Human Gene Module / Chromosome 15 / NIPA2

NIPA2non imprinted in Prader-Willi/Angelman syndrome 2

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
2 / 2
Rare Variants / Common Variants
2 / 0
Aliases
-
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
15q11.2
Associated Disorders
ID
Relevance to Autism

A rare NIPA2 deletion was found in a patient with PDD-NOS and mild intellectual disability (Leblond et al., 2012).

Molecular Function

This gene encodes a possible magnesium transporter. This gene is located adjacent to the imprinted domain in the Prader-Willi syndrome deletion region of chromosome 15. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 3, 7 and 21.

Reports related to NIPA2 (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support A co-segregating microduplication of chromosome 15q11.2 pinpoints two risk genes for autism spectrum disorder. van der Zwaag B , et al. (2009) Yes -
2 Primary Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders. Leblond CS , et al. (2012) Yes ID
Rare Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss Familial Paternal Simplex 22346768 Leblond CS , et al. (2012)
- - copy_number_gain Familial Paternal Multi-generational 20029941 van der Zwaag B , et al. (2009)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

NIPA2 is one of four genes that resides within the 15q11.2 CNV locus, a chromosomal region between breakpoints 1 (BP1) and 2 (BP2) of the Prader-Willi/Angelman syndrome critical region in which deletions and duplications are associated with increased susceptibility to neurodevelopmental disorders, including autism (van der Zwaag et al., 2010; Leblond et al., 2012).

Score Delta: Decreased from 4 to 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.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

NIPA2 is one of four genes that resides within the 15q11.2 CNV locus, a chromosomal region between breakpoints 1 (BP1) and 2 (BP2) of the Prader-Willi/Angelman syndrome critical region in which deletions and duplications are associated with increased susceptibility to neurodevelopmental disorders, including autism (van der Zwaag et al., 2010; Leblond et al., 2012).

Reports Added
[New Scoring Scheme]
10/1/2017
icon
4

Increased from to 4

Description

NIPA2 is one of four genes that resides within the 15q11.2 CNV locus, a chromosomal region between breakpoints 1 (BP1) and 2 (BP2) of the Prader-Willi/Angelman syndrome critical region in which deletions and duplications are associated with increased susceptibility to neurodevelopmental disorders, including autism (van der Zwaag et al., 2010; Leblond et al., 2012).

Krishnan Probability Score

Score 0.4490718568878

Ranking 11305/25841 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 0.48719375365062

Ranking 5520/18225 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 0.8950968507404

Ranking 5927/18665 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 -0.11400718603516

Ranking 12897/20870 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 NIPA2(1 CNVs)
15q11.2 93 Deletion-Duplication 131  /  2196
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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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