HLA-Amajor histocompatibility complex, class I, A
Autism Reports / Total Reports
7 / 10Rare Variants / Common Variants
0 / 7Aliases
HLA-A, HLA AAssociated Syndromes
-Chromosome Band
6p22.1Associated Disorders
-Relevance to Autism
Genetic association has been found between the HLA-A gene and autism in a Caucasian population cohort (Torres et al., 2006) as well as with an increase in CD4+ memory T cells in autistic children bearing the HLA A2 and DR11 alleles.
Molecular Function
The encoded protein belongs to the MHC class I receptor and plays a central role in the immune response.
External Links
SFARI Genomic Platforms
Reports related to HLA-A (10 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Positive Association | Significant association of HLA A2-DR11 with CD4 naive decrease in autistic children | Ferrante P , et al. (2003) | Yes | - |
| 2 | Primary | The association and linkage of the HLA-A2 class I allele with autism | Torres AR , et al. (2006) | Yes | - |
| 3 | Recent Recommendation | Cross-presentation of HLA class I epitopes from influenza matrix protein produced in Saccharomyces cerevisiae | Wadle A , et al. (2006) | No | - |
| 4 | Positive Association | Associations of HLA alleles with specific language impairment | Nudel R , et al. (2014) | No | - |
| 5 | 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 | - |
| 6 | Negative 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 | - |
| 7 | Positive Association | Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia | Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017) | Yes | - |
| 8 | Negative Association | Association of HLA alleles with autism | Sayad A , et al. (2018) | Yes | - |
| 9 | 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 | - |
| 10 | Highly Cited | Structure of the human class I histocompatibility antigen, HLA-A2 | Bjorkman PJ , et al. (1987) | No | - |
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 |
|---|---|---|---|---|---|---|---|---|
| c.73+54T>G;c.64+54T>G | - | intron_variant | - | - | - | 28540026 | Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017) | |
| - | - | allele | - | - | - | 30976114 | Nudel R , et al. (2019) | |
| A1 allele | - | allele | - | - | - | 24433325 | Nudel R , et al. (2014) | |
| A3 allele | - | allele | - | - | - | 24433325 | Nudel R , et al. (2014) | |
| A2 allele | N/A | allele | - | - | - | 16720216 | Torres AR , et al. (2006) | |
| A*01 allele | - | allele | - | - | - | 24672722 | Al-Hakbany M , et al. (2014) | |
| A*02 allele | - | allele | - | - | - | 24672722 | Al-Hakbany M , et al. (2014) |
SFARI Gene score
2
Strong Candidate
There is minimal evidence for the role of HLA-A in autism. Two association studies have been published showing association with different HLA-A alleles.
Score Delta: Score remained at 2
criteria met
See SFARI Gene'scoring criteriaWe 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
2
Decreased from 3 to 2
Description
There is minimal evidence for the role of HLA-A in autism. Two association studies have been published showing association with different HLA-A alleles.
10/1/2019
4
3
Decreased from 4 to 3
New Scoring Scheme
Description
There is minimal evidence for the role of HLA-A in autism. Two association studies have been published showing association with different HLA-A alleles.
Reports Added
[New Scoring Scheme]4/1/2019
4
4
Decreased from 4 to 4
Description
There is minimal evidence for the role of HLA-A in autism. Two association studies have been published showing association with different HLA-A alleles.
1/1/2019
4
4
Decreased from 4 to 4
Description
There is minimal evidence for the role of HLA-A in autism. Two association studies have been published showing association with different HLA-A alleles.
Reports Added
[Association of HLA alleles with autism.2018]4/1/2017
4
4
Decreased from 4 to 4
Description
There is minimal evidence for the role of HLA-A in autism. Two association studies have been published showing association with different HLA-A alleles.
Reports Added
[Significant association of HLA A2-DR11 with CD4 naive decrease in autistic children.2003] [The association and linkage of the HLA-A2 class I allele with autism.2006] [The Relationship of HLA Class I and II Alleles and Haplotypes with Autism: A Case Control Study.2014] [Associations of HLA alleles with specific language impairment.2014] [Structure of the human class I histocompatibility antigen, HLA-A2.1987] [Cross-presentation of HLA class I epitopes from influenza matrix protein produced in Saccharomyces cerevisiae.2006] [DNA typing of HLA-A, -C, -B, AND -DRB1 in the children with autism in the Republic of Macedonia.2015] [Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with ...2017]1/1/2016
4
4
Decreased from 4 to 4
Description
There is minimal evidence for the role of HLA-A in autism. Two association studies have been published showing association with different HLA-A alleles.
Reports Added
[Significant association of HLA A2-DR11 with CD4 naive decrease in autistic children.2003] [The association and linkage of the HLA-A2 class I allele with autism.2006] [The Relationship of HLA Class I and II Alleles and Haplotypes with Autism: A Case Control Study.2014] [Associations of HLA alleles with specific language impairment.2014] [Structure of the human class I histocompatibility antigen, HLA-A2.1987] [Cross-presentation of HLA class I epitopes from influenza matrix protein produced in Saccharomyces cerevisiae.2006] [DNA typing of HLA-A, -C, -B, AND -DRB1 in the children with autism in the Republic of Macedonia.2015]7/1/2014
No data
4
Increased from No data to 4
Description
There is minimal evidence for the role of HLA-A in autism. Two association studies have been published showing association with different HLA-A alleles.
4/1/2014
No data
4
Increased from No data to 4
Description
There is minimal evidence for the role of HLA-A in autism. Two association studies have been published showing association with different HLA-A alleles.
Krishnan Probability Score
Score 0.49509053513749
Ranking 3215/25841 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.
ExAC Score
Score 0.13277966482776
Ranking 7541/18225 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
Sanders TADA Score
Score 0.9356057271185
Ranking 12930/18665 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).
Larsen Cumulative Evidence Score
Score 3
Ranking 343/461 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.
Zhang D Score
Score -0.03334955997745
Ranking 9810/20870 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.
Interactome
- Protein Binding
- DNA Binding
- RNA Binding
- Protein Modification
- Direct Regulation
- ASD-Linked Genes
Interaction Table
| Interactor Symbol | Interactor Name | Interactor Organism | Interactor Type | Entrez ID | Uniprot ID |
|---|---|---|---|---|---|
| ADAM33 | Disintegrin and metalloproteinase domain-containing protein 33 | Human | Protein Binding | 80332 | Q9BZ11 |
| CD1B | T-cell surface glycoprotein CD1b | Human | Protein Binding | 910 | P29016 |
| HLA-DPA1 | HLA class II histocompatibility antigen, DP alpha 1 chain | Human | Protein Binding | 3113 | P20036 |
| HLA-G | HLA class I histocompatibility antigen, alpha chain G | Human | Protein Binding | 3135 | P17693 |
| TAPBPL | TAP binding protein-like | Human | Protein Binding | 55080 | Q9BX59 |
| TMPRSS11B | Transmembrane protease serine 11B | Human | Protein Binding | 132724 | Q86T26 |
| TRAC | T-cell receptor alpha constant | Human | Protein Binding | 28755 | P01848 |