Human Gene Module / Chromosome 2 / DLX2

DLX2distal-less homeobox 2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
1 / 11
Rare Variants / Common Variants
0 / 2
Aliases
DLX2, DLX-2,  TES1,  TES-1
Associated Syndromes
-
Chromosome Band
2q31.1
Associated Disorders
-
Relevance to Autism

Genetic association has been found between the DLX2 gene and autism in AGRE and ASD-CARC cohorts (Liu et al., 2009).

Molecular Function

The encoded protein is a homeobox transcription factor.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to DLX2 (11 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Origin of GABAergic neurons in the human neocortex Letinic K , et al. (2002) No -
2 Recent Recommendation Dlx1 and Dlx2 control neuronal versus oligodendroglial cell fate acquisition in the developing forebrain Petryniak MA , et al. (2007) No -
3 Recent Recommendation A dlx2- and pax6-dependent transcriptional code for periglomerular neuron specification in the adult olfactory bulb Brill MS , et al. (2008) No -
4 Recent Recommendation Dlx genes pattern mammalian jaw primordium by regulating both lower jaw-specific and upper jaw-specific genetic programs Jeong J , et al. (2008) No -
5 Recent Recommendation Characterization of a distinct subpopulation of striatal projection neurons expressing the Dlx genes in the basal ganglia through the activity of the I56ii enhancer Ghanem N , et al. (2008) No -
6 Primary The DLX1and DLX2 genes and susceptibility to autism spectrum disorders Liu X , et al. (2008) Yes -
7 Recent Recommendation Generation of Cre-transgenic mice using Dlx1/Dlx2 enhancers and their characterization in GABAergic interneurons Potter GB , et al. (2008) No -
8 Recent Recommendation Dlx1&2 and Mash1 transcription factors control MGE and CGE patterning and differentiation through parallel and overlapping pathways Long JE , et al. (2009) No -
9 Highly Cited Null mutation of Dlx-2 results in abnormal morphogenesis of proximal first and second branchial arch derivatives and abnormal differentiation in the forebrain Qiu M , et al. (1995) No -
10 Highly Cited Mutations of the homeobox genes Dlx-1 and Dlx-2 disrupt the striatal subventricular zone and differentiation of late born striatal neurons Anderson SA , et al. (1997) No -
11 Highly Cited Interneuron migration from basal forebrain to neocortex: dependence on Dlx genes Anderson SA , et al. (1997) No -
Rare Variants  

No rare variants reported.

Common Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
- A to T 5KB_downstream_variant - - - 18728693 Liu X , et al. (2008)
c.-36G>A A to G 5_prime_UTR_variant - - - 18728693 Liu X , et al. (2008)
SFARI Gene score
2

Strong Candidate

DLX2 is within a replicated genome-wide significant linkage peak (IMGSAC). Association was observed in a multiplex cohort of 139 families and then replicated in a second larger cohort. The result is significant in both populations after correction but this accounts only for markers evaluated in this study (best p values ~ p x 10-3) (Liu X et al.). Rare variants were also observed in 4/94 cases and 2/396 controls, and segregation with disease was described as poor in the families examined (Hamilton SP et al.).

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

DLX2 is within a replicated genome-wide significant linkage peak (IMGSAC). Association was observed in a multiplex cohort of 139 families and then replicated in a second larger cohort. The result is significant in both populations after correction but this accounts only for markers evaluated in this study (best p values ~ p x 10-3) (Liu X et al.). Rare variants were also observed in 4/94 cases and 2/396 controls, and segregation with disease was described as poor in the families examined (Hamilton SP et al.).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

DLX2 is within a replicated genome-wide significant linkage peak (IMGSAC). Association was observed in a multiplex cohort of 139 families and then replicated in a second larger cohort. The result is significant in both populations after correction but this accounts only for markers evaluated in this study (best p values ~ p x 10-3) (Liu X et al.). Rare variants were also observed in 4/94 cases and 2/396 controls, and segregation with disease was described as poor in the families examined (Hamilton SP et al.).

Reports Added
[New Scoring Scheme]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

DLX2 is within a replicated genome-wide significant linkage peak (IMGSAC). Association was observed in a multiplex cohort of 139 families and then replicated in a second larger cohort. The result is significant in both populations after correction but this accounts only for markers evaluated in this study (best p values ~ p x 10-3) (Liu X et al.). Rare variants were also observed in 4/94 cases and 2/396 controls, and segregation with disease was described as poor in the families examined (Hamilton SP et al.).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

DLX2 is within a replicated genome-wide significant linkage peak (IMGSAC). Association was observed in a multiplex cohort of 139 families and then replicated in a second larger cohort. The result is significant in both populations after correction but this accounts only for markers evaluated in this study (best p values ~ p x 10-3) (Liu X et al.). Rare variants were also observed in 4/94 cases and 2/396 controls, and segregation with disease was described as poor in the families examined (Hamilton SP et al.).

Krishnan Probability Score

Score 0.56561383740702

Ranking 1235/25841 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 0.88761061403722

Ranking 3328/18225 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 0.74315936592693

Ranking 1489/18665 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 2

Ranking 378/461 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 0.30157916476668

Ranking 2716/20870 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
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
DLX5 Homeobox protein DLX-5 Mouse Protein Binding 13395 P70396
GRN granulin Human Protein Binding 2896 P28799
MSX1 Homeobox protein MSX-1 Mouse Protein Binding 17701 P13297
NRP2 neuropilin 2 Human DNA Binding 8828 O60462
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