Human Gene Module / Chromosome 7 / NXPH1

NXPH1neurexophilin 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
6 / 6
Rare Variants / Common Variants
9 / 0
Aliases
NXPH1, Nbla00697,  NPH1
Associated Syndromes
-
Chromosome Band
7p21.3
Associated Disorders
ID
Relevance to Autism

A rare duplication in the NXPH1 gene has been identified with ASD (Salyakina et al., 2011).

Molecular Function

This gene is a member of the neurexophilin family and encodes a secreted protein with a variable N-terminal domain, a highly conserved, N-glycosylated central domain, a short linker region, and a cysteine-rich C-terminal domain. This protein forms a very tight complex with alpha neurexins, a group of proteins that promote adhesion between dendrites and axons.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to NXPH1 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Copy number variants in extended autism spectrum disorder families reveal candidates potentially involved in autism risk Salyakina D , et al. (2011) Yes ID
2 Support A discovery resource of rare copy number variations in individuals with autism spectrum disorder Prasad A , et al. (2013) Yes -
3 Support Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder Girirajan S , et al. (2013) Yes -
4 Support Prospective diagnostic analysis of copy number variants using SNP microarrays in individuals with autism spectrum disorders Nava C , et al. (2013) Yes ID
5 Support Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder Takata A , et al. (2018) Yes -
6 Support - Zhou X et al. (2022) Yes -
Rare Variants   (9)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain Familial Maternal Simplex 23632794 Nava C , et al. (2013)
c.307A>G p.Arg103Gly missense_variant De novo - - 35982159 Zhou X et al. (2022)
- - copy_number_loss Familial Maternal Unknown 23275889 Prasad A , et al. (2013)
- - copy_number_gain Familial Paternal Simplex 23375656 Girirajan S , et al. (2013)
- - copy_number_loss Familial Paternal Simplex 23375656 Girirajan S , et al. (2013)
- - copy_number_gain Familial Paternal Multiplex 23375656 Girirajan S , et al. (2013)
c.130C>A p.His44Asn missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.307A>G p.Arg103Gly missense_variant De novo - Simplex 29346770 Takata A , et al. (2018)
- - copy_number_gain Familial Maternal Extended multiplex 22016809 Salyakina D , et al. (2011)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A study tested 42 ASD multiplex families for CNVs (PMID 22016809). It found one with a 7p21 duplication that included NXPH1. Another study also found a 7p21 duplication that included NXPH1 (PMID 21358714).

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

A study tested 42 ASD multiplex families for CNVs (PMID 22016809). It found one with a 7p21 duplication that included NXPH1. Another study also found a 7p21 duplication that included NXPH1 (PMID 21358714).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A study tested 42 ASD multiplex families for CNVs (PMID 22016809). It found one with a 7p21 duplication that included NXPH1. Another study also found a 7p21 duplication that included NXPH1 (PMID 21358714).

Reports Added
[New Scoring Scheme]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

A study tested 42 ASD multiplex families for CNVs (PMID 22016809). It found one with a 7p21 duplication that included NXPH1. Another study also found a 7p21 duplication that included NXPH1 (PMID 21358714).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

A study tested 42 ASD multiplex families for CNVs (PMID 22016809). It found one with a 7p21 duplication that included NXPH1. Another study also found a 7p21 duplication that included NXPH1 (PMID 21358714).

Krishnan Probability Score

Score 0.5679624304545

Ranking 1146/25841 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 0.55586107220294

Ranking 5185/18225 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 0.2728313059513

Ranking 159/18665 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 -0.17430413085823

Ranking 14819/20870 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
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