DLX6distal-less homeobox 6
Autism Reports / Total Reports
3 / 10Rare Variants / Common Variants
4 / 0Aliases
DLX6, MGC125282, MGC125283, MGC125284, MGC125285, DLX6Associated Syndromes
-Chromosome Band
7q21.3Associated Disorders
-Relevance to Autism
Rare mutations in the DLX6 gene have been identified with autism (Nakashima et al., 2010).
Molecular Function
Transcription factor
External Links
SFARI Genomic Platforms
Reports related to DLX6 (10 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Highly Cited | Specification of jaw subdivisions by Dlx genes | Depew MJ , et al. (2002) | No | - |
| 2 | Highly Cited | Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome | Horike S , et al. (2004) | No | - |
| 3 | Highly Cited | DNA binding selectivity of MeCP2 due to a requirement for A/T sequences adjacent to methyl-CpG | Klose RJ , et al. (2005) | No | - |
| 4 | Recent Recommendation | The transcription factor MEF2C is required for craniofacial development | Verzi MP , et al. (2007) | No | - |
| 5 | Recent Recommendation | Positive regulation of steroidogenic acute regulatory protein gene expression through the interaction between Dlx and GATA-4 for testicular steroidogenesis | Nishida H , et al. (2008) | No | - |
| 6 | Recent Recommendation | Regulation of Dlx5 and Dlx6 gene expression by p63 is involved in EEC and SHFM congenital limb defects | Lo Iacono N , et al. (2008) | No | - |
| 7 | Primary | Expression analysis and mutation detection of DLX5 and DLX6 in autism | Nakashima N , et al. (2009) | Yes | - |
| 8 | Recent Recommendation | An SNP in an ultraconserved regulatory element affects Dlx5/Dlx6 regulation in the forebrain | Poitras L , et al. (2010) | No | - |
| 9 | Support | Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism | Chen R , et al. (2017) | Yes | - |
| 10 | Support | - | Zhou X et al. (2022) | Yes | - |
Rare Variants (4)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.390C>T | p.Ser130%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.744G>A | p.Ser248%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| c.390C>T | p.Ser130= | synonymous_variant | De novo | - | Simplex | 28344757 | Chen R , et al. (2017) | |
| c.656G>A | p.Arg219His | missense_variant | - | - | Multiplex | 19195802 | Nakashima N , et al. (2009) |
Common Variants
No common variants reported.
SFARI Gene score
2
Strong Candidate
An unreplicated association has been reported: the R219H variant was found in 2/64 patient lymphoblastoid cell lines in Nakashima et al. (2010) (PMID: 19195802).
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
An unreplicated association has been reported: the R219H variant was found in 2/64 patient lymphoblastoid cell lines in Nakashima et al. (2010) (PMID: 19195802).
10/1/2019
4
3
Decreased from 4 to 3
New Scoring Scheme
Description
An unreplicated association has been reported: the R219H variant was found in 2/64 patient lymphoblastoid cell lines in Nakashima et al. (2010) (PMID: 19195802).
Reports Added
[New Scoring Scheme]4/1/2017
4
4
Decreased from 4 to 4
Description
An unreplicated association has been reported: the R219H variant was found in 2/64 patient lymphoblastoid cell lines in Nakashima et al. (2010) (PMID: 19195802).
Reports Added
[Expression analysis and mutation detection of DLX5 and DLX6 in autism.2009] [Specification of jaw subdivisions by Dlx genes.2002] [Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome.2004] [DNA binding selectivity of MeCP2 due to a requirement for A/T sequences adjacent to methyl-CpG.2005] [The transcription factor MEF2C is required for craniofacial development.2007] [Positive regulation of steroidogenic acute regulatory protein gene expression through the interaction between Dlx and GATA-4 for testicular steroid...2008] [Regulation of Dlx5 and Dlx6 gene expression by p63 is involved in EEC and SHFM congenital limb defects.2008] [An SNP in an ultraconserved regulatory element affects Dlx5/Dlx6 regulation in the forebrain.2010] [Leveraging blood serotonin as an endophenotype to identify de novo and rare variants involved in autism.2017]7/1/2014
No data
4
Increased from No data to 4
Description
An unreplicated association has been reported: the R219H variant was found in 2/64 patient lymphoblastoid cell lines in Nakashima et al. (2010) (PMID: 19195802).
4/1/2014
No data
4
Increased from No data to 4
Description
An unreplicated association has been reported: the R219H variant was found in 2/64 patient lymphoblastoid cell lines in Nakashima et al. (2010) (PMID: 19195802).
Krishnan Probability Score
Score 0.49481613871588
Ranking 3405/25841 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 0.8428304334751
Ranking 3664/18225 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 0.9017117526605
Ranking 6554/18665 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 4
Ranking 305/461 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 0.023563069941924
Ranking 7974/20870 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.