Human Gene Module / Chromosome 19 / LILRB2

LILRB2leukocyte immunoglobulin like receptor B2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
8 / 0
Aliases
LILRB2, CD85D,  ILT-4,  ILT4,  LIR-2,  LIR2,  MIR-10,  MIR10
Associated Syndromes
-
Chromosome Band
19q13.42
Associated Disorders
-
Relevance to Autism

Rare inherited loss-of-function variants in the LILRB2 gene were identified in ASD probands from the Simons Simplex Collection (Krumm et al., 2015) and in Chinese ASD probands (Guo et al., 2017). Transmission and De Novo Association (TADA) analysis of a cohort of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified the LILRB2 gene as an ASD candidate gene with a PTADA between 0.001 and 0.005 (0.009208); however, PTADA for this gene failed to reach significance (P < 0.01) following TADA analysis using a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium.

Molecular Function

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.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to LILRB2 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Excess of rare, inherited truncating mutations in autism Krumm N , et al. (2015) Yes -
2 Recent Recommendation Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders Li J , et al. (2017) Yes -
3 Support - Zhou X et al. (2022) Yes -
Rare Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1259-1G>A - splice_site_variant De novo - - 35982159 Zhou X et al. (2022)
c.1393C>T p.Gln465Ter stop_gained Familial - - 28831199 Li J , et al. (2017)
c.1396del p.Val466TrpfsTer70 frameshift_variant Familial - - 28831199 Li J , et al. (2017)
c.1403dup p.Val469ArgfsTer31 frameshift_variant Familial - - 28831199 Li J , et al. (2017)
c.931G>A p.Asp311Asn missense_variant Familial Maternal Simplex 25961944 Krumm N , et al. (2015)
c.1337del p.Thr446MetfsTer16 frameshift_variant Familial Paternal Simplex 25961944 Krumm N , et al. (2015)
c.368_369del p.Lys123ThrfsTer22 frameshift_variant Familial Maternal Simplex 25961944 Krumm N , et al. (2015)
c.363_364insAG p.Pro122SerfsTer14 frameshift_variant Familial Maternal Simplex 25961944 Krumm N , et al. (2015)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Rare inherited loss-of-function variants in the LILRB2 gene were identified in ASD probands from the Simons Simplex Collection (Krumm et al., 2015) and in Chinese ASD probands (Guo et al., 2017). Transmission and De Novo Association (TADA) analysis of a cohort of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified the LILRB2 gene as an ASD candidate gene with a PTADA between 0.001 and 0.005 (0.009208); however, PTADA for this gene failed to reach significance (P < 0.01) following TADA analysis using a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium.

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

Rare inherited loss-of-function variants in the LILRB2 gene were identified in ASD probands from the Simons Simplex Collection (Krumm et al., 2015) and in Chinese ASD probands (Guo et al., 2017). Transmission and De Novo Association (TADA) analysis of a cohort of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified the LILRB2 gene as an ASD candidate gene with a PTADA between 0.001 and 0.005 (0.009208); however, PTADA for this gene failed to reach significance (P < 0.01) following TADA analysis using a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Rare inherited loss-of-function variants in the LILRB2 gene were identified in ASD probands from the Simons Simplex Collection (Krumm et al., 2015) and in Chinese ASD probands (Guo et al., 2017). Transmission and De Novo Association (TADA) analysis of a cohort of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified the LILRB2 gene as an ASD candidate gene with a PTADA between 0.001 and 0.005 (0.009208); however, PTADA for this gene failed to reach significance (P < 0.01) following TADA analysis using a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium.

Reports Added
[New Scoring Scheme]
7/1/2017
icon
4

Increased from to 4

Description

Rare inherited loss-of-function variants in the LILRB2 gene were identified in ASD probands from the Simons Simplex Collection (Krumm et al., 2015) and in Chinese ASD probands (Guo et al., 2017). Transmission and De Novo Association (TADA) analysis of a cohort of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 identified the LILRB2 gene as an ASD candidate gene with a PTADA between 0.001 and 0.005 (0.009208); however, PTADA for this gene failed to reach significance (P < 0.01) following TADA analysis using a combined cohort of Chinese ASD probands and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium.

Krishnan Probability Score

Score 0.44604519522328

Ranking 15033/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 7.8294121030718E-6

Ranking 14333/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.94455928428453

Ranking 16123/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
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