Human Gene Module / Chromosome 7 / DDC

DDCdopa decarboxylase

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 8
Rare Variants / Common Variants
7 / 1
Aliases
DDC, AADC
Associated Syndromes
-
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.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to DDC (8 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 -
3 Support - Alonso-Gonzalez A et al. (2021) Yes -
4 Support - Mitani T et al. (2021) No -
5 Support - Zhou X et al. (2022) Yes -
6 Support - Cirnigliaro M et al. (2023) Yes -
7 Support - Amerh S Alqahtani et al. (2023) No -
8 Support - Axel Schmidt et al. (2024) No -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.849G>C p.Glu283Asp missense_variant Unknown - - 39039281 Axel Schmidt et al. (2024)
c.759T>A p.Asn253Lys missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1066_1068del p.Arg356del inframe_deletion Unknown - - 39039281 Axel Schmidt et al. (2024)
c.1331T>C p.Phe444Ser missense_variant De novo - Simplex 33431980 Alonso-Gonzalez A et al. (2021)
c.1040G>A p.Arg347Gln missense_variant Familial Both parents Simplex 34582790 Mitani T et al. (2021)
c.1234C>T p.Arg412Trp missense_variant Familial Both parents Simplex 37799141 Amerh S Alqahtani et al. (2023)
c.480del p.Thr161ProfsTer3 frameshift_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
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
2

Strong Candidate

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 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

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.

1/1/2021
3
icon
3

Decreased from 3 to 3

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
[Exploring the biological role of postzygotic and germinal de novo mutations in ASD2021]
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]
7/1/2018
icon
4

Increased from to 4

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.

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.
Original Source
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
Original Source
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).
Original Source
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.
Original Source
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.
Original Source
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