Human Gene Module / Chromosome 2 / PARD3B

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

Score
3
Suggestive Evidence Criteria 3.1
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 disorderspi. 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 - - 27479843 Lelieveld SH , et al. (2016)
c.3129C>G p.Tyr1043Ter stop_gained De novo - 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.2081_2082del p.Val694AspfsTer7 frameshift_variant De novo - - 28191889 Stessman HA , et al. (2017)
c.598_599del p.Met200AspfsTer37 frameshift_variant Familial Paternal - 27824329 Wang T , et al. (2016)
c.2186-726_2186-725delinsG p.? splice_site_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
3

Suggestive Evidence

3

Score Delta: Score remained at 3.3

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.

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.
CNVs associated with PARD3B(1 CNVs)
2q33.3 8 Deletion-Duplication 19  /  30
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