DCCDCCnetrin 1 receptor
Autism Reports / Total Reports
4 / 6Rare Variants / Common Variants
4 / 3Aliases
DCC, CRC18, CRCR1, HGPPS2, IGDCC1, MRMV1, NTN1R1Associated Syndromes
-Chromosome Band
18q21.2Associated Disorders
-Relevance to Autism
A cross-trait meta-analysis of genome-wide association studies on schizophrenia (65,967 cases), bipolar disorder (41,653 cases), autism spectrum disorder (46,350 cases), ADHD (55,374 cases) and depression (688,809 cases) identified an intronic SNP in the DCC gene that reached genome-wide significance for ASD following MTAG analysis (P-value 2.69E-08) (Wu et al., 2020). Other SNPs in this gene have previously been shown to reach genome-wide significance for association with depression (Wray et al., 2018; Howard et al., 2019).
Molecular Function
This gene encodes a netrin 1 receptor. The transmembrane protein is a member of the immunoglobulin superfamily of cell adhesion molecules, and mediates axon guidance of neuronal growth cones towards sources of netrin 1 ligand. The cytoplasmic tail interacts with the tyrosine kinases Src and focal adhesion kinase (FAK, also known as PTK2) to mediate axon attraction.
External Links
SFARI Genomic Platforms
Reports related to DCC (6 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Positive Association | Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression | Wray NR , et al. (2018) | No | - |
| 2 | Positive Association | Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions | Howard DM et al. (2019) | No | - |
| 3 | Primary | Multi-trait analysis for genome-wide association study of five psychiatric disorders | Wu Y et al. (2020) | Yes | - |
| 4 | Support | - | Tuncay IO et al. (2023) | Yes | - |
| 5 | Support | - | Cirnigliaro M et al. (2023) | Yes | - |
| 6 | Support | - | Duyen T Bui et al. (2024) | Yes | - |
Rare Variants (4)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.526A>G | p.Asn176Asp | missense_variant | Familial | Maternal | - | 37492102 | Tuncay IO et al. (2023) | |
| c.2260G>A | p.Val754Met | missense_variant | Unknown | - | Unknown | 38287090 | Duyen T Bui et al. (2024) | |
| c.3797C>T | p.Pro1266Leu | missense_variant | Familial | Paternal | - | 37492102 | Tuncay IO et al. (2023) | |
| c.2869G>T | p.Glu957Ter | stop_gained | Familial | Maternal | Multiplex | 37506195 | Cirnigliaro M et al. (2023) |
Common Variants (3)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.1911+5224A>C | - | intron_variant | - | - | - | 32606422 | Wu Y et al. (2020) | |
| c.1722+68G>A | - | intron_variant | - | - | - | 30718901 | Howard DM et al. (2019) | |
| c.1261+22196G>A | - | intron_variant | - | - | - | 29700475 | Wray NR , et al. (2018) |
SFARI Gene score
2
Strong Candidate
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
2
Increased from to 2
Krishnan Probability Score
Score 0.5671383423216
Ranking 1193/25841 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 0.99999895681268
Ranking 302/18225 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 0.95033410170057
Ranking 18451/18665 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 0.087193753130986
Ranking 6391/20870 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.