NRP2neuropilin 2
Autism Reports / Total Reports
5 / 10Rare Variants / Common Variants
4 / 2Aliases
NRP2, NP2, NPN2, PRO2714, MGC126574, VEGF165R2Associated Syndromes
-Chromosome Band
2q33.3Associated 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
External Links
SFARI Genomic Platforms
Reports related to NRP2 (10 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 | Support | - | Zhou X et al. (2022) | Yes | - |
| 10 | Highly Cited | Neuropilin is a semaphorin III receptor | Kolodkin AL , et al. (1997) | No | - |
Rare Variants (4)
| 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.2114C>G | p.Pro705Arg | missense_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.2001C>T | p.Thr667= | synonymous_variant | De novo | - | 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.
Score Delta: Score remained at 2
criteria met
See SFARI Gene'scoring criteriaWe 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
2
Decreased from 3 to 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.
10/1/2019
4
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
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
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
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
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.
External PIN Data
Interactome
- Protein Binding
- DNA Binding
- RNA Binding
- Protein Modification
- Direct Regulation
- ASD-Linked Genes
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 |