LILRB2

protein-coding

leukocyte immunoglobulin like receptor B2, the group of CD molecules|Inhibitory leukocyte immunoglobulin like receptors|Ig-like cell adhesion molecule family

Gene summary

This gene is a member of the leukocyte immunoglobulin-like receptor (LIR) family, which is found in a gene cluster at chromosomal region 19q13.4. The encoded protein belongs to the subfamily B class of LIR receptors which contain two or four extracellular immunoglobulin domains, a transmembrane domain, and two to four cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs). The receptor is expressed on immune cells where it binds to MHC class I molecules on antigen-presenting cells and transduces a negative signal that inhibits stimulation of an immune response. It is thought to control inflammatory responses and cytotoxicity to help focus the immune response and limit autoreactivity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001080978.4

Inheritance

—

ClinVar variants

U:125B:21

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.8

Max pathogenic AF

—

Genomic locus

chr19:54,273,812-54,281,184

External References & Databases

Ensembl (ENSG00000131042)

Transcript & Mutation Effects

hg38 • Region Span ~7.4 kb

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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 LILRB2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 129

not providedTotal: 12

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001080978.4. 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			2 clinvar	10 clinvar		12
missense			121 clinvar	11 clinvar		132
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	125	21	0	146

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 51 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001080978.4	RefSeq	NP_001074447.2	13	MANE Select
ENST00000314446.10	Ensembl	ENSP00000319960.5	13	MANE Select
NM_001278403.3	RefSeq	NP_001265332.2	13	Standard
NM_001278404.3	RefSeq	NP_001265333.2	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

adaptive immune response
negative regulation of antigen processing and presentation
positive regulation of tolerance induction
positive regulation of T cell tolerance induction
immune response-inhibiting cell surface receptor signaling pathway

Molecular Function

amyloid-beta binding
protein binding
protein phosphatase 1 binding
MHC class Ib protein binding
inhibitory MHC class I receptor activity

Cellular Component

extracellular space
cytoplasm
plasma membrane
integral component of plasma membrane
cell surface

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000391749
Coding exons: 13
Length: 7365
Individuals with no LoFs: 125675
Homozygous LoFs: 0
Heterozygous LoFs: 70
Defined: 125745
p: 0.000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-2.30	455	336	1.35	0.0000207	3719
Missense (PolyPhen)		96	92.747	1.0351		1177
Synonymous	-2.10	178	146	1.22	0.00000955	1269
Loss of Function	1.03	25	31.2	0.801	0.00000169	330

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00045	0.00043	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000054	0.000053	rare
South Asian	0.0014	0.0014	notable
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for class I MHC antigens. Recognizes a broad spectrum of HLA-A, HLA-B, HLA-C and HLA-G alleles. Involved in the down-regulation of the immune response and the development of tolerance. Competes with CD8A for binding to class I MHC antigens. Inhibits FCGR1A-mediated phosphorylation of cellular proteins and mobilization of intracellular calcium ions. {ECO:0000269|PubMed:11875462, ECO:0000269|PubMed:12853576, ECO:0000269|PubMed:9548455, ECO:0000269|PubMed:9842885}.;

Intolerance Scores

LoFtool: 0.874
RVIS EVS: 2.83
RVIS percentile EVS: 99.09

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.344

Gene Damage Prediction

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