Human Gene Module / Chromosome 1 / NEGR1

NEGR1neuronal growth regulator 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
1 / 6
Rare Variants / Common Variants
1 / 1
Aliases
NEGR1, DMML2433,  IGLON4,  KILON,  Ntra
Associated Syndromes
-
Chromosome Band
1p31.1
Associated Disorders
-
Relevance to Autism

Negr1 knockout mice displayed abnormal neuronal growth, impaired social behavior, reversal learning deficits, and increased susceptibility to pentylenetetrazol (PTZ)-induced seizures (Singh et al., 2018). siRNA-mediated downregulation of Negr1 in mice resulted in abnormal neuronal migration and spine density during cortical development, as well as reduced ultrasonic vocalizations and impaired social interactions; Negr1 knockout mice presented with similar phenotypes (Szczurkowska et al., 2018). A 1p31.1 microdeletion affecting the NEGR1 gene was identified in two siblings presenting with learning disabilities, ADHD, and autistic features (Genovese et al., 2015).

Molecular Function

May be involved in cell-adhesion. May function as a trans-neural growth-promoting factor in regenerative axon sprouting in the mammalian brain

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to NEGR1 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Partial Deletion of Chromosome 1p31.1 Including only the Neuronal Growth Regulator 1 Gene in Two Siblings Genovese A , et al. (2015) No -
2 Primary Neuronal Growth and Behavioral Alterations in Mice Deficient for the Psychiatric Disease-Associated Negr1 Gene Singh K , et al. (2018) No -
3 Support Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression Wray NR , et al. (2018) No -
4 Recent Recommendation NEGR1 and FGFR2 cooperatively regulate cortical development and core behaviours related to autism disorders in mice Szczurkowska J , et al. (2018) No -
5 Recent Recommendation Identification of common genetic risk variants for autism spectrum disorder Grove J , et al. (2019) Yes -
6 Support Neural cell adhesion molecule Negr1 deficiency in mouse results in structural brain endophenotypes and behavioral deviations related to psychiatric disorders Singh K , et al. (2019) No -
Rare Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss Unknown - Multiplex 27617112 Genovese A , et al. (2015)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.176+18860T>C - intron_variant - - - 30804558 Grove J , et al. (2019)
SFARI Gene score
2

Strong Candidate

Negr1 knockout mice displayed abnormal neuronal growth, impaired social behavior, reversal learning deficits, and increased susceptibility to pentylenetetrazol (PTZ)-induced seizures (Singh et al., 2018). siRNA-mediated downregulation of Negr1 in mice resulted in abnormal neuronal migration and spine density during cortical development, as well as reduced ultrasonic vocalizations and impaired social interactions; Negr1 knockout mice presented with similar phenotypes (Szczurkowska et al., 2018). A 1p31.1 microdeletion affecting the NEGR1 gene was identified in two siblings presenting with learning disabilities, ADHD, and autistic features (Genovese et al., 2015). A genome-wide association meta-analysis of 18,381 ASD cases and 27,969 controls in Grove et al., 2019 identified an intronic SNP in NEGR1 (rs1620977) as the index variant for a locus demonstrating association with ASD (P = 1.2 x 10-4); this locus reached genome-wide significance (P = 6.66 x 10-9) following multi-trait analysis of genome-wide association (MTAG) using GWAS data for ASD from Grove et al., 2019 and major depressive disorder from Wray et al., 2018.

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

Negr1 knockout mice displayed abnormal neuronal growth, impaired social behavior, reversal learning deficits, and increased susceptibility to pentylenetetrazol (PTZ)-induced seizures (Singh et al., 2018). siRNA-mediated downregulation of Negr1 in mice resulted in abnormal neuronal migration and spine density during cortical development, as well as reduced ultrasonic vocalizations and impaired social interactions; Negr1 knockout mice presented with similar phenotypes (Szczurkowska et al., 2018). A 1p31.1 microdeletion affecting the NEGR1 gene was identified in two siblings presenting with learning disabilities, ADHD, and autistic features (Genovese et al., 2015). A genome-wide association meta-analysis of 18,381 ASD cases and 27,969 controls in Grove et al., 2019 identified an intronic SNP in NEGR1 (rs1620977) as the index variant for a locus demonstrating association with ASD (P = 1.2 x 10-4); this locus reached genome-wide significance (P = 6.66 x 10-9) following multi-trait analysis of genome-wide association (MTAG) using GWAS data for ASD from Grove et al., 2019 and major depressive disorder from Wray et al., 2018.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Negr1 knockout mice displayed abnormal neuronal growth, impaired social behavior, reversal learning deficits, and increased susceptibility to pentylenetetrazol (PTZ)-induced seizures (Singh et al., 2018). siRNA-mediated downregulation of Negr1 in mice resulted in abnormal neuronal migration and spine density during cortical development, as well as reduced ultrasonic vocalizations and impaired social interactions; Negr1 knockout mice presented with similar phenotypes (Szczurkowska et al., 2018). A 1p31.1 microdeletion affecting the NEGR1 gene was identified in two siblings presenting with learning disabilities, ADHD, and autistic features (Genovese et al., 2015). A genome-wide association meta-analysis of 18,381 ASD cases and 27,969 controls in Grove et al., 2019 identified an intronic SNP in NEGR1 (rs1620977) as the index variant for a locus demonstrating association with ASD (P = 1.2 x 10-4); this locus reached genome-wide significance (P = 6.66 x 10-9) following multi-trait analysis of genome-wide association (MTAG) using GWAS data for ASD from Grove et al., 2019 and major depressive disorder from Wray et al., 2018.

