Human Gene Module / Chromosome 20 / NINL

NINLNinein-like

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
10 / 10
Rare Variants / Common Variants
11 / 0
Aliases
NINL, NLP,  dJ691N24.1
Associated Syndromes
-
Chromosome Band
20p11.21
Associated Disorders
-
Relevance to Autism

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015); among the variants identified in this gene was one de novo loss-of-function (LoF) variant.

Molecular Function

The protein encoded by this gene is involved in the microtubule organization in interphase cells. Overexpression induces the fragmentation of the Golgi, and causes lysosomes to disperse toward the cell periphery; it also interferes with mitotic spindle assembly

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to NINL (10 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
3 Primary Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci Sanders SJ , et al. (2015) Yes -
4 Support Both rare and common genetic variants contribute to autism in the Faroe Islands Leblond CS , et al. (2019) Yes -
5 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
6 Support Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort Wu H , et al. (2019) Yes Macrocephaly
7 Support - Woodbury-Smith M et al. (2022) Yes -
8 Support - Zhou X et al. (2022) Yes -
9 Support - Hu C et al. (2023) Yes -
10 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (11)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1170-49T>G - intron_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.2050G>A p.Glu684Lys missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.285C>T p.Ser95%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.3285G>T p.Leu1095Phe missense_variant De novo - - 35982159 Zhou X et al. (2022)
- - copy_number_loss Familial Paternal Simplex 30675382 Leblond CS , et al. (2019)
c.3349C>T p.Gln1117Ter stop_gained Familial Maternal - 37007974 Hu C et al. (2023)
c.1951A>T p.Lys651Ter stop_gained De novo - Simplex 25363768 Iossifov I et al. (2014)
c.2092C>T p.Gln698Ter stop_gained Familial Paternal Simplex 31674007 Wu H , et al. (2019)
c.3656G>T p.Trp1219Leu missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.2535+1G>A - splice_site_variant Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.2201+2078C>T - stop_gained Familial Paternal Multiplex (monozygotic twins) 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of < 0.1 (Sanders et al., 2015); among the variants identified in this gene was one de novo loss-of-function (LoF) variant.

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.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of < 0.1 (Sanders et al., 2015); among the variants identified in this gene was one de novo loss-of-function (LoF) variant.

Reports Added
[Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort.2019] [New Scoring Scheme]
7/1/2019
3
icon
3

Decreased from 3 to 3

Description

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of < 0.1 (Sanders et al., 2015); among the variants identified in this gene was one de novo loss-of-function (LoF) variant.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
1/1/2019
3
icon
3

Decreased from 3 to 3

Description

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of < 0.1 (Sanders et al., 2015); among the variants identified in this gene was one de novo loss-of-function (LoF) variant.

Reports Added
[Both rare and common genetic variants contribute to autism in the Faroe Islands.2019]
10/1/2015
icon
3

Increased from to 3

Description

This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015); among the variants identified in this gene was one de novo loss-of-function (LoF) variant.

Krishnan Probability Score

Score 0.49491765029868

Ranking 3343/25841 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 3.9683078919321E-33

Ranking 18178/18225 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 0.060407456000486

Ranking 50/18665 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 -0.05535052027541

Ranking 10607/20870 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
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
ACTR10 actin-related protein 10 homolog (S. cerevisiae) Human Protein Binding 55860 Q9NZ32
C10ORF96 Coiled-coil domain-containing protein 172 Human Protein Binding 374355 P0C7W6
DCTN3 dynactin subunit 3 Human Protein Binding 11258 O75935
DZANK1 double zinc ribbon and ankyrin repeat domains 1 Human Protein Binding 55184 Q9NVP4
RGS2 regulator of G-protein signaling 2, 24kDa Human Protein Binding 5997 P41220
TPM2 Tropomyosin beta chain Human Protein Binding 7169 P07951-2
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