Human Gene Module / Chromosome 6 / HLA-A

HLA-Amajor histocompatibility complex, class I, A

Minimal Evidence Criteria 4.1
Autism Reports / Total Reports
7 / 10
Rare Variants / Common Variants
0 / 7
Associated Syndromes
Genetic Category
Genetic Association
Chromosome Band
Associated 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.

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 ... 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

Minimal Evidence


Score Delta: Score remained at 4.3


Minimal Evidence

See all Category 4 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as 'acc" in the score cards) could also boost a gene from category 4 to 3.

No data

Increased from No data to 4


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.

No data

Increased from No data to 4


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: A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at
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 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: 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
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.
CNVs associated with HLA-A(1 CNVs)
6p22.1 19 Deletion-Duplication 31  /  133
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
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