Reports Added
[New Scoring Scheme]
4/1/2019
4
icon
4

Decreased from 4 to 4

Description

Negr1 knockout mice displayed abnormal neuronal growth, impaired social behavior, reversal learning deficits, and increased susceptibility to pentylenetetrazol (PTZ)-induced seizures (Singh et al., 2018). siRNA-mediated downregulation of Negr1 in mice resulted in abnormal neuronal migration and spine density during cortical development, as well as reduced ultrasonic vocalizations and impaired social interactions; Negr1 knockout mice presented with similar phenotypes (Szczurkowska et al., 2018). A 1p31.1 microdeletion affecting the NEGR1 gene was identified in two siblings presenting with learning disabilities, ADHD, and autistic features (Genovese et al., 2015). A genome-wide association meta-analysis of 18,381 ASD cases and 27,969 controls in Grove et al., 2019 identified an intronic SNP in NEGR1 (rs1620977) as the index variant for a locus demonstrating association with ASD (P = 1.2 x 10-4); this locus reached genome-wide significance (P = 6.66 x 10-9) following multi-trait analysis of genome-wide association (MTAG) using GWAS data for ASD from Grove et al., 2019 and major depressive disorder from Wray et al., 2018.

Reports Added
[Neural cell adhesion molecule Negr1 deficiency in mouse results in structural brain endophenotypes and behavioral deviations related to psychiatric...2019]
1/1/2019
5
icon
4

Decreased from 5 to 4

Description

Negr1 knockout mice displayed abnormal neuronal growth, impaired social behavior, reversal learning deficits, and increased susceptibility to pentylenetetrazol (PTZ)-induced seizures (Singh et al., 2018). siRNA-mediated downregulation of Negr1 in mice resulted in abnormal neuronal migration and spine density during cortical development, as well as reduced ultrasonic vocalizations and impaired social interactions; Negr1 knockout mice presented with similar phenotypes (Szczurkowska et al., 2018). A 1p31.1 microdeletion affecting the NEGR1 gene was identified in two siblings presenting with learning disabilities, ADHD, and autistic features (Genovese et al., 2015). A genome-wide association meta-analysis of 18,381 ASD cases and 27,969 controls in Grove et al., 2019 identified an intronic SNP in NEGR1 (rs1620977) as the index variant for a locus demonstrating association with ASD (P = 1.2 x 10-4); this locus reached genome-wide significance (P = 6.66 x 10-9) following multi-trait analysis of genome-wide association (MTAG) using GWAS data for ASD from Grove et al., 2019 and major depressive disorder from Wray et al., 2018.

7/1/2018
icon
5

Increased from to 5

Description

Negr1 knockout mice displayed abnormal neuronal growth, impaired social behavior, reversal learning deficits, and increased susceptibility to pentylenetetrazol (PTZ)-induced seizures (Singh et al., 2018). siRNA-mediated downregulation of Negr1 in mice resulted in abnormal neuronal migration and spine density during cortical development, as well as reduced ultrasonic vocalizations and impaired social interactions; Negr1 knockout mice presented with similar phenotypes (Szczurkowska et al., 2018). A 1p31.1 microdeletion affecting the NEGR1 gene was identified in two siblings presenting with learning disabilities, ADHD, and autistic features (Genovese et al., 2015).

Krishnan Probability Score

Score 0.5712752808406

Ranking 799/25841 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 0.95134939497736

Ranking 2656/18225 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 0.91337750626707

Ranking 8004/18665 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 0.51888959366254

Ranking 386/20870 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
Submit New Gene

Report an Error