Human Gene Module / Chromosome 6 / HLA-DRB1

HLA-DRB1major histocompatibility complex, class II, DR beta 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
8 / 11
Rare Variants / Common Variants
0 / 7
Aliases
HLA-DRB1, DRB1,  HLA DRB1,  HLA-DR1B
Associated Syndromes
-
Chromosome Band
6p21.32
Associated Disorders
-
Relevance to Autism

The third hypervariable region (HVR-3) of certain DR beta 1 alleles have been found to have very strong association with autism (Warren et al., 1996).

Molecular Function

The encoded protein belongs to the MHC class II receptor and plays a central role in the immune response.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to HLA-DRB1 (11 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Positive Association The transmission disequilibrium test suggests that HLA-DR4 and DR13 are linked to autism spectrum disorder Torres AR , et al. (2002) Yes -
2 Highly Cited The influence of HLA-DRB1 genes on disease severity in rheumatoid arthritis Weyand CM , et al. (1992) No -
3 Recent Recommendation Extensive multiallelic analysis of the relationship between HLA-DRB1 and rheumatoid arthritis using a Bayesian partition model Marotte H , et al. (2006) No -
4 Positive Association Association of HLA-DRB1 alleles and neuropsychological function in autism Chien YL , et al. (2011) Yes -
5 Positive Association Associations of HLA alleles with specific language impairment Nudel R , et al. (2014) No -
6 Positive Association The Relationship of HLA Class I and II Alleles and Haplotypes with Autism: A Case Control Study Al-Hakbany M , et al. (2014) Yes -
7 Positive Association DNA typing of HLA-A, -C, -B, AND -DRB1 in the children with autism in the Republic of Macedonia Trajkovski V and Spiroski M (2015) Yes -
8 Positive Association HLA-class II haplotypes and Autism Spectrum Disorders Bennabi M , et al. (2018) Yes -
9 Negative Association Association of HLA alleles with autism Sayad A , et al. (2018) Yes -
10 Positive Association Immunity and mental illness: findings from a Danish population-based immunogenetic study of seven psychiatric and neurodevelopmental disorders Nudel R , et al. (2019) Yes -
11 Primary Strong association of the third hypervariable region of HLA-DR beta 1 with autism Warren RP , et al. (1996) Yes -
Rare Variants  

No rare variants reported.

Common Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
- - allele - - - 30976114 Nudel R , et al. (2019)
N/A N/A allele - - - 8765331 Warren RP , et al. (1996)
DR10 allele - allele - - - 24433325 Nudel R , et al. (2014)
DR14 allele - allele - - - 21716163 Chien YL , et al. (2011)
DR4 allele - allele - - - 12039413 Torres AR , et al. (2002)
DRB1*1104 allele - allele - - - 24672722 Al-Hakbany M , et al. (2014)
DRB1*01 allele - allele - - - 25666956 Trajkovski V and Spiroski M (2015)
SFARI Gene score
2

Strong Candidate

Specific alleles and/or haplotypes of the HLA-DRB1 gene have been found to associate with ASD in cohorts of Caucasian, Han Chinese, and Saudi Arabian ancestry (Warren et al., 1996; Torres et al., 2002; Chien et al., 2012; Al-Hakbany et al., 2014; Trajkovski et al., 2015; Bennabi et al., 2018), as well as with specific language impairment (SLI) (Nudel et al., 2014).

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

Specific alleles and/or haplotypes of the HLA-DRB1 gene have been found to associate with ASD in cohorts of Caucasian, Han Chinese, and Saudi Arabian ancestry (Warren et al., 1996; Torres et al., 2002; Chien et al., 2012; Al-Hakbany et al., 2014; Trajkovski et al., 2015; Bennabi et al., 2018), as well as with specific language impairment (SLI) (Nudel et al., 2014).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Specific alleles and/or haplotypes of the HLA-DRB1 gene have been found to associate with ASD in cohorts of Caucasian, Han Chinese, and Saudi Arabian ancestry (Warren et al., 1996; Torres et al., 2002; Chien et al., 2012; Al-Hakbany et al., 2014; Trajkovski et al., 2015; Bennabi et al., 2018), as well as with specific language impairment (SLI) (Nudel et al., 2014).

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

Decreased from 4 to 4

Description

Specific alleles and/or haplotypes of the HLA-DRB1 gene have been found to associate with ASD in cohorts of Caucasian, Han Chinese, and Saudi Arabian ancestry (Warren et al., 1996; Torres et al., 2002; Chien et al., 2012; Al-Hakbany et al., 2014; Trajkovski et al., 2015; Bennabi et al., 2018), as well as with specific language impairment (SLI) (Nudel et al., 2014).

Reports Added
[Immunity and mental illness: findings from a Danish population-based immunogenetic study of seven psychiatric and neurodevelopmental disorders.2019]
1/1/2019
4
icon
4

Decreased from 4 to 4

Description

Specific alleles and/or haplotypes of the HLA-DRB1 gene have been found to associate with ASD in cohorts of Caucasian, Han Chinese, and Saudi Arabian ancestry (Warren et al., 1996; Torres et al., 2002; Chien et al., 2012; Al-Hakbany et al., 2014; Trajkovski et al., 2015; Bennabi et al., 2018), as well as with specific language impairment (SLI) (Nudel et al., 2014).

Reports Added
[Association of HLA alleles with autism.2018]
7/1/2018
icon
4

Increased from to 4

Description

Specific alleles and/or haplotypes of the HLA-DRB1 gene have been found to associate with ASD in cohorts of Caucasian, Han Chinese, and Saudi Arabian ancestry (Warren et al., 1996; Torres et al., 2002; Chien et al., 2012; Al-Hakbany et al., 2014; Trajkovski et al., 2015; Bennabi et al., 2018), as well as with specific language impairment (SLI) (Nudel et al., 2014).

Reports Added
[The transmission disequilibrium test suggests that HLA-DR4 and DR13 are linked to autism spectrum disorder.2002] [Association of HLA-DRB1 alleles and neuropsychological function in autism.2011] [DNA typing of HLA-A, -C, -B, AND -DRB1 in the children with autism in the Republic of Macedonia.2015]
Krishnan Probability Score

Score 0.40750859096381

Ranking 23030/25841 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 5.623528794949E-5

Ranking 13401/18225 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 0.71870835490622

Ranking 1285/18665 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
Larsen Cumulative Evidence Score

Score 3

Ranking 344/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score -0.55726492737541

Ranking 19655/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
Submit New Gene

Report an Error