Human Gene Module / Chromosome 1 / RIMS3

RIMS3regulating synaptic membrane exocytosis 3

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
1 / 4
Rare Variants / Common Variants
7 / 0
Aliases
RIMS3, NIM3,  RIM3,  KIAA0237,  RIMS3
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
1p34.2
Associated Disorders
-
Relevance to Autism

Rare variants in the RIMS3 gene have been identified with autism (Kumar et al., 2010).

Molecular Function

Synaptic protein essential for vesicle fusion and normal neurotransmitter release

Reports related to RIMS3 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited The RIM/NIM family of neuronal C2 domain proteins. Interactions with Rab3 and a new class of Src homology 3 domain proteins. Wang Y , et al. (2000) No -
2 Recent Recommendation Investigation of the expression of genes affecting cytomatrix active zone function in the amygdala in schizophrenia: effects of antipsychotic drugs. Weidenhofer J , et al. (2008) No -
3 Primary A de novo 1p34.2 microdeletion identifies the synaptic vesicle gene RIMS3 as a novel candidate for autism. Kumar RA , et al. (2009) Yes -
4 Recent Recommendation Rab3 interacting molecule 3 mutations associated with autism alter regulation of voltage-dependent Ca(2) channels. Takada Y , et al. (2015) No -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
23661G>A - 5_prime_UTR_variant - - - 19546099 Kumar RA , et al. (2009)
c.801C>T p.(=) synonymous_variant Familial Maternal - 19546099 Kumar RA , et al. (2009)
c.619G>A p.Ala207Thr missense_variant Familial Paternal - 19546099 Kumar RA , et al. (2009)
c.7A>C p.Asn3His missense_variant Familial Maternal Multiplex 19546099 Kumar RA , et al. (2009)
c.530A>C p.Glu177Ala missense_variant Familial Maternal Multiplex 19546099 Kumar RA , et al. (2009)
c.778A>G p.Met260Val missense_variant Familial Paternal Multiplex 19546099 Kumar RA , et al. (2009)
c.472+31G>A;c.484+31G>A;c.433+31G>A;c.190+31G>A - intron_variant Familial Paternal Multiplex 19546099 Kumar RA , et al. (2009)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

Rare variants were identified in a multi-genic CNV region (Kumar et al., 2010; PMID: 19546099). Functional analysis of two of the missense variants identified in Kumar et al., 2010 revealed an effect of these variants on regulation of voltage-dependent Ca2+ channels (PMID 26142343).

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.

7/1/2015
7/1/2014
No data
icon
4

Increased from No data to 4

Description

Rare variants were identified in a multi-genic CNV region (Kumar et al., 2010; PMID: 19546099).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

Rare variants were identified in a multi-genic CNV region (Kumar et al., 2010; PMID: 19546099).

Krishnan Probability Score

Score 0.61236874911701

Ranking 173/25841 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 0.0072511083199778

Ranking 10278/18225 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 0.93649029943967

Ranking 13213/18665 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 0

Ranking 457/461 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 0.28256948760825

Ranking 2992/20870 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.
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