Human Gene Module / Chromosome 6 / KHDRBS2

KHDRBS2KH domain containing, RNA binding, signal transduction associated 2

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
4 / 0
Aliases
KHDRBS2, SLM-1,  SLM1,  bA535F17.1
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
6q11.1
Associated Disorders
ASD
Relevance to Autism

A rare deletion of an intronic segment within the KHDRBS2 gene has been identified with ASD (Salyakina et al., 2011).

Molecular Function

RNA-binding protein that plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion. Its phosphorylation by FYN inhibits its ability to regulate splice site selection. Its phosphorylation by PTK6 inhibits its RNA-binding ability. May function as an adapter protein for Src kinases during mitosis. Binds both poly(A) and poly(U) homopolymers.

Reports related to KHDRBS2 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Copy number variants in extended autism spectrum disorder families reveal candidates potentially involved in autism risk. Salyakina D , et al. (2011) Yes AS
2 Support Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder. Girirajan S , et al. (2013) Yes -
3 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks. Ruzzo EK , et al. (2019) Yes -
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain Familial Maternal Simplex 23375656 Girirajan S , et al. (2013)
- - copy_number_gain Familial Paternal Multiplex 23375656 Girirajan S , et al. (2013)
- - copy_number_loss Familial Maternal Extended multiplex 22016809 Salyakina D , et al. (2011)
c.736C>T p.Arg246Ter stop_gained Familial Maternal Multiplex (monozygotic twins) 31398340 Ruzzo EK , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

A rare deletion of an intronic segment within the KHDRBS2 gene has been identified with ASD (Salyakina et al., 2011).

Score Delta: Score remained at 4

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A rare deletion of an intronic segment within the KHDRBS2 gene has been identified with ASD (Salyakina et al., 2011).

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

A rare deletion of an intronic segment within the KHDRBS2 gene has been identified with ASD (Salyakina et al., 2011).

7/1/2014
No data
icon
4

Increased from No data to 4

Description

A rare deletion of an intronic segment within the KHDRBS2 gene has been identified with ASD (Salyakina et al., 2011).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

A rare deletion of an intronic segment within the KHDRBS2 gene has been identified with ASD (Salyakina et al., 2011).

Krishnan Probability Score

Score 0.55881486701041

Ranking 1324/25841 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 0.14287830225093

Ranking 7447/18225 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 0.94429883351144

Ranking 16021/18665 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).
Zhang D Score

Score 0.33504803298628

Ranking 2208/20870 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
ACAA1 3-ketoacyl-CoA thiolase, peroxisomal Human Protein Binding 30 P09110
ACAD11 Acyl-CoA dehydrogenase family member 11 Human Protein Binding 84129 Q709F0
CAPG Macrophage-capping protein Human Protein Binding 822 P40121
CATSPER1 cation channel, sperm associated 1 Human Protein Binding 117144 Q8NEC5
DSG1 desmoglein 1 Human Protein Binding 1828 Q02413
FOXA3 Hepatocyte nuclear factor 3-gamma Human Protein Binding 3171 P55318
HBZ hemoglobin, zeta Human Protein Binding 3050 P02008
HRNR hornerin Human Protein Binding 388697 Q86YZ3
LINC01018 long intergenic non-protein coding RNA 1018 Human Protein Binding 255167
NABP1 nucleic acid binding protein 1 Human Protein Binding 64859 Q96AH0
SULT1A3 sulfotransferase family, cytosolic, 1A, phenol-preferring, member 3 Human Protein Binding 6818 P0DMM9
TYMSOS TYMS opposite strand Human Protein Binding 494514 Q8TAI1
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