Human Gene Module / Chromosome 5 / NUDCD2

NUDCD2NudC domain containing 2

Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
3 / 0
Aliases
NUDCD2, NudCL2
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
5q34
Associated Disorders
-
Relevance to Autism

A de novo missense variant in the NUDCD2 gene was identified in two ASD probands from Yuen et al., 2017. CNV analysis of 1,108 ASD cases, 2,458 schizophrenia (SCZ) cases, and 2,095 controls from a Japanese population in Kushima et al., 2018 demonstrated that significant enrichment of exonic CNVs affecting the NUDCD2 gene was observed in a combined cohort of ASD and SCZ cases compared to controls [3 CNVs from ASD cases and 3 CNVs from SCZ cases (6 total) vs. 1 CNV in controls (Odds ratio 2.75, P = 3.2E-02)].

Molecular Function

May regulate the LIS1/dynein pathway by stabilizing LIS1 with Hsp90 chaperone.

Reports related to NUDCD2 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. C Yuen RK , et al. (2017) Yes -
2 Recent Recommendation Comparative Analyses of Copy-Number Variation in Autism Spectrum Disorder and Schizophrenia Reveal Etiological Overlap and Biological Insights. Kushima I , et al. (2018) Yes -
3 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks. Ruzzo EK , et al. (2019) Yes -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain Unknown - - 30208311 Kushima I , et al. (2018)
c.218A>T p.Asp73Val missense_variant De novo NA Multiplex 28263302 C Yuen RK , et al. (2017)
c.131_134del p.Arg44MetfsTer10 frameshift_variant Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo missense variant in the NUDCD2 gene was identified in two ASD probands from Yuen et al., 2017. CNV analysis of 1,108 ASD cases, 2,458 schizophrenia (SCZ) cases, and 2,095 controls from a Japanese population in Kushima et al., 2018 demonstrated that significant enrichment of exonic CNVs affecting the NUDCD2 gene was observed in a combined cohort of ASD and SCZ cases compared to controls [3 CNVs from ASD cases and 3 CNVs from SCZ cases (6 total) vs. 1 CNV in controls (Odds ratio 2.75, P = 3.2E-02)].

Score Delta: Score remained at 3

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.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

A de novo missense variant in the NUDCD2 gene was identified in two ASD probands from Yuen et al., 2017. CNV analysis of 1,108 ASD cases, 2,458 schizophrenia (SCZ) cases, and 2,095 controls from a Japanese population in Kushima et al., 2018 demonstrated that significant enrichment of exonic CNVs affecting the NUDCD2 gene was observed in a combined cohort of ASD and SCZ cases compared to controls [3 CNVs from ASD cases and 3 CNVs from SCZ cases (6 total) vs. 1 CNV in controls (Odds ratio 2.75, P = 3.2E-02)].

Reports Added
[New Scoring Scheme]
7/1/2019
3
icon
3

Decreased from 3 to 3

Description

A de novo missense variant in the NUDCD2 gene was identified in two ASD probands from Yuen et al., 2017. CNV analysis of 1,108 ASD cases, 2,458 schizophrenia (SCZ) cases, and 2,095 controls from a Japanese population in Kushima et al., 2018 demonstrated that significant enrichment of exonic CNVs affecting the NUDCD2 gene was observed in a combined cohort of ASD and SCZ cases compared to controls [3 CNVs from ASD cases and 3 CNVs from SCZ cases (6 total) vs. 1 CNV in controls (Odds ratio 2.75, P = 3.2E-02)].

10/1/2018
icon
3

Increased from to 3

Description

A de novo missense variant in the NUDCD2 gene was identified in two ASD probands from Yuen et al., 2017. CNV analysis of 1,108 ASD cases, 2,458 schizophrenia (SCZ) cases, and 2,095 controls from a Japanese population in Kushima et al., 2018 demonstrated that significant enrichment of exonic CNVs affecting the NUDCD2 gene was observed in a combined cohort of ASD and SCZ cases compared to controls [3 CNVs from ASD cases and 3 CNVs from SCZ cases (6 total) vs. 1 CNV in controls (Odds ratio 2.75, P = 3.2E-02)].

Krishnan Probability Score

Score 0.33024194756793

Ranking 24861/25841 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 0.00081208219306306

Ranking 11928/18225 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 0.91841061725129

Ranking 8817/18665 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 -0.20417165448258

Ranking 15518/20870 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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