P74606, Q8BZT9, Q92HU9, Q9ZD53, O66554, P33663, P45496, Q87AR8, Q89ZI8, Q9CCE3, Q9PN78

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

76 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	3
Uncertain significance	48
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
2202782	NM_153218.4(LACC1):c.296del (p.Asn99fs)	Pathogenic
814022	NM_153218.4(LACC1):c.827del (p.Thr276fs)	Pathogenic
814023	NM_153218.4(LACC1):c.3G>A (p.Met1Ile)	Pathogenic
814024	NM_153218.4(LACC1):c.1240C>T (p.Arg414Ter)	Pathogenic
814026	NM_153218.4(LACC1):c.128_129del (p.Cys43fs)	Pathogenic
1686635	NM_153218.4(LACC1):c.783_797del (p.Glu261_Tyr265del)	Likely pathogenic
814025	NM_153218.4(LACC1):c.988_990del (p.Ile330del)	Likely pathogenic
993005	NM_153218.4(LACC1):c.268_272dup (p.Lys92fs)	Likely pathogenic

SpliceAI

1767 predictions. Top by Δscore:

Variant	Effect	Δscore
13:43883756:C:G	acceptor_gain	1.0000
13:43883762:T:A	acceptor_gain	1.0000
13:43883932:CGCTG:C	donor_gain	1.0000
13:43883933:GCTG:G	donor_gain	1.0000
13:43883933:GCTGG:G	donor_gain	1.0000
13:43883937:G:A	donor_loss	1.0000
13:43883937:G:C	donor_loss	1.0000
13:43883937:G:GG	donor_gain	1.0000
13:43883938:T:A	donor_loss	1.0000
13:43883938:TAA:T	donor_loss	1.0000
13:43883939:AAGTA:A	donor_loss	1.0000
13:43888748:A:AG	acceptor_gain	1.0000
13:43888753:CCAGG:C	acceptor_loss	1.0000
13:43888755:A:AG	acceptor_gain	1.0000
13:43888756:G:GG	acceptor_gain	1.0000
13:43888981:AGG:A	donor_loss	1.0000
13:43888982:GGT:G	donor_loss	1.0000
13:43888983:G:GG	donor_gain	1.0000
13:43888983:GTAT:G	donor_loss	1.0000
13:43888984:T:A	donor_loss	1.0000
13:43879370:T:TA	donor_gain	0.9900
13:43879428:C:CA	donor_gain	0.9900
13:43879458:T:TA	donor_gain	0.9900
13:43879464:T:A	donor_gain	0.9900
13:43879732:GAGG:G	donor_loss	0.9900
13:43879734:GG:G	donor_loss	0.9900
13:43879735:G:GA	donor_loss	0.9900
13:43880036:G:GT	donor_gain	0.9900
13:43880947:TGCA:T	acceptor_loss	0.9900
13:43880950:AGGT:A	acceptor_gain	0.9900

AlphaMissense

2863 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:43882202:T:C	F194L	0.981
13:43882204:T:A	F194L	0.981
13:43882204:T:G	F194L	0.981
13:43890208:T:C	F410L	0.980
13:43890210:C:A	F410L	0.980
13:43890210:C:G	F410L	0.980
13:43890257:T:A	I426K	0.978
13:43881261:A:C	K92N	0.975
13:43881261:A:T	K92N	0.975
13:43883877:A:T	D283V	0.974
13:43890239:G:A	G420D	0.974
13:43882306:T:A	N228K	0.973
13:43882306:T:G	N228K	0.973
13:43890235:T:C	F419L	0.973
13:43890237:T:A	F419L	0.973
13:43890237:T:G	F419L	0.973
13:43882255:T:A	N211K	0.972
13:43882255:T:G	N211K	0.972
13:43883878:C:A	D283E	0.971
13:43883878:C:G	D283E	0.971
13:43890221:G:C	R414P	0.971
13:43883876:G:C	D283H	0.970
13:43890253:T:C	F425L	0.967
13:43890255:C:A	F425L	0.967
13:43890255:C:G	F425L	0.967
13:43883930:C:G	H301D	0.966
13:43883922:G:A	G298E	0.965
13:43888906:T:C	F353L	0.965
13:43888908:T:A	F353L	0.965
13:43888908:T:G	F353L	0.965

