Human Gene Module / Chromosome 6 / HLA-DPB1

HLA-DPB1major histocompatibility complex, class II, DP beta 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
2 / 2
Rare Variants / Common Variants
1 / 1
Aliases
HLA-DPB1, DPB1,  HLA-DP,  HLA-DP1B,  HLA-DPB
Associated Syndromes
-
Chromosome Band
6p21.32
Associated Disorders
-
Relevance to Autism

Association analysis of human leukocyte antigen (HLA) genes in a large dataset of 65,534 genotyped individuals consisting of controls and cases having one or more of autism spectrum disorder, ADHD, schizophrenia, bipolar disorder, depression, anorexia, or intellectual disability demonstrated a pronounced protective effect of the HLA-DPB1*1501 allele on susceptibility to autism (p = 0.0094, odds ratio = 0.72) and intellectual disability (p = 0.00099, odds ratio = 0.41), with an increased protective effect on a comorbid diagnosis of both disorders (p = 0.003, odds ratio = 0.29) (Nudel et al., 2019).

Molecular Function

HLA-DPB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DPA) and a beta chain (DPB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The beta chain is approximately 26-28 kDa and its gene contains 6 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail. Within the DP molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to 4 different molecules.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to HLA-DPB1 (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Immunity and mental illness: findings from a Danish population-based immunogenetic study of seven psychiatric and neurodevelopmental disorders Nudel R , et al. (2019) Yes -
2 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
Rare Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.390dup p.Ser131LeufsTer47 frameshift_variant Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
- - allele - - - 30976114 Nudel R , et al. (2019)
SFARI Gene score
2

Strong Candidate

Association analysis of human leukocyte antigen (HLA) genes in a large dataset of 65,534 genotyped individuals consisting of controls and cases having one or more of autism spectrum disorder, ADHD, schizophrenia, bipolar disorder, depression, anorexia, or intellectual disability demonstrated a pronounced protective effect of the HLA-DPB1*1501 allele on susceptibility to autism (p = 0.0094, odds ratio = 0.72) and intellectual disability (p = 0.00099, odds ratio = 0.41), with an increased protective effect on a comorbid diagnosis of both disorders (p = 0.003, odds ratio = 0.29) (Nudel et al., 2019).

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

Association analysis of human leukocyte antigen (HLA) genes in a large dataset of 65,534 genotyped individuals consisting of controls and cases having one or more of autism spectrum disorder, ADHD, schizophrenia, bipolar disorder, depression, anorexia, or intellectual disability demonstrated a pronounced protective effect of the HLA-DPB1*1501 allele on susceptibility to autism (p = 0.0094, odds ratio = 0.72) and intellectual disability (p = 0.00099, odds ratio = 0.41), with an increased protective effect on a comorbid diagnosis of both disorders (p = 0.003, odds ratio = 0.29) (Nudel et al., 2019).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Association analysis of human leukocyte antigen (HLA) genes in a large dataset of 65,534 genotyped individuals consisting of controls and cases having one or more of autism spectrum disorder, ADHD, schizophrenia, bipolar disorder, depression, anorexia, or intellectual disability demonstrated a pronounced protective effect of the HLA-DPB1*1501 allele on susceptibility to autism (p = 0.0094, odds ratio = 0.72) and intellectual disability (p = 0.00099, odds ratio = 0.41), with an increased protective effect on a comorbid diagnosis of both disorders (p = 0.003, odds ratio = 0.29) (Nudel et al., 2019).

Reports Added
[New Scoring Scheme]
7/1/2019
icon
4

Increased from to 4

Description

Association analysis of human leukocyte antigen (HLA) genes in a large dataset of 65,534 genotyped individuals consisting of controls and cases having one or more of autism spectrum disorder, ADHD, schizophrenia, bipolar disorder, depression, anorexia, or intellectual disability demonstrated a pronounced protective effect of the HLA-DPB1*1501 allele on susceptibility to autism (p = 0.0094, odds ratio = 0.72) and intellectual disability (p = 0.00099, odds ratio = 0.41), with an increased protective effect on a comorbid diagnosis of both disorders (p = 0.003, odds ratio = 0.29) (Nudel et al., 2019).

Krishnan Probability Score

Score 0.44664484905847

Ranking 14599/25841 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 7.1846578895033E-9

Ranking 16268/18225 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 0.94466121571882

Ranking 16163/18665 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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