Human Gene Module / Chromosome 1 / RASSF5

RASSF5Ras association domain family member 5

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 4
Rare Variants / Common Variants
3 / 1
Aliases
RASSF5, Maxp1,  NORE1,  NORE1A,  NORE1B,  RAPL,  RASSF3
Associated Syndromes
-
Chromosome Band
1q32.1
Associated Disorders
-
Relevance to Autism

A SNP within the RASSF5 gene showed association in the secondary analyses in a combined AGP GWA sample (Anney et al., 2012).

Molecular Function

This gene is a member of the Ras association domain family. It functions as a tumor suppressor, and is inactivated in a variety of cancers. The encoded protein localizes to centrosomes and microtubules, and associates with the GTP-activated forms of Ras, Rap1, and several other Ras-like small GTPases. The protein regulates lymphocyte adhesion and suppresses cell growth in response to activated Rap1 or Ras.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to RASSF5 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Individual common variants exert weak effects on the risk for autism spectrum disorders Anney R , et al. (2012) Yes -
2 Support Large-scale discovery of novel genetic causes of developmental disorders Deciphering Developmental Disorders Study (2014) No -
3 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
4 Support - Woodbury-Smith M et al. (2022) Yes -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.646G>A p.Asp216Asn missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.409T>C p.Cys137Arg missense_variant De novo - Multiplex 31398340 Ruzzo EK , et al. (2019)
c.1239C>A p.Ser413= synonymous_variant De novo - Unknown 25533962 Deciphering Developmental Disorders Study (2014)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.458-13252G>A;c.458-13256G>A - intron_variant - - - 22843504 Anney R , et al. (2012)
SFARI Gene score
2

Strong Candidate

A SNP within the RASSF5 gene showed association (P = 2.452E-07) in the secondary analyses in the combined Autism Genome Project GWA sample (Diagnosis: Spectrum; Subgroup: All; Inheritance: Maternal) in Anney et al., 2012.

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

A SNP within the RASSF5 gene showed association (P = 2.452E-07) in the secondary analyses in the combined Autism Genome Project GWA sample (Diagnosis: Spectrum; Subgroup: All; Inheritance: Maternal) in Anney et al., 2012.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A SNP within the RASSF5 gene showed association (P = 2.452E-07) in the secondary analyses in the combined Autism Genome Project GWA sample (Diagnosis: Spectrum; Subgroup: All; Inheritance: Maternal) in Anney et al., 2012.

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

Decreased from 4 to 4

Description

A SNP within the RASSF5 gene showed association (P = 2.452E-07) in the secondary analyses in the combined Autism Genome Project GWA sample (Diagnosis: Spectrum; Subgroup: All; Inheritance: Maternal) in Anney et al., 2012.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
7/1/2018
icon
4

Increased from to 4

Description

A SNP within the RASSF5 gene showed association (P = 2.452E-07) in the secondary analyses in the combined Autism Genome Project GWA sample (Diagnosis: Spectrum; Subgroup: All; Inheritance: Maternal) in Anney et al., 2012.

Krishnan Probability Score

Score 0.49001800914282

Ranking 6299/25841 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 0.24871106576521

Ranking 6760/18225 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 0.92310132809403

Ranking 9708/18665 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
Larsen Cumulative Evidence Score

Score 3

Ranking 357/461 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.
Original Source
Zhang D Score

Score -0.082597967553505

Ranking 11678/20870 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
VPS28 vacuolar protein sorting 28 homolog (S. cerevisiae) Human Protein Binding 51160 Q548N1
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