LACC1

protein-coding

laccase domain containing 1

Gene summary

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]

Previous symbols:

C13orf31

MANE transcript

NM_153218.4

Inheritance

ClinVar variants

P:8U:50B:9

Top phenotype

Juvenile arthritis

gnomAD constraint

pLI —, LoF o/e 0.63

Max pathogenic AF

—

Genomic locus

chr13:43,879,284-43,893,932

External References & Databases

Ensembl (ENSG00000179630)

Transcript & Mutation Effects

hg38 • Region Span ~14.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

juvenile arthritis due to defect in LACC1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032920

Submitter: PanelApp Australia

juvenile arthritis due to defect in LACC1LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032920

Submitter: Ambry Genetics

juvenile arthritis due to defect in LACC1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032920

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Juvenile arthritisAR

Manifestation: Allergy/Immunology/Infectious; Oncologic

Intervention: Allergy/Immunology/Infectious; Oncologic

Rationale: Individuals have been described as benefiting from specific medications (with non-efficacy of other medications), and knowledge may help with medication selection; The condition may involve increased risk of malignancy, and awareness may allow prompt diagnosis and management; BMT has been described

Refs: 25220867; 27881174; 29717096; 30872671

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LACC1 variants in ClinVar

5 Conditions Cataloged

Inborn genetic diseasesTotal: 47

not providedTotal: 11

Juvenile arthritis due to defect in LACC1Total: 9

not specifiedTotal: 2

LACC1-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_153218.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				3 clinvar	1 clinvar	4
missense		1 clinvar	49 clinvar	4 clinvar	1 clinvar	55
nonsense	1 clinvar	1 clinvar				2
start loss	1 clinvar					1
frameshift	3 clinvar	1 clinvar				4
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	5	3	50	7	2	67

Highest pathogenic variant AF is 0.000019844838

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 84 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_153218.4	RefSeq	NP_694950.2	5	MANE Select
ENST00000325686.7	Ensembl	ENSP00000317619.5	5	MANE Select
NM_001128303.2	RefSeq	NP_001121775.1	5	Standard
NM_001350638.2	RefSeq	NP_001337567.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

copper ion binding
protein binding

Cellular Component

peroxisome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000441843
Coding exons: 5
Length: 14649
Individuals with no LoFs: 125696
Homozygous LoFs: 0
Heterozygous LoFs: 37
Defined: 125733
p: 0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.64	157	226	0.693	0.0000107	2854
Missense (PolyPhen)		30	57.459	0.52212		731
Synonymous	0.234	74	76.6	0.966	0.00000369	819
Loss of Function	1.35	10	15.8	0.634	8.24e-7	205

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.0012	0.0012	notable
East Asian	0	0.0	absent
Finnish	0.00042	0.00042	rare
European (Non-Finnish)	0.000097	0.000097	rare
South Asian	0.000033	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Central regulator of the metabolic function and bioenergetic state of macrophages. In macrophages, promotes flux through de novo lipogenesis to concomitantly drive high levels of both fatty-acid oxidation and glycolysis. {ECO:0000250|UniProtKB:Q8BZT9}.;
Disease: DISEASE: Rheumatoid arthritis systemic juvenile (RASJ) [MIM:604302]: An inflammatory articular disorder with systemic- onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis. {ECO:0000269|PubMed:25220867}. Note=The gene represented in this entry may be involved in disease pathogenesis.;

Recessive Scores

pRec: 0.0899

Intolerance Scores

RVIS EVS: 0.02
RVIS percentile EVS: 55.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium