Human Gene Module / Chromosome 2 / NRP2

NRP2neuropilin 2

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
3 / 8
Rare Variants / Common Variants
2 / 2
Aliases
NRP2, NP2,  NPN2,  PRO2714,  MGC126574,  VEGF165R2
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Genetic Association
Chromosome Band
2q33.3
Associated Disorders
-
Relevance to Autism

Genetic association has been found between the NRP2 gene and autism in a Chinese Han population cohort (Wu et al., 2007).

Molecular Function

High affinity receptor for semaphorins 3C, 3F, VEGF-165 and VEGF-145 isoforms of VEGF, and the PLGF-2 isoform of PGF

Reports related to NRP2 (8 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Neuropilin-2 regulates the development of selective cranial and sensory nerves and hippocampal mossy fiber projections. Chen H , et al. (2000) No -
2 Recent Recommendation Dlx homeobox genes promote cortical interneuron migration from the basal forebrain by direct repression of the semaphorin receptor neuropilin-2. Le TN , et al. (2007) No -
3 Recent Recommendation Neuropilins and their ligands are important in the migration of gonadotropin-releasing hormone neurons. Cariboni A , et al. (2007) No -
4 Primary Association of the neuropilin-2 (NRP2) gene polymorphisms with autism in Chinese Han population. Wu S , et al. (2007) Yes -
5 Recent Recommendation Neuropilin 2/semaphorin 3F signaling is essential for cranial neural crest migration and trigeminal ganglion condensation. Gammill LS , et al. (2007) No -
6 Support Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior. Doan RN , et al. (2016) Yes -
7 Support Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder. Lim ET , et al. (2017) Yes -
8 Highly Cited Neuropilin is a semaphorin III receptor. Kolodkin AL , et al. (1997) No -
Rare Variants   (2)
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.2001C>T p.Thr667= synonymous_variant De novo NA Simplex 28714951 Lim ET , et al. (2017)
Common Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.1147-1721G>T C/A intron_variant - - - 17427189 Wu S , et al. (2007)
c.1674T>G p.(=) synonymous_variant - - - 17427189 Wu S , et al. (2007)
SFARI Gene score
3

Suggestive Evidence

There is a single association study of 169 Han Chinese trios reporting two SNPs with significant association. This study has not been replicated.

Score Delta: Score remained at 4

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

There is a single association study of 169 Han Chinese trios reporting two SNPs with significant association. This study has not been replicated.

Reports Added
[New Scoring Scheme]
7/1/2017
4
icon
4

Decreased from 4 to 4

Description

There is a single association study of 169 Han Chinese trios reporting two SNPs with significant association. This study has not been replicated.

10/1/2016
4
icon
4

Decreased from 4 to 4

Description

There is a single association study of 169 Han Chinese trios reporting two SNPs with significant association. This study has not been replicated.

7/1/2014
No data
icon
4

Increased from No data to 4

Description

There is a single association study of 169 Han Chinese trios reporting two SNPs with significant association. This study has not been replicated.

4/1/2014
No data
icon
4

Increased from No data to 4

Description

There is a single association study of 169 Han Chinese trios reporting two SNPs with significant association. This study has not been replicated.

Krishnan Probability Score

Score 0.55283659444413

Ranking 1360/25841 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 0.0017116502518865

Ranking 11379/18225 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 0.94806195306934

Ranking 17530/18665 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 2

Ranking 400/461 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 -0.12583105412229

Ranking 13336/20870 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.
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
FCGR3B Low affinity immunoglobulin gamma Fc region receptor III-B Human Protein Binding E9PNY5
LYZL1 Lysozyme-like protein 1 Human Protein Binding 84569 Q6UWQ5-2
MIR188 microRNA 188 Human DNA Binding 406964 N/A
SEMA3F sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3F Human Protein Binding 6405 Q13275
SIAE sialic acid acetylesterase Human Protein Binding 54414 Q9HAT2
ST8SIA3 Sia-alpha-2,3-Gal-beta-1,4-GlcNAc-R:alpha 2,8-sialyltransferase Human Protein Binding 51046 O43173
TAZ Tafazzin Human Protein Binding 6901 Q16635-2
TSPAN11 Tetraspanin-11 Human Protein Binding 441631 A1L157
VEGFC vascular endothelial growth factor C Human Protein Binding 7424 P49767
Submit New Gene

Report an Error