LILRA2

protein-coding

leukocyte immunoglobulin like receptor A2, the group of CD molecules|Activating leukocyte immunoglobulin like receptors

Gene summary

This gene encodes a member of a family of immunoreceptors that are expressed predominantly on monocytes and B cells, and at lower levels on dendritic cells and natural killer cells. The encoded protein is an activating receptor that inhibits dendritic cell differentiation and antigen presentation and suppresses innate immune response. Alternatively spliced transcript variants encoding different isoforms have been found. This gene is located in a cluster of related genes on chromosome 19 and there is a pseudogene for this gene on chromosome 3. [provided by RefSeq, Mar 2014]

MANE transcript

NM_001130917.3

Inheritance

—

ClinVar variants

U:109B:17

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.28

Max pathogenic AF

—

Genomic locus

chr19:54,572,920-54,590,287

External References & Databases

Ensembl (ENSG00000239998)

Transcript & Mutation Effects

hg38 • Region Span ~17.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LILRA2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 116

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001130917.3. 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	5 clinvar		8
missense			105 clinvar	12 clinvar		117
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	109	17	0	126

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001130917.3	RefSeq	NP_001124389.2	8	MANE Select
ENST00000391738.8	Ensembl	ENSP00000375618.3	8	MANE Select
NM_001290270.1	RefSeq	NP_001277199.1	6	Standard
NM_001290271.2	RefSeq	NP_001277200.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Osteoclast differentiation - Homo sapiens (human)
Immune System
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
Adaptive Immune System

Biological Process

innate immune response activating cell surface receptor signaling pathway
neutrophil activation involved in immune response
defense response
signal transduction
negative regulation of lipopolysaccharide-mediated signaling pathway

Molecular Function

IgM binding
antigen binding
signaling receptor activity

Cellular Component

extracellular region
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000251377
Coding exons: 8
Length: 14641
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125747
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-2.70	389	265	1.47	0.0000151	3024
Missense (PolyPhen)		112	83.523	1.341		1056
Synonymous	-2.99	154	113	1.36	0.00000655	999
Loss of Function	-1.16	26	20.3	1.28	8.87e-7	240

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.000065	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Part of the innate immune responses against microbial infection (PubMed:12529506, PubMed:27572839). Specifically recognizes a set of N-terminally truncated immunoglobulins that are produced via cleavage by proteases from a range of pathogenic bacteria and fungi, including L.pneumophila, M.hyorhinis, S.pneumoniae, S.aureus and C.albicans (PubMed:27572839). Recognizes epitopes that are in part in the variable region of the immunoglobulin light chains, but requires also the constant region for signaling (PubMed:27572839). Binds to a subset of cleaved IgM, IgG3 and IgG4 molecules, but does not bind cleaved IgA1 (PubMed:27572839). Binding of N-terminally truncated immunoglobulins mediates activation of neutrophils (PubMed:27572839). In monocytes, activation leads to the release of CSF2, CF3, IL6, CXCL8 and CCL3 and down-regulates responses to bacterial lipopolysaccharide (LPS), possibly via down-regulation of TLR4 expression and reduced signaling via TLR4 (PubMed:22479404). In eosinophils, activation by ligand binding leads to the release of RNASE2, IL4 and leukotriene C4 (PubMed:12529506). Does not bind class I MHC antigens (PubMed:19230061). {ECO:0000269|PubMed:12529506, ECO:0000269|PubMed:19230061, ECO:0000269|PubMed:22479404, ECO:0000269|PubMed:27572839}.;

Intolerance Scores

LoFtool: 0.899
RVIS EVS: 3.23
RVIS percentile EVS: 99.37

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.142

Gene Damage Prediction

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