SOX6SRY-box transcription factor 6
Autism Reports / Total Reports
2 / 4Rare Variants / Common Variants
18 / 0Aliases
SOX6, HSSOX6, SOXDAssociated Syndromes
-Chromosome Band
11p15.2Associated Disorders
ADHD, ASDRelevance to Autism
Tolchin et al., 2020 characterized 19 individuals from 17 unrelated families presenting with a neurodevelopmental syndrome; behavioral abnormalities were frequently observed in affected individuals, with 10/19 presenting with ADHD and 4/19 with autism spectrum disorder.
Molecular Function
This gene encodes a member of the D subfamily of sex determining region y-related transcription factors that are characterized by a conserved DNA-binding domain termed the high mobility group box and by their ability to bind the minor groove of DNA. The encoded protein is a transcriptional activator that is required for normal development of the central nervous system, chondrogenesis and maintenance of cardiac and skeletal muscle cells. The encoded protein interacts with other family members to cooperatively activate gene expression.
External Links
SFARI Genomic Platforms
Reports related to SOX6 (4 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Primary | De Novo SOX6 Variants Cause a Neurodevelopmental Syndrome Associated with ADHD, Craniosynostosis, and Osteochondromas | Tolchin D et al. (2020) | No | ASD, ADHD |
| 2 | Support | - | Mahjani B et al. (2021) | Yes | - |
| 3 | Support | - | Zhou X et al. (2022) | Yes | - |
| 4 | Support | - | Hosneara Akter et al. () | No | - |
Rare Variants (18)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | translocation | De novo | - | - | 32442410 | Tolchin D et al. (2020) | |
| - | - | copy_number_loss | De novo | - | - | 32442410 | Tolchin D et al. (2020) | |
| - | - | copy_number_loss | Familial | Paternal | - | 32442410 | Tolchin D et al. (2020) | |
| c.242C>G | p.Ser81Ter | stop_gained | De novo | - | - | 32442410 | Tolchin D et al. (2020) | |
| c.277C>T | p.Arg93Ter | stop_gained | Unknown | - | - | 32442410 | Tolchin D et al. (2020) | |
| c.293C>G | p.Ser98Ter | stop_gained | De novo | - | - | 32442410 | Tolchin D et al. (2020) | |
| c.718C>T | p.Gln240Ter | stop_gained | De novo | - | - | 32442410 | Tolchin D et al. (2020) | |
| - | - | copy_number_loss | Familial | Paternal | Simplex | 32442410 | Tolchin D et al. (2020) | |
| - | - | copy_number_loss | Familial | Paternal | Multiplex | 32442410 | Tolchin D et al. (2020) | |
| c.483G>C | p.Trp161Cys | missense_variant | De novo | - | - | 32442410 | Tolchin D et al. (2020) | |
| c.1814T>C | p.Met605Thr | missense_variant | De novo | - | - | 32442410 | Tolchin D et al. (2020) | |
| c.1915T>A | p.Trp639Arg | missense_variant | De novo | - | - | 32442410 | Tolchin D et al. (2020) | |
| c.2237C>T | p.Ser746Leu | missense_variant | De novo | - | - | 32442410 | Tolchin D et al. (2020) | |
| c.2191C>A | p.Pro731Thr | missense_variant | Unknown | - | - | 34615535 | Mahjani B et al. (2021) | |
| c.874C>T | p.Pro292Ser | missense_variant | Unknown | - | - | 39342494 | Hosneara Akter et al. () | |
| c.1087C>G | p.His363Asp | missense_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.878del | p.Pro293LeufsTer3 | frameshift_variant | De novo | - | - | 32442410 | Tolchin D et al. (2020) | |
| c.1728del | p.Ser576ArgfsTer9 | frameshift_variant | De novo | - | - | 32442410 | Tolchin D et al. (2020) |
Common Variants
No common variants reported.
SFARI Gene score
S
Syndromic
Score Delta: Score remained at S
criteria met
See SFARI Gene'scoring criteriaThe syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."
Krishnan Probability Score
Score 0.50363035443954
Ranking 1939/25841 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 0.99953095987012
Ranking 925/18225 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 0.94396232079011
Ranking 15890/18665 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).
Zhang D Score
Score -0.006260625565627
Ranking 8878/20870 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.