Human Gene Module / Chromosome 2 / NRP2

NRP2neuropilin 2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 9
Rare Variants / Common Variants
3 / 2
Aliases
NRP2, NP2,  NPN2,  PRO2714,  MGC126574,  VEGF165R2
Associated Syndromes
-
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 (9 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 Support - Woodbury-Smith M et al. (2022) Yes -
9 Highly Cited Neuropilin is a semaphorin III receptor Kolodkin AL , et al. (1997) No -
Rare Variants   (3)
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)
c.1858G>A p.Glu620Lys missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
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
2

Strong Candidate

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

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
2

Initial score established: 2

Description

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

10/1/2021
3

Initial score established: 3

Description

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

7/1/2021
3

Initial score established: 3

Description

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

4/1/2021
3

Initial score established: 3

Description

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

1/1/2021
3

Initial score established: 3

Description

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

10/1/2020
3

Initial score established: 3

Description

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

7/1/2020
3

Initial score established: 3

Description

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

4/1/2020
3

Initial score established: 3

Description

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

1/1/2020
3

Initial score established: 3

Description

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

10/1/2019
3

Initial score established: 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]
7/1/2019
3

Initial score established: 3

Description

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

4/1/2019
3

Initial score established: 3

Description

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

1/1/2019
3

Initial score established: 3

Description

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

10/1/2018
3

Initial score established: 3

Description

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

7/1/2018
4

Initial score established: 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.

4/1/2018
4.3

Initial score established: 4.3

Description

4

1/1/2018
4

Initial score established: 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.

10/1/2017
3

Initial score established: 3

Description

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

7/1/2017
4

Initial score established: 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.

4/1/2017
4

Initial score established: 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.

1/1/2017
4

Initial score established: 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
3

Initial score established: 3

Description

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

7/1/2016
4

Initial score established: 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.

4/1/2016
4

Initial score established: 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.

1/1/2016
4

Initial score established: 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.

10/1/2015
3

Initial score established: 3

Description

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

7/1/2015
4

Initial score established: 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.

4/1/2015
4

Initial score established: 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.

1/1/2015
4

Initial score established: 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.

10/1/2014
3

Initial score established: 3

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
4

Initial score established: 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
4

Initial score established: 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
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