Human Gene Module / Chromosome 15 / NIPA2

NIPA2non imprinted in Prader-Willi/Angelman syndrome 2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
3 / 0
Aliases
-
Associated Syndromes
-
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.

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Reports related to NIPA2 (3 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
3 Support - Zhou X et al. (2022) Yes -
Rare Variants   (3)
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)
c.432C>G p.His144Gln missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
- - copy_number_gain Familial Paternal Multi-generational 20029941 van der Zwaag B , et al. (2009)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

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: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
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.

4/1/2022
3
icon
2

Decreased from 3 to 2

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).

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.
Original Source
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
Original Source
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).
Original Source
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.
Original Source
CNVs associated with NIPA2(1 CNVs)
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15q11.2 114 Deletion-Duplication 153  /  2238
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