Human Gene Module / Chromosome 7 / DDC

DDCdopa decarboxylase

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
2 / 2
Rare Variants / Common Variants
0 / 1
Aliases
DDC, AADC
Associated Syndromes
-
Genetic Category
Genetic Association
Chromosome Band
7p12.2-p12.1
Associated Disorders
-
Relevance to Autism

A significant association was obtained between the DDC gene and autism in the single-marker analysis (rs6592961, P = 0.00047) in a case-control genetic association study consisting of 326 unrelated autistic patients and 350 gender-matched controls from Spain (Toma et al., 2012). These findings suggest that common allelic variants in the DDC gene may be involved in autism susceptibility.

Molecular Function

The encoded protein catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine. Defects in this gene are the cause of aromatic L-amino-acid decarboxylase deficiency (AADCD). AADCD deficiency is an inborn error in neurotransmitter metabolism that leads to combined serotonin and catecholamine deficiency.

Reports related to DDC (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Negative Association Investigation of two variants in the DOPA decarboxylase gene in patients with autism. Lauritsen MB , et al. (2002) Yes -
2 Primary Neurotransmitter systems and neurotrophic factors in autism: association study of 37 genes suggests involvement of DDC. Toma C , et al. (2012) Yes -
Rare Variants  

No rare variants reported.

Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.715-1133C>T;c.601-1133C>T;c.571-1133C>T;c.481-1133C>T;c.436-1133C>T G/A intron_variant - - - 22397633 Toma C , et al. (2012)
SFARI Gene score
3

Suggestive Evidence

Two variants in the DDC gene were investigated for their potential to increase the susceptibility to autism by investigating a total of 90 parent-offspring trios recruited in Denmark and France using the transmission disequilibrium test (TDT) in Lauritsen et al., 2002, but no evidence of linkage disequilibrium was found between autism and either of the two polymorphisms, nor was linkage disequilibrium between autism and haplotypes of the two variants using a multiallelic TDT. However, significant association was obtained between the DDC gene and autism in the single-marker analysis (rs6592961, P = 0.00047) in a case-control genetic association study consisting of 326 unrelated autistic patients and 350 gender-matched controls from Spain (Toma et al., 2012). These findings suggested that common allelic variants in the DDC gene may be involved in autism susceptibility.

Score Delta: Score remained at 4

3

Suggestive Evidence

See all Category 3 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.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Two variants in the DDC gene were investigated for their potential to increase the susceptibility to autism by investigating a total of 90 parent-offspring trios recruited in Denmark and France using the transmission disequilibrium test (TDT) in Lauritsen et al., 2002, but no evidence of linkage disequilibrium was found between autism and either of the two polymorphisms, nor was linkage disequilibrium between autism and haplotypes of the two variants using a multiallelic TDT. However, significant association was obtained between the DDC gene and autism in the single-marker analysis (rs6592961, P = 0.00047) in a case-control genetic association study consisting of 326 unrelated autistic patients and 350 gender-matched controls from Spain (Toma et al., 2012). These findings suggested that common allelic variants in the DDC gene may be involved in autism susceptibility.

Reports Added
[New Scoring Scheme]
4/1/2018
icon
4.3

Increased from to 4.3

Description

4

Krishnan Probability Score

Score 0.49169387155049

Ranking 5222/25841 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 4.6066122919396E-5

Ranking 13498/18225 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 0.87668696579982

Ranking 4652/18665 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 1

Ranking 419/461 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 -0.23724792267025

Ranking 16150/20870 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.
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SFARI Gene Update

We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
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