Human Gene Module / Chromosome 12 / DENR

DENRdensity-regulated protein

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 4
Rare Variants / Common Variants
3 / 0
Aliases
DENR, DRP,  DRP1,  SMAP-3
Associated Syndromes
-
Chromosome Band
12q24.31
Associated Disorders
ASD
Relevance to Autism

De novo missense variants in the DENR gene were identified in two unrelated ASD probands (Neale et al., 2012; Haas et al., 2016); additional functional characterization of these variants in Haas et al., 2016 demonstrated effects on migration, dendritic branching, and dendritic spine properties of cortical neurons.

Molecular Function

This gene encodes a protein that is involved in mRNA translation initiation by promoting the recruitment of aminoacetyled initiator tRNA to P site of 40S ribosomes. Haas et al., 2016 demonstrated that DENR controls radial migration in the mouse brain through its binding partner MCTS1.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to DENR (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Patterns and rates of exonic de novo mutations in autism spectrum disorders Neale BM , et al. (2012) Yes -
2 Recent Recommendation De Novo Mutations in DENR Disrupt Neuronal Development and Link Congenital Neurological Disorders to Faulty mRNA Translation Re-initiation Haas MA , et al. (2016) Yes -
3 Support Contribution of rare and common variants to intellectual disability in a sub-isolate of Northern Finland Kurki MI , et al. (2019) No ASD
4 Support - Young DJ et al. (2021) Yes -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.67T>G p.Leu23Val missense_variant Unknown - - 30679432 Kurki MI , et al. (2019)
c.362C>T p.Pro121Leu missense_variant De novo - Simplex 27239039 Haas MA , et al. (2016)
c.110G>A p.Cys37Tyr missense_variant De novo - Simplex 22495311 Neale BM , et al. (2012)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Haas et al., 2016 demonstrated that DENR controls radial migration in the mouse brain through its binding partner MCTS1. De novo missense variants in the DENR gene were identified in two unrelated ASD probands (Neale et al., 2012; Haas et al., 2016); additional functional characterization of these variants in Haas et al., 2016 demonstrated effects on migration, dendritic branching, and dendritic spine properties of cortical neurons.

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.

4/1/2021
2
icon
2

Score remained at 2

Description

Haas et al., 2016 demonstrated that DENR controls radial migration in the mouse brain through its binding partner MCTS1. De novo missense variants in the DENR gene were identified in two unrelated ASD probands (Neale et al., 2012; Haas et al., 2016); additional functional characterization of these variants in Haas et al., 2016 demonstrated effects on migration, dendritic branching, and dendritic spine properties of cortical neurons.

Reports Added
[40S ribosome profiling reveals distinct roles for Tma20/Tma22 (MCT-1/DENR) and Tma64 (eIF2D) in 40S subunit recycling2021]
10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

Haas et al., 2016 demonstrated that DENR controls radial migration in the mouse brain through its binding partner MCTS1. De novo missense variants in the DENR gene were identified in two unrelated ASD probands (Neale et al., 2012; Haas et al., 2016); additional functional characterization of these variants in Haas et al., 2016 demonstrated effects on migration, dendritic branching, and dendritic spine properties of cortical neurons.

Reports Added
[New Scoring Scheme]
4/1/2019
3
icon
3

Decreased from 3 to 3

Description

Haas et al., 2016 demonstrated that DENR controls radial migration in the mouse brain through its binding partner MCTS1. De novo missense variants in the DENR gene were identified in two unrelated ASD probands (Neale et al., 2012; Haas et al., 2016); additional functional characterization of these variants in Haas et al., 2016 demonstrated effects on migration, dendritic branching, and dendritic spine properties of cortical neurons.

Reports Added
[Contribution of rare and common variants to intellectual disability in a sub-isolate of Northern Finland.2019]
4/1/2016
icon
3

Increased from to 3

Description

Haas et al., 2016 demonstrated that DENR controls radial migration in the mouse brain through its binding partner MCTS1. De novo missense variants in the DENR gene were identified in two unrelated ASD probands (Neale et al., 2012; Haas et al., 2016); additional functional characterization of these variants in Haas et al., 2016 demonstrated effects on migration, dendritic branching, and dendritic spine properties of cortical neurons.

Krishnan Probability Score

Score 0.45586873127629

Ranking 9971/25841 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 0.8462527825805

Ranking 3642/18225 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 0.63511971856949

Ranking 835/18665 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 -0.12070284478322

Ranking 13163/20870 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
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