dbSNP variants (sampled 300 via entrez): RS1000256501 (13:43883351 A>C), RS1000345289 (13:43892059 T>C), RS1000751873 (13:43893868 A>G), RS1000810830 (13:43885295 C>T), RS1000966546 (13:43892266 A>G), RS1001139162 (13:43889736 G>A), RS1001155137 (13:43877904 T>A), RS1001307260 (13:43886519 A>G,T), RS1001417220 (13:43891909 C>G), RS1001617282 (13:43893137 T>C), RS1001960815 (13:43894219 A>G), RS1002143369 (13:43891467 G>A), RS1002146305 (13:43887312 C>G), RS1002863435 (13:43887840 A>G), RS1003166166 (13:43880804 A>G)

Disease associations

OMIM: gene MIM:613409 | disease phenotypes: MIM:618795, MIM:609888

GenCC curated gene-disease

Disease	Classification	Inheritance
juvenile arthritis due to defect in LACC1	Strong	Autosomal recessive

Mondo (2): juvenile arthritis due to defect in LACC1 (MONDO:0032920), leprosy, susceptibility to, 1 (MONDO:0012358)

Orphanet (1): Leprosy (Orphanet:548)

HPO phenotypes

29 total (29 of 29 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000099	Glomerulonephritis
HP:0000938	Osteopenia
HP:0000988	Skin rash
HP:0001369	Arthritis
HP:0001386	Joint swelling
HP:0001510	Growth delay
HP:0001701	Pericarditis
HP:0001744	Splenomegaly
HP:0001894	Thrombocytosis
HP:0001945	Fever
HP:0001974	Increased total leukocyte count
HP:0002027	Abdominal pain
HP:0002202	Pleural effusion
HP:0002240	Hepatomegaly
HP:0002716	Lymphadenopathy
HP:0002829	Arthralgia
HP:0002960	Autoimmunity
HP:0003281	Increased circulating ferritin concentration
HP:0003493	Antinuclear antibody positivity
HP:0003565	Elevated erythrocyte sedimentation rate
HP:0004890	Elevated pulmonary artery pressure
HP:0005681	Juvenile rheumatoid arthritis
HP:0011227	Elevated circulating C-reactive protein concentration
HP:0011463	Childhood onset
HP:0012122	Anterior uveitis
HP:0032323	Periodic fever
HP:0033087	Quotidian fever
HP:0033430	Non-infectious meningitis

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST000546_2	Leprosy	4.000000e-54
GCST000879_1	Crohn’s disease	1.000000e-10
GCST001729_19	Crohn’s disease	2.000000e-21
GCST002772_21	Leprosy	1.000000e-93
GCST002772_8	Leprosy	7.000000e-06
GCST004009_12	Leprosy	5.000000e-08
GCST004131_66	Inflammatory bowel disease	3.000000e-08
GCST004132_108	Crohn’s disease	1.000000e-13
GCST005839_43	Depression	3.000000e-08
GCST008595_124	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	3.000000e-08
GCST010457_4	Leprosy	5.000000e-14
GCST012073_8	Behcet’s disease	9.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

50 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	8
Benzo(a)pyrene	increases expression	6
Aflatoxin B1	affects expression, decreases methylation, increases expression	5
trichostatin A	increases expression, affects cotreatment	3
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Doxorubicin	affects expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
GSK-J4	decreases expression	1
bismuth tripotassium dicitrate	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	increases expression	1
butylbenzyl phthalate	increases expression	1
polyhexamethyleneguanidine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
perfluorohexanesulfonic acid	increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
eprenetapopt	affects expression, affects reaction	1
jinfukang	increases expression, decreases expression, affects cotreatment	1
NSC 689534	affects binding, increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.