Human Gene Module / Chromosome 2 / PARD3B

PARD3BPar-3 partitioning defective 3 homolog B (C. elegans)

Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
6 / 7
Rare Variants / Common Variants
9 / 1
Aliases
PARD3B, ALS2CR19,  PAR3B,  PAR3L,  PAR3LC,  PAR3beta,  Par3Lb
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Genetic Association
Chromosome Band
2q33.3
Associated Disorders
-
Relevance to Autism

A SNP within the PARD3B gene showed association in the primary analyses of a combined AGP GWA sample (Anney et al., 2012).

Molecular Function

Putative adapter protein involved in asymmetrical cell division and cell polarization processes. May play a role in the formation of epithelial tight junctions.

Reports related to PARD3B (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Individual common variants exert weak effects on the risk for autism spectrum disorders Anney R , et al. (2012) Yes -
2 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
3 Support Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability Lelieveld SH et al. (2016) No -
4 Support Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior Doan RN , et al. (2016) Yes -
5 Support De novo genic mutations among a Chinese autism spectrum disorder cohort Wang T , et al. (2016) Yes -
6 Support Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases Stessman HA , et al. (2017) Yes -
7 Support Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model Guo H , et al. (2018) Yes -
Rare Variants   (9)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
G>T - intergenic_variant - - Unknown 27667684 Doan RN , et al. (2016)
c.476G>C p.Gly159Ala missense_variant De novo NA - 27479843 Lelieveld SH et al. (2016)
c.3129C>G p.Tyr1043Ter stop_gained De novo NA Simplex 25363768 Iossifov I et al. (2014)
c.1519G>A p.Ala507Thr missense_variant Familial Maternal - 27824329 Wang T , et al. (2016)
c.1424C>T p.Pro475Leu missense_variant Familial Paternal Simplex 30564305 Guo H , et al. (2018)
c.1693G>A p.Glu565Lys missense_variant Familial paternal/maternal - 27824329 Wang T , et al. (2016)
c.2186-726_2186-725delinsG - splice_site_variant Familial Paternal - 27824329 Wang T , et al. (2016)
c.2081_2082del p.Val694AspfsTer7 frameshift_variant De novo NA - 28191889 Stessman HA , et al. (2017)
c.598_599del p.Met200AspfsTer37 frameshift_variant Familial Paternal - 27824329 Wang T , et al. (2016)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.2141-24331G>A;c.1955-24331G>A;c.1544-24331G>A - intron_variant - - - 22843504 Anney R , et al. (2012)
SFARI Gene score
2

Strong Candidate

A SNP within the PARD3B gene showed association in the primary analyses of a combined AGP GWA sample with a P-value of 4.340E07 (PMID 22843504). Two de novo loss-of-function variants in PARD3B were identified in ASD probands (the first in a proband from the Simons Simplex Collection in Iossifov et al., 2014, and the second in a proband from the Autism Genetic Resource Exchange in Stessman et al., 2017).

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 SNP within the PARD3B gene showed association in the primary analyses of a combined AGP GWA sample with a P-value of 4.340E07 (PMID 22843504). Two de novo loss-of-function variants in PARD3B were identified in ASD probands (the first in a proband from the Simons Simplex Collection in Iossifov et al., 2014, and the second in a proband from the Autism Genetic Resource Exchange in Stessman et al., 2017).

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

Decreased from 3 to 3

Description

A SNP within the PARD3B gene showed association in the primary analyses of a combined AGP GWA sample with a P-value of 4.340E07 (PMID 22843504). Two de novo loss-of-function variants in PARD3B were identified in ASD probands (the first in a proband from the Simons Simplex Collection in Iossifov et al., 2014, and the second in a proband from the Autism Genetic Resource Exchange in Stessman et al., 2017).

1/1/2017
4
icon
3

Decreased from 4 to 3

Description

A SNP within the PARD3B gene showed association in the primary analyses of a combined AGP GWA sample with a P-value of 4.340E?07 (PMID 22843504). Two de novo loss-of-function variants in PARD3B were identified in ASD probands (the first in a proband from the Simons Simplex Collection in Iossifov et al., 2014, and the second in a proband from the Autism Genetic Resource Exchange in Stessman et al., 2017).

10/1/2016
4
icon
4

Decreased from 4 to 4

Description

A SNP within the PARD3B gene showed association in the primary analyses of a combined AGP GWA sample with a P-value of 4.340E?07 (PMID 22843504).

7/1/2016
4
icon
4

Decreased from 4 to 4

Description

A SNP within the PARD3B gene showed association in the primary analyses of a combined AGP GWA sample with a P-value of 4.340E?07 (PMID 22843504).

1/1/2016
4
icon
4

Decreased from 4 to 4

Description

A SNP within the PARD3B gene showed association in the primary analyses of a combined AGP GWA sample with a P-value of 4.340E?07 (PMID 22843504).

7/1/2015
icon
4

Increased from to 4

Description

A SNP within the PARD3B gene showed association in the primary analyses of a combined AGP GWA sample with a P-value of 4.340E?07 (PMID 22843504).

Krishnan Probability Score

Score 0.49357276231536

Ranking 4073/25841 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 8.6451881387333E-8

Ranking 15717/18225 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 0.7239525501577

Ranking 1325/18665 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 7

Ranking 245/461 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 -0.39586271297124

Ranking 18326/20870 